REV1

gene
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Summary

REV1 (REV1 DNA directed polymerase, HGNC:14060) is a protein-coding gene on chromosome 2q11.2, encoding Translesion synthesis protein REV1 (Q9UBZ9). Bifunctional protein involved in the maintenance of genome stability through translesion DNA synthesis (TLS) and antibody diversification via somatic hypermutation.

This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA.

Source: NCBI Gene 51455 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 176 total
  • Druggable target: yes
  • MANE Select transcript: NM_016316

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14060
Approved symbolREV1
NameREV1 DNA directed polymerase
Location2q11.2
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000135945
Ensembl biotypeprotein_coding
OMIM606134
Entrez51455

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 7 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000258428, ENST00000393445, ENST00000413697, ENST00000438366, ENST00000450415, ENST00000465086, ENST00000465835, ENST00000472000, ENST00000473819, ENST00000477121, ENST00000481719, ENST00000482595, ENST00000482887, ENST00000485487, ENST00000486117, ENST00000491752, ENST00000879663, ENST00000879664, ENST00000879665, ENST00000879666, ENST00000920275, ENST00000920276, ENST00000920277, ENST00000920278, ENST00000920279, ENST00000920280, ENST00000920281, ENST00000949065, ENST00000949066, ENST00000949067

RefSeq mRNA: 7 — MANE Select: NM_016316 NM_001037872, NM_001321454, NM_001321455, NM_001321458, NM_001321459, NM_001321460, NM_016316

CCDS: CCDS2045, CCDS42722

Canonical transcript exons

ENST00000258428 — 23 exons

ExonStartEnd
ENSE000009218419940224499402346
ENSE000009218429940264499402800
ENSE000009218609946249699462622
ENSE000009218619946492299464985
ENSE000034656599941273199412951
ENSE000034812289942415299424280
ENSE000034869139940632599406490
ENSE000035044549940369599403815
ENSE000035127359940444499404677
ENSE000035128919941882899418947
ENSE000035464059943433299434448
ENSE000035737019943860199439310
ENSE000035830009940288999403106
ENSE000036069839941069599410867
ENSE000036397649942984099429948
ENSE000036399679942149999421653
ENSE000036442629940591099406106
ENSE000036552819943583499435941
ENSE000036663949944933699449504
ENSE000036776089944231799442469
ENSE000036799169940802999408131
ENSE000038451939940047799401352
ENSE000038469299948981799490017

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6764 / max 446.2443, expressed in 1772 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
2988410.67641772

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065597.63gold quality
oocyteCL:000002397.51gold quality
calcaneal tendonUBERON:000370196.79gold quality
cerebellar hemisphereUBERON:000224596.45gold quality
cerebellar cortexUBERON:000212996.42gold quality
cerebellumUBERON:000203796.16gold quality
right hemisphere of cerebellumUBERON:001489096.12gold quality
adrenal tissueUBERON:001830396.09gold quality
right uterine tubeUBERON:000130295.47gold quality
ectocervixUBERON:001224994.35gold quality
mucosa of stomachUBERON:000119994.30gold quality
skin of abdomenUBERON:000141694.05gold quality
body of uterusUBERON:000985394.05gold quality
left ovaryUBERON:000211994.04gold quality
cortical plateUBERON:000534394.03gold quality
right lungUBERON:000216793.97gold quality
tibiaUBERON:000097993.91gold quality
skin of legUBERON:000151193.85gold quality
vaginaUBERON:000099693.66gold quality
metanephros cortexUBERON:001053393.61gold quality
right ovaryUBERON:000211893.60gold quality
left uterine tubeUBERON:000130393.56gold quality
diaphragmUBERON:000110393.51gold quality
corpus callosumUBERON:000233693.48gold quality
endocervixUBERON:000045893.47gold quality
pituitary glandUBERON:000000793.39gold quality
minor salivary glandUBERON:000183093.39gold quality
lower esophagus mucosaUBERON:003583493.32gold quality
upper lobe of left lungUBERON:000895293.31gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047393.23gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes14.13
E-MTAB-6379no593.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting REV1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4668-3P100.0068.742635
HSA-MIR-4455100.0065.481587
HSA-MIR-340-5P100.0072.504437
HSA-MIR-30A-5P100.0076.313233
HSA-MIR-30B-5P100.0076.293248
HSA-MIR-30C-5P100.0076.293248
HSA-MIR-30D-5P100.0076.323233
HSA-MIR-30E-5P100.0076.323242
HSA-MIR-6748-5P100.0065.811057
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-480399.9871.993117
HSA-MIR-568899.9673.234504
HSA-MIR-495-3P99.9672.814197
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-96-5P99.9572.802140
HSA-LET-7C-3P99.9573.422862
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-1213399.9271.822006
HSA-MIR-1271-5P99.9171.991972
HSA-MIR-568099.9169.833421
HSA-MIR-182-5P99.8774.032589
HSA-MIR-5582-3P99.8672.484221
HSA-MIR-548AR-3P99.8571.263889

Literature-anchored findings (GeneRIF, showing 40)

  • purified human REV1 and REV7 proteins form a heterodimer in solution, which is stable through intensive purification steps. (PMID:12529368)
  • UV-induced mutant frequencies at the HPRT locus were reduced up to 75% in cells with reduced levels of REV1 mRNA and data support that targeting the mutagenic translesion DNA replication pathway can greatly reduce the frequency of induced mutations. (PMID:12930947)
  • REV1 interacts with three Y-family DNA polymerases. (PMID:15189446)
  • REV1 interacts with pol eta in translesion synthesis of damaged DNA (PMID:15380106)
  • REV1-dependent processes are important determinants of cisplatin-induced genomic instability and the development of resistance. (PMID:16495473)
  • a novel biochemical activity of human REV1 protein, due to higher affinity for single-stranded DNA (ssDNA) than the primer terminus (PMID:16803901)
  • Rev1 is a polypeptide associated with Poleta. The study results suggest that arrested replication forks strengthen interactions among Poleta, Rad18/Rad6 and Rev1, consistent with the requirement for effective TLS by Poleta at sites of DNA lesions. (PMID:16824193)
  • Results support Phe257Ser and Ser257Ser genotypes are associated with a decreased risk for cervical carcinoma, while Asn373Ser and Ser373Ser genotypes increased the risk. (PMID:18470628)
  • Data show that PCNA ubiquitination and REV1 play distinct roles in the coordination of DNA damage bypass that are temporally separated relative to replication fork arrest. (PMID:18498753)
  • human REV1, apparently the slowest Y family polymerase, is kinetically highly tolerant to N(2)-adduct at G but not to O(6)-adducts. (PMID:18591245)
  • plays a role in mutagenesis and translesin DNA synthesis. (review) (PMID:18975621)
  • Poleta-REV1 interactions prevent spontaneous mutations, probably by promoting accurate translesion DNA synthesis past endogenous DNA lesions (PMID:19157994)
  • Novel structural features are important for providing Rev1 greater latitude in promoting efficient and error-free translesion DNA synthesis through the diverse array of bulky and potentially carcinogenic N(2)-deoxyguanosine DNA adducts in human cells. (PMID:19464298)
  • Translesional DNA synthesis through a C8-guanyl adduct of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Vitro: REV1 inserts dC opposite the lesion, and DNA polymerase kappa potentially catalyzes extension reaction from the 3’-dC terminus. (PMID:19628463)
  • REV1 and Polzeta facilitate repair of interstrand cross-links independently of PCNA monoubiquitination and Poleta, whereas RAD18 plus Poleta, REV1, and Polzeta are all necessary for replicative bypass of cisplatin intrastrand DNA cross-links. (PMID:20028736)
  • The results suggest that the positive charge on R357 could prevent interaction of REV1 with dGTP. (PMID:20059978)
  • the interaction between REV7 and REV3 creates a structural interface for REV1 binding (PMID:20164194)
  • WRN facilitates REV1-dependent translesion synthesis. (PMID:20691646)
  • Results suggest that abasic sites might be bypassed by single B- and Y-family pols or combinations, possibly by REV1 and pols iota, eta, and delta/PCNA at the insertion step opposite the lesion and by pols eta and delta/PCNA at the subsequent extension step. (PMID:20888339)
  • Hsp90 promotes folding of REV1 into a stable and/or functional form(s) to bind to monoubiquitinated proliferating cell nuclear antigen in the regulation of translesion DNA synthesis-mediated mutagenesis (PMID:21690293)
  • The REV1/Polzeta complex maintains genomic stability by directly participating in DNA double-stranded break repair. (PMID:21926160)
  • FAAP20 binding stabilizes Rev1 nuclear foci and promotes interaction of the Fanconi anemia core with PCNA-Rev1 DNA damage bypass complexes. (PMID:22266823)
  • REV7 subunit of pol zeta mediated the interaction between REV3 and the REV1 C terminus. (PMID:22303021)
  • a structural basis for understanding the recognition of the Rev1-CT by Y-family DNA polymerases (PMID:22691049)
  • Findings indicate that miR-96 regulates DNA repair and chemosensitivity by repressing RAD51 and REV1. (PMID:22761336)
  • the Rev1 C-terminal domain utilizes independent interaction interfaces to simultaneously bind a fragment of the ‘inserter’ poleta and Rev7 subunit of the ’extender’ polvarsigma, thereby serving as a cassette that may accommodate several polymerases (PMID:22828282)
  • analysis of the crystal structure of the ternary complex composed of the C-terminal domain of human REV1, REV7, and a REV3 fragment (PMID:22859296)
  • ternary complex of the C-terminal domain of human REV1 in complex with REV7 bound to a REV3 fragment has been crystallized. The crystals belonged to space group P3(1)21, with unit-cell parameters a = b = 74.7, c = 124.5 A (PMID:22869133)
  • the first structural insights into the regulation of human Rev1 for TLS polymerases. (PMID:23220741)
  • Rev1 but not Poleta depletion is epistatic to the lack of PCNA ubiquitination. (PMID:23761444)
  • The results show that human Rev1 disrupts G4 DNA structures and prevents refolding in vitro. (PMID:24366879)
  • Structural studies suggest the possible involvement of XRCC1 and its associated repair factors, REV1 in post replication repair. (PMID:24409475)
  • Our results suggest for the first time that REV1 and REV3L SNPs might serve as potential predictive markers of outcome of cisplatin-based chemotherapy (PMID:24956248)
  • The molecular mechanism of 3-nitrobenzanthrone genotoxicity in HEK293 cells is reported. (PMID:25080294)
  • show that REV1 is a novel binding partner of the tumor suppressor p53 and regulates its activity (PMID:25614517)
  • Data suggest Rev1 protein recognition mechanism by Fanconi anemia-associated protein 20 (FAAP20). (PMID:26318859)
  • Rev1 is indispensable for Translesion synthesis mediated by Poleta, Poliota, and Polkappa but is not required for TLS by Polzeta. (PMID:26680302)
  • REV1 can promote PCNA monoubiquitylation after UV radiation through interacting with ubiquitylated RAD18. (PMID:26795561)
  • Saccharomyces cerevisiae (PMID:26903512)
  • the catalytic function of REV1 is moderately or slightly altered by at least nine genetic variations, and the G4 DNA processing function of REV1 is slightly enhanced by the N373S variation, which might provide the possibility that certain germline missense REV1 variations affect the individual susceptibility to carcinogenesis by modifying the capability of REV1 for replicative bypass past DNA lesions and G4 motifs derived (PMID:26914252)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriorev1ENSDARG00000018296
mus_musculusRev1ENSMUSG00000026082
rattus_norvegicusRev1ENSRNOG00000018623
drosophila_melanogasterRev1FBGN0035150
caenorhabditis_elegansWBGENE00014066

Paralogs (5): POLI (ENSG00000101751), POLK (ENSG00000122008), ESCO1 (ENSG00000141446), POLH (ENSG00000170734), ESCO2 (ENSG00000171320)

Protein

Protein identifiers

Translesion synthesis protein REV1Q9UBZ9 (reviewed: Q9UBZ9)

Alternative names: Alpha integrin-binding protein 80, Molecular adapter protein REV1, Rev1-like terminal deoxycytidyl transferase, Reversionless protein 1 homolog, Template-dependent deoxycytidyl transferase REV1

All UniProt accessions (4): C9JPS2, Q9UBZ9, F8WCR0, H7C263

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional protein involved in the maintenance of genome stability through translesion DNA synthesis (TLS) and antibody diversification via somatic hypermutation. Functions as a molecular adapter protein at stalled DNA replication, coordinating polymerases recruitment, selection, and switching, in a manner independent of its deoxycytidyl transferase activity. At the site of DNA lesion, recruits and mediates the switch between low-fidelity inserter DNA polymerases, such as POLK, that incorporate nucleotides opposite lesions and the extender DNA polymerase zeta complex which continues DNA synthesis from distorted primer termini. In vitro, acts as a template-dependent deoxycytidyl transferase that preferentially incorporates deoxycytidine residues from dCTP to the 3’-end of a DNA primer opposite apurinic/apyrimidinic (AP) site, uracil, undamaged DNA templates (G > A > C > T) and a variety of damaged DNA templates. Opposite template guanine, efficiently incorporates not only dCMP but also non-complementary dGMP and dTMP, with lower efficiency for dAMP, demonstrating low fidelity on undamaged DNA. This catalytic activity has been implicated in somatic hypermutation, likely achieved by incorporation of deoxycytidine opposite abasic sites, generated at cytidines via activation-induced deoxycytidine deaminase (AID)-mediated deamination and uracil DNA glycosylase (UNG) activity, respectively. In addition, exhibits a 5’-deoxyribose-5-phosphate lyase activity in vitro, though its necessity in vivo is not confirmed.

