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Protein

E3 ubiquitin-protein ligase RNF126

Gene

RNF126

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

Functioni

E3 ubiquitin-protein ligase that regulates several biological processes through ubiquitination of various target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Through their polyubiquitination, may play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4. May also be part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. May provide the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the mislocalized proteins and their targeting to the proteasome (PubMed:24981174). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564).1 PublicationBy similarity3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.2 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 fingeri229 – 270RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cytoplasm-associated proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • negative regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein monoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: GO_Central
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000070423-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF126Curated (EC:6.3.2.-2 Publications)
Alternative name(s):
RING finger protein 126Imported
Gene namesi
Name:RNF126Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:21151. RNF126.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GOC
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi229C → A: Loss of E3 ligase activity; when associated with A-232. 1 Publication1
Mutagenesisi232C → A: Loss of E3 ligase activity; when associated with A-229. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000070423.
PharmGKBiPA134876469.

Polymorphism and mutation databases

BioMutaiRNF126.
DMDMi74762712.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000560932 – 326E3 ubiquitin-protein ligase RNF126Add BLAST325

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei5PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated. May undergo autoubiquitination.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9BV68.
MaxQBiQ9BV68.
PaxDbiQ9BV68.
PeptideAtlasiQ9BV68.
PRIDEiQ9BV68.

PTM databases

iPTMnetiQ9BV68.
PhosphoSitePlusiQ9BV68.

Expressioni

Tissue specificityi

Highly expressed in liver and testis.1 Publication

Gene expression databases

BgeeiENSG00000070423.
CleanExiHS_RNF126.
ExpressionAtlasiQ9BV68. baseline and differential.
GenevisibleiQ9BV68. HS.

Organism-specific databases

HPAiHPA043050.

Interactioni

Subunit structurei

Interacts with CCDC50, EGFR, FLT3 and SCAMP3. Interacts with BAG6 (via ubiquitin-like domain); required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol. Interacts with CDKN1A. Interacts with AICDA.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BAG6P463794EBI-357322,EBI-347552
UBE2D1P516688EBI-357322,EBI-743540
UBE2D2P628374EBI-357322,EBI-347677
UBE2D3P610775EBI-357322,EBI-348268
UBE2D4Q9Y2X85EBI-357322,EBI-745527

Protein-protein interaction databases

BioGridi120790. 92 interactors.
IntActiQ9BV68. 26 interactors.
MINTiMINT-1032305.
STRINGi9606.ENSP00000292363.

Structurei

Secondary structure

1326
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi11 – 13Combined sources3
Turni14 – 17Combined sources4
Beta strandi18 – 20Combined sources3
Turni24 – 26Combined sources3
Turni30 – 32Combined sources3
Beta strandi37 – 39Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N9ONMR-A1-40[»]
2N9PNMR-A1-40[»]
ProteinModelPortaliQ9BV68.
SMRiQ9BV68.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni5 – 100Required for interaction with BAG61 PublicationAdd BLAST96
Regioni200 – 304Sufficient for interaction with AICDA1 PublicationAdd BLAST105

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi289 – 303Ser-richAdd BLAST15

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri229 – 270RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00530000062967.
HOGENOMiHOG000116417.
HOVERGENiHBG059832.
InParanoidiQ9BV68.
KOiK11982.
OMAiFCHRCSE.
OrthoDBiEOG091G0SOO.
PhylomeDBiQ9BV68.
TreeFamiTF317985.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. 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: Q9BV68-1) [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
MAEASPHPGR YFCHCCSVEI VPRLPDYICP RCESGFIEEL PEETRSTENG
60 70 80 90 100
SAPSTAPTDQ SRPPLEHVDQ HLFTLPQGYG QFAFGIFDDS FEIPTFPPGA
110 120 130 140 150
QADDGRDPES RRERDHPSRH RYGARQPRAR LTTRRATGRH EGVPTLEGII
160 170 180 190 200
QQLVNGIITP ATIPSLGPWG VLHSNPMDYA WGANGLDAII TQLLNQFENT
210 220 230 240 250
GPPPADKEKI QALPTVPVTE EHVGSGLECP VCKDDYALGE RVRQLPCNHL
260 270 280 290 300
FHDGCIVPWL EQHDSCPVCR KSLTGQNTAT NPPGLTGVSF SSSSSSSSSS
310 320
SPSNENATWS PLGRPQPPRP LSNLTL
Length:326
Mass (Da):35,585
Last modified:June 1, 2001 - v1
Checksum:iD422FFB090362F46
GO
Isoform 2 (identifier: Q9BV68-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     309-311: WSP → SNS
     312-326: Missing.

