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O14512 (SOCS7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Suppressor of cytokine signaling 7

Short name=SOCS-7
Alternative name(s):
Nck, Ash and phospholipase C gamma-binding protein
Nck-associated protein 4
Short name=NAP-4
Gene names
Name:SOCS7
Synonyms:NAP4, SOCS6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length581 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins By similarity. Ref.6 Ref.7

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with phosphorylated IRS4 and PIK3R1 By similarity. Interacts, via the third proline-rich region, with the second SH3 domain of the adapter protein NCK1. Also interacts with GRB2, INSR, IRS1, PLCG1, SORBS3/vinexin, and phosphorylated STAT3 and STAT5. Interacts with SEPT6. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Note: Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Rapidly relocalizes to the nucleus after UV irradiation. Cytoplasmic location depends upon SEPT7 presence. Ref.5 Ref.8

Tissue specificity

Expressed in brain and leukocytes. Also in fetal lung fibroblasts and fetal brain. Ref.1

Induction

By IL6/interleukin-6, prolactin and growth hormone. Ref.4

Domain

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes By similarity. It is required for IRS1 ubiquitination and subsequent proteasomal degradation.

Sequence similarities

Contains 1 SH2 domain.

Contains 1 SOCS box domain.

Sequence caution

The sequence AAI28608.1 differs from that shown. Reason: Contaminating sequence. The N-terminus may be contaminated with vector sequence.

The sequence BAA22432.1 differs from that shown. Reason: Erroneous termination at position 582. Translated as stop.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14512-1)

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: O14512-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-250: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 581581Suppressor of cytokine signaling 7
PRO_0000181253

Regions

Domain400 – 509110SH2
Domain504 – 55451SOCS box
Region124 – 494371Mediates interaction with SORBS3
Compositional bias82 – 9716Poly-Pro
Compositional bias141 – 1488Poly-Gly
Compositional bias180 – 1878Poly-Gln
Compositional bias188 – 19710Poly-Pro
Compositional bias303 – 31210Poly-Pro
Compositional bias343 – 3508Poly-Pro

Natural variations

Alternative sequence1 – 250250Missing in isoform 2.
VSP_021645

Experimental info

Mutagenesis425 – 4273RDS → KDC: Loss of IRS1 ubiquitination and degradation. Ref.7
Sequence conflict3571P → S in AAI28608. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 28, 2006. Version 2.
Checksum: 3F326532262AF6AA

FASTA58162,969
        10         20         30         40         50         60 
MVFRNVGRPP EEEDVEAAPE PGPSELLCPR HRCALDPKAL PPGLALERTW GPAAGLEAQL 

        70         80         90        100        110        120 
AALGLGQPAG PGVKTVGGGC CPCPCPPQPP PPQPQPPAAA PQAGEDPTET SDALLVLEGL 

       130        140        150        160        170        180 
ESEAESLETN SCSEEELSSP GRGGGGGGRL LLQPPGPELP PVPFPLQDLV PLGRLSRGEQ 

       190        200        210        220        230        240 
QQQQQQQPPP PPPPPGPLRP LAGPSRKGSF KIRLSRLFRT KSCNGGSGGG DGTGKRPSGE 

       250        260        270        280        290        300 
LAASAASLTD MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL 

       310        320        330        340        350        360 
TSPHPPTPPP PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP HAPDAFPRIA 

       370        380        390        400        410        420 
PIRAAESLHS QPPQHLQCPL YRPDSSSFAA SLRELEKCGW YWGPMNWEDA EMKLKGKPDG 

       430        440        450        460        470        480 
SFLVRDSSDP RYILSLSFRS QGITHHTRME HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM 

       490        500        510        520        530        540 
HSKNGKFLYF LRSRVPGLPP TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL 

       550        560        570        580 
PKPLISYIRK FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T 

« Hide

Isoform 2 [UniParc].

Checksum: C0D465C715B14D11
Show »

FASTA33137,461

References

« Hide 'large scale' references
[1]"A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs."
Matuoka K., Miki H., Takahashi K., Takenawa T.
Biochem. Biophys. Res. Commun. 239:488-492(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH NCK1; GRB2 AND PLCG1.
Tissue: Brain.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
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] OF 147-581.
[4]"Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines."
Dogusan Z., Hooghe-Peters E.L., Berus D., Velkeniers B., Hooghe R.
J. Neuroimmunol. 109:34-39(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[5]"The suppressor of cytokine signaling (SOCS)-7 interacts with the actin cytoskeleton through vinexin."
Martens N., Wery M., Wang P., Braet F., Gertler A., Hooghe R., Vandenhaute J., Hooghe-Peters E.L.
Exp. Cell Res. 298:239-248(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SORBS3, SUBCELLULAR LOCATION.
[6]"Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation."
Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.
J. Biol. Chem. 280:13817-13823(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STAT3 AND STAT5.
[7]"Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans."
Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D., Rothman P.B.
J. Clin. Invest. 115:2462-2471(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH INSR AND IRS1, MUTAGENESIS OF 425-ARG--SER-427.
[8]"Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7."
Kremer B.E., Adang L.A., Macara I.G.
Cell 130:837-850(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SEPT6, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB005216 mRNA. Translation: BAA22432.1. Sequence problems.
AC115992 Genomic DNA. No translation available.
AC124789 Genomic DNA. No translation available.
BC128607 mRNA. Translation: AAI28608.1. Sequence problems.
CCDSCCDS32637.1. [O14512-1]
PIRPC4427.
RefSeqNP_055413.1. NM_014598.3. [O14512-1]
UniGeneHs.514132.

3D structure databases

ProteinModelPortalO14512.
SMRO14512. Positions 385-553.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119053. 6 interactions.
IntActO14512. 2 interactions.
MINTMINT-1202522.
STRING9606.ENSP00000330659.

PTM databases

PhosphoSiteO14512.

Proteomic databases

PaxDbO14512.
PRIDEO14512.

Protocols and materials databases

DNASU30837.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000566881; ENSP00000455646; ENSG00000261413. [O14512-1]
ENST00000577233; ENSP00000464034; ENSG00000174111. [O14512-1]
GeneID30837.
KEGGhsa:30837.
UCSCuc002hqa.3. human. [O14512-1]

Organism-specific databases

CTD30837.
GeneCardsGC17P036508.
HGNCHGNC:29846. SOCS7.
HPAHPA003484.
HPA004475.
MIM608788. gene.
neXtProtNX_O14512.
PharmGKBPA164742488.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG318341.
HOGENOMHOG000035093.
HOVERGENHBG079201.
InParanoidO14512.
KOK04699.
OMAKTVGGGC.
PhylomeDBO14512.
TreeFamTF321368.

Enzyme and pathway databases

SignaLinkO14512.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO14512.
BgeeO14512.
CleanExHS_SOCS6.
HS_SOCS7.
GenevestigatorO14512.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
IPR028413. SOCS.
IPR028423. SOCS7.
IPR001496. SOCS_C.
[Graphical view]
PANTHERPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF30. PTHR10385:SF30. 1 hit.
PfamPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSOCS7.
GenomeRNAi30837.
NextBio52958.
PROO14512.
SOURCESearch...

Entry information

Entry nameSOCS7_HUMAN
AccessionPrimary (citable) accession number: O14512
Secondary accession number(s): A2VCU2, Q0IJ63
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: November 28, 2006
Last modified: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM