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O14512

- SOCS7_HUMAN

UniProt

O14512 - SOCS7_HUMAN

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Protein

Suppressor of cytokine signaling 7

Gene
SOCS7, NAP4, SOCS6
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

Pathwayi

GO - Molecular functioni

  1. protein binding Source: IntAct
  2. SH3 domain binding Source: UniProtKB

GO - Biological processi

  1. fat cell differentiation Source: Ensembl
  2. insulin receptor signaling pathway Source: Ensembl
  3. intracellular signal transduction Source: InterPro
  4. negative regulation of signal transduction Source: UniProtKB-KW
  5. protein ubiquitination Source: UniProtKB-UniPathway
  6. regulation of growth Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

SignaLinkiO14512.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SOCS7
Synonyms:NAP4, SOCS6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:29846. SOCS7.

Subcellular locationi

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.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. intracellular membrane-bounded organelle Source: HPA
  3. nucleolus Source: HPA
  4. nucleus Source: HPA
  5. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi425 – 4273RDS → KDC: Loss of IRS1 ubiquitination and degradation. 1 Publication

Organism-specific databases

PharmGKBiPA164742488.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 581581Suppressor of cytokine signaling 7PRO_0000181253Add
BLAST

Proteomic databases

PaxDbiO14512.
PRIDEiO14512.

PTM databases

PhosphoSiteiO14512.

Expressioni

Tissue specificityi

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

Inductioni

By IL6/interleukin-6, prolactin and growth hormone.1 Publication

Gene expression databases

ArrayExpressiO14512.
BgeeiO14512.
CleanExiHS_SOCS6.
HS_SOCS7.
GenevestigatoriO14512.

Organism-specific databases

HPAiHPA003484.
HPA004475.

Interactioni

Subunit structurei

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 SEPT6.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABI1Q8IZP02EBI-1539606,EBI-375446
SEPT6Q141412EBI-1539617,EBI-745901

Protein-protein interaction databases

BioGridi119053. 6 interactions.
IntActiO14512. 2 interactions.
MINTiMINT-1202522.
STRINGi9606.ENSP00000330659.

Structurei

3D structure databases

ProteinModelPortaliO14512.
SMRiO14512. Positions 385-553.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini400 – 509110SH2Add
BLAST
Domaini504 – 55451SOCS boxAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni124 – 494371Mediates interaction with SORBS3Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi82 – 9716Poly-ProAdd
BLAST
Compositional biasi141 – 1488Poly-Gly
Compositional biasi180 – 1878Poly-Gln
Compositional biasi188 – 19710Poly-Pro
Compositional biasi303 – 31210Poly-Pro
Compositional biasi343 – 3508Poly-Pro

Domaini

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 similaritiesi

Contains 1 SH2 domain.
Contains 1 SOCS box domain.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG318341.
HOGENOMiHOG000035093.
HOVERGENiHBG079201.
InParanoidiO14512.
KOiK04699.
OMAiKTVGGGC.
PhylomeDBiO14512.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR028423. SOCS7.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF30. PTHR10385:SF30. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
SMARTiSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O14512-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MVFRNVGRPP EEEDVEAAPE PGPSELLCPR HRCALDPKAL PPGLALERTW    50
GPAAGLEAQL AALGLGQPAG PGVKTVGGGC CPCPCPPQPP PPQPQPPAAA 100
PQAGEDPTET SDALLVLEGL ESEAESLETN SCSEEELSSP GRGGGGGGRL 150
LLQPPGPELP PVPFPLQDLV PLGRLSRGEQ QQQQQQQPPP PPPPPGPLRP 200
LAGPSRKGSF KIRLSRLFRT KSCNGGSGGG DGTGKRPSGE LAASAASLTD 250
MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL 300
TSPHPPTPPP PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP 350
HAPDAFPRIA PIRAAESLHS QPPQHLQCPL YRPDSSSFAA SLRELEKCGW 400
YWGPMNWEDA EMKLKGKPDG SFLVRDSSDP RYILSLSFRS QGITHHTRME 450
HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM HSKNGKFLYF LRSRVPGLPP 500
TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL PKPLISYIRK 550
FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T 581
Length:581
Mass (Da):62,969
Last modified:November 28, 2006 - v2
Checksum:i3F326532262AF6AA
GO
Isoform 2 (identifier: O14512-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:331
Mass (Da):37,461
Checksum:iC0D465C715B14D11
GO

Sequence cautioni

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.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 250250Missing in isoform 2. VSP_021645Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti357 – 3571P → S in AAI28608. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS32637.1. [O14512-1]
PIRiPC4427.
RefSeqiNP_055413.1. NM_014598.3. [O14512-1]
UniGeneiHs.514132.

Genome annotation databases

EnsembliENST00000566881; ENSP00000455646; ENSG00000261413. [O14512-1]
ENST00000577233; ENSP00000464034; ENSG00000174111. [O14512-1]
GeneIDi30837.
KEGGihsa:30837.
UCSCiuc002hqa.3. human. [O14512-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS32637.1. [O14512-1 ]
PIRi PC4427.
RefSeqi NP_055413.1. NM_014598.3. [O14512-1 ]
UniGenei Hs.514132.

3D structure databases

ProteinModelPortali O14512.
SMRi O14512. Positions 385-553.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119053. 6 interactions.
IntActi O14512. 2 interactions.
MINTi MINT-1202522.
STRINGi 9606.ENSP00000330659.

PTM databases

PhosphoSitei O14512.

Proteomic databases

PaxDbi O14512.
PRIDEi O14512.

Protocols and materials databases

DNASUi 30837.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000566881 ; ENSP00000455646 ; ENSG00000261413 . [O14512-1 ]
ENST00000577233 ; ENSP00000464034 ; ENSG00000174111 . [O14512-1 ]
GeneIDi 30837.
KEGGi hsa:30837.
UCSCi uc002hqa.3. human. [O14512-1 ]

Organism-specific databases

CTDi 30837.
GeneCardsi GC17P036508.
HGNCi HGNC:29846. SOCS7.
HPAi HPA003484.
HPA004475.
MIMi 608788. gene.
neXtProti NX_O14512.
PharmGKBi PA164742488.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG318341.
HOGENOMi HOG000035093.
HOVERGENi HBG079201.
InParanoidi O14512.
KOi K04699.
OMAi KTVGGGC.
PhylomeDBi O14512.
TreeFami TF321368.

Enzyme and pathway databases

UniPathwayi UPA00143 .
SignaLinki O14512.

Miscellaneous databases

GeneWikii SOCS7.
GenomeRNAii 30837.
NextBioi 52958.
PROi O14512.
SOURCEi Search...

Gene expression databases

ArrayExpressi O14512.
Bgeei O14512.
CleanExi HS_SOCS6.
HS_SOCS7.
Genevestigatori O14512.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR000980. SH2.
IPR028413. SOCS.
IPR028423. SOCS7.
IPR001496. SOCS_C.
[Graphical view ]
PANTHERi PTHR10385. PTHR10385. 1 hit.
PTHR10385:SF30. PTHR10385:SF30. 1 hit.
Pfami PF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view ]
SMARTi SM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 1 hit.
PROSITEi PS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiSOCS7_HUMAN
AccessioniPrimary (citable) accession number: O14512
Secondary accession number(s): A2VCU2, Q0IJ63
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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