UniProtKB - Q8WVD3 (RN138_HUMAN)
Protein
E3 ubiquitin-protein ligase RNF138
Gene
RNF138
Organism
Homo sapiens (Human)
Status
Functioni
E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination (PubMed:26502055, PubMed:26502057). Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination (PubMed:26502055, PubMed:26502057). Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination (PubMed:26502055). According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP (PubMed:26502057). Together with NLK, involved in the ubiquitination and degradation of TCF/LEF (PubMed:16714285). Also exhibits auto-ubiquitination activity in combination with UBE2K (PubMed:16714285). May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway (PubMed:16714285).3 Publications
Catalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.Curated EC:2.3.2.27
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.3 PublicationsView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 18 – 58 | RING-typePROSITE-ProRule annotationAdd BLAST | 41 | |
Zinc fingeri | 86 – 105 | C2HC RNF-typePROSITE-ProRule annotationCuratedAdd BLAST | 20 | |
Zinc fingeri | 157 – 180 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 187 – 215 | C2H2-type 2CuratedAdd BLAST | 29 |
GO - Molecular functioni
- metal ion binding Source: UniProtKB-KW
- protein kinase binding Source: UniProtKB
- single-stranded DNA binding Source: UniProtKB
- ubiquitin protein ligase activity Source: UniProtKB
GO - Biological processi
- cellular response to leukemia inhibitory factor Source: Ensembl
- DNA double-strand break processing involved in repair via single-strand annealing Source: UniProtKB
- double-strand break repair via homologous recombination Source: UniProtKB
- protein ubiquitination Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | DNA-binding, Transferase |
Biological process | DNA damage, DNA repair, Ubl conjugation pathway, Wnt signaling pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q8WVD3 |
Reactomei | R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase RNF138Curated (EC:2.3.2.27Curated)Alternative name(s): Nemo-like kinase-associated RING finger protein1 Publication Short name: NLK-associated RING finger protein1 Publication Short name: hNARF1 Publication RING finger protein 138Curated RING-type E3 ubiquitin transferase RNF138Curated |
Gene namesi | ORF Names:HSD-4, HSD4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17765, RNF138 |
MIMi | 616319, gene |
neXtProti | NX_Q8WVD3 |
VEuPathDBi | HostDB:ENSG00000134758.13 |
Subcellular locationi
Other locations
- Chromosome 2 Publications
Note: Recruited at DNA damage sites (PubMed:26502055). Localizes to sites of double-strand break: localization to double-strand break sites is mediated by the zinc fingers (PubMed:26502055, PubMed:26502057).2 Publications
Nucleus
- nucleus Source: UniProtKB
Other locations
- site of double-strand break Source: UniProtKB
Keywords - Cellular componenti
ChromosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 18 – 21 | CPVC → APVA: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination. 1 Publication | 4 | |
Mutagenesisi | 18 | C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-54. 1 Publication | 1 | |
Mutagenesisi | 54 | C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-18. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 51444 |
OpenTargetsi | ENSG00000134758 |
PharmGKBi | PA134952071 |
Miscellaneous databases
Pharosi | Q8WVD3, Tbio |
Genetic variation databases
BioMutai | RNF138 |
DMDMi | 74762632 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000261607 | 2 – 245 | E3 ubiquitin-protein ligase RNF138Add BLAST | 244 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 142 | PhosphothreonineCombined sources | 1 |
