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Protein

E3 ubiquitin-protein ligase RNF6

Gene

RNF6

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

Functioni

E3 ubiquitin-protein ligase mediating 'Lys-48'-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation. Negatively regulates axonal outgrowth through regulation of the LIMK1 turnover. Mediates 'Lys-6' and 'Lys-27'-linked polyubiquitination of AR/androgen receptor thereby modulating its transcriptional activity. May also bind DNA and function as a transcriptional regulator.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
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 fingeri632 – 67342RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • DNA binding Source: Ensembl
  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • negative regulation of axon extension Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein K27-linked ubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K6-linked ubiquitination Source: UniProtKB
  • regulation of androgen receptor signaling pathway Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

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 RNF6 (EC:6.3.2.-)
Gene namesi
Name:RNF6
Synonyms:SPG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:10069. RNF6.

Subcellular locationi

GO - Cellular componenti

  • axon Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • nuclear membrane Source: HPA
  • nucleoplasm Source: GO_Central
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Esophageal cancer (ESCR)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
See also OMIM:133239

Organism-specific databases

MalaCardsiRNF6.
MIMi133239. phenotype.
PharmGKBiPA34443.

Polymorphism and mutation databases

BioMutaiRNF6.
DMDMi13124536.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 685685E3 ubiquitin-protein ligase RNF6PRO_0000056047Add
BLAST

Proteomic databases

EPDiQ9Y252.
MaxQBiQ9Y252.
PaxDbiQ9Y252.
PeptideAtlasiQ9Y252.
PRIDEiQ9Y252.

PTM databases

iPTMnetiQ9Y252.
PhosphoSiteiQ9Y252.

Expressioni

Tissue specificityi

Weakly expressed in peripheral blood, spleen, prostate, testis and ovary. According to PubMed:18368307, it is preferentially expressed in testis and ovary and hardly detected in other tissues.2 Publications

Developmental stagei

Expressed in embryo and adult testis.1 Publication

Gene expression databases

BgeeiENSG00000127870.
CleanExiHS_RNF6.
ExpressionAtlasiQ9Y252. baseline and differential.
GenevisibleiQ9Y252. HS.

Organism-specific databases

HPAiHPA039343.
HPA040048.

Interactioni

Subunit structurei

Interacts with LIMK1 (By similarity). Interacts with AR.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP1027510EBI-2341483,EBI-608057

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111976. 8 interactions.
IntActiQ9Y252. 3 interactions.
STRINGi9606.ENSP00000342121.

Structurei

3D structure databases

ProteinModelPortaliQ9Y252.
SMRiQ9Y252. Positions 632-673.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni607 – 68579Required for polyubiquitinationBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi292 – 424133Arg-richAdd
BLAST
Compositional biasi598 – 6014Poly-Asp

Sequence similaritiesi

Belongs to the RNF12 family.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri632 – 67342RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00730000110459.
HOGENOMiHOG000273881.
HOVERGENiHBG009886.
InParanoidiQ9Y252.
OMAiTIRIPLR.
OrthoDBiEOG091G04S3.
PhylomeDBiQ9Y252.
TreeFamiTF325756.

