ZRANB1 Data Analysis

HGNC Gene Name
zinc finger RANBP2-type containing 1
HGNC Gene Symbol
ZRANB1
Identifiers
hgnc:18224 NCBIGene:54764 uniprot:Q9UGI0
Orthologs
mgi:106441 rgd:2321751
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for ZRANB1
Number of Papers
27 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
HECTD1 HECT domain E3 ubiquitin protein ligase 1 0.451 BioGRID IntAct INDRA (4)
ZGPAT zinc finger CCCH-type and G-patch domain containing 0.247 -90.91 kd
OR2L5 olfactory receptor family 2 subfamily L member 5 0.241
TEX36 testis expressed 36 0.233
KCMF1 potassium channel modulatory factor 1 0.224
SNX1 sorting nexin 1 -0.221
METTL13 methyltransferase 13, eEF1A lysine and N-terminal methyltransferase -0.215

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with ZRANB1using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out ZRANB1 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
ANKRD1 ankyrin repeat domain 1 4.75e-01 3.58e-09 1.01e-05
PTBP1 polypyrimidine tract binding protein 1 9.13e-01 8.97e-08 1.26e-04
MYH9 myosin heavy chain 9 6.32e-01 3.40e-07 3.19e-04
TAF15 TATA-box binding protein associated factor 15 8.60e-01 2.29e-06 1.61e-03
CALR calreticulin 4.21e-01 3.24e-06 1.81e-03
SPTBN1 spectrin beta, non-erythrocytic 1 5.15e-01 3.86e-06 1.81e-03
HNRNPA2B1 heterogeneous nuclear ribonucleoprotein A2/B1 3.09e-01 5.48e-06 2.20e-03
G0S2 G0/G1 switch 2 -4.14e-01 6.55e-06 2.31e-03
NRDC nardilysin convertase 5.98e-01 4.80e-05 1.50e-02
MACF1 microtubule actin crosslinking factor 1 5.53e-01 5.88e-05 1.59e-02
PSMB1 proteasome 20S subunit beta 1 -2.93e-01 6.75e-05 1.59e-02
TPM4 tropomyosin 4 3.67e-01 6.79e-05 1.59e-02
NAXE NAD(P)HX epimerase -8.12e-01 1.04e-04 2.24e-02
PTTG1IP PTTG1 interacting protein 4.11e-01 1.21e-04 2.44e-02
GMFB glia maturation factor beta -3.11e-01 1.48e-04 2.77e-02
BIRC3 baculoviral IAP repeat containing 3 -5.87e-01 1.75e-04 2.89e-02
LACTB lactamase beta 5.60e-01 1.67e-04 2.89e-02
CGAS cyclic GMP-AMP synthase 5.97e-01 2.00e-04 3.12e-02
NCL nucleolin 3.99e-01 2.38e-04 3.53e-02
ILF3 interleukin enhancer binding factor 3 4.40e-01 2.54e-04 3.57e-02
SMC3 structural maintenance of chromosomes 3 3.59e-01 3.01e-04 4.04e-02
KIF4A kinesin family member 4A 5.15e-01 3.61e-04 4.24e-02
RBM8A RNA binding motif protein 8A -3.03e-01 3.61e-04 4.24e-02
ZFR zinc finger RNA binding protein 4.52e-01 3.50e-04 4.24e-02
GTF2F1 general transcription factor IIF subunit 1 5.13e-01 4.11e-04 4.62e-02
CLINT1 clathrin interactor 1 5.49e-01 4.58e-04 4.67e-02
NOP14 NOP14 nucleolar protein 6.09e-01 4.42e-04 4.67e-02
PRRG3 proline rich and Gla domain 3 3.28e-01 4.86e-04 4.67e-02
SUPT6H SPT6 homolog, histone chaperone and transcription elongation factor 5.48e-01 4.95e-04 4.67e-02
TPM3 tropomyosin 3 3.70e-01 4.98e-04 4.67e-02

Gene Set Enrichment Analysis

The GSEA method was applied for all genes whose knockout resulted in at least 20 significantly differentially expressed genes.