Subunit / interactions. Monomer. Homodimer. Homotetramer. Interacts (via C-terminal domain) with the DNA polymerase zeta complex which is composed of REV3L and MAD2L2; the interaction with MAD2L2 is direct, and REV3L forms and stabilizes the DNA polymerase zeta complex before being recruited by REV1 to the DNA lesion site. Forms a quaternary complex with POLK, MAD2L2 and REV3L, where REV3L-bound MAD2L2 and POLK are able to bind simultaneously to REV1 forming the stable translesion synthesis (TLS) machinery therefore bridging the inserter and extender polymerases. May bind ITGA3. Interacts with FAAP20 (via UBZ2-type zinc finger); this interaction contributes to the stable association of the two proteins in nuclear foci in response to replication stress. Interacts (via C-terminal domain) with POLH. Interacts (via C-terminal domain) with POLD3. Interacts with UBB. Interacts (via C-terminal domain) with POLK; POLK competes with MAD2L2 for binding to REV1. Interacts (via C-terminal domain) with POLI. Interacts (via BRCT domain) with PCNA; this interaction is enhanced with a monoubiquitinated form of PCNA and mediates the recruitment of REV1 to stalled DNA replication.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Monoubiquitinated. Undergoes a ubiquitination-deubiquitination cycle. The monoubiquitination is not required for FAAP20 interaction but enhances it, contributing to the stable association of the two proteins at DNA lesions in response to replication stress.

Domain organisation. The C-terminal domain mediates interaction with the major translesion synthesis (TLS) polymerases, POLH, POLI, and POLK, and the adapter subunit MAD2L2 of DNA polymerase zeta complex and is essential for tolerance of DNA damage caused by a number of mutagens. The C-terminal domain can binds simultaneously both POLK and the MAD2L2 subunit of DNA polymerase zeta complex, bridging the inserter and extender polymerases during TLS. The BRCT domain promotes resistance to DNA damage by mediating interaction with PCNA and localization to nuclear foci. Ubiquitin-binding motif (UBM) domains contribute to DNA damage tolerance and damage-induced mutagenesis by enhancing both REV1’s interaction with monoubiquitinated PCNA and association with replication foci. Only the UBM2 domain mediates UBB binding.

Similarity. Belongs to the DNA polymerase type-Y family.

Isoforms (3)

UniProt IDNamesCanonical?
Q9UBZ9-11, REV1yes
Q9UBZ9-22, REV1S
Q9UBZ9-33

RefSeq proteins (7): NP_001032961, NP_001308383, NP_001308384, NP_001308387, NP_001308388, NP_001308389, NP_057400* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001126UmuCDomain
IPR001357BRCT_domDomain
IPR012112REV1Family
IPR017961DNA_pol_Y-fam_little_fingerDomain
IPR025527HUWE1/Rev1_UBMConserved_site
IPR031991Rev1_CDomain
IPR036420BRCT_dom_sfHomologous_superfamily
IPR036775DNA_pol_Y-fam_lit_finger_sfHomologous_superfamily
IPR038401Rev1_C_sfHomologous_superfamily
IPR043128Rev_trsase/Diguanyl_cyclaseHomologous_superfamily
IPR043502DNA/RNA_pol_sfHomologous_superfamily
IPR047346Rev1_UBM1/2Conserved_site
IPR053848IMS_HHH_1Domain

Pfam: PF00533, PF00817, PF11799, PF14377, PF16727, PF21999

Catalyzed reactions (Rhea), 1 shown:

  • DNA(n) + dCTP = DNA(n)-C + diphosphate (RHEA:86319)

UniProt features (137 total): helix 38, binding site 23, strand 19, sequence variant 16, mutagenesis site 9, turn 7, compositionally biased region 6, region of interest 5, domain 4, splice variant 4, active site 3, chain 1, short sequence motif 1, site 1

Structure

Experimental structures (PDB)

17 structures.

PDBMethodResolution (Å)
4EXTX-RAY DIFFRACTION1.9
6WS0X-RAY DIFFRACTION2.24
6ASRX-RAY DIFFRACTION2.36
6WS5X-RAY DIFFRACTION2.47
3GQCX-RAY DIFFRACTION2.5
4GK0X-RAY DIFFRACTION2.7
9VGWX-RAY DIFFRACTION2.7
4BA9X-RAY DIFFRACTION2.73
3VU7X-RAY DIFFRACTION2.8
4GK5X-RAY DIFFRACTION3.21
2EBWSOLUTION NMR
2LSISOLUTION NMR
2LSKSOLUTION NMR
2LSYSOLUTION NMR
2N1GSOLUTION NMR
5VZMSOLUTION NMR
6AXDSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9UBZ9-F167.200.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 423; 570; 571; 428 (substrate discrimination)

Ligand- & substrate-binding residues (23): 357; 423; 424; 424; 426; 427; 428; 510; 513; 516; 522; 570

Mutagenesis-validated functional residues (9):

