Q9Y252 (RNF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RNF6
EC=6.3.2.-

Gene names

Name:	RNF6
Synonyms:	SPG2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	685 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.5
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with LIMK1 By similarity. Interacts with AR. Ref.5
Subcellular location	Nucleus. Cytoplasm. Cell projection › axon By similarity. Nucleus › PML body By similarity. Note: Localizes to the PML nuclear bodies in Sertoli cells By similarity. Ref.5
Tissue specificity	Weakly expressed in peripheral blood, spleen, prostate, testis and ovary. According to Ref.2, it is preferentially expressed in testis and ovary and hardly detected in other tissues. Ref.2 Ref.5
Developmental stage	Expressed in embryo and adult testis. Ref.2
Involvement in disease	Defects in RNF6 may be a cause of esophageal cancer (ESCR) [MIM:133239]. A 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. Ref.6
Miscellaneous	Required for prostate tumor cell growth.
Sequence similarities	Belongs to the RNF12 family. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell projection Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of axon extension Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype Ref.5. Source: UniProtKB protein K27-linked ubiquitination Inferred from direct assay Ref.5. Source: UniProtKB protein K48-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB protein K6-linked ubiquitination Inferred from direct assay Ref.5. Source: UniProtKB regulation of androgen receptor signaling pathway Inferred from mutant phenotype Ref.5. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	PML body Inferred from electronic annotation. Source: UniProtKB-SubCell axon Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from direct assay Ref.5. Source: UniProtKB
Molecular function	androgen receptor binding Inferred from physical interaction Ref.5. Source: UniProtKB ubiquitin-protein ligase activity Inferred from mutant phenotype Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	10	EBI-2341483,EBI-608057

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 685	685	E3 ubiquitin-protein ligase RNF6		PRO_0000056047
Regions
	Zinc finger	632 – 673	42	RING-type
	Region	607 – 685	79	Required for polyubiquitination By similarity
	Compositional bias	292 – 424	133	Arg-rich
	Compositional bias	598 – 601	4	Poly-Asp
Natural variations
	Natural variant	48	1	N → S. Ref.6 Corresponds to variant rs3910433 [ dbSNP | Ensembl ].		VAR_034465
	Natural variant	102	1	R → K Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. Ref.6		VAR_063490
	Natural variant	164	1	I → T. Ref.6		VAR_063491
	Natural variant	203	1	V → E. Corresponds to variant rs7990167 [ dbSNP | Ensembl ].		VAR_052094
	Natural variant	242	1	A → T Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. Ref.6		VAR_063492
	Natural variant	244	1	G → D Found in an esophageal cancer sample; esophageal squamous cell carcinoma; somatic mutation. Ref.6		VAR_063493
	Natural variant	572	1	R → Q. Ref.6		VAR_063494
	Natural variant	623	1	S → N. Ref.6 Corresponds to variant rs17083436 [ dbSNP | Ensembl ].		VAR_052095

Sequences

	Sequence		Length	Mass (Da)
	Q9Y252 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 344584773F2E5EFC	FASTA	685	78,091
	10 20 30 40 50 60 MNQSRSRSDG GSEETLPQDH NHHENERRWQ QERLHREEAY YQFINELNDE DYRLMRDHNL 70 80 90 100 110 120 LGTPGEITSE ELQQRLDGVK EQLASQPDLR DGTNYRDSEV PRESSHEDSL LEWLNTFRRT 130 140 150 160 170 180 GNATRSGQNG NQTWRAVSRT NPNNGEFRFS LEIHVNHENR GFEIHGEDYT DIPLSDSNRD 190 200 210 220 230 240 HTANRQQRST SPVARRTRSQ TSVNFNGSSS NIPRTRLASR GQNPAEGSFS TLGRLRNGIG 250 260 270 280 290 300 GAAGIPRANA SRTNFSSHTN QSGGSELRQR EGQRFGAAHV WENGARSNVT VRNTNQRLEP 310 320 330 340 350 360 IRLRSTSNSR SRSPIQRQSG TVYHNSQRES RPVQQTTRRS VRRRGRTRVF LEQDRERERR 370 380 390 400 410 420 GTAYTPFSNS RLVSRITVEE GEESSRSSTA VRRHPTITLD LQVRRIRPGE NRDRDSIANR 430 440 450 460 470 480 TRSRVGLAEN TVTIESNSGG FRRTISRLER SGIRTYVSTI TVPLRRISEN ELVEPSSVAL 490 500 510 520 530 540 RSILRQIMTG FGELSSLMEA DSESELQRNG QHLPDMHSEL SNLGTDNNRS QHREGSSQDR 550 560 570 580 590 600 QAQGDSTEMH GENETTQPHT RNSDSRGGRQ LRNPNNLVET GTLPILRLAH FFLLNESDDD 610 620 630 640 650 660 DRIRGLTKEQ IDNLSTRHYE HNSIDSELGK ICSVCISDYV TGNKLRQLPC MHEFHIHCID 670 680 RWLSENCTCP ICRQPVLGSN IANNG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of RNF6, a novel RING finger gene mapping to 13q12." Macdonald D.H.C., Lahiri D., Sampath A., Chase A., Sohal J., Cross N.C.P. Genomics 58:94-97(1999) [PubMed: 10331950] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Leukocyte.
[2]	"Cloning and identification of a novel RNF6 transcriptional splice variant Spg2 in human development." Zhu L., Tong G., Chen J., Wang Y., Wang S., Zhao M., Li J., Ma J. Sci. China, Ser. C, Life Sci. 51:302-307(2008) [PubMed: 18368307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY. Tissue: Testis.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 320-685. Tissue: Testis.
[5]	"Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination." Xu K., Shimelis H., Linn D.E., Jiang R., Yang X., Sun F., Guo Z., Chen H., Li W., Chen H., Kong X., Melamed J., Fang S., Xiao Z., Veenstra T.D., Qiu Y. Cancer Cell 15:270-282(2009) [PubMed: 19345326] [Abstract] Cited for: FUNCTION, INTERACTION WITH AR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"Identification of somatic mutations of the RNF6 gene in human esophageal squamous cell carcinoma." Lo H.S., Hu N., Gere S., Lu N., Su H., Goldstein A.M., Taylor P.R., Lee M.P. Cancer Res. 62:4191-4193(2002) [PubMed: 12154016] [Abstract] Cited for: INVOLVEMENT IN ESCR, VARIANTS SER-48; LYS-102; THR-164; THR-242; ASP-244; GLN-572 AND ASN-623.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ010347 mRNA. Translation: CAB40414.1. AJ010346 mRNA. Translation: CAB40413.1. AY009109 mRNA. Translation: AAG49400.1. BC034688 mRNA. Translation: AAH34688.1. AL133621 mRNA. Translation: CAB63747.1.
IPI	IPI00031752.
PIR	T43459.
RefSeq	NP_005968.1. NM_005977.3. NP_898864.1. NM_183043.2. NP_898865.1. NM_183044.2.
UniGene	Hs.136885.
3D structure databases
ProteinModelPortal	Q9Y252.
SMR	Q9Y252. Positions 607-682.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y252. 3 interactions.
STRING	Q9Y252.
PTM databases
PhosphoSite	Q9Y252.
Polymorphism databases
DMDM	13124536.
Proteomic databases
PRIDE	Q9Y252.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000346166; ENSP00000342121; ENSG00000127870. ENST00000381570; ENSP00000370982; ENSG00000127870. ENST00000381588; ENSP00000371000; ENSG00000127870. ENST00000399762; ENSP00000382665; ENSG00000127870.
GeneID	6049.
KEGG	hsa:6049.
UCSC	uc001uqo.1. human.
Organism-specific databases
CTD	6049.
GeneCards	GC13M026706.
H-InvDB	HIX0011186.
HGNC	HGNC:10069. RNF6.
HPA	HPA040048.
MIM	133239. phenotype. 604242. gene.
neXtProt	NX_Q9Y252.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00530000062973.
HOGENOM	HBG715746.
HOVERGEN	HBG009886.
InParanoid	Q9Y252.
OMA	LGRLRNG.
OrthoDB	EOG4N04DD.
PhylomeDB	Q9Y252.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9Y252.
Bgee	Q9Y252.
CleanEx	HS_RNF6.
Genevestigator	Q9Y252.
GermOnline	ENSG00000127870. Homo sapiens.
Family and domain databases
InterPro	IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
Pfam	PF00097. zf-C3HC4. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	23569.
SOURCE	Search...

Entry information

Entry name

RNF6_HUMAN

Accession

Primary (citable) accession number: Q9Y252
Secondary accession number(s): Q9UF41

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1999
Last modified:	January 25, 2012
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.