ID Name p-value p-value (adj.) log2 Error ES NES
go:0008092 cytoskeletal protein binding 2.39e-09 5.78e-06 7.75e-01 4.45e-01 2.09e+00
go:0019866 organelle inner membrane 1.11e-08 8.96e-06 7.48e-01 -3.92e-01 -1.98e+00
go:0044429 7.43e-09 8.96e-06 7.61e-01 -3.44e-01 -1.83e+00
go:0051052 regulation of DNA metabolic process 3.97e-08 1.61e-05 7.20e-01 5.76e-01 2.31e+00
go:0005740 mitochondrial envelope 2.86e-08 1.61e-05 7.34e-01 -3.59e-01 -1.88e+00
go:0007010 cytoskeleton organization 3.65e-08 1.61e-05 7.20e-01 3.94e-01 1.93e+00
go:0003779 actin binding 1.07e-07 3.24e-05 7.05e-01 5.26e-01 2.22e+00
go:0003735 structural constituent of ribosome 9.79e-08 3.24e-05 7.05e-01 -4.53e-01 -2.09e+00
go:0099080 supramolecular complex 2.14e-07 5.75e-05 6.90e-01 4.39e-01 2.02e+00
go:0044877 protein-containing complex binding 3.07e-07 7.45e-05 6.75e-01 3.76e-01 1.84e+00
go:0044391 ribosomal subunit 3.64e-07 7.79e-05 6.75e-01 -4.29e-01 -2.02e+00
msig:M5893 HALLMARK_MITOTIC_SPINDLE 4.41e-07 8.23e-05 6.75e-01 5.83e-01 2.28e+00
go:0006091 generation of precursor metabolites and energy 5.63e-07 9.76e-05 6.59e-01 -3.82e-01 -1.87e+00
go:0022610 biological adhesion 6.09e-07 9.85e-05 6.59e-01 4.12e-01 1.94e+00
msig:M18937 KEGG_NUCLEOTIDE_EXCISION_REPAIR 1.85e-06 2.81e-04 6.44e-01 -7.90e-01 -2.35e+00
go:0044430 2.01e-06 2.85e-04 6.27e-01 3.51e-01 1.74e+00
go:0033043 regulation of organelle organization 2.12e-06 2.85e-04 6.27e-01 3.48e-01 1.72e+00
go:0005759 mitochondrial matrix 3.09e-06 3.95e-04 6.27e-01 -4.01e-01 -1.92e+00
go:0099513 polymeric cytoskeletal fiber 3.74e-06 4.53e-04 6.27e-01 4.36e-01 1.93e+00
msig:M5901 HALLMARK_G2M_CHECKPOINT 4.07e-06 4.71e-04 6.11e-01 4.86e-01 2.07e+00
go:0050839 cell adhesion molecule binding 4.96e-06 5.27e-04 6.11e-01 3.99e-01 1.85e+00
go:0005739 mitochondrion 5.00e-06 5.27e-04 6.11e-01 -2.86e-01 -1.55e+00
go:0001726 ruffle 9.47e-06 9.18e-04 5.93e-01 6.11e-01 2.16e+00
go:0051015 actin filament binding 1.03e-05 9.58e-04 5.93e-01 5.84e-01 2.18e+00
go:0032989 cellular component morphogenesis 1.28e-05 1.15e-03 5.93e-01 4.02e-01 1.83e+00
go:0005819 spindle 1.43e-05 1.23e-03 5.93e-01 4.45e-01 1.93e+00
go:0033044 regulation of chromosome organization 1.47e-05 1.23e-03 5.93e-01 4.76e-01 2.00e+00
go:0032432 actin filament bundle 1.76e-05 1.42e-03 5.76e-01 7.78e-01 2.19e+00
go:0031252 cell leading edge 1.99e-05 1.56e-03 5.76e-01 4.97e-01 2.03e+00
go:0005884 actin filament 2.42e-05 1.78e-03 5.76e-01 7.07e-01 2.10e+00
go:0015629 actin cytoskeleton 2.38e-05 1.78e-03 5.76e-01 4.39e-01 1.90e+00
reactome:R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 2.57e-05 1.83e-03 5.76e-01 -5.85e-01 -2.11e+00
reactome:R-HSA-72766 Translation 2.86e-05 1.98e-03 5.76e-01 -3.39e-01 -1.70e+00
go:0015630 microtubule cytoskeleton 3.06e-05 2.03e-03 5.57e-01 3.45e-01 1.68e+00
reactome:R-HSA-9010553 Regulation of expression of SLITs and ROBOs 3.47e-05 2.20e-03 5.57e-01 -3.88e-01 -1.82e+00
go:0005516 calmodulin binding 3.53e-05 2.20e-03 5.57e-01 6.75e-01 2.14e+00
go:0097435 supramolecular fiber organization 4.24e-05 2.57e-03 5.57e-01 4.13e-01 1.85e+00
msig:M189 KEGG_RIBOSOME 5.74e-05 3.40e-03 5.57e-01 -4.38e-01 -1.88e+00
go:0051261 protein depolymerization 6.58e-05 3.73e-03 5.38e-01 6.35e-01 2.10e+00
go:0061061 muscle structure development 6.61e-05 3.73e-03 5.38e-01 4.58e-01 1.92e+00
go:0015934 large ribosomal subunit 7.06e-05 3.89e-03 5.38e-01 -4.37e-01 -1.88e+00
go:0031253 cell projection membrane 7.63e-05 3.94e-03 5.38e-01 5.93e-01 2.10e+00
reactome:R-HSA-5696400 Dual Incision in GG-NER 7.56e-05 3.94e-03 5.38e-01 -6.97e-01 -2.14e+00
go:0010639 negative regulation of organelle organization 7.45e-05 3.94e-03 5.38e-01 4.33e-01 1.86e+00
go:0003682 chromatin binding 8.07e-05 4.07e-03 5.38e-01 4.20e-01 1.82e+00
reactome:R-HSA-376176 Signaling by ROBO receptors 8.92e-05 4.33e-03 5.38e-01 -3.65e-01 -1.72e+00
go:0043292 contractile fiber 8.75e-05 4.33e-03 5.38e-01 5.46e-01 2.05e+00
msig:M5936 HALLMARK_OXIDATIVE_PHOSPHORYLATION 9.49e-05 4.51e-03 5.38e-01 -3.72e-01 -1.73e+00
go:0031589 cell-substrate adhesion 1.13e-04 5.25e-03 5.38e-01 4.73e-01 1.87e+00
go:0098590 plasma membrane region 1.21e-04 5.54e-03 5.38e-01 4.00e-01 1.76e+00
go:0005178 integrin binding 1.25e-04 5.62e-03 5.19e-01 6.47e-01 2.06e+00
go:0010628 positive regulation of gene expression 1.40e-04 6.19e-03 5.19e-01 3.10e-01 1.54e+00
go:0042692 muscle cell differentiation 1.47e-04 6.28e-03 5.19e-01 5.28e-01 2.00e+00
go:0045333 cellular respiration 1.77e-04 7.16e-03 5.19e-01 -3.97e-01 -1.77e+00
reactome:R-HSA-71291 Metabolism of amino acids and derivatives 1.76e-04 7.16e-03 5.19e-01 -3.52e-01 -1.69e+00
go:0006283 transcription-coupled nucleotide-excision repair 1.76e-04 7.16e-03 5.19e-01 -5.73e-01 -2.02e+00
go:0040011 locomotion 1.89e-04 7.50e-03 5.19e-01 3.25e-01 1.59e+00
go:0022626 cytosolic ribosome 2.16e-04 8.06e-03 5.19e-01 -4.19e-01 -1.82e+00
go:1903827 regulation of cellular protein localization 2.12e-04 8.06e-03 5.19e-01 3.80e-01 1.70e+00
go:0031975 envelope 2.15e-04 8.06e-03 5.19e-01 -2.78e-01 -1.48e+00
reactome:R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 2.14e-04 8.06e-03 5.19e-01 -5.56e-01 -2.04e+00
go:0006325 chromatin organization 2.43e-04 8.92e-03 5.19e-01 3.64e-01 1.67e+00
go:0005840 ribosome 2.51e-04 9.07e-03 4.98e-01 -3.54e-01 -1.70e+00
reactome:R-HSA-6782135 Dual incision in TC-NER 2.56e-04 9.14e-03 4.98e-01 -5.79e-01 -2.02e+00
go:0045934 negative regulation of nucleobase-containing compound metabolic process 2.73e-04 9.58e-03 4.98e-01 5.45e-01 1.95e+00
go:0015980 energy derivation by oxidation of organic compounds 2.81e-04 9.59e-03 4.98e-01 -3.73e-01 -1.70e+00
go:1901879 regulation of protein depolymerization 2.80e-04 9.59e-03 4.98e-01 6.35e-01 1.96e+00
go:0016126 sterol biosynthetic process 3.08e-04 1.02e-02 4.98e-01 6.66e-01 1.99e+00
go:0051235 maintenance of location 3.11e-04 1.02e-02 4.98e-01 4.83e-01 1.84e+00
go:0000904 cell morphogenesis involved in differentiation 3.10e-04 1.02e-02 4.98e-01 4.24e-01 1.81e+00
go:0006282 regulation of DNA repair 3.25e-04 1.05e-02 4.98e-01 6.34e-01 1.98e+00
go:0000226 microtubule cytoskeleton organization 3.42e-04 1.08e-02 4.98e-01 3.80e-01 1.67e+00
go:0006414 translational elongation 3.46e-04 1.08e-02 4.98e-01 -4.28e-01 -1.81e+00
go:0044455 3.41e-04 1.08e-02 4.98e-01 -3.68e-01 -1.71e+00
go:0009060 aerobic respiration 3.53e-04 1.08e-02 4.98e-01 -5.01e-01 -1.92e+00
go:0000018 regulation of DNA recombination 3.68e-04 1.10e-02 4.98e-01 6.93e-01 2.01e+00
go:0032543 mitochondrial translation 3.67e-04 1.10e-02 4.98e-01 -4.41e-01 -1.85e+00
reactome:R-HSA-5368287 Mitochondrial translation 3.90e-04 1.15e-02 4.98e-01 -4.53e-01 -1.84e+00
go:1902275 regulation of chromatin organization 4.00e-04 1.17e-02 4.98e-01 5.40e-01 1.97e+00
go:0015631 tubulin binding 4.23e-04 1.22e-02 4.98e-01 4.48e-01 1.80e+00
go:0034728 nucleosome organization 4.33e-04 1.24e-02 4.98e-01 5.38e-01 1.96e+00
go:0008202 steroid metabolic process 4.41e-04 1.24e-02 4.98e-01 5.20e-01 1.93e+00
go:0000956 nuclear-transcribed mRNA catabolic process 4.70e-04 1.31e-02 4.98e-01 -3.54e-01 -1.64e+00
reactome:R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 4.89e-04 1.35e-02 4.77e-01 -6.84e-01 -2.04e+00
go:0033683 nucleotide-excision repair, DNA incision 4.94e-04 1.35e-02 4.77e-01 -6.84e-01 -2.04e+00
