Suppressor of cytokine signaling 1 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot O15524 (SOCS1_HUMAN)

Last modified June 16, 2009. Version 72. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.
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 with TRIM8 By similarity. Interacts with CUL2.
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.

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Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Gene Ontology (GO)
Biological process	JAK-STAT cascade Ref.6 Traceable author statement. Source: ProtInc cytokine-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW 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 regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Ref.6 Traceable author statement. Source: ProtInc
Molecular function	insulin-like growth factor receptor binding Inferred from physical interaction. Source: UniProtKB protein kinase binding Inferred from physical interaction. Source: UniProtKB protein kinase inhibitor activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

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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

SH2

Domain

161 – 210

SOCS box

Region

55 – 66

Kinase inhibitory region (KIR)

Region

67 – 78

Extended SH2 subdomain (ESS)

Region

173 – 182

Interaction with Elongin BC complex By similarity

Compositional bias

26 – 32

Poly-Ser

Experimental info

Sequence conflict

A → G in CAB92528. Ref.5

Sequence conflict

15 – 16

TA → CP in BAA21537. Ref.6

Sequence conflict

A → G in CAB92528. Ref.5

Sequence conflict

178

C → F in CAB92528. Ref.5

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Sequences

Sequence

Length

Mass (Da)

Tools

O15524-1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 7CC983533F78B127
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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

« Hide

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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: 9266833] [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: 9341160] [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: 9202125] [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: 10512686] [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: 9202126] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-211. Tissue: B-cell.
[7]	"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: 11278610] [Abstract] Cited for: FUNCTION AS E3 UBIQUITIN LIGASE, INTERACTION WITH CUL2.
[8]	"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: 11313480] [Abstract] Cited for: FUNCTION AS E3 UBIQUITIN LIGASE.
[9]	"SOCS proteins: negative regulators of cytokine signaling." Krebs D.L., Hilton D.J. Stem Cells 19:378-387(2001) [PubMed: 11553846] [Abstract] Cited for: REVIEW.
[10]	"Cytokine signaling in the brain: putting a SOCS in it?" Wang J., Campbell I.L. J. Neurosci. Res. 67:423-427(2002) [PubMed: 11835308] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases
	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.
UniGene	Hs.50640
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	O15524.
Genome annotation databases
Ensembl	ENSG00000185338. Homo sapiens. [Contig view]
GeneID	8651.
KEGG	hsa:8651.
Organism-specific databases
GeneCards	GC16M011255.
H-InvDB	HIX0026929.
HGNC	HGNC:19383. SOCS1.
HPA	CAB010355.
MIM	603597. gene.
PharmGKB	PA134863068.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O15524.
HOVERGEN	O15524.
OMA	O15524. EYRRITR.
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).
Gene expression databases
ArrayExpress	O15524.
Bgee	O15524.
CleanEx	HS_SOCS1.
GermOnline	ENSG00000185338. Homo sapiens.
Family and domain databases
InterPro	IPR000980. SH2. IPR001496. SOCS_C. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF00017. SH2. 1 hit. PF07525. SOCS_box. 1 hit. [Graphical view]
ProDom	PD000093. SH2. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00252. SH2. 1 hit. SM00253. SOCS. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. PS50225. SOCS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32445.
SOURCE	Search...

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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:	June 16, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents