O75159 (SOCS5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Suppressor of cytokine signaling 5
Short name=SOCS-5

Alternative name(s):
Cytokine-inducible SH2 protein 6
Short name=CIS-6
Cytokine-inducible SH2-containing protein 5

Gene names

Name:	SOCS5
Synonyms:	CIS6, CISH5, CISH6, KIAA0671

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	536 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T-helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes differentiation into the Th2 phenotype. Can also partially inhibit IL6 and LIF signaling. Ref.8
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with IL4R; inhibits IL4 signaling By similarity. Interacts with EGFR. Interacts with TCEB1 AND TCEB2; mediates EGFR ubiquitination and degradation. Ref.8
Induction	Up-regulated by EGF (at protein level). Ref.8
Domain	The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
Post-translational modification	Phosphorylated. Phosphorylation is induced by EGF. Ref.8
Sequence similarities	Contains 1 SH2 domain. Contains 1 SOCS box domain.
Sequence caution	The sequence BAA31646.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Growth regulation Ubl conjugation pathway
Domain	SH2 domain
Molecular function	Signal transduction inhibitor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell growth Non-traceable author statement PubMed 11837794. Source: UniProtKB cytokine-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB epidermal growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of T-helper 2 cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epidermal growth factor-activated receptor activity Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of T-helper 1 cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.8. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 536	536	Suppressor of cytokine signaling 5		PRO_0000181249
Regions
	Domain	381 – 476	96	SH2
	Domain	471 – 520	50	SOCS box
	Region	1 – 50	50	Required for interaction with IL4R By similarity
Experimental info
	Mutagenesis	406	1	R → K: Abrogates the ability to induce EGFR degradation. Ref.8
	Mutagenesis	484	1	L → P: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with F-488. Ref.8
	Mutagenesis	488	1	C → F: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with P-484. Ref.8
	Sequence conflict	478	1	R → M in AAH32862. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	O75159 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 0629CDCF2A97E9D8	FASTA	536	61,246
	10 20 30 40 50 60 MDKVGKMWNN FKYRCQNLFG HEGGSRSENV DMNSNRCLSV KEKNISIGDS TPQQQSSPLR 70 80 90 100 110 120 ENIALQLGLS PSKNSSRRNQ NCATEIPQIV EISIEKDNDS CVTPGTRLAR RDSYSRHAPW 130 140 150 160 170 180 GGKKKHSCST KTQSSLDADK KFGRTRSGLQ RRERRYGVSS VHDMDSVSSR TVGSRSLRQR 190 200 210 220 230 240 LQDTVGLCFP MRTYSKQSKP LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV 250 260 270 280 