go:0045296 cadherin binding 5.06e-04 1.36e-02 4.77e-01 3.66e-01 1.65e+00
reactome:R-HSA-162909 Host Interactions of HIV factors 5.46e-04 1.46e-02 4.77e-01 -4.20e-01 -1.78e+00
go:0005694 chromosome 5.56e-04 1.46e-02 4.77e-01 3.13e-01 1.53e+00
go:0000313 organellar ribosome 5.62e-04 1.46e-02 4.77e-01 -4.67e-01 -1.85e+00
go:0032553 ribonucleotide binding 5.93e-04 1.49e-02 4.77e-01 2.99e-01 1.49e+00
reactome:R-HSA-5696398 Nucleotide Excision Repair 5.87e-04 1.49e-02 4.77e-01 -4.82e-01 -1.88e+00
go:0045785 positive regulation of cell adhesion 5.82e-04 1.49e-02 4.77e-01 4.45e-01 1.75e+00
go:0061572 actin filament bundle organization 6.27e-04 1.54e-02 4.77e-01 5.77e-01 1.96e+00
go:0002377 immunoglobulin production 6.22e-04 1.54e-02 4.77e-01 7.04e-01 1.98e+00
go:0042641 actomyosin 6.83e-04 1.66e-02 4.77e-01 6.99e-01 2.01e+00
go:0051129 negative regulation of cellular component organization 6.99e-04 1.68e-02 4.77e-01 3.57e-01 1.62e+00
go:0044291 cell-cell contact zone 7.21e-04 1.71e-02 4.77e-01 6.79e-01 1.97e+00
go:0043565 sequence-specific DNA binding 7.39e-04 1.73e-02 4.77e-01 3.67e-01 1.63e+00
reactome:R-HSA-5656169 Termination of translesion DNA synthesis 7.41e-04 1.73e-02 4.77e-01 -6.82e-01 -1.99e+00
go:0006119 oxidative phosphorylation 7.50e-04 1.73e-02 4.77e-01 -3.76e-01 -1.67e+00
go:0007229 integrin-mediated signaling pathway 7.72e-04 1.75e-02 4.77e-01 6.10e-01 1.90e+00
go:0072686 mitotic spindle 7.72e-04 1.75e-02 4.77e-01 5.21e-01 1.86e+00
go:0007051 spindle organization 8.37e-04 1.86e-02 4.77e-01 4.65e-01 1.82e+00
go:0098609 cell-cell adhesion 8.35e-04 1.86e-02 4.77e-01 3.94e-01 1.69e+00
go:0051270 regulation of cellular component movement 8.61e-04 1.90e-02 4.77e-01 3.49e-01 1.61e+00
go:0030424 axon 8.77e-04 1.92e-02 4.77e-01 4.25e-01 1.76e+00
go:0070161 anchoring junction 8.99e-04 1.95e-02 4.77e-01 3.35e-01 1.58e+00
go:0006289 nucleotide-excision repair 9.07e-04 1.95e-02 4.77e-01 -5.13e-01 -1.92e+00
go:0030054 cell junction 9.29e-04 1.96e-02 4.77e-01 3.14e-01 1.53e+00
reactome:R-HSA-1428517 The citric acid (TCA) cycle and respiratory electron transport 9.31e-04 1.96e-02 4.77e-01 -3.59e-01 -1.63e+00
go:0048667 cell morphogenesis involved in neuron differentiation 9.48e-04 1.98e-02 4.77e-01 4.43e-01 1.75e+00
go:0051053 negative regulation of DNA metabolic process 9.69e-04 2.01e-02 4.77e-01 6.68e-01 1.93e+00
reactome:R-HSA-373760 L1CAM interactions 1.03e-03 2.08e-02 4.55e-01 5.40e-01 1.87e+00
go:0030029 actin filament-based process 1.01e-03 2.08e-02 4.55e-01 3.60e-01 1.62e+00
reactome:R-HSA-2408522 Selenoamino acid metabolism 1.03e-03 2.08e-02 4.55e-01 -3.86e-01 -1.69e+00
go:0031012 extracellular matrix 1.07e-03 2.13e-02 4.55e-01 4.67e-01 1.80e+00
go:0032990 cell part morphogenesis 1.08e-03 2.13e-02 4.55e-01 4.14e-01 1.73e+00
go:0008017 microtubule binding 1.06e-03 2.13e-02 4.55e-01 4.88e-01 1.84e+00
go:0097485 neuron projection guidance 1.13e-03 2.20e-02 4.55e-01 6.08e-01 1.85e+00
go:0031256 leading edge membrane 1.17e-03 2.24e-02 4.55e-01 5.97e-01 1.84e+00
go:0005874 microtubule 1.18e-03 2.24e-02 4.55e-01 4.07e-01 1.71e+00
go:0051054 positive regulation of DNA metabolic process 1.18e-03 2.24e-02 4.55e-01 4.96e-01 1.82e+00
go:0032880 regulation of protein localization 1.16e-03 2.24e-02 4.55e-01 3.23e-01 1.53e+00
msig:M18306 KEGG_REGULATION_OF_ACTIN_CYTOSKELETON 1.26e-03 2.34e-02 4.55e-01 4.51e-01 1.73e+00
go:0030554 adenyl nucleotide binding 1.27e-03 2.34e-02 4.55e-01 3.05e-01 1.49e+00
reactome:R-HSA-927802 Nonsense-Mediated Decay (NMD) 1.27e-03 2.34e-02 4.55e-01 -3.73e-01 -1.64e+00
go:0006413 translational initiation 1.31e-03 2.38e-02 4.55e-01 -3.28e-01 -1.55e+00
go:0002285 lymphocyte activation involved in immune response 1.35e-03 2.43e-02 4.55e-01 6.30e-01 1.88e+00
go:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay 1.35e-03 2.43e-02 4.55e-01 -3.75e-01 -1.65e+00
go:0030030 cell projection organization 1.40e-03 2.50e-02 4.55e-01 3.19e-01 1.52e+00
reactome:R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template 1.42e-03 2.51e-02 4.55e-01 -6.25e-01 -1.95e+00
go:0061564 axon development 1.43e-03 2.52e-02 4.55e-01 4.62e-01 1.80e+00
go:0051276 chromosome organization 1.48e-03 2.58e-02 4.55e-01 3.03e-01 1.48e+00
go:0007015 actin filament organization 1.54e-03 2.65e-02 4.55e-01 4.05e-01 1.70e+00
reactome:R-HSA-73893 DNA Damage Bypass 1.63e-03 2.76e-02 4.55e-01 -5.74e-01 -1.87e+00
go:0071407 cellular response to organic cyclic compound 1.65e-03 2.78e-02 4.55e-01 3.93e-01 1.68e+00
go:0062023 collagen-containing extracellular matrix 1.74e-03 2.90e-02 4.55e-01 4.57e-01 1.73e+00
go:0032153 cell division site 1.83e-03 2.98e-02 4.55e-01 6.11e-01 1.81e+00
go:0070126 mitochondrial translational termination 1.86e-03 2.98e-02 4.55e-01 -4.35e-01 -1.75e+00
reactome:R-HSA-8951664 Neddylation 1.84e-03 2.98e-02 4.55e-01 -3.95e-01 -1.67e+00
go:0034330 cell junction organization 1.83e-03 2.98e-02 4.55e-01 4.47e-01 1.75e+00
go:0048738 cardiac muscle tissue development 1.88e-03 2.98e-02 4.55e-01 5.77e-01 1.84e+00
go:0022900 electron transport chain 1.92e-03 3.03e-02 4.55e-01 -3.60e-01 -1.61e+00
go:1903829 positive regulation of cellular protein localization 1.95e-03 3.05e-02 4.55e-01 3.88e-01 1.66e+00
reactome:R-HSA-69306 DNA Replication 1.97e-03 3.06e-02 4.32e-01 -4.08e-01 -1.69e+00
go:0140053 mitochondrial gene expression 2.05e-03 3.13e-02 4.32e-01 -3.89e-01 -1.65e+00
go:0051783 regulation of nuclear division 2.08e-03 3.13e-02 4.32e-01 4.37e-01 1.71e+00
go:0072359 circulatory system development 2.06e-03 3.13e-02 4.32e-01 3.45e-01 1.55e+00
go:0072659 protein localization to plasma membrane 2.08e-03 3.13e-02 4.32e-01 4.50e-01 1.70e+00
go:0009719 response to endogenous stimulus 2.05e-03 3.13e-02 4.32e-01 2.94e-01 1.45e+00
go:0034332 adherens junction organization 2.14e-03 3.21e-02 4.32e-01 5.42e-01 1.84e+00
go:0022625 cytosolic large ribosomal subunit 2.22e-03 3.30e-02 4.32e-01 -4.36e-01 -1.73e+00
go:0019904 protein domain specific binding 2.28e-03 3.34e-02 4.32e-01 3.32e-01 1.53e+00
go:0051146 striated muscle cell differentiation 2.29e-03 3.34e-02 4.32e-01 4.97e-01 1.77e+00
go:2001252 positive regulation of chromosome organization 2.26e-03 3.34e-02 4.32e-01 4.48e-01 1.69e+00
go:0007005 mitochondrion organization 2.34e-03 3.39e-02 4.32e-01 -3.00e-01 -1.48e+00
go:0030055 cell-substrate junction 2.36e-03 3.40e-02 4.32e-01 3.29e-01 1.53e+00
msig:M5892 HALLMARK_CHOLESTEROL_HOMEOSTASIS 2.46e-03 3.51e-02 4.32e-01 5.76e-01 1.82e+00
go:0042393 histone binding 2.54e-03 3.60e-02 4.32e-01 4.70e-01 1.77e+00
go:0030182 neuron differentiation 2.57e-03 3.61e-02 4.32e-01 3.23e-01 1.49e+00
go:0007017 microtubule-based process 2.57e-03 3.61e-02 4.32e-01 3.29e-01 1.51e+00
go:0010810 regulation of cell-substrate adhesion 2.61e-03 3.62e-02 4.32e-01 4.69e-01 1.77e+00
go:2001020 regulation of response to DNA damage stimulus 2.64e-03 3.63e-02 4.32e-01 4.86e-01 1.80e+00
go:2001251 negative regulation of chromosome organization 2.65e-03 3.63e-02 4.32e-01 4.97e-01 1.78e+00
reactome:R-HSA-163200 Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. 2.73e-03 3.69e-02 4.32e-01 -3.58e-01 -1.58e+00
reactome:R-HSA-9609507 Protein localization 2.74e-03 3.69e-02 4.32e-01 -4.24e-01 -1.70e+00