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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y252-1) [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
MNQSRSRSDG GSEETLPQDH NHHENERRWQ QERLHREEAY YQFINELNDE
60 70 80 90 100
DYRLMRDHNL LGTPGEITSE ELQQRLDGVK EQLASQPDLR DGTNYRDSEV
110 120 130 140 150
PRESSHEDSL LEWLNTFRRT GNATRSGQNG NQTWRAVSRT NPNNGEFRFS
160 170 180 190 200
LEIHVNHENR GFEIHGEDYT DIPLSDSNRD HTANRQQRST SPVARRTRSQ
210 220 230 240 250
TSVNFNGSSS NIPRTRLASR GQNPAEGSFS TLGRLRNGIG GAAGIPRANA
260 270 280 290 300
SRTNFSSHTN QSGGSELRQR EGQRFGAAHV WENGARSNVT VRNTNQRLEP
310 320 330 340 350
IRLRSTSNSR SRSPIQRQSG TVYHNSQRES RPVQQTTRRS VRRRGRTRVF
360 370 380 390 400
LEQDRERERR GTAYTPFSNS RLVSRITVEE GEESSRSSTA VRRHPTITLD
410 420 430 440 450
LQVRRIRPGE NRDRDSIANR TRSRVGLAEN TVTIESNSGG FRRTISRLER
460 470 480 490 500
SGIRTYVSTI TVPLRRISEN ELVEPSSVAL RSILRQIMTG FGELSSLMEA
510 520 530 540 550
DSESELQRNG QHLPDMHSEL SNLGTDNNRS QHREGSSQDR QAQGDSTEMH
560 570 580 590 600
GENETTQPHT RNSDSRGGRQ LRNPNNLVET GTLPILRLAH FFLLNESDDD
610 620 630 640 650
DRIRGLTKEQ IDNLSTRHYE HNSIDSELGK ICSVCISDYV TGNKLRQLPC
660 670 680
MHEFHIHCID RWLSENCTCP ICRQPVLGSN IANNG
Length:685
Mass (Da):78,091
Last modified:November 1, 1999 - v1
Checksum:i344584773F2E5EFC
GO
Isoform 2 (identifier: Q9Y252-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MNQSRSRSDGGSEET → MQLEVDKMGTKLGEL
     16-371: Missing.

Note: No experimental confirmation available.
Show »
Length:329
Mass (Da):37,094
Checksum:i03CCF8BF21E456F6
GO
Isoform 3 (identifier: Q9Y252-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-142: VSRTNP → ALPDTS
     143-685: Missing.

Show »
Length:142
Mass (Da):16,680
Checksum:i6ED5C036833DD1DD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti48 – 481N → S.1 Publication
Corresponds to variant rs3910433 [ dbSNP | Ensembl ].
VAR_034465
Natural varianti102 – 1021R → K Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. 1 Publication
Corresponds to variant rs121434522 [ dbSNP | Ensembl ].
VAR_063490
Natural varianti164 – 1641I → T.1 Publication
Corresponds to variant rs61760897 [ dbSNP | Ensembl ].
VAR_063491
Natural varianti203 – 2031V → E.
Corresponds to variant rs7990167 [ dbSNP | Ensembl ].
VAR_052094
Natural varianti242 – 2421A → T Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. 1 Publication
Corresponds to variant rs121434523 [ dbSNP | Ensembl ].
VAR_063492
Natural varianti244 – 2441G → D Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. 1 Publication
Corresponds to variant rs121434524 [ dbSNP | Ensembl ].
VAR_063493
Natural varianti572 – 5721R → Q.1 Publication
Corresponds to variant rs138379662 [ dbSNP | Ensembl ].
VAR_063494
Natural varianti623 – 6231S → N.1 Publication
Corresponds to variant rs17083436 [ dbSNP | Ensembl ].
VAR_052095

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MNQSR…GSEET → MQLEVDKMGTKLGEL in isoform 2. 1 PublicationVSP_055424Add
BLAST
Alternative sequencei16 – 371356Missing in isoform 2. 1 PublicationVSP_055425Add
BLAST
Alternative sequencei137 – 1426VSRTNP → ALPDTS in isoform 3. 1 PublicationVSP_055426
Alternative sequencei143 – 685543Missing in isoform 3. 1 PublicationVSP_055427Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ010347 mRNA. Translation: CAB40414.1.
AJ010346 mRNA. Translation: CAB40413.1.
AF293342 mRNA. Translation: AAK00848.1.
AY009109 mRNA. Translation: AAG49400.1.
AK293272 mRNA. Translation: BAG56801.1.
AK312435 mRNA. Translation: BAG35344.1.
AL138966 Genomic DNA. Translation: CAH73183.1.
CH471075 Genomic DNA. Translation: EAX08380.1.
BC034688 mRNA. Translation: AAH34688.1.
AL133621 mRNA. Translation: CAB63747.1.
CCDSiCCDS9316.1. [Q9Y252-1]
PIRiT43459.
RefSeqiNP_005968.1. NM_005977.3. [Q9Y252-1]
NP_898864.1. NM_183043.2. [Q9Y252-1]
NP_898865.1. NM_183044.2. [Q9Y252-1]
NP_898866.1. NM_183045.1. [Q9Y252-3]
XP_005266542.1. XM_005266485.2. [Q9Y252-1]
XP_005266543.1. XM_005266486.2. [Q9Y252-1]
XP_011533479.1. XM_011535177.2. [Q9Y252-1]
XP_011533480.1. XM_011535178.1. [Q9Y252-3]
UniGeneiHs.136885.