PositionPhenotype
570–571loss of deoxycytidyl transferase activity.
570abolishes transferase activity; when associated with a-571.
571abolishes transferase activity; when associated with a-570.
946loss of monoubiquitination; when associated with a-947, a-1024 and a-1025.
947loss of monoubiquitination; when associated with a-946, a-1024 and a-1025.
958does not affect ubb binding; when associated with a-977.
977does not affect ubb binding; when associated with a-977.
1024loss of monoubiquitination; when associated with a-946, a-947 and a-1025.
1025loss of monoubiquitination; when associated with a-946, a-947 and a-1024.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-110312Translesion synthesis by REV1
R-HSA-5655862Translesion synthesis by POLK
R-HSA-5656121Translesion synthesis by POLI
R-HSA-5656169Termination of translesion DNA synthesis

MSigDB gene sets: 164 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_DNA_DAMAGE_TOLERANCE, KAUFFMANN_DNA_REPAIR_GENES, GTACAGG_MIR486, GOCC_NUCLEAR_REPLICATION_FORK, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_ERROR_FREE_TRANSLESION_SYNTHESIS, GOMF_DNA_POLYMERASE_ACTIVITY, GOBP_IMMUNOGLOBULIN_PRODUCTION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GOBP_DNA_BIOSYNTHETIC_PROCESS, HIF1_Q3, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN

GO Biological Process (10): DNA repair (GO:0006281), somatic hypermutation of immunoglobulin genes (GO:0016446), translesion synthesis (GO:0019985), error-prone translesion synthesis (GO:0042276), error-free translesion synthesis (GO:0070987), DNA biosynthetic process (GO:0071897), DNA metabolic process (GO:0006259), DNA replication (GO:0006260), DNA damage response (GO:0006974), response to UV (GO:0009411)

GO Molecular Function (11): DNA binding (GO:0003677), damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), deoxycytidyl transferase activity (GO:0017125), protein-macromolecule adaptor activity (GO:0030674), ubiquitin binding (GO:0043130), metal ion binding (GO:0046872), DNA-(abasic site) binding (GO:0140431), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (4): nucleoplasm (GO:0005654), nuclear replication fork (GO:0043596), site of DNA damage (GO:0090734), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template4

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
DNA metabolic process3
translesion synthesis2
cellular anatomical structure2
DNA damage response1
somatic diversification of immune receptors via somatic mutation1
somatic diversification of immunoglobulins1
DNA damage tolerance1
DNA synthesis involved in DNA replication1
nucleic acid biosynthetic process1
nucleic acid metabolic process1
DNA biosynthetic process1
cellular response to stress1
response to light stimulus1
nucleic acid binding1
DNA binding1
DNA polymerase activity1
nucleotidyltransferase activity1
protein binding1
molecular adaptor activity1
ubiquitin-like protein binding1
cation binding1
damaged DNA binding1
binding1
catalytic activity1
transferase activity, transferring phosphorus-containing groups1
nuclear lumen1
nuclear chromosome1
nucleus1
replication fork1
CMG complex1
chromosome1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

2080 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
REV1MAD2L2Q9UI95999
REV1REV3LO60673999
REV1POLMQ9NP87992
REV1POLLQ9UGP5961
REV1UNGP13051899
REV1RAD18Q9NS91846
REV1POLD2P49005828
REV1UBE2V2Q15819818
REV1POLD3Q15054800
REV1UBE2NP61088783
REV1POLHQ9Y253775
REV1FANCD2Q9BXW9773
REV1F6S8H2F6S8H2754
REV1OGG1P78554742
REV1LIG1P18858738

IntAct

14 interactions, top by confidence:

ABTypeScore
MAD2L2REV3Lpsi-mi:“MI:0915”(physical association)0.640
REV1FAAP20psi-mi:“MI:0407”(direct interaction)0.540
REV1FAAP20psi-mi:“MI:0915”(physical association)0.540
FHL2REV1psi-mi:“MI:0915”(physical association)0.510
REV1FHL2psi-mi:“MI:0915”(physical association)0.510
POLHREV1psi-mi:“MI:0407”(direct interaction)0.440
REV1TUFMpsi-mi:“MI:0915”(physical association)0.400
Mpsi-mi:“MI:0914”(association)0.350
GPKOWESYT2psi-mi:“MI:2364”(proximity)0.270
RPS11ESYT2psi-mi:“MI:2364”(proximity)0.270

BioGRID (98): REV1 (Affinity Capture-MS), REV1 (Co-crystal Structure), REV1 (Biochemical Activity), PIAS4 (Affinity Capture-Western), TP53 (Affinity Capture-Western), PCNA (Affinity Capture-Western), Mad2l2 (Affinity Capture-Western), REV1 (Affinity Capture-Western), REV1 (Affinity Capture-Western), REV1 (Reconstituted Complex), REV1 (Two-hybrid), REV1 (Affinity Capture-Western), FHL2 (Affinity Capture-Western), REV1 (Reconstituted Complex), REV1 (Two-hybrid)