go:0022904 respiratory electron transport chain 2.79e-03 3.73e-02 4.32e-01 -3.74e-01 -1.60e+00
reactome:R-HSA-5685942 HDR through Homologous Recombination (HRR) 2.93e-03 3.89e-02 4.32e-01 -6.14e-01 -1.84e+00
go:0030155 regulation of cell adhesion 2.99e-03 3.94e-02 4.32e-01 3.64e-01 1.58e+00
go:1901361 organic cyclic compound catabolic process 3.04e-03 3.97e-02 4.32e-01 -2.76e-01 -1.40e+00
reactome:R-HSA-72613 Eukaryotic Translation Initiation 3.04e-03 3.97e-02 4.32e-01 -3.39e-01 -1.53e+00
reactome:R-HSA-162906 HIV Infection 3.12e-03 4.01e-02 4.32e-01 -3.37e-01 -1.53e+00
go:0060341 regulation of cellular localization 3.11e-03 4.01e-02 4.32e-01 3.18e-01 1.49e+00
go:0006323 DNA packaging 3.19e-03 4.05e-02 4.32e-01 4.82e-01 1.78e+00
go:0034333 adherens junction assembly 3.19e-03 4.05e-02 4.32e-01 5.63e-01 1.79e+00
go:0019985 translesion synthesis 3.49e-03 4.36e-02 4.32e-01 -6.07e-01 -1.82e+00
go:0051494 negative regulation of cytoskeleton organization 3.48e-03 4.36e-02 4.32e-01 5.55e-01 1.80e+00
go:0000731 DNA synthesis involved in DNA repair 3.49e-03 4.36e-02 4.32e-01 -6.07e-01 -1.82e+00
go:2001022 positive regulation of response to DNA damage stimulus 3.52e-03 4.37e-02 4.32e-01 5.68e-01 1.80e+00
go:0034399 nuclear periphery 3.54e-03 4.38e-02 4.32e-01 4.75e-01 1.73e+00
go:0051493 regulation of cytoskeleton organization 3.61e-03 4.44e-02 4.32e-01 3.53e-01 1.54e+00
go:0043043 peptide biosynthetic process 3.70e-03 4.54e-02 4.32e-01 -2.65e-01 -1.39e+00
go:0036002 pre-mRNA binding 3.82e-03 4.62e-02 4.32e-01 6.53e-01 1.83e+00
go:1904356 regulation of telomere maintenance via telomere lengthening 3.80e-03 4.62e-02 4.32e-01 5.98e-01 1.79e+00
go:0034329 cell junction assembly 3.84e-03 4.62e-02 4.32e-01 4.37e-01 1.66e+00
go:0098800 inner mitochondrial membrane protein complex 3.85e-03 4.62e-02 4.32e-01 -3.58e-01 -1.58e+00
reactome:R-HSA-5663205 Infectious disease 3.89e-03 4.65e-02 4.32e-01 -2.84e-01 -1.41e+00
go:0006333 chromatin assembly or disassembly 3.97e-03 4.72e-02 4.07e-01 4.62e-01 1.70e+00
go:0043604 amide biosynthetic process 4.08e-03 4.83e-02 4.07e-01 -2.54e-01 -1.34e+00
go:0070646 protein modification by small protein removal 4.11e-03 4.84e-02 4.07e-01 -3.56e-01 -1.57e+00
go:0007507 heart development 4.13e-03 4.84e-02 4.07e-01 4.04e-01 1.62e+00
go:0030042 actin filament depolymerization 4.19e-03 4.89e-02 4.07e-01 6.09e-01 1.79e+00
go:0015935 small ribosomal subunit 4.34e-03 4.94e-02 4.07e-01 -4.08e-01 -1.64e+00
go:0005815 microtubule organizing center 4.34e-03 4.94e-02 4.07e-01 3.31e-01 1.50e+00
go:0048471 perinuclear region of cytoplasm 4.27e-03 4.94e-02 4.07e-01 3.31e-01 1.50e+00
go:0008134 transcription factor binding 4.29e-03 4.94e-02 4.07e-01 3.34e-01 1.48e+00
go:0009055 electron transfer activity 4.34e-03 4.94e-02 4.07e-01 -4.08e-01 -1.64e+00
go:0051094 positive regulation of developmental process 4.41e-03 5.00e-02 4.07e-01 3.13e-01 1.46e+00
go:0045944 positive regulation of transcription by RNA polymerase II 4.64e-03 5.23e-02 4.07e-01 3.15e-01 1.45e+00
go:0022008 neurogenesis 4.70e-03 5.27e-02 4.07e-01 3.16e-01 1.49e+00
go:0071496 cellular response to external stimulus 4.80e-03 5.36e-02 4.07e-01 3.97e-01 1.57e+00
reactome:R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 4.85e-03 5.39e-02 4.07e-01 -4.46e-01 -1.71e+00
go:0045787 positive regulation of cell cycle 5.00e-03 5.49e-02 4.07e-01 3.77e-01 1.60e+00
go:0051187 5.00e-03 5.49e-02 4.07e-01 -6.28e-01 -1.79e+00
go:0032204 regulation of telomere maintenance 4.96e-03 5.49e-02 4.07e-01 5.51e-01 1.76e+00
go:0022604 regulation of cell morphogenesis 5.06e-03 5.52e-02 4.07e-01 4.18e-01 1.71e+00
go:0032886 regulation of microtubule-based process 5.10e-03 5.55e-02 4.07e-01 4.48e-01 1.68e+00
reactome:R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 5.18e-03 5.61e-02 4.07e-01 -4.27e-01 -1.67e+00
go:0042113 B cell activation 5.22e-03 5.63e-02 4.07e-01 5.23e-01 1.74e+00
go:0005770 late endosome 5.33e-03 5.65e-02 4.07e-01 -4.31e-01 -1.70e+00
go:0032784 regulation of DNA-templated transcription, elongation 5.32e-03 5.65e-02 4.07e-01 6.34e-01 1.82e+00
reactome:R-HSA-157579 Telomere Maintenance 5.33e-03 5.65e-02 4.07e-01 -6.10e-01 -1.81e+00
msig:M14314 KEGG_PURINE_METABOLISM 5.33e-03 5.65e-02 4.07e-01 -4.46e-01 -1.69e+00
go:1902904 negative regulation of supramolecular fiber organization 5.37e-03 5.66e-02 4.07e-01 5.42e-01 1.76e+00
go:0032535 regulation of cellular component size 5.42e-03 5.69e-02 4.07e-01 3.96e-01 1.64e+00
go:0006605 protein targeting 5.52e-03 5.77e-02 4.07e-01 -2.90e-01 -1.41e+00
go:0010811 positive regulation of cell-substrate adhesion 5.63e-03 5.86e-02 4.07e-01 5.08e-01 1.71e+00
go:0051668 localization within membrane 5.67e-03 5.88e-02 4.07e-01 5.52e-01 1.72e+00
reactome:R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 5.83e-03 5.99e-02 4.07e-01 -3.45e-01 -1.52e+00
go:0003727 single-stranded RNA binding 5.89e-03 6.02e-02 4.07e-01 4.94e-01 1.72e+00
msig:M5908 HALLMARK_ANDROGEN_RESPONSE 6.01e-03 6.10e-02 4.07e-01 4.91e-01 1.70e+00
go:0051147 regulation of muscle cell differentiation 6.11e-03 6.10e-02 4.07e-01 5.48e-01 1.73e+00
reactome:R-HSA-5696395 Formation of Incision Complex in GG-NER 6.11e-03 6.10e-02 4.07e-01 -5.41e-01 -1.70e+00
go:0003725 double-stranded RNA binding 6.07e-03 6.10e-02 4.07e-01 5.19e-01 1.73e+00
go:0045931 positive regulation of mitotic cell cycle 6.32e-03 6.28e-02 4.07e-01 4.47e-01 1.67e+00
reactome:R-HSA-611105 Respiratory electron transport 6.36e-03 6.29e-02 4.07e-01 -3.72e-01 -1.58e+00
go:0072599 establishment of protein localization to endoplasmic reticulum 6.38e-03 6.29e-02 4.07e-01 -3.48e-01 -1.53e+00
reactome:R-HSA-73884 Base Excision Repair 6.74e-03 6.59e-02 4.07e-01 -6.03e-01 -1.79e+00
go:0051301 cell division 6.80e-03 6.62e-02 4.07e-01 3.14e-01 1.46e+00
go:0000910 cytokinesis 6.91e-03 6.70e-02 4.07e-01 4.43e-01 1.67e+00
go:1903391 regulation of adherens junction organization 6.97e-03 6.74e-02 4.07e-01 5.49e-01 1.67e+00
go:0051130 positive regulation of cellular component organization 7.04e-03 6.78e-02 4.07e-01 2.85e-01 1.40e+00
go:0042769 DNA damage response, detection of DNA damage 7.23e-03 6.90e-02 4.07e-01 -5.31e-01 -1.71e+00
go:0006694 steroid biosynthetic process 7.23e-03 6.90e-02 4.07e-01 5.00e-01 1.70e+00
go:1905475 regulation of protein localization to membrane 7.34e-03 6.96e-02 4.07e-01 4.41e-01 1.65e+00
go:0031032 actomyosin structure organization 7.34e-03 6.96e-02 4.07e-01 4.77e-01 1.69e+00
go:0000139 Golgi membrane 7.42e-03 7.01e-02 4.07e-01 3.28e-01 1.45e+00
reactome:R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 7.48e-03 7.03e-02 4.07e-01 -5.13e-01 -1.69e+00
go:0030496 midbody 7.60e-03 7.07e-02 4.07e-01 4.11e-01 1.61e+00
reactome:R-HSA-1500931 Cell-Cell communication 7.56e-03 7.07e-02 4.07e-01 5.37e-01 1.66e+00
go:0070069 cytochrome complex 7.60e-03 7.07e-02 4.07e-01 -5.29e-01 -1.67e+00
reactome:R-HSA-109582 Hemostasis 7.73e-03 7.09e-02 4.07e-01 3.28e-01 1.44e+00
reactome:R-HSA-397014 Muscle contraction 7.72e-03 7.09e-02 4.07e-01 5.18e-01 1.71e+00
go:0032587 ruffle membrane 7.72e-03 7.09e-02 4.07e-01 5.90e-01 1.73e+00
reactome:R-HSA-1474244 Extracellular matrix organization 7.75e-03 7.09e-02 4.07e-01 4.37e-01 1.64e+00
reactome:R-HSA-437239 Recycling pathway of L1 7.88e-03 7.13e-02 3.81e-01 5.46e-01 1.66e+00
