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Protein

E3 ubiquitin-protein ligase RNF138

Gene

RNF138

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.3 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri18 – 5841RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri86 – 10520C2HC RNF-typePROSITE-ProRule annotationCuratedAdd
BLAST
Zinc fingeri157 – 18024C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri187 – 21529C2H2-type 2CuratedAdd
BLAST

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • protein kinase binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: GO_Central
  • ubiquitin protein ligase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • DNA double-strand break processing involved in repair via single-strand annealing Source: UniProtKB
  • double-strand break repair via homologous recombination Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein polyubiquitination Source: GO_Central
  • protein ubiquitination Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF138Curated (EC:6.3.2.-Curated)
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
Gene namesi
Name:RNF138Imported
Synonyms:NARF1 Publication
ORF Names:HSD-4, HSD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:17765. RNF138.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: UniProtKB
  • site of double-strand break Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi18 – 214CPVC → APVA: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination. 1 Publication
Mutagenesisi18 – 181C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-54. 1 Publication
Mutagenesisi54 – 541C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-18. 1 Publication

Organism-specific databases

PharmGKBiPA134952071.

Polymorphism and mutation databases

BioMutaiRNF138.
DMDMi74762632.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 245244E3 ubiquitin-protein ligase RNF138PRO_0000261607Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei142 – 1421PhosphothreonineCombined sources

Post-translational modificationi

Auto-ubiquitinated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8WVD3.
MaxQBiQ8WVD3.
PaxDbiQ8WVD3.
PeptideAtlasiQ8WVD3.
PRIDEiQ8WVD3.

PTM databases

iPTMnetiQ8WVD3.
PhosphoSiteiQ8WVD3.

Expressioni

Gene expression databases

BgeeiENSG00000134758.
CleanExiHS_NARF.
HS_RNF138.
ExpressionAtlasiQ8WVD3. baseline and differential.
GenevisibleiQ8WVD3. HS.

Organism-specific databases

HPAiHPA041101.
HPA041373.

Interactioni

Subunit structurei

Interacts with NLK (PubMed:16714285). Interacts with XRCC5/Ku80 (PubMed:26502055). Interacts with RBBP8/CtIP (PubMed:26502057).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
UBE2KP610864EBI-749039,EBI-473850

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: GO_Central

Protein-protein interaction databases

BioGridi119545. 36 interactions.
IntActiQ8WVD3. 13 interactions.
MINTiMINT-1479614.
STRINGi9606.ENSP00000261593.

Structurei

3D structure databases

ProteinModelPortaliQ8WVD3.
SMRiQ8WVD3. Positions 18-107.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini225 – 24319UIMCuratedAdd
BLAST

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

Sequence similaritiesi

Contains 2 C2H2-type zinc fingers.PROSITE-ProRule annotation
Contains 1 C2HC RNF-type zinc finger.PROSITE-ProRule annotationCurated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri18 – 5841RING-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri86 – 10520C2HC RNF-typePROSITE-ProRule annotationCuratedAdd
BLAST
Zinc fingeri157 – 18024C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri187 – 21529C2H2-type 2CuratedAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITGW. Eukaryota.
ENOG410Y7SI. LUCA.
GeneTreeiENSGT00530000063064.
HOGENOMiHOG000230946.
HOVERGENiHBG074331.
InParanoidiQ8WVD3.
KOiK10668.
OMAiEANFTRQ.
OrthoDBiEOG091G0F2K.
PhylomeDBiQ8WVD3.
TreeFamiTF331012.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR008598. Di19_Zn_binding_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF05605. zf-Di19. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS51803. ZF_C2HC_RNF. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WVD3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:245
Mass (Da):28,193
Last modified:March 1, 2002 - v1
Checksum:i807EE4500BE0919C
GO
Isoform 2 (identifier: Q8WVD3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     38-131: Missing.

Note: No experimental confirmation available.
Show »
Length:151
Mass (Da):17,262
Checksum:i4FDCD6069E17B2BB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti118 – 1181I → V in AAD46623 (Ref. 1) Curated
Sequence conflicti215 – 2151H → R in AAD46623 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811K → R.
Corresponds to variant rs7229690 [ dbSNP | Ensembl ].
VAR_052109

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei38 – 13194Missing in isoform 2. 1 PublicationVSP_021732Add
BLAST

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.
CCDSiCCDS11903.1. [Q8WVD3-1]
CCDS11904.1. [Q8WVD3-2]
PIRiT43439.
RefSeqiNP_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]
UniGeneiHs.302408.

Genome annotation databases

EnsembliENST00000257190; ENSP00000257190; ENSG00000134758. [Q8WVD3-2]
ENST00000261593; ENSP00000261593; ENSG00000134758. [Q8WVD3-1]
GeneIDi51444.
KEGGihsa:51444.
UCSCiuc002kxg.3. human. [Q8WVD3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
CCDSiCCDS11903.1. [Q8WVD3-1]
CCDS11904.1. [Q8WVD3-2]
PIRiT43439.
RefSeqiNP_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]
UniGeneiHs.302408.

3D structure databases

ProteinModelPortaliQ8WVD3.
SMRiQ8WVD3. Positions 18-107.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119545. 36 interactions.
IntActiQ8WVD3. 13 interactions.
MINTiMINT-1479614.
STRINGi9606.ENSP00000261593.

PTM databases

iPTMnetiQ8WVD3.
PhosphoSiteiQ8WVD3.

Polymorphism and mutation databases

BioMutaiRNF138.
DMDMi74762632.

Proteomic databases

EPDiQ8WVD3.
MaxQBiQ8WVD3.
PaxDbiQ8WVD3.
PeptideAtlasiQ8WVD3.
PRIDEiQ8WVD3.

Protocols and materials databases

DNASUi51444.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257190; ENSP00000257190; ENSG00000134758. [Q8WVD3-2]
ENST00000261593; ENSP00000261593; ENSG00000134758. [Q8WVD3-1]
GeneIDi51444.
KEGGihsa:51444.
UCSCiuc002kxg.3. human. [Q8WVD3-1]

Organism-specific databases

CTDi51444.
GeneCardsiRNF138.
HGNCiHGNC:17765. RNF138.
HPAiHPA041101.
HPA041373.
MIMi616319. gene.
neXtProtiNX_Q8WVD3.
PharmGKBiPA134952071.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITGW. Eukaryota.
ENOG410Y7SI. LUCA.
GeneTreeiENSGT00530000063064.
HOGENOMiHOG000230946.
HOVERGENiHBG074331.
InParanoidiQ8WVD3.
KOiK10668.
OMAiEANFTRQ.
OrthoDBiEOG091G0F2K.
PhylomeDBiQ8WVD3.
TreeFamiTF331012.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

GenomeRNAii51444.
PROiQ8WVD3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134758.
CleanExiHS_NARF.
HS_RNF138.
ExpressionAtlasiQ8WVD3. baseline and differential.
GenevisibleiQ8WVD3. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR008598. Di19_Zn_binding_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF05605. zf-Di19. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 2 hits.
[Graphical view]
PROSITEiPS51803. ZF_C2HC_RNF. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN138_HUMAN
AccessioniPrimary (citable) accession number: Q8WVD3
Secondary accession number(s): B2RE17
, Q9H8K2, Q9UF87, Q9UKI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: March 1, 2002
Last modified: September 7, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.