Q9Y6I7 (WSB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
WD repeat and SOCS box-containing protein 1
Short name=WSB-1

Alternative name(s):
SOCS box-containing WD protein SWiP-1

Gene names

Name:	WSB1
Synonyms:	SWIP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	421 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes type II iodothyronine deiodinase/DIO2. Confers constitutive instability to HIPK2 through proteasomal degradation. Ref.8 Ref.9 Ref.10
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with DIO2. Component of the probable ECS(WSB1) E3 ubiquitin ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and WSB1. Component of a probable ECS-like E3 ubiquitin-protein ligase complex which contains CUL5, RBX1, Elongin BC complex and WSB1. Interacts with CUL5, RNF7, TCEB1 and TCEB2. Binds to HIPK2 through WD40 repeats. Ref.8 Ref.9 Ref.10
Domain	The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes By similarity.
Sequence similarities	Contains 1 SOCS box domain. Contains 6 WD repeats.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	intracellular Inferred from direct assay. Source: LIFEdb
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Hipk2	Q9QZR5	5	EBI-1171494,EBI-366905	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6I7-1)

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.

Isoform 2 (identifier: Q9Y6I7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     14-159: Missing.

Isoform 3 (identifier: Q9Y6I7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     239-244: FLWNMD → VAAILV
     245-421: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 421	421	WD repeat and SOCS box-containing protein 1		PRO_0000051457
Regions
	Repeat	32 – 71	40	WD 1
	Repeat	124 – 165	42	WD 2
	Repeat	168 – 208	41	WD 3
	Repeat	212 – 251	40	WD 4
	Repeat	254 – 293	40	WD 5
	Repeat	309 – 346	38	WD 6
	Domain	372 – 421	50	SOCS box
Natural variations
	Alternative sequence	14 – 159	146	Missing in isoform 2.		VSP_006792
	Alternative sequence	239 – 244	6	FLWNMD → VAAILV in isoform 3.		VSP_039111
	Alternative sequence	245 – 421	177	Missing in isoform 3.		VSP_039112
	Natural variant	16	1	L → S. Ref.3 Ref.4 Corresponds to variant rs9303634 [ dbSNP | Ensembl ].		VAR_024701
Experimental info
	Sequence conflict	149	1	N → S in CAB53708. Ref.6
	Sequence conflict	171	1	E → G in CAB53708. Ref.6
	Sequence conflict	178	1	F → L in AAD43036. Ref.5
	Sequence conflict	201	1	K → R in CAB53708. Ref.6
	Sequence conflict	231	1	S → P in AAD43036. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 650D4942E97D4BED	FASTA	421	47,432
	10 20 30 40 50 60 MASFPPRVNE KEIVRLRTIG ELLAPAAPFD KKCGRENWTV AFAPDGSYFA WSQGHRTVKL 70 80 90 100 110 120 VPWSQCLQNF LLHGTKNVTN SSSLRLPRQN SDGGQKNKPR EHIIDCGDIV WSLAFGSSVP 130 140 150 160 170 180 EKQSRCVNIE WHRFRFGQDQ LLLATGLNNG RIKIWDVYTG KLLLNLVDHT EVVRDLTFAP 190 200 210 220 230 240 DGSLILVSAS RDKTLRVWDL KDDGNMMKVL RGHQNWVYSC AFSPDSSMLC SVGASKAVFL 250 260 270 280 290 300 WNMDKYTMIR KLEGHHHDVV ACDFSPDGAL LATASYDTRV YIWDPHNGDI LMEFGHLFPP 310 320 330 340 350 360 PTPIFAGGAN DRWVRSVSFS HDGLHVASLA DDKMVRFWRI DEDYPVQVAP LSNGLCCAFS 370 380 390 400 410 420 TDGSVLAAGT HDGSVYFWAT PRQVPSLQHL CRMSIRRVMP TQEVQELPIP SKLLEFLSYR I
	Isoform 2 [UniParc]. Checksum: 8F3B7D4C581CBD3D	FASTA	275	30,883
	10 20 30 40 50 60 MASFPPRVNE KEIGKLLLNL VDHTEVVRDL TFAPDGSLIL VSASRDKTLR VWDLKDDGNM 70 80 90 100 110 120 MKVLRGHQNW VYSCAFSPDS SMLCSVGASK AVFLWNMDKY TMIRKLEGHH HDVVACDFSP 130 140 150 160 170 180 DGALLATASY DTRVYIWDPH NGDILMEFGH LFPPPTPIFA GGANDRWVRS VSFSHDGLHV 190 200 210 220 230 240 ASLADDKMVR FWRIDEDYPV QVAPLSNGLC CAFSTDGSVL AAGTHDGSVY FWATPRQVPS 250 260 270 LQHLCRMSIR RVMPTQEVQE LPIPSKLLEF LSYRI
	Isoform 3 [UniParc]. Checksum: E3D403F3CEB81109	FASTA	244	27,295
	10 20 30 40 50 60 MASFPPRVNE KEIVRLRTIG ELLAPAAPFD KKCGRENWTV AFAPDGSYFA WSQGHRTVKL 70 80 90 100 110 120 VPWSQCLQNF LLHGTKNVTN SSSLRLPRQN SDGGQKNKPR EHIIDCGDIV WSLAFGSSVP 130 140 150 160 170 180 EKQSRCVNIE WHRFRFGQDQ LLLATGLNNG RIKIWDVYTG KLLLNLVDHT EVVRDLTFAP 190 200 210 220 230 240 DGSLILVSAS RDKTLRVWDL KDDGNMMKVL RGHQNWVYSC AFSPDSSMLC SVGASKAVVA AILV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SWiP-1: novel SOCS box containing WD-protein regulated by signalling centres and by Shh during development." Vasiliauskas D., Hancock S., Stern C.D. Mech. Dev. 82:79-94(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	Zhang J.W., Liu T.X., Shen Y., Chen S.J., Chen Z. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-16. Tissue: Brain.
[4]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-16. Tissue: Hypothalamus.
[5]	Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G., Luo M., Chen J., Hu R. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Pituitary.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[8]	"VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases." Kamura T., Maenaka K., Kotoshiba S., Matsumoto M., Kohda D., Conaway R.C., Conaway J.W., Nakayama K.I. Genes Dev. 18:3055-3065(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN AN E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, MASS SPECTROMETRY, INTERACTION WITH CUL5; RNF7; TCEB1 AND TCEB2.
[9]	"The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate." Dentice M., Bandyopadhyay A., Gereben B., Callebaut I., Christoffolete M.A., Kim B.W., Nissim S., Mornon J.P., Zavacki A.M., Zeold A., Capelo L.P., Curcio-Morelli C., Ribeiro R., Harney J.W., Tabin C.J., Bianco A.C. Nat. Cell Biol. 7:698-705(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH DIO2.
[10]	"Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by WD40 repeat/SOCS box protein WSB-1." Choi D.W., Seo Y.-M., Kim E.-A., Sung K.S., Ahn J.W., Park S.-J., Lee S.-R., Choi C.Y. J. Biol. Chem. 283:4682-4689(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HIPK2.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF072880 mRNA. Translation: AAD28808.1. AF069313 mRNA. Translation: AAD20954.2. AF240696 mRNA. Translation: AAF82746.1. AL110243 mRNA. Translation: CAB53693.1. AF112205 mRNA. Translation: AAF17193.1. AF106683 mRNA. Translation: AAD43036.1. AL110269 mRNA. Translation: CAB53708.2. BC021110 mRNA. Translation: AAH21110.1.
IPI	IPI00107502. IPI00146203. IPI00794974.
PIR	T14773. T14788.
RefSeq	NP_056441.6. NM_015626.8. NP_599027.1. NM_134265.2.
UniGene	Hs.446017.
3D structure databases
ProteinModelPortal	Q9Y6I7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6I7. 4 interactions.
MINT	MINT-4713879.
STRING	9606.ENSP00000262394.
PTM databases
PhosphoSite	Q9Y6I7.
Polymorphism databases
DMDM	20532298.
Proteomic databases
PaxDb	Q9Y6I7.
PRIDE	Q9Y6I7.
Protocols and materials databases
DNASU	26118.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262394; ENSP00000262394; ENSG00000109046. ENST00000348811; ENSP00000327055; ENSG00000109046.
GeneID	26118.
KEGG	hsa:26118.
UCSC	uc002gzd.1. human. uc002gze.1. human.
Organism-specific databases
CTD	26118.
GeneCards	GC17P025621.
HGNC	HGNC:19221. WSB1.
HPA	HPA003293.
MIM	610091. gene.
neXtProt	NX_Q9Y6I7.
PharmGKB	PA134867554.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2319.
HOGENOM	HOG000063727.
HOVERGEN	HBG034543.
InParanoid	Q9Y6I7.
KO	K10341.
OMA	GHHNDVV.
OrthoDB	EOG40ZQXJ.
PhylomeDB	Q9Y6I7.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
SignaLink	Q9Y6I7.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9Y6I7.
Bgee	Q9Y6I7.
CleanEx	HS_WSB1.
Genevestigator	Q9Y6I7.
GermOnline	ENSG00000109046. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR020472. G-protein_beta_WD-40_rep. IPR001496. SOCS_C. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF07525. SOCS_box. 1 hit. PF00400. WD40. 5 hits. [Graphical view]
PRINTS	PR00320. GPROTEINBRPT.
SMART	SM00253. SOCS. 1 hit. SM00969. SOCS_box. 1 hit. SM00320. WD40. 6 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS50225. SOCS. 1 hit. PS00678. WD_REPEATS_1. 2 hits. PS50082. WD_REPEATS_2. 6 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	WSB1. human.
GenomeRNAi	26118.
NextBio	48120.
SOURCE	Search...

Entry information

Entry name

WSB1_HUMAN

Accession

Primary (citable) accession number: Q9Y6I7
Secondary accession number(s): Q9NRB1 , Q9UBH9, Q9UG25, Q9UNN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2002
Last sequence update:	November 1, 1999
Last modified:	May 29, 2013
This is version 119 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.