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Protein

Suppressor of cytokine signaling 7

Gene

SOCS7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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).By similarity

Pathway:iprotein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • SH3 domain binding Source: UniProtKB

GO - Biological processi

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 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:29846. SOCS7.

Subcellular locationi

GO - Cellular componenti

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.

Polymorphism and mutation databases

BioMutaiSOCS7.

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

BgeeiO14512.
CleanExiHS_SOCS6.
HS_SOCS7.
ExpressionAtlasiO14512. baseline and differential.
GenevisibleiO14512. HS.

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.By similarity5 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.ENSP00000464034.

Structurei

3D structure databases

ProteinModelPortaliO14512.
SMRiO14512. Positions 385-553.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini400 – 509110SH2PROSITE-ProRule annotationAdd
BLAST
Domaini504 – 55451SOCS boxPROSITE-ProRule annotationAdd
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.By similarity

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SOCS box domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG318341.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000035093.
HOVERGENiHBG079201.
InParanoidiO14512.
KOiK04699.
OMAiFPMQDLV.
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. AlignAdd to basket

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

        10         20         30         40         50
MVFRNVGRPP EEEDVEAAPE PGPSELLCPR HRCALDPKAL PPGLALERTW
60 70 80 90 100
GPAAGLEAQL AALGLGQPAG PGVKTVGGGC CPCPCPPQPP PPQPQPPAAA
110 120 130 140 150
PQAGEDPTET SDALLVLEGL ESEAESLETN SCSEEELSSP GRGGGGGGRL
160 170 180 190 200
LLQPPGPELP PVPFPLQDLV PLGRLSRGEQ QQQQQQQPPP PPPPPGPLRP
210 220 230 240 250
LAGPSRKGSF KIRLSRLFRT KSCNGGSGGG DGTGKRPSGE LAASAASLTD
260 270 280 290 300
MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL
310 320 330 340 350
TSPHPPTPPP PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP
360 370 380 390 400
HAPDAFPRIA PIRAAESLHS QPPQHLQCPL YRPDSSSFAA SLRELEKCGW
410 420 430 440 450
YWGPMNWEDA EMKLKGKPDG SFLVRDSSDP RYILSLSFRS QGITHHTRME
460 470 480 490 500
HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM HSKNGKFLYF LRSRVPGLPP
510 520 530 540 550
TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL PKPLISYIRK
560 570 580
FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T
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.Contaminating sequence. The N-terminus may be contaminated with vector sequence.Curated
The sequence BAA22432.1 differs from that shown. Reason: Erroneous termination at position 582. Translated as stop.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti357 – 3571P → S in AAI28608 (PubMed:15489334).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 250250Missing in isoform 2. 1 PublicationVSP_021645Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

EnsembliENST00000612932; ENSP00000482229; ENSG00000274211.
ENST00000615473; ENSP00000480736; ENSG00000274229.
GeneIDi30837.
KEGGihsa:30837.
UCSCiuc002hqa.3. human. [O14512-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO14512.
SMRiO14512. Positions 385-553.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119053. 6 interactions.
IntActiO14512. 2 interactions.
MINTiMINT-1202522.
STRINGi9606.ENSP00000464034.

PTM databases

PhosphoSiteiO14512.

Polymorphism and mutation databases

BioMutaiSOCS7.

Proteomic databases

PaxDbiO14512.
PRIDEiO14512.

Protocols and materials databases

DNASUi30837.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000612932; ENSP00000482229; ENSG00000274211.
ENST00000615473; ENSP00000480736; ENSG00000274229.
GeneIDi30837.
KEGGihsa:30837.
UCSCiuc002hqa.3. human. [O14512-1]

Organism-specific databases

CTDi30837.
GeneCardsiGC17P036508.
HGNCiHGNC:29846. SOCS7.
HPAiHPA003484.
HPA004475.
MIMi608788. gene.
neXtProtiNX_O14512.
PharmGKBiPA164742488.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG318341.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000035093.
HOVERGENiHBG079201.
InParanoidiO14512.
KOiK04699.
OMAiFPMQDLV.
PhylomeDBiO14512.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
SignaLinkiO14512.

Miscellaneous databases

ChiTaRSiSOCS7. human.
GeneWikiiSOCS7.
GenomeRNAii30837.
NextBioi52958.
PROiO14512.
SOURCEiSearch...

Gene expression databases

BgeeiO14512.
CleanExiHS_SOCS6.
HS_SOCS7.
ExpressionAtlasiO14512. baseline and differential.
GenevisibleiO14512. HS.

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]
ProtoNetiSearch...

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 22, 2015
This is version 136 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.