go:0048588 developmental cell growth 7.91e-03 7.13e-02 3.81e-01 4.89e-01 1.71e+00
reactome:R-HSA-8948751 Regulation of PTEN stability and activity 7.83e-03 7.13e-02 3.81e-01 -4.32e-01 -1.65e+00
go:0003690 double-stranded DNA binding 7.86e-03 7.13e-02 3.81e-01 3.36e-01 1.48e+00
go:0099568 cytoplasmic region 7.95e-03 7.14e-02 3.81e-01 3.63e-01 1.54e+00
go:0051983 regulation of chromosome segregation 8.07e-03 7.22e-02 3.81e-01 4.72e-01 1.67e+00
go:0031145 anaphase-promoting complex-dependent catabolic process 8.37e-03 7.43e-02 3.81e-01 -4.01e-01 -1.59e+00
go:0042060 wound healing 8.35e-03 7.43e-02 3.81e-01 3.54e-01 1.52e+00
go:0019724 B cell mediated immunity 8.55e-03 7.57e-02 3.81e-01 6.28e-01 1.76e+00
go:0051186 8.88e-03 7.77e-02 3.81e-01 -3.41e-01 -1.50e+00
reactome:R-HSA-69242 S Phase 8.91e-03 7.77e-02 3.81e-01 -3.58e-01 -1.52e+00
go:0007160 cell-matrix adhesion 9.24e-03 7.86e-02 3.81e-01 4.80e-01 1.71e+00
reactome:R-HSA-5610780 Degradation of GLI1 by the proteasome 9.21e-03 7.86e-02 3.81e-01 -4.22e-01 -1.61e+00
reactome:R-HSA-8939902 Regulation of RUNX2 expression and activity 9.21e-03 7.86e-02 3.81e-01 -4.22e-01 -1.61e+00
reactome:R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 9.24e-03 7.86e-02 3.81e-01 -5.52e-01 -1.73e+00
go:0070647 protein modification by small protein conjugation or removal 9.13e-03 7.86e-02 3.81e-01 -2.65e-01 -1.34e+00
go:0034446 substrate adhesion-dependent cell spreading 9.28e-03 7.86e-02 3.81e-01 5.39e-01 1.64e+00
go:0048675 axon extension 9.09e-03 7.86e-02 3.81e-01 5.63e-01 1.69e+00
go:0009891 positive regulation of biosynthetic process 9.55e-03 8.07e-02 3.81e-01 2.67e-01 1.33e+00
go:0009890 negative regulation of biosynthetic process 9.74e-03 8.12e-02 3.81e-01 2.75e-01 1.34e+00
go:0022402 cell cycle process 9.85e-03 8.12e-02 3.81e-01 2.69e-01 1.35e+00
go:0044463 9.65e-03 8.12e-02 3.81e-01 3.02e-01 1.42e+00
go:0031461 cullin-RING ubiquitin ligase complex 9.72e-03 8.12e-02 3.81e-01 -5.06e-01 -1.69e+00
go:0035303 regulation of dephosphorylation 9.85e-03 8.12e-02 3.81e-01 4.55e-01 1.63e+00
go:0043467 regulation of generation of precursor metabolites and energy 9.85e-03 8.12e-02 3.81e-01 -4.26e-01 -1.61e+00
reactome:R-HSA-169911 Regulation of Apoptosis 9.85e-03 8.12e-02 3.81e-01 -4.27e-01 -1.62e+00
reactome:R-HSA-6802952 Signaling by BRAF and RAF1 fusions 9.98e-03 8.20e-02 3.81e-01 5.59e-01 1.66e+00
msig:M5898 HALLMARK_DNA_REPAIR 1.01e-02 8.29e-02 3.81e-01 -3.71e-01 -1.53e+00
go:0002250 adaptive immune response 1.03e-02 8.32e-02 3.81e-01 4.89e-01 1.64e+00
reactome:R-HSA-453276 Regulation of mitotic cell cycle 1.03e-02 8.32e-02 3.81e-01 -3.84e-01 -1.55e+00
go:0070469 respirasome 1.02e-02 8.32e-02 3.81e-01 -3.51e-01 -1.49e+00
go:0006338 chromatin remodeling 1.03e-02 8.33e-02 3.81e-01 4.11e-01 1.55e+00
go:0032154 cleavage furrow 1.06e-02 8.50e-02 3.81e-01 6.10e-01 1.75e+00
go:0009636 response to toxic substance 1.07e-02 8.57e-02 3.81e-01 -3.37e-01 -1.49e+00
go:0090068 positive regulation of cell cycle process 1.07e-02 8.57e-02 3.81e-01 3.85e-01 1.58e+00
go:0007517 muscle organ development 1.09e-02 8.66e-02 3.81e-01 4.09e-01 1.55e+00
go:0097237 cellular response to toxic substance 1.10e-02 8.75e-02 3.81e-01 -3.86e-01 -1.55e+00
go:0009725 response to hormone 1.12e-02 8.80e-02 3.81e-01 3.01e-01 1.40e+00
go:0046825 regulation of protein export from nucleus 1.12e-02 8.80e-02 3.81e-01 6.16e-01 1.73e+00
go:0010833 telomere maintenance via telomere lengthening 1.13e-02 8.84e-02 3.81e-01 5.08e-01 1.68e+00
go:0033238 regulation of cellular amine metabolic process 1.17e-02 9.10e-02 3.81e-01 -4.17e-01 -1.60e+00
go:1901615 organic hydroxy compound metabolic process 1.16e-02 9.10e-02 3.81e-01 4.09e-01 1.59e+00
go:0000122 negative regulation of transcription by RNA polymerase II 1.18e-02 9.10e-02 3.81e-01 3.19e-01 1.41e+00
go:0090305 nucleic acid phosphodiester bond hydrolysis 1.17e-02 9.10e-02 3.81e-01 -3.53e-01 -1.50e+00
msig:M5915 HALLMARK_APICAL_JUNCTION 1.18e-02 9.11e-02 3.81e-01 4.71e-01 1.68e+00
go:0003007 heart morphogenesis 1.19e-02 9.11e-02 3.81e-01 5.22e-01 1.65e+00
go:0048771 tissue remodeling 1.19e-02 9.11e-02 3.81e-01 5.21e-01 1.65e+00
reactome:R-HSA-73894 DNA Repair 1.19e-02 9.13e-02 3.81e-01 -3.32e-01 -1.46e+00
go:0016491 oxidoreductase activity 1.20e-02 9.14e-02 3.81e-01 -2.70e-01 -1.33e+00
go:0030518 intracellular steroid hormone receptor signaling pathway 1.21e-02 9.14e-02 3.81e-01 5.30e-01 1.61e+00
go:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway 1.20e-02 9.14e-02 3.81e-01 4.20e-01 1.58e+00
go:1901566 organonitrogen compound biosynthetic process 1.21e-02 9.14e-02 3.81e-01 -2.24e-01 -1.22e+00
reactome:R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 1.22e-02 9.22e-02 3.81e-01 -4.19e-01 -1.59e+00
go:0060537 muscle tissue development 1.23e-02 9.27e-02 3.81e-01 4.05e-01 1.53e+00
go:0060284 regulation of cell development 1.24e-02 9.30e-02 3.81e-01 3.32e-01 1.48e+00
go:0008144 drug binding 1.25e-02 9.31e-02 3.81e-01 2.74e-01 1.35e+00
reactome:R-HSA-4641257 Degradation of AXIN 1.28e-02 9.41e-02 3.81e-01 -4.17e-01 -1.58e+00
reactome:R-HSA-5658442 Regulation of RAS by GAPs 1.28e-02 9.41e-02 3.81e-01 -4.17e-01 -1.58e+00
reactome:R-HSA-4641258 Degradation of DVL 1.28e-02 9.41e-02 3.81e-01 -4.17e-01 -1.58e+00
reactome:R-HSA-4608870 Asymmetric localization of PCP proteins 1.28e-02 9.41e-02 3.81e-01 -4.17e-01 -1.58e+00
go:0010564 regulation of cell cycle process 1.28e-02 9.41e-02 3.81e-01 2.89e-01 1.38e+00
go:0046649 lymphocyte activation 1.29e-02 9.45e-02 3.81e-01 3.59e-01 1.51e+00
go:0006401 RNA catabolic process 1.30e-02 9.47e-02 3.81e-01 -2.74e-01 -1.36e+00
go:0071103 DNA conformation change 1.32e-02 9.50e-02 3.81e-01 3.80e-01 1.56e+00
go:1904950 negative regulation of establishment of protein localization 1.33e-02 9.50e-02 3.81e-01 4.74e-01 1.66e+00
go:0043603 cellular amide metabolic process 1.32e-02 9.50e-02 3.81e-01 -2.44e-01 -1.30e+00
go:0008361 regulation of cell size 1.31e-02 9.50e-02 3.81e-01 4.86e-01 1.65e+00
reactome:R-HSA-9604323 Negative regulation of NOTCH4 signaling 1.33e-02 9.50e-02 3.81e-01 -4.14e-01 -1.58e+00
go:0006732 1.33e-02 9.50e-02 3.81e-01 -4.13e-01 -1.58e+00
go:1990138 neuron projection extension 1.31e-02 9.50e-02 3.81e-01 5.11e-01 1.64e+00
msig:M7272 KEGG_PARKINSONS_DISEASE 1.33e-02 9.50e-02 3.81e-01 -3.32e-01 -1.47e+00
reactome:R-HSA-180585 Vif-mediated degradation of APOBEC3G 1.34e-02 9.55e-02 3.81e-01 -4.13e-01 -1.58e+00
go:0140014 mitotic nuclear division 1.35e-02 9.55e-02 3.81e-01 3.58e-01 1.51e+00
go:0042773 ATP synthesis coupled electron transport 1.35e-02 9.55e-02 3.81e-01 -3.55e-01 -1.51e+00
go:0016054 organic acid catabolic process 1.38e-02 9.69e-02 3.81e-01 -4.56e-01 -1.63e+00
reactome:R-HSA-5610787 Hedgehog 'off' state 1.38e-02 9.69e-02 3.81e-01 -3.97e-01 -1.57e+00
reactome:R-HSA-1268020 Mitochondrial protein import 1.40e-02 9.82e-02 3.81e-01 -4.44e-01 -1.65e+00
go:0003774 motor activity 1.40e-02 9.82e-02 3.81e-01 5.25e-01 1.60e+00
go:0048666 neuron development 1.42e-02 9.92e-02 3.81e-01 3.21e-01 1.44e+00
go:0005911 cell-cell junction 1.43e-02 9.92e-02 3.81e-01 3.80e-01 1.57e+00
go:0006310 DNA recombination 1.44e-02 9.97e-02 3.81e-01 3.87e-01 1.52e+00
go:0000922 spindle pole 1.44e-02 9.97e-02 3.81e-01 4.03e-01 1.53e+00