Post-translational modificationi
Auto-ubiquitinated.1 Publication
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q8WVD3 |
jPOSTi | Q8WVD3 |
MassIVEi | Q8WVD3 |
MaxQBi | Q8WVD3 |
PaxDbi | Q8WVD3 |
PeptideAtlasi | Q8WVD3 |
PRIDEi | Q8WVD3 |
ProteomicsDBi | 74778 [Q8WVD3-1] 74779 [Q8WVD3-2] |
PTM databases
iPTMneti | Q8WVD3 |
PhosphoSitePlusi | Q8WVD3 |
Expressioni
Gene expression databases
Bgeei | ENSG00000134758, Expressed in testis and 238 other tissues |
ExpressionAtlasi | Q8WVD3, baseline and differential |
Genevisiblei | Q8WVD3, HS |
Organism-specific databases
HPAi | ENSG00000134758, Group enriched (blood, bone marrow, lymphoid tissue, testis) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ8WVD3
GO - Molecular functioni
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119545, 77 interactors |
IntActi | Q8WVD3, 59 interactors |
STRINGi | 9606.ENSP00000261593 |
Miscellaneous databases
RNActi | Q8WVD3, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 225 – 243 | UIMCuratedAdd BLAST | 19 |
Domaini
The zinc finger domains (C2H2-type and C2HC-type zinc fingers) bind DNA and mediate recruitment to double-strand break sites. They show strong preference for DNA with 5'- or 3'-single-stranded overhangs, while they do not bind blunt-ended double-stranded DNA or poly(ADP-ribose) (PAR) polymers.1 Publication
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 18 – 58 | RING-typePROSITE-ProRule annotationAdd BLAST | 41 | |
Zinc fingeri | 86 – 105 | C2HC RNF-typePROSITE-ProRule annotationCuratedAdd BLAST | 20 | |
Zinc fingeri | 157 – 180 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 24 | |
Zinc fingeri | 187 – 215 | C2H2-type 2CuratedAdd BLAST | 29 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502RP2G, Eukaryota |
GeneTreei | ENSGT00950000182909 |
HOGENOMi | CLU_092448_0_0_1 |
InParanoidi | Q8WVD3 |
OMAi | QETNFTR |
PhylomeDBi | Q8WVD3 |
TreeFami | TF331012 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR008598, Di19_Zn-bd IPR034734, ZF_C2HC_RNF IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF05605, zf-Di19, 1 hit PF18574, zf_C2HC_14, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 2 hits |
PROSITEi | View protein in PROSITE PS51803, ZF_C2HC_RNF, 1 hit PS50089, ZF_RING_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8WVD3-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAEDLSAATS YTEDDFYCPV CQEVLKTPVR TTACQHVFCR KCFLTAMRES
60 70 80 90 100
GAHCPLCRGN VTRRERACPE RALDLENIMR KFSGSCRCCA KQIKFYRMRH
110 120 130 140 150
HYKSCKKYQD EYGVSSIIPN FQISQDSVGN SNRSETSTSD NTETYQENTS
160 170 180 190 200
SSGHPTFKCP LCQESNFTRQ RLLDHCNSNH LFQIVPVTCP ICVSLPWGDP
210 220 230 240
SQITRNFVSH LNQRHQFDYG EFVNLQLDEE TQYQTAVEES FQVNI
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3KSI2 | J3KSI2_HUMAN | RING-type E3 ubiquitin transferase | RNF138 | 108 | Annotation score: | ||
J3QKM8 | J3QKM8_HUMAN | RING-type E3 ubiquitin transferase | RNF138 | 142 | Annotation score: | ||
J3KRU4 | J3KRU4_HUMAN | RING-type E3 ubiquitin transferase | RNF138 | 80 | Annotation score: | ||
J3QLQ3 | J3QLQ3_HUMAN | E3 ubiquitin-protein ligase RNF138 | RNF138 | 66 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 118 | I → V in AAD46623 (Ref. 1) Curated | 1 | |
Sequence conflicti | 215 | H → R in AAD46623 (Ref. 1) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052109 | 81 | K → R. Corresponds to variant dbSNP:rs7229690Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_021732 | 38 – 131 | Missing in isoform 2. 1 PublicationAdd BLAST | 94 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF162680 mRNA Translation: AAD46623.2 AK023579 mRNA Translation: BAB14614.1 AK315761 mRNA Translation: BAG38114.1 BT006878 mRNA Translation: AAP35524.1 CR457150 mRNA Translation: CAG33431.1 CH471088 Genomic DNA Translation: EAX01280.1 BC018107 mRNA Translation: AAH18107.1 AL133557 mRNA Translation: CAB63712.1 |