ESM2 similar proteins: D4A6L0, F1M5F3, F1N2W9, F1QDI9, F6RIX4, I0IUP4, O75808, P22681, P22682, P55266, Q14432, Q15047, Q2KHI9, Q3U269, Q496Y0, Q4KWZ7, Q52L14, Q5C9Z4, Q5R4N7, Q5R6Z9, Q5RCP1, Q5T7W7, Q5T848, Q5XIX3, Q62865, Q642B6, Q66JB6, Q69ZT1, Q6NRM6, Q6P3Z3, Q7TPQ3, Q8BUM9, Q8HXH0, Q8IYL2, Q8K214, Q8K2I9, Q8K4J0, Q8NFZ0, Q8WY91, Q920Q2

Diamond homologs: A0Q6K9, A1A7U2, A1KUQ3, A1RMZ5, A1S8M3, A2RNH9, A3EWL3, A3N148, A3QGY9, A4TPK8, A4W6W8, A5IH02, A5IU61, A6QIC3, A6U2Z9, A6VA50, A7MEN4, A7NC07, A7X420, A7ZHZ2, A7ZWJ6, A8AKQ2, A8FYV3, A8GAC8, A8H771, A9MNS1, A9MY13, B0BPX9, B0TQD1, B0TZS5, B1J100, B1KD33, B2FLR2, B2SH34, B2U3S3, B2UKN1, B4SIF5, B8F542, B9DMT3, P58963

SIGNOR signaling

4 interactions.

AEffectBMechanism
CDC20“down-regulates quantity by destabilization”REV1binding
FZR1“down-regulates quantity by destabilization”REV1binding
APC-c“down-regulates quantity by destabilization”REV1polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance137
Likely benign11
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4190 predictions. Top by Δscore:

VariantEffectΔscore
2:99401348:TCAGC:Tacceptor_gain1.0000
2:99401349:CAGC:Cacceptor_gain1.0000
2:99401349:CAGCC:Cacceptor_gain1.0000
2:99401350:AGCC:Aacceptor_loss1.0000
2:99401352:CCTAA:Cacceptor_loss1.0000
2:99401353:C:CCacceptor_gain1.0000
2:99401353:CT:Cacceptor_loss1.0000
2:99401354:T:Cacceptor_loss1.0000
2:99402238:TACTA:Tdonor_loss1.0000
2:99402241:TAC:Tdonor_loss1.0000
2:99402242:ACCTT:Adonor_loss1.0000
2:99402243:C:Tdonor_loss1.0000
2:99402347:C:CCacceptor_gain1.0000
2:99403683:T:TAdonor_gain1.0000
2:99403815:CC:Cacceptor_loss1.0000
2:99403815:CCTAG:Cacceptor_gain1.0000
2:99403816:C:CAacceptor_loss1.0000
2:99403819:G:Cacceptor_gain1.0000
2:99403819:G:GCacceptor_gain1.0000
2:99404439:CTTA:Cdonor_loss1.0000
2:99404440:TTAC:Tdonor_loss1.0000
2:99404441:TA:Tdonor_loss1.0000
2:99404442:A:ACdonor_gain1.0000
2:99404443:C:CAdonor_loss1.0000
2:99404443:C:CCdonor_gain1.0000
2:99404674:CCAG:Cacceptor_gain1.0000
2:99404675:CAGC:Cacceptor_gain1.0000
2:99404678:C:CCacceptor_gain1.0000
2:99406000:AG:Adonor_gain1.0000
2:99406105:TA:Tacceptor_gain1.0000

AlphaMissense

8229 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
2:99401324:A:GW1225R1.000
2:99401324:A:TW1225R1.000
2:99402298:A:GL1197P1.000
2:99402662:A:GW1175R1.000
2:99402662:A:TW1175R1.000
2:99449349:A:GW113R1.000
2:99449349:A:TW113R1.000
2:99401290:A:TV1236D0.999
2:99401299:A:GL1233P0.999
2:99401304:A:CF1231L0.999
2:99401304:A:TF1231L0.999
2:99401306:A:GF1231L0.999
2:99401322:C:AW1225C0.999
2:99401322:C:GW1225C0.999
2:99402271:A:GL1206P0.999
2:99402308:A:GC1194R0.999
2:99402311:A:CY1193D0.999
2:99402331:T:GD1186A0.999
2:99402332:C:GD1186H0.999
2:99402343:G:TP1182Q0.999
2:99402660:C:AW1175C0.999
2:99402660:C:GW1175C0.999
2:99402670:A:GL1172P0.999
2:99402709:A:GL1159P0.999
2:99403790:A:GL1024P0.999
2:99403790:A:TL1024H0.999
2:99412816:C:GR696P0.999
2:99449402:A:GL95P0.999
2:99449411:G:TA92D0.999
2:99462510:A:TV56D0.999

