O15524 (SOCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Suppressor of cytokine signaling 1
Short name=SOCS-1

Alternative name(s):
JAK-binding protein
Short name=JAB
STAT-induced STAT inhibitor 1
Short name=SSI-1
Tec-interacting protein 3
Short name=TIP-3

Gene names

Name:	SOCS1
Synonyms:	SSI1, TIP3

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	211 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. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival By similarity. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2. SOCS1 appears to be a negative regulator in IGF1R signaling pathway. Ref.8 Ref.9
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with multiple activated signaling proteins of the tyrosine kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2 and VAV. Binding to JAKs is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK JH1 domain. Binds the SH3 domain of GRB2 via diproline determinants in the N-terminus, and the N-terminal regulatory domain of VAV By similarity. Interacts with the Elongin BC complex (TCEB1 and TCEB2). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains Elongin BC, CUL5, RBX1 and SOCS1 By similarity. Interacts (via SH2 domain and SOCS box) with TRIM8 By similarity. Interacts with AXL, CUL2 and FGFR3. Interacts with INSR By similarity. Ref.7 Ref.8 Ref.11 Ref.13
Subcellular location	Nucleus. Cytoplasmic vesicle. Note: Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3. Ref.13
Tissue specificity	Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.
Induction	By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families.
Domain	The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box By similarity.
Sequence similarities	Contains 1 SH2 domain. Contains 1 SOCS box domain.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Cellular component	Cytoplasmic vesicle Nucleus
Coding sequence diversity	Polymorphism
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	JAK-STAT cascade involved in growth hormone signaling pathway Traceable author statement. Source: Reactome cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara fat cell differentiation Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of tyrosine phosphorylation of Stat3 protein Inferred from sequence or structural similarity. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW regulation of interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein kinase inhibitor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 211	211	Suppressor of cytokine signaling 1		PRO_0000181235
Regions
	Domain	79 – 174	96	SH2
	Domain	161 – 210	50	SOCS box
	Region	55 – 66	12	Kinase inhibitory region (KIR)
	Region	67 – 78	12	Extended SH2 subdomain (ESS)
	Region	173 – 182	10	Interaction with Elongin BC complex By similarity
	Compositional bias	26 – 32	7	Poly-Ser
Natural variations
	Natural variant	210	1	Q → H. Corresponds to variant rs11549428 [ dbSNP | Ensembl ].		VAR_061808
Experimental info
	Sequence conflict	9	1	A → G in CAB92528. Ref.5
	Sequence conflict	15 – 16	2	TA → CP in BAA21537. Ref.6
	Sequence conflict	35	1	A → G in CAB92528. Ref.5
	Sequence conflict	178	1	C → F in CAB92528. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O15524 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 7CC983533F78B127	FASTA	211	23,551
	10 20 30 40 50 60 MVAHNQVAAD NAVSTAAEPR RRPEPSSSSS SSPAAPARPR PCPAVPAPAP GDTHFRTFRS 70 80 90 100 110 120 HADYRRITRA SALLDACGFY WGPLSVHGAH ERLRAEPVGT FLVRDSRQRN CFFALSVKMA 130 140 150 160 170 180 SGPTSIRVHF QAGRFHLDGS RESFDCLFEL LEHYVAAPRR MLGAPLRQRR VRPLQELCRQ 190 200 210 RIVATVGREN LARIPLNPVL RDYLSSFPFQ I

References

[1]	"Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3." Minamoto S., Ikegame K., Ueno K., Narazaki M., Naka T., Yamamoto H., Matsumoto T., Saito H., Hosoe S., Kishimoto T. Biochem. Biophys. Res. Commun. 237:79-83(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell lymphoma.
[2]	"SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase." Ohya K., Kajigaya S., Yamashita Y., Miyazato A., Hatake K., Miura Y., Ikeda U., Shimada K., Ozawa K., Mano H. J. Biol. Chem. 272:27178-27182(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Myeloid leukemia cell.
[3]	"A family of cytokine-inducible inhibitors of signaling." Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R., Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A., Hilton D.J. Nature 387:917-921(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively." Yandava C.N., Pillari A., Drazen J.M. Genomics 61:108-111(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Schlueter G. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"A new protein containing an SH2 domain that inhibits JAK kinases." Endo T.A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H., Mitsui K., Matsumoto A., Tanimura S., Ohtsubo M., Misawa H., Miyazaki T., Leonor N., Taniguchi T., Fujita T., Kanakura Y., Komiya S., Yoshimura A. Nature 387:921-924(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-211. Tissue: B-cell.
[7]	"Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor." Dey B.R., Spence S.L., Nissley P., Furlanetto R.W. J. Biol. Chem. 273:24095-24101(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH IGF1R.
[8]	"The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2." Kamizono S., Hanada T., Yasukawa H., Minoguchi S., Kato R., Minoguchi M., Hattori K., Hatakeyama S., Yada M., Morita S., Kitamura T., Kato H., Nakayama K.I., Yoshimura A. J. Biol. Chem. 276:12530-12538(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL2.
[9]	"Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome-mediated degradation." Frantsve J., Schwaller J., Sternberg D.W., Kutok J., Gilliland D.G. Mol. Cell. Biol. 21:3547-3557(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.
[10]	"SOCS proteins: negative regulators of cytokine signaling." Krebs D.L., Hilton D.J. Stem Cells 19:378-387(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[11]	"Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin." Hafizi S., Alindri F., Karlsson R., Dahlbaeck B. Biochem. Biophys. Res. Commun. 299:793-800(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AXL.
[12]	"Cytokine signaling in the brain: putting a SOCS in it?" Wang J., Campbell I.L. J. Neurosci. Res. 67:423-427(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling." Ben-Zvi T., Yayon A., Gertler A., Monsonego-Ornan E. J. Cell Sci. 119:380-387(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFR3, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB005043 mRNA. Translation: BAA22431.1. AB000734 mRNA. Translation: BAA23521.1. U88326 mRNA. Translation: AAB62401.1. AF132440 Genomic DNA. Translation: AAD27709.1. Z46940 Genomic DNA. Translation: CAB92528.1. AB000676 mRNA. Translation: BAA21537.1.
IPI	IPI00021491.
RefSeq	NP_003736.1. NM_003745.1.
UniGene	Hs.50640.
3D structure databases
ProteinModelPortal	O15524.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29662N.
MINT	MINT-196452.
STRING	9606.ENSP00000329418.
Proteomic databases
PaxDb	O15524.
PRIDE	O15524.
Protocols and materials databases
DNASU	8651.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332029; ENSP00000329418; ENSG00000185338.
GeneID	8651.
KEGG	hsa:8651.
UCSC	uc002dar.1. human.
Organism-specific databases
CTD	8651.
GeneCards	GC16M011255.
HGNC	HGNC:19383. SOCS1.
HPA	CAB010355.
MIM	603597. gene.
neXtProt	NX_O15524.
PharmGKB	PA134863068.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG298538.
HOGENOM	HOG000236320.
HOVERGEN	HBG002457.
InParanoid	O15524.
KO	K04694.
OMA	ADYRRIT.
OrthoDB	EOG4R7VC2.
Enzyme and pathway databases
Pathway_Interaction_DB	ifngpathway. IFN-gamma pathway. il12_2pathway. IL12-mediated signaling events. il2_1pathway. IL2-mediated signaling events. il4_2pathway. IL4-mediated signaling events. kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
Reactome	REACT_111102. Signal Transduction. REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	O15524.
Bgee	O15524.
CleanEx	HS_SOCS1.
Genevestigator	O15524.
GermOnline	ENSG00000185338. 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
GenomeRNAi	8651.
NextBio	32445.
SOURCE	Search...

Entry information

Entry name

SOCS1_HUMAN

Accession

Primary (citable) accession number: O15524
Secondary accession number(s): O15097, Q9NSA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 109 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.