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Protein

E3 ubiquitin-protein ligase RNF138

Gene

RNF138

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.Curated

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)DescriptionActionsGraphical viewLength
Zinc fingeri18 – 58RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri86 – 105C2HC RNF-typePROSITE-ProRule annotationCuratedAdd BLAST20
Zinc fingeri157 – 180C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri187 – 215C2H2-type 2CuratedAdd BLAST29

GO - Molecular functioni

  • metal ion binding 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

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
  • 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

Keywordsi

Molecular functionDNA-binding, Transferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway, Wnt signaling pathway
LigandMetal-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: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
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

EuPathDBiHostDB:ENSG00000134758.13
HGNCiHGNC:17765 RNF138
MIMi616319 gene
neXtProtiNX_Q8WVD3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18 – 21CPVC → APVA: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination. 1 Publication4
Mutagenesisi18C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-54. 1 Publication1
Mutagenesisi54C → A: Catalytic inactive mutant that abolishes ability to promote DNA resection and homologous recombination; when associated with A-18. 1 Publication1

Organism-specific databases

DisGeNETi51444
OpenTargetsiENSG00000134758
PharmGKBiPA134952071

Polymorphism and mutation databases

BioMutaiRNF138
DMDMi74762632

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002616072 – 245E3 ubiquitin-protein ligase RNF138Add BLAST244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei142PhosphothreonineCombined sources1

Post-translational modificationi

Auto-ubiquitinated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8WVD3
MaxQBiQ8WVD3
PaxDbiQ8WVD3
PeptideAtlasiQ8WVD3
PRIDEiQ8WVD3

PTM databases

iPTMnetiQ8WVD3
PhosphoSitePlusiQ8WVD3

Expressioni

Gene expression databases

BgeeiENSG00000134758
CleanExiHS_NARF
HS_RNF138
ExpressionAtlasiQ8WVD3 baseline and differential
GenevisibleiQ8WVD3 HS

Organism-specific databases

HPAiHPA041101

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi119545, 49 interactors
IntActiQ8WVD3, 16 interactors
STRINGi9606.ENSP00000261593

Structurei

3D structure databases

ProteinModelPortaliQ8WVD3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini225 – 243UIMCuratedAdd BLAST19

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 keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri18 – 58RING-typePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri86 – 105C2HC RNF-typePROSITE-ProRule annotationCuratedAdd BLAST20
Zinc fingeri157 – 180C2H2-type 1PROSITE-ProRule annotationAdd BLAST24
Zinc fingeri187 – 215C2H2-type 2CuratedAdd BLAST29

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
InterProiView protein in InterPro
IPR008598 Di19_Zn_binding_dom
IPR034734 ZF_C2HC_RNF
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF05605 zf-Di19, 1 hit
SMARTiView protein in SMART
SM00184 RING, 2 hits
PROSITEiView protein in PROSITE
PS51803 ZF_C2HC_RNF, 1 hit
PS50089 ZF_RING_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti118I → V in AAD46623 (Ref. 1) Curated1
Sequence conflicti215H → R in AAD46623 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05210981K → R. Corresponds to variant dbSNP:rs7229690Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02173238 – 131Missing in isoform 2. 1 PublicationAdd BLAST94

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

Similar proteinsi

Entry informationi

Entry nameiRN138_HUMAN
AccessioniPrimary (citable) accession number: Q8WVD3
Secondary accession number(s): B2RE17
, Q9H8K2, Q9UF87, Q9UKI6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: March 1, 2002
Last modified: May 23, 2018
This is version 144 of the entry and version 1 of the sequence. See 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

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