Literature Mining

INDRA was used to automatically assemble known mechanisms related to ZRANB1 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
ZRANB1 deubiquitinates APC. 2 / 2
| 2

reach
For example, Trabid and Cezanne, both deubiquitinating (DUB) enzymes, antagonize the ubiquitination of APC, resulting in activation of beta-catenin and TCF-mediated transcription.

reach
Trabid binds to and deubiquitylates APC.
ZRANB1 deubiquitinates EZH2. 2 / 2
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ZRANB1 purified from insect cells markedly decreased EZH2 polyubiquitination in vitro (XREF_FIG), suggesting that EZH2 is a substrate of ZRANB1.

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To further determine whether ZRANB1 directly deubiquitinates EZH2, we incubated purified ZRANB1 and ubiquitinated EZH2 purified from ZRANB1-knockout HEK293A cells in a cell-free system.
ZRANB1 leads to the deubiquitination of KDM4D. 2 / 2
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When transfected into HEK293 cells, wild-type Trabid, but not C443A Trabid, inhibited Jmjd2d ubiquitination (XREF_FIG), and the transfected Jmjd2d was abundantly conjugated with both K11- and K29 linked polyubiquitin chains (XREF_FIG).

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DC-cKO BMDCs had markedly more abundant Jmjd2d ubiquitination than the wild-type BMDCs (XREF_FIG), suggesting that Trabid negatively regulated Jmjd2d ubiquitination.
ZRANB1 leads to the deubiquitination of PIK3C3 on K29. 2 / 2
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TRABID antagonizes VPS34 K29 and K48 heterotypic ubiquitination even though it can not hydrolyze unanchored K48 diubiquitin chains 37.

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TRABID reduces VPS34 K29 and K48 ubiquitination to stabilize VPS34.
Modified ZRANB1 leads to the deubiquitination of EZH2. 1 / 1
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Indeed, overexpression of ZRANB1 in ZRANB1-knockout HEK293A cells substantially reduced EZH2 polyubiquitination (XREF_FIG, denaturing condition).
ZRANB1 leads to the deubiquitination of MAP3K7. 1 / 1
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Trabid has also been shown to interact with and inhibits K63 ubiquitination of Drosophila TAK1, reducing the expression of downstream genes encoding antimicrobial peptides in flies 42.
ZRANB1 deubiquitinates UVRAG. 1 / 1
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However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquitin chains from UVRAG, thereby increasing the binding of UVRAG to RUBCN and inhibiting autophagy flux.

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
ZRANB1 affects PIK3C3
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ZRANB1 activates PIK3C3.
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ZRANB1 activates PIK3C3. 8 / 8
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Thus, our results highlight the importance of TRABID mediated VPS34 stabilization in maintaining normal liver metabolism and uncover the contribution of TRABID downregulation to the pathogenesis of liver steatosis through VPS34 destabilization and autophagy deficiency.

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TRABID knockdown decreased VPS34 protein abundance and half-life, whereas TRABID overexpression enhanced VPS34 expression and stability.

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To interrogate the in vivo function of TRABID mediated VPS34 stabilization in liver metabolism, we set up a mouse model of nonalcoholic fatty liver disease (NAFLD) via feeding mice with a high-fat diet (HFD).

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We provide evidence that this switch of UBE3C localization plays a critical role for cells to cope with the stressed conditions by favoring TRABID mediated VPS34 stabilization and autophagy induction, as prevention of this switch by an enforced association of UBE3C with VPS34 impairs autophagy and compromises proteostasis, ER quality control and cell survival.

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Our findings suggest that the balance between UBE3C and TRABID on VPS34 regulation is disturbed by various ER/proteotoxic stressors to favor TRABID mediated VPS34 stabilization, thus facilitating autophagy induction.

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Specifically in the liver, we show that TRABID mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis.

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In the liver, TRABID mediated VPS34 stabilization is important for lipid metabolism and is downregulated in a mouse model of NAFLD.

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We next investigated the functional consequence of TRABID mediated VPS34 deubiquitnation.
ZRANB1 decreases the amount of PIK3C3.
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ZRANB1 decreases the amount of PIK3C3. 2 / 2
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TRABID knockdown decreased VPS34 protein abundance and half-life, whereas TRABID overexpression enhanced VPS34 expression and stability.

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Among the subunits of VPS34 complex, TRABID overexpression reduced the ubiquitination level of transfected and endogenous VPS34, but not AMBRA1, Beclin-1, ATG14 and UVRAG.
ZRANB1 increases the amount of PIK3C3.
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ZRANB1 increases the amount of PIK3C3. 1 / 1
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In line with the latter notion, 4-week treatment of rAAV-TRABID not only restored VPS34 expression and autophagy activity, but greatly alleviated HFD induced increase of liver and body weight and lipid accumulation in the liver, which was evident by gross anatomical view of the livers as well as H&E staining and Oil Red O staining of the liver sections.
ZRANB1 affects IL12
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ZRANB1 activates IL12.
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ZRANB1 activates IL12. 5 / 5
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Our data further suggested that Trabid mediated IL-12 and IL-23 induction plays an important role in mediating inflammatory T cell responses and the pathogenesis of EAE, an animal model of the autoimmune neuroinflammatory disease multiple sclerosis.

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DC-conditional deletion of Trabid impairs IL-12 and IL-23 production in DCs and the generation of Th1 and Th17 subsets of inflammatory T cells, rendering mice refractory to the induction of EAE 180.

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Conditional deletion of Zranb1 in dendritic cells impairs IL-12 and IL-23 production and the generation of T H 1 and T H 17 subsets of inflammatory T cells, rendering mice refractory to the induction of experimental autoimmune encephalomyelitis (EAE) 191 .

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Collectively, these results suggest that Trabid mediates induction of IL-12 and IL-23, thereby promoting T H 1 and T H 17 differentiation.

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To elucidate the molecular mechanism by which Trabid mediates induction of IL-12 family of cytokines, we examined the role of Trabid in regulating TLR mediated activation of MAP kinases (MAPKs), IkappaB kinase (IKK) and downstream transcription factors known to regulate Il12 and Il23 gene induction XREF_BIBR, XREF_BIBR, XREF_BIBR.
ZRANB1 inhibits IL12.
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ZRANB1 inhibits IL12. 2 / 2
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By employing a gene targeting approach, we show that Trabid deficiency in DCs and macrophages impaired the induction of Il12 and Il23 genes without affecting the induction of many other cytokine genes.

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Moreover ZRANB1 deficiency in macrophages and dendritic cells impairs the induction of IL-12 and IL-23 by the regulation of histone modifications at the IL-12 promoter, indicating a role of ZRANB1 in mediating inflammatory responses 18 and macrophage activation 19.
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ZRANB1 increases the amount of IL12.
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ZRANB1 increases the amount of IL12. 1 / 1
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Deletion of Zranb1 (which encodes Trabid) in dendritic cells inhibited induction of the expression of Il12 and Il23 by Toll like receptors (TLRs), which impaired the differentiation of inflammatory T cells and protected mice from autoimmune inflammation.
ZRANB1 affects EZH2
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ZRANB1 activates EZH2.
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ZRANB1 activates EZH2. 4 / 4
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Ectopic expression of ZRANB1 in both LM2 cells (XREF_FIG) and HEK293T cells (XREF_SUPPLEMENTARY) markedly upregulated endogenous EZH2 protein and increased cell proliferation, which could be reversed by knockdown of EZH2.

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Furthermore, purified His ZRANB1 could bind to purified GST-EZH2 under cell-free conditions (XREF_FIG), suggesting that ZRANB1 may directly regulate EZH2.

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To determine whether the six EZH2 interacting DUBs affect EZH2 ubiquitination and protein levels, we transfected them individually into HEK293T cells, and we found that USP22 and ZRANB1 decreased the polyubiquitination of EZH2 (XREF_SUPPLEMENTARY); however, only ZRANB1 upregulated endogenous EZH2 protein (XREF_SUPPLEMENTARY).

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The histone methyltransferase EZH2 also appears to be a target of TRABID DUB activity , and TRABID depletion has been shown to decrease EZH2 levels ( 38 ) .
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ZRANB1 increases the amount of EZH2.
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Modified ZRANB1 increases the amount of EZH2. 1 / 1
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Conversely, silencing ZRANB1 expression in MDA-MB-231 cells by two independent small interfering RNAs (siRNAs) (2 and 5) reduced endogenous EZH2 protein levels by 70% and 60%, respectively (XREF_FIG).
ZRANB1 decreases the amount of EZH2.
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ZRANB1 decreases the amount of EZH2. 1 / 1
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The histone methyltransferase EZH2 also appears to be a target of TRABID DUB activity, and TRABID depletion has been shown to decrease EZH2 levels.
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ZRANB1 affects Wnt
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ZRANB1 activates Wnt.
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ZRANB1 activates Wnt. 3 / 3
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Although Trabid was first reported to activate the Wnt pathway by cleavage of the K63 linked chains, it was recently demonstrated to be 40-fold more active toward the K29 linked chains.

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TRABID, one of K63 specific DUB enzymes, became an attractive candidate to achieve this task since it has been reported to regulate Wnt signal positively [XREF_BIBR], as inhibition of TRABID presumably decreases Wnt signaling activity.

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However, in this study, we failed to confirm the notion that TRABID positively regulates canonical Wnt signaling based on several lines of evidence.
ZRANB1 inhibits Wnt.
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ZRANB1 inhibits Wnt. 1 / 1
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Knockdown of TRABID with RNAi resulted in downregulated expression of canonical Wnt target genes and decreased Wnt transcription activity, whereas its knockdown does not affect TNF-2 pathway [XREF_BIBR].
ZRANB1 decreases the amount of Wnt.
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ZRANB1 decreases the amount of Wnt. 1 / 1
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Secondly, the TRABID shRNAs failed to downregulate Wnt and beta-catenin-mediated transcription activity or endogenous Wnt target gene Axin2 mRNA levels in these tumor cells.
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We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis in vitro and in vivo .

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More importantly, ZRANB1 regulated LOXL2 through specificity protein 1 (SP1) and SP1 overexpression rescued the suppression of HCC growth and metastasis induced by ZRANB1 knockdown.
ZRANB1 bound to EZH2 activates Neoplasm Metastasis. 1 / 1
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They demonstrated that ZRANB1 can bind, deubiquitinate, and stabilize EZH2, which enhances breast cancer tumorigenesis and metastasis.
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The reintroduction of Trabid expression in tumor cells significantly decreases HCC progression as well as pulmonary metastasis.
ZRANB1 affects IL23A
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ZRANB1 activates IL23A.
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ZRANB1 activates IL23A. 2 / 2
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DC-conditional deletion of Trabid impairs IL-12 and IL-23 production in DCs and the generation of Th1 and Th17 subsets of inflammatory T cells, rendering mice refractory to the induction of EAE 180.