Show »
Length:311
Mass (Da):33,861
Checksum:i0C748E78E6719C3E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05721768V → M.Corresponds to variant rs2285751dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015693309 – 311WSP → SNS in isoform 2. 2 Publications3
Alternative sequenceiVSP_015694312 – 326Missing in isoform 2. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000559 mRNA. Translation: BAA91254.1.
BC001442 mRNA. Translation: AAH01442.1.
BC025374 mRNA. Translation: AAH25374.1.
CCDSiCCDS12039.1. [Q9BV68-2]
RefSeqiNP_919442.1. NM_194460.2. [Q9BV68-2]
UniGeneiHs.69554.

Genome annotation databases

EnsembliENST00000292363; ENSP00000292363; ENSG00000070423. [Q9BV68-2]
GeneIDi55658.
KEGGihsa:55658.
UCSCiuc010drs.4. human. [Q9BV68-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000559 mRNA. Translation: BAA91254.1.
BC001442 mRNA. Translation: AAH01442.1.
BC025374 mRNA. Translation: AAH25374.1.
CCDSiCCDS12039.1. [Q9BV68-2]
RefSeqiNP_919442.1. NM_194460.2. [Q9BV68-2]
UniGeneiHs.69554.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N9ONMR-A1-40[»]
2N9PNMR-A1-40[»]
ProteinModelPortaliQ9BV68.
SMRiQ9BV68.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120790. 92 interactors.
IntActiQ9BV68. 26 interactors.
MINTiMINT-1032305.
STRINGi9606.ENSP00000292363.

PTM databases

iPTMnetiQ9BV68.
PhosphoSitePlusiQ9BV68.

Polymorphism and mutation databases

BioMutaiRNF126.
DMDMi74762712.

Proteomic databases

EPDiQ9BV68.
MaxQBiQ9BV68.
PaxDbiQ9BV68.
PeptideAtlasiQ9BV68.
PRIDEiQ9BV68.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292363; ENSP00000292363; ENSG00000070423. [Q9BV68-2]
GeneIDi55658.
KEGGihsa:55658.
UCSCiuc010drs.4. human. [Q9BV68-1]

Organism-specific databases

CTDi55658.
GeneCardsiRNF126.
H-InvDBHIX0014558.
HGNCiHGNC:21151. RNF126.
HPAiHPA043050.
MIMi615177. gene.
neXtProtiNX_Q9BV68.
OpenTargetsiENSG00000070423.
PharmGKBiPA134876469.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00530000062967.
HOGENOMiHOG000116417.
HOVERGENiHBG059832.
InParanoidiQ9BV68.
KOiK11982.
OMAiFCHRCSE.
OrthoDBiEOG091G0SOO.
PhylomeDBiQ9BV68.
TreeFamiTF317985.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000070423-MONOMER.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiRNF126. human.
GenomeRNAii55658.
PROiQ9BV68.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070423.
CleanExiHS_RNF126.
ExpressionAtlasiQ9BV68. baseline and differential.
GenevisibleiQ9BV68. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN126_HUMAN
AccessioniPrimary (citable) accession number: Q9BV68
Secondary accession number(s): Q9NWX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: June 1, 2001
Last modified: November 30, 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.