CCDSi | CCDS11903.1 [Q8WVD3-1] CCDS11904.1 [Q8WVD3-2] |
PIRi | T43439 |
RefSeqi | NP_001178253.2, NM_001191324.1 [Q8WVD3-1] NP_057355.2, NM_016271.4 [Q8WVD3-1] NP_937761.1, NM_198128.2 [Q8WVD3-2] XP_005258343.1, XM_005258286.1 [Q8WVD3-2] |
Genome annotation databases
Ensembli | ENST00000257190; ENSP00000257190; ENSG00000134758 [Q8WVD3-2] ENST00000261593; ENSP00000261593; ENSG00000134758 [Q8WVD3-1] |
GeneIDi | 51444 |
KEGGi | hsa:51444 |
UCSCi | uc002kxg.3, human [Q8WVD3-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF162680 mRNA Translation: AAD46623.2 AK023579 mRNA Translation: BAB14614.1 AK315761 mRNA Translation: BAG38114.1 BT006878 mRNA Translation: AAP35524.1 CR457150 mRNA Translation: CAG33431.1 CH471088 Genomic DNA Translation: EAX01280.1 BC018107 mRNA Translation: AAH18107.1 AL133557 mRNA Translation: CAB63712.1 |
CCDSi | CCDS11903.1 [Q8WVD3-1] CCDS11904.1 [Q8WVD3-2] |
PIRi | T43439 |
RefSeqi | NP_001178253.2, NM_001191324.1 [Q8WVD3-1] NP_057355.2, NM_016271.4 [Q8WVD3-1] NP_937761.1, NM_198128.2 [Q8WVD3-2] XP_005258343.1, XM_005258286.1 [Q8WVD3-2] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 119545, 77 interactors |
IntActi | Q8WVD3, 59 interactors |
STRINGi | 9606.ENSP00000261593 |
PTM databases
iPTMneti | Q8WVD3 |
PhosphoSitePlusi | Q8WVD3 |
Genetic variation databases
BioMutai | RNF138 |
DMDMi | 74762632 |
Proteomic databases
EPDi | Q8WVD3 |
jPOSTi | Q8WVD3 |
MassIVEi | Q8WVD3 |
MaxQBi | Q8WVD3 |
PaxDbi | Q8WVD3 |
PeptideAtlasi | Q8WVD3 |
PRIDEi | Q8WVD3 |
ProteomicsDBi | 74778 [Q8WVD3-1] 74779 [Q8WVD3-2] |
Protocols and materials databases
Antibodypediai | 22190, 200 antibodies |
DNASUi | 51444 |
Genome annotation databases
Ensembli | ENST00000257190; ENSP00000257190; ENSG00000134758 [Q8WVD3-2] ENST00000261593; ENSP00000261593; ENSG00000134758 [Q8WVD3-1] |
GeneIDi | 51444 |
KEGGi | hsa:51444 |
UCSCi | uc002kxg.3, human [Q8WVD3-1] |
Organism-specific databases
CTDi | 51444 |
DisGeNETi | 51444 |
GeneCardsi | RNF138 |
HGNCi | HGNC:17765, RNF138 |
HPAi | ENSG00000134758, Group enriched (blood, bone marrow, lymphoid tissue, testis) |
MIMi | 616319, gene |
neXtProti | NX_Q8WVD3 |
OpenTargetsi | ENSG00000134758 |
PharmGKBi | PA134952071 |
VEuPathDBi | HostDB:ENSG00000134758.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RP2G, Eukaryota |
GeneTreei | ENSGT00950000182909 |
HOGENOMi | CLU_092448_0_0_1 |
InParanoidi | Q8WVD3 |
OMAi | QETNFTR |
PhylomeDBi | Q8WVD3 |
TreeFami | TF331012 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | Q8WVD3 |
Reactomei | R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
BioGRID-ORCSi | 51444, 4 hits in 894 CRISPR screens |
ChiTaRSi | RNF138, human |
GenomeRNAii | 51444 |
Pharosi | Q8WVD3, Tbio |
PROi | PR:Q8WVD3 |
RNActi | Q8WVD3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134758, Expressed in testis and 238 other tissues |
ExpressionAtlasi | Q8WVD3, baseline and differential |
Genevisiblei | Q8WVD3, HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR008598, Di19_Zn-bd IPR034734, ZF_C2HC_RNF IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF05605, zf-Di19, 1 hit PF18574, zf_C2HC_14, 1 hit |
SMARTi | View protein in SMART SM00184, RING, 2 hits |
PROSITEi | View protein in PROSITE PS51803, ZF_C2HC_RNF, 1 hit PS50089, ZF_RING_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RN138_HUMAN | |
Accessioni | Q8WVD3Primary (citable) accession number: Q8WVD3 Secondary accession number(s): B2RE17 Q9UKI6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2006 |
Last sequence update: | March 1, 2002 | |
Last modified: | February 10, 2021 | |
This is version 164 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants