O14512 (SOCS7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SOCS7
Synonyms:	NAP4, SOCS6

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	581 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fat cell differentiation Inferred from electronic annotation. Source: Compara insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	SH3 domain binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SEPT6	Q14141	2	EBI-1539617,EBI-745901

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 581	581	Suppressor of cytokine signaling 7		PRO_0000181253
Regions
	Domain	400 – 509	110	SH2
	Domain	504 – 554	51	SOCS box
	Region	124 – 494	371	Mediates interaction with SORBS3
	Compositional bias	82 – 97	16	Poly-Pro
	Compositional bias	141 – 148	8	Poly-Gly
	Compositional bias	180 – 187	8	Poly-Gln
	Compositional bias	188 – 197	10	Poly-Pro
	Compositional bias	303 – 312	10	Poly-Pro
	Compositional bias	343 – 350	8	Poly-Pro
Natural variations
	Alternative sequence	1 – 250	250	Missing in isoform 2.		VSP_021645
Experimental info
	Mutagenesis	425 – 427	3	RDS → KDC: Loss of IRS1 ubiquitination and degradation. Ref.7
	Sequence conflict	357	1	P → S in AAI28608. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: 3F326532262AF6AA	FASTA	581	62,969
	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
	Isoform 2 [UniParc]. Checksum: C0D465C715B14D11	FASTA	331	37,461
	10 20 30 40 50 60 MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL TSPHPPTPPP 70 80 90 100 110 120 PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP HAPDAFPRIA PIRAAESLHS 130 140 150 160 170 180 QPPQHLQCPL YRPDSSSFAA SLRELEKCGW YWGPMNWEDA EMKLKGKPDG SFLVRDSSDP 190 200 210 220 230 240 RYILSLSFRS QGITHHTRME HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM HSKNGKFLYF 250 260 270 280 290 300 LRSRVPGLPP TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL PKPLISYIRK 310 320 330 FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00022329. IPI00807330.
PIR	PC4427.
RefSeq	NP_055413.1. NM_014598.2.
UniGene	Hs.514132.
3D structure databases
ProteinModelPortal	O14512.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14512. 1 interaction.
MINT	MINT-1202522.
STRING	9606.ENSP00000330659.
PTM databases
PhosphoSite	O14512.
Proteomic databases
PaxDb	O14512.
PRIDE	O14512.
Protocols and materials databases
DNASU	30837.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000566881; ENSP00000455646; ENSG00000261413. ENST00000577233; ENSP00000464034; ENSG00000174111.
GeneID	30837.
KEGG	hsa:30837.
UCSC	uc002hqa.3. human.
Organism-specific databases
CTD	30837.
GeneCards	GC17P036508.
HGNC	HGNC:29846. SOCS7.
HPA	HPA004475.
MIM	608788. gene.
neXtProt	NX_O14512.
PharmGKB	PA164742488.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG318341.
HOGENOM	HOG000035093.
HOVERGEN	HBG079201.
InParanoid	O14512.
KO	K04699.
OMA	APFPLQD.
OrthoDB	EOG4Q58QF.
PhylomeDB	O14512.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Bgee	O14512.
CleanEx	HS_SOCS6. HS_SOCS7.
Genevestigator	O14512.
GermOnline	ENSG00000174111. 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	30837.
NextBio	52958.
SOURCE	Search...

Entry information

Entry name

SOCS7_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 114 of the entry and version 2 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.