dbSNP variants (sampled 300 via entrez): RS1000025189 (2:99473867 A>G), RS1000030994 (2:99434539 G>A,C,T), RS1000075241 (2:99491132 A>G), RS1000107181 (2:99480539 A>C,G), RS1000127959 (2:99451028 T>C,G), RS1000147496 (2:99462945 G>A), RS1000167264 (2:99438583 A>G), RS1000174640 (2:99481919 G>C), RS1000231138 (2:99402042 T>C,G), RS1000240863 (2:99401781 T>C), RS1000292705 (2:99468160 A>C,G), RS1000305520 (2:99444390 C>T), RS1000409 (2:99441727 A>G,T), RS1000421326 (2:99418561 T>C), RS1000434346 (2:99408493 C>T)

Disease associations

OMIM: gene MIM:606134 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (1): preeclampsia (MONDO:0005081)

Orphanet (1): Preeclampsia (Orphanet:275555)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

StudyTraitp-value
GCST001241_13Bipolar disorder3.000000e-06

MeSH disease descriptors (1)

DescriptorNameTree numbers
D011225Pre-EclampsiaC12.050.703.395.249

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295973 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs3087403Efficacy3cisplatinOsteosarcoma

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs3087386REV10.000
rs3087399REV10.000
rs3087403REV132.751cisplatin

ChEMBL bioactivities

38 potent at pChembl≥5 of 63 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.70Ki2000nMCHEMBL4240676
5.68Kd2100nMCHEMBL4240676
5.60IC502500nMCHEMBL4238011
5.60IC502500nMCHEMBL4249624
5.60IC502500nMCHEMBL4240676
5.54Kd2900nMCHEMBL1717725
5.52Ki3000nMCHEMBL1717725
5.46IC503500nMCHEMBL1717725
5.46Kd3500nMCHEMBL4245882
5.44Ki3600nMCHEMBL4245882
5.44Kd3600nMCHEMBL4246571
5.44Ki3600nMCHEMBL1721787
5.44Kd3600nMCHEMBL1721787
5.43Kd3700nMCHEMBL4249812
5.39IC504100nMCHEMBL4245882
5.37Kd4300nMCHEMBL4237457
5.36Kd4400nMCHEMBL4249624
5.34IC504600nMCHEMBL4237457
5.34Ki4600nMCHEMBL4249624
5.34IC504600nMCHEMBL4244874
5.33Ki4700nMCHEMBL4237457
5.32Ki4800nMCHEMBL4249812
5.31IC504900nMCHEMBL4241371
5.31Ki4900nMCHEMBL4246571
5.26IC505500nMCHEMBL1721787
5.23IC505900nMCHEMBL4238016
5.23IC505900nMCHEMBL4246571
5.21IC506200nMCHEMBL4249812
5.19Kd6500nMCHEMBL4238011
5.17Kd6700nMCHEMBL4245882
5.16Ki6900nMCHEMBL4238011
5.16Kd6900nMCHEMBL4244874
5.13Ki7400nMCHEMBL4244254
5.11Kd7800nMCHEMBL4238016
5.09Kd8200nMCHEMBL4244254
5.05Ki8900nMCHEMBL4244874
5.03IC509400nMCHEMBL4244254
5.02Kd9500nMCHEMBL4241371

PubChem BioAssay actives

38 with measured affinity, of 127 total; 13 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
8-[[4-(3-chlorophenyl)piperazin-1-yl]methyl]-1,3-dimethyl-7-(3-oxobutan-2-yl)purine-2,6-dione1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayki2.0000uM
1-acetyl-N-[3-(cyclopropylcarbamoyl)-6-methyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl]piperidine-4-carboxamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayic502.5000uM
N-(4-ethylphenyl)-2-[4-(4-fluorophenyl)piperazin-1-yl]acetamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayic502.5000uM
(4-methyl-3-morpholin-4-ylsulfonylphenyl)-(4-phenylpiperazin-1-yl)methanone1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assaykd2.9000uM
methyl 2-[(1-acetylpiperidine-4-carbonyl)amino]-5-propylthiophene-3-carboxylate1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assaykd3.5000uM
N-(4-ethylphenyl)-2-[4-(4-methoxyphenyl)piperazin-1-yl]acetamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayki3.6000uM
1-(4-butylphenyl)-N-(1,1-dioxothiolan-3-yl)-N,5-dimethyltriazole-4-carboxamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assaykd3.6000uM
[4-[4-(2,5-dimethoxyphenyl)-1,3-thiazol-2-yl]piperazin-1-yl]-(furan-2-yl)methanone1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assaykd3.7000uM
N-[4-[4-(2-methoxyphenyl)piperazine-1-carbonyl]phenyl]-N-methylethanesulfonamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assaykd4.3000uM
4-acetyl-N-(9-ethylcarbazol-3-yl)piperidine-1-carboxamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayic504.6000uM
1-acetyl-N-(3-carbamoyl-6-propyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)piperidine-4-carboxamide1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayic504.9000uM
ethyl 2-[(1-acetylpiperidine-4-carbonyl)amino]-5-propylthiophene-3-carboxylate1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayic505.9000uM
methyl 2-[(1-acetylpiperidine-4-carbonyl)amino]-5-methylthiophene-3-carboxylate1398243: Displacement of FAM-labelled polkappa-RIR peptide from recombinant human C-terminal Rev1 (1158 to 1251 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by fluorescence polarization assayki7.4000uM

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, decreases methylation3
sodium arsenitedecreases expression, increases abundance, increases expression2
Phenylmercuric Acetateaffects cotreatment, increases expression2
Cadmium Chloridedecreases expression, affects expression, increases abundance2
aristolochic acid Idecreases expression1
FR900359decreases phosphorylation1
TAK-243increases sumoylation1
dicrotophosdecreases expression1
methylmercuric chloridedecreases expression1
myristicindecreases expression1
trichostatin Aaffects expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
butyraldehydedecreases expression1
quinoline yellowincreases expression1
di-n-butylphosphoric acidaffects expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
abrineincreases expression1
dorsomorphinincreases expression, affects cotreatment1
bisphenol Sdecreases methylation1
Resveratrolaffects cotreatment, increases expression1
Air Pollutantsdecreases expression, increases abundance1
Arsenicdecreases expression, increases abundance1
Cadmiumincreases abundance, affects expression1
Caffeineincreases phosphorylation1
Coaldecreases expression, increases abundance1
Demecolcinedecreases expression1
Doxorubicindecreases expression, affects expression, affects response to substance1
Erythrosinedecreases expression1
Fluorouracilaffects expression1
Formaldehydedecreases expression1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4222910BindingBinding affinity to recombinant human REV1 UBM1/UBM2 domain (137 residues) expressed in Escherichia coli BL21(DE3) assessed as increase in NOE peaks at 200 uM by STD NMR spectral analysisSmall-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1 interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_1R10HCT116-REV1(+/-)Cancer cell lineMale
CVCL_1R11HCT116-REV1(-/-)Cancer cell lineMale
CVCL_D8UKUbigene HCT 116 REV1 KOCancer cell lineMale
CVCL_TI85HAP1 REV1 (-) 1Cancer cell lineMale
CVCL_TI86HAP1 REV1 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00117546PHASE4UNKNOWNCardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957PHASE4UNKNOWNRemifentanil for General Anesthesia in Preeclamptics
NCT01030627PHASE4COMPLETEDTreatment Approaches to Preeclampsia
NCT01352234PHASE4COMPLETEDComparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425PHASE4UNKNOWNAnti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468PHASE4COMPLETEDPrevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916PHASE4COMPLETEDClonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677PHASE4COMPLETEDOral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426PHASE4TERMINATEDPhenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401PHASE4COMPLETEDA Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655PHASE4COMPLETEDDiuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687PHASE4COMPLETEDLow Dose Calcium to Prevent Preeclampsia
NCT02396030PHASE4TERMINATEDDifferent Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490PHASE4UNKNOWNEarly Vascular Adjustments During Hypertensive Pregnancy
NCT02699827PHASE4COMPLETEDAdding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339PHASE4COMPLETEDMagnesium Sulfate in Obese Preeclamptics
NCT02891174PHASE4COMPLETEDThe Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701PHASE4COMPLETEDEffect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480PHASE4COMPLETEDUse of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880PHASE4UNKNOWNImpact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000PHASE4UNKNOWNEffect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724PHASE4COMPLETEDResponse to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606PHASE4COMPLETEDTrial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433PHASE4TERMINATEDThe Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119PHASE4UNKNOWNPostpartum NSAIDS and Maternal Hypertension
NCT04051567PHASE4UNKNOWNLow-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853PHASE4COMPLETEDProgesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830PHASE4WITHDRAWNAspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693PHASE4UNKNOWNComparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627PHASE4UNKNOWNEarly Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665PHASE4UNKNOWNThe Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949PHASE4WITHDRAWNAdherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982PHASE4UNKNOWNAspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164PHASE4UNKNOWN162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952PHASE4UNKNOWNco Ihibtory Receptor in Preeclampsia
NCT05514847PHASE4ACTIVE_NOT_RECRUITINGLow Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373PHASE4COMPLETEDIbuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102PHASE4COMPLETEDOptimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335PHASE4NOT_YET_RECRUITINGEffect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665PHASE4RECRUITINGTreatment With Aspirin After Preeclampsia: TAP Trial
  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): preeclampsia