O14544 (SOCS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Suppressor of cytokine signaling 6
Short name=SOCS-6

Alternative name(s):
Cytokine-inducible SH2 protein 4
Short name=CIS-4
Suppressor of cytokine signaling 4
Short name=SOCS-4

Gene names

Name:	SOCS6
Synonyms:	CIS4, SOCS4

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	535 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins By similarity. Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor. Ref.5
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with RBCK1. Interacts with phosphorylated IRS4 By similarity. Interacts with PIM3 By similarity. Interacts with KIT (phosphorylated).
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 SH2 domain. Contains 1 SOCS box domain.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade Traceable author statement Ref.1. Source: ProtInc defense response Traceable author statement Ref.1. Source: ProtInc negative regulation of T cell activation Inferred from electronic annotation. Source: Compara negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW proteasomal protein catabolic process Inferred from mutant phenotype PubMed 20007709. Source: MGI protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Traceable author statement Ref.1. Source: ProtInc immunological synapse Inferred from direct assay PubMed 20007709. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 535

535

Suppressor of cytokine signaling 6

PRO_0000181251

Regions

Domain

384 – 491

108

SH2

Domain

486 – 535

50

SOCS box

Compositional bias

105 – 108

4

Poly-Ser

Experimental info

Sequence conflict

74

1

M → I in BAA22538. Ref.1

Sequence conflict

161

1

S → T in BAA22538. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

535

Helix Strand Turn

Details...

Helix

372 – 382

11

Helix

391 – 397

7

Turn

398 – 400

3

Beta strand

406 – 410

5

Beta strand

417 – 424

8

Beta strand

427 – 436

10

Beta strand

439 – 442

4

Beta strand

451 – 453

3

Helix

454 – 467

14

Beta strand

471 – 474

4

Sequences

	Sequence		Length	Mass (Da)
	O14544 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: AE513312A999B763	FASTA	535	59,528
	10 20 30 40 50 60 MKKISLKTLR KSFNLNKSKE ETDFMVVQQP SLASDFGKDD SLFGSCYGKD MASCDINGED 70 80 90 100 110 120 EKGGKNRSKS ESLMGTLKRR LSAKQKSKGK AGTPSGSSAD EDTFSSSSAP IVFKDVRAQR 130 140 150 160 170 180 PIRSTSLRSH HYSPAPWPLR PTNSEETCIK MEVRVKALVH SSSPSPALNG VRKDFHDLQS 190 200 210 220 230 240 ETTCQEQANS LKSSASHNGD LHLHLDEHVP VVIGLMPQDY IQYTVPLDEG MYPLEGSRSY 250 260 270 280 290 300 CLDSSSPMEV SAVPPQVGGR AFPEDESQVD QDLVVAPEIF VDQSVNGLLI GTTGVMLQSP 310 320 330 340 350 360 RAGHDDVPPL SPLLPPMQNN QIQRNFSGLT GTEAHVAESM RCHLNFDPNS APGVARVYDS 370 380 390 400 410 420 VQSSGPMVVT SLTEELKKLA KQGWYWGPIT RWEAEGKLAN VPDGSFLVRD SSDDRYLLSL 430 440 450 460 470 480 SFRSHGKTLH TRIEHSNGRF SFYEQPDVEG HTSIVDLIEH SIRDSENGAF CYSRSRLPGS 490 500 510 520 530 ATYPVRLTNP VSRFMQVRSL QYLCRFVIRQ YTRIDLIQKL PLPNKMKDYL QEKHY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of novel CIS family genes." Masuhara M., Sakamoto H., Matsumoto A., Suzuki R., Yasukawa H., Mitsui K., Wakioka T., Tanimura S., Sasaki A., Misawa H., Yokouchi M., Ohtsubo M., Yoshimura A. Biochem. Biophys. Res. Commun. 239:439-446(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[4]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION.
[5]	"Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase." Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S., Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A. J. Biol. Chem. 286:480-490(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 361-499 IN COMPLEX WITH KIT, FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE FOR KIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB006968 mRNA. Translation: BAA22538.1.
CH471117 Genomic DNA. Translation: EAW66522.1.
BC020082 mRNA. Translation: AAH20082.1.

IPI

IPI00297351.

PIR

JC5762.

RefSeq

NP_004223.2. NM_004232.3.

UniGene

Hs.44439.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VIF	X-ray	1.45	A	361-499	[»]

ProteinModelPortal

O14544.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14544. 7 interactions.

STRING

9606.ENSP00000306939.

PTM databases

PhosphoSite

O14544.

Proteomic databases

PaxDb

O14544.

PRIDE

O14544.

Protocols and materials databases

DNASU

9306.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000397942; ENSP00000381034; ENSG00000170677.
ENST00000582322; ENSP00000463395; ENSG00000170677.

GeneID

9306.

KEGG

hsa:9306.

UCSC

uc002lkr.1. human.

Organism-specific databases

CTD

9306.

GeneCards

GC18P067956.

HGNC

HGNC:16833. SOCS6.

HPA

CAB010189.

MIM

605118. gene.

neXtProt

NX_O14544.

PharmGKB

PA134917653.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG318341.

HOGENOM

HOG000027792.

HOVERGEN

HBG057479.

InParanoid

O14544.

KO

K10322.

OMA

TRWEAEG.

OrthoDB

EOG4P8FHX.

PhylomeDB

O14544.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

UniPathway

UPA00143.

Gene expression databases

Bgee

O14544.

CleanEx

HS_SOCS4.
HS_SOCS6.

Genevestigator

O14544.

GermOnline

ENSG00000170677. Homo sapiens.

Family and domain databases

Gene3D

3.30.505.10. 1 hit.

InterPro

IPR000980. SH2.
IPR001496. SOCS_C.
[Graphical view]

Pfam

PF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]

SMART

SM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]

PROSITE

PS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O14544.

GenomeRNAi

9306.

NextBio

34859.

SOURCE

Search...

Entry information

Entry name

SOCS6_HUMAN

Accession

Primary (citable) accession number: O14544
Secondary accession number(s): Q8WUM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	September 23, 2008
Last modified:	May 1, 2013
This is version 112 of the entry and version 2 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.