Genome annotation databases

EnsembliENST00000346166; ENSP00000342121; ENSG00000127870. [Q9Y252-1]
ENST00000381570; ENSP00000370982; ENSG00000127870. [Q9Y252-1]
ENST00000381588; ENSP00000371000; ENSG00000127870. [Q9Y252-1]
GeneIDi6049.
KEGGihsa:6049.
UCSCiuc001uqo.4. human. [Q9Y252-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ010347 mRNA. Translation: CAB40414.1.
AJ010346 mRNA. Translation: CAB40413.1.
AF293342 mRNA. Translation: AAK00848.1.
AY009109 mRNA. Translation: AAG49400.1.
AK293272 mRNA. Translation: BAG56801.1.
AK312435 mRNA. Translation: BAG35344.1.
AL138966 Genomic DNA. Translation: CAH73183.1.
CH471075 Genomic DNA. Translation: EAX08380.1.
BC034688 mRNA. Translation: AAH34688.1.
AL133621 mRNA. Translation: CAB63747.1.
CCDSiCCDS9316.1. [Q9Y252-1]
PIRiT43459.
RefSeqiNP_005968.1. NM_005977.3. [Q9Y252-1]
NP_898864.1. NM_183043.2. [Q9Y252-1]
NP_898865.1. NM_183044.2. [Q9Y252-1]
NP_898866.1. NM_183045.1. [Q9Y252-3]
XP_005266542.1. XM_005266485.2. [Q9Y252-1]
XP_005266543.1. XM_005266486.2. [Q9Y252-1]
XP_011533479.1. XM_011535177.2. [Q9Y252-1]
XP_011533480.1. XM_011535178.1. [Q9Y252-3]
UniGeneiHs.136885.

3D structure databases

ProteinModelPortaliQ9Y252.
SMRiQ9Y252. Positions 632-673.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111976. 8 interactions.
IntActiQ9Y252. 3 interactions.
STRINGi9606.ENSP00000342121.

PTM databases

iPTMnetiQ9Y252.
PhosphoSiteiQ9Y252.

Polymorphism and mutation databases

BioMutaiRNF6.
DMDMi13124536.

Proteomic databases

EPDiQ9Y252.
MaxQBiQ9Y252.
PaxDbiQ9Y252.
PeptideAtlasiQ9Y252.
PRIDEiQ9Y252.

Protocols and materials databases

DNASUi6049.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000346166; ENSP00000342121; ENSG00000127870. [Q9Y252-1]
ENST00000381570; ENSP00000370982; ENSG00000127870. [Q9Y252-1]
ENST00000381588; ENSP00000371000; ENSG00000127870. [Q9Y252-1]
GeneIDi6049.
KEGGihsa:6049.
UCSCiuc001uqo.4. human. [Q9Y252-1]

Organism-specific databases

CTDi6049.
GeneCardsiRNF6.
HGNCiHGNC:10069. RNF6.
HPAiHPA039343.
HPA040048.
MalaCardsiRNF6.
MIMi133239. phenotype.
604242. gene.
neXtProtiNX_Q9Y252.
PharmGKBiPA34443.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0800. Eukaryota.
ENOG41121N2. LUCA.
GeneTreeiENSGT00730000110459.
HOGENOMiHOG000273881.
HOVERGENiHBG009886.
InParanoidiQ9Y252.
OMAiTIRIPLR.
OrthoDBiEOG091G04S3.
PhylomeDBiQ9Y252.
TreeFamiTF325756.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiRNF6. human.
GenomeRNAii6049.
PROiQ9Y252.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000127870.
CleanExiHS_RNF6.
ExpressionAtlasiQ9Y252. baseline and differential.
GenevisibleiQ9Y252. 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 nameiRNF6_HUMAN
AccessioniPrimary (citable) accession number: Q9Y252
Secondary accession number(s): B4DDP0
, Q5W0H0, Q9BZP5, Q9UF41
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1999
Last modified: September 7, 2016
This is version 134 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

Miscellaneous

Required for prostate tumor cell growth.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: 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.