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Collectively, these results suggest that Trabid mediates induction of IL-12 and IL-23, thereby promoting T H 1 and T H 17 differentiation.
ZRANB1-C443A activates IL23A. 1 / 1
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In similar experiments using BMDCs, reconstitution of DC-cKO BMDCs with wild-type Trabid, but not C443A Trabid, rescued the induction of Il12a, Il12b, and Il23a genes (XREF_FIG).
ZRANB1 increases the amount of IL23A.
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ZRANB1 increases the amount of IL23A. 1 / 1
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Deletion of Zranb1, the gene encoding Trabid, in dendritic cells inhibited the induction of IL-12 and IL-23 expression by Toll like receptors (TLR), impairing the differentiation of inflammatory T cells and protecting mice from autoimmune inflammation.

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TRABID diminishes the K29 / K48 ubiquitination on VPS34 and promotes autophagosome maturation .

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Thus , besides autophagosome formation , TRABID promotes autophagosome maturation .

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We found that TRABID knockdown decreased autophagosome maturation into autolysosome , whereas TRABID overexpression enhanced it ( Fig. 2n , o and Supplementary Fig. 2j , k ) .
ZRANB1 affects MAP1LC3
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Accordingly, LC3 lipidation was also enhanced by TRABID overexpression in DMEM- or EBSS cultured cells treated with bafilomycin A1.

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Remarkably, UBE3C depletion induced upregulation of VPS34 expression, LC3 puncta and LC3 lipidation in cells cultured in DMEM or EBSS were all reversed by TRABID knockdown.

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Furthermore, in cells treated with bafilomycin A1 to block autophagic turnover, TRABID knockdown still reduced LC3 lipidation but did not alter p62 level, indicating a promoting role of TRABID in autophagosome formation.
TFAP4 affects ZRANB1
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TFAP4 decreases the amount of ZRANB1. 3 / 3
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Valproic acid decreases the amount of ZRANB1.
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Valproic acid decreases the amount of ZRANB1. 2 / 2
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Valproic acid increases the amount of ZRANB1.
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Valproic acid increases the amount of ZRANB1. 1 / 1
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However, non TNBC cell lines, T47D (ER+HER 2-), ZR75-1 (ER+HER 2+), SKBR3 (ER-HER2+), and MCF7 (ER+HER 2-), showed variable responses : knockdown of ZRANB1 inhibited the proliferation of SKBR3 and MCF7 cells, but not T47D and ZR75-1 cells, even though EZH2 was downregulated (XREF_SUPPLEMENTARY).

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Ectopic expression of ZRANB1 in both LM2 cells (XREF_FIG) and HEK293T cells (XREF_SUPPLEMENTARY) markedly upregulated endogenous EZH2 protein and increased cell proliferation, which could be reversed by knockdown of EZH2.

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In contrast, depletion of ZRANB1 in TNBC cells markedly suppressed cell proliferation and migration and induced apoptosis, and systemic delivery of nanoliposome encapsulated ZRANB1 siRNA led to pronounced anticancer effects in xenograft models of TNBC, suggesting that ZRANB1 could be a novel therapeutic target.
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In contrast, depletion of ZRANB1 in TNBC cells markedly suppressed cell proliferation and migration and induced apoptosis, and systemic delivery of nanoliposome encapsulated ZRANB1 siRNA led to pronounced anticancer effects in xenograft models of TNBC, suggesting that ZRANB1 could be a novel therapeutic target.

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Moreover, ZRANB1 knockdown reduced glaucoma induced RGC apoptosis.
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In addition, knockdown of ZRANB1 in MDA-MB-231 cells increased early apoptosis and late apoptosis (cell death) by 3-fold and 9-fold, respectively (XREF_SUPPLEMENTARY).
Succimer affects ZRANB1
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Succimer decreases the amount of ZRANB1. 2 / 2
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Magnetite nanoparticle decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-933 decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-892a decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-6867-5p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-574-5p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548x-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548j-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548g-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548f-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548e-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548az-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548ar-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548aq-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548am-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548aj-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548ah-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548ae-3p decreases the amount of ZRANB1. 2 / 2
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Hsa-miR-548a-3p decreases the amount of ZRANB1. 2 / 2
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ZRANB1 affects TWIST1
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Trabid inactivates Twist1 by cleaving RNF8-mediated Twist1 K63-linked ubiquitination.

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Taken together, Trabid inactivates Twist1 by cleaving RNF8-mediated Twist1 K63-linked ubiquitination, facilitating the complex formation of β-TrCP1 with Twist1, whereby enhancing K48-linked ubiquitination of Twist1 by β-TrCP1.
ZRANB1 affects IL12B
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ZRANB1-C443A activates IL12B. 2 / 2
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Consistently, reconstitution of KO MEFs with wild-type Trabid, but not C443A Trabid, greatly promoted poly (I : C)-induced Il12b, Il12a and Il23a mRNA expression in these cells (XREF_FIG) but had no effect on the induction of the control gene Il6 (XREF_FIG).

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In similar experiments using BMDCs, reconstitution of DC-cKO BMDCs with wild-type Trabid, but not C443A Trabid, rescued the induction of Il12a, Il12b, and Il23a genes (XREF_FIG).
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The upregulation of ZRANB1 promoted tumorigenesis in vivo .

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The upregulation of ZRANB1 promoted tumorigenesis in vivo.
SF1 affects ZRANB1
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SF1 decreases the amount of ZRANB1. 2 / 2
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S1 affects ZRANB1
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S1 inhibits ZRANB1. 2 / 2
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Table S1) inhibition of TRABID DUB activity.

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Table S1, which share similar chemical structures to NSC112200 and NSC267309, did not inhibit TRABID DUB activity, suggesting that the two hydroxyl groups and their locations on the benzene ring may be important for the inhibitory activity.
MYOD1 affects ZRANB1
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MYOD1 decreases the amount of ZRANB1. 2 / 2
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ESRRA affects ZRANB1
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ESRRA decreases the amount of ZRANB1. 2 / 2
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ZRANB1 inhibits cell growth.
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The observation that the TRABID inhibitors were able to inhibit cell growth suggests that TRABID may have a role in cell growth regulation.
ZRANB1 activates cell growth.
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Nevertheless, inhibition of TRABID may inhibit cell growth.
ZRANB1 affects LOXL2
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ZRANB1 increases the amount of LOXL2.
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ZRANB1 increases the amount of LOXL2. 1 / 1
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We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis in vitro and in vivo .
ZRANB1 activates LOXL2.
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ZRANB1 activates LOXL2. 1 / 1
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We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis in vitro and in vivo .
ZRANB1 affects Il23
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ZRANB1 inhibits Il23.
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ZRANB1 inhibits Il23. 1 / 1
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By employing a gene targeting approach, we show that Trabid deficiency in DCs and macrophages impaired the induction of Il12 and Il23 genes without affecting the induction of many other cytokine genes.
ZRANB1 increases the amount of Il23.
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ZRANB1 increases the amount of Il23. 1 / 1
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Deletion of Zranb1 (which encodes Trabid) in dendritic cells inhibited induction of the expression of Il12 and Il23 by Toll like receptors (TLRs), which impaired the differentiation of inflammatory T cells and protected mice from autoimmune inflammation.
ZRANB1 affects ATG14
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ZRANB1 inhibits ATG14.
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ZRANB1 inhibits ATG14. 1 / 1
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Among the subunits of VPS34 complex, TRABID overexpression reduced the ubiquitination level of transfected and endogenous VPS34, but not AMBRA1, Beclin-1, ATG14 and UVRAG.
ZRANB1 activates ATG14.
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ZRANB1 activates ATG14. 1 / 1
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However, TRABID knockdown diminished DFCP1 puncta, ATG16 puncta, and ATG14 puncta.
EZH2 affects ZRANB1
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EZH2 inhibits ZRANB1.
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EZH2 inhibits ZRANB1. 1 / 1
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Interestingly, knockdown of EZH2 impaired but did not abolish the interaction of ZRANB1 with SUZ12, RBBP4, and EED (XREF_SUPPLEMENTARY), indicating that EZH2 partially mediates the association of ZRANB1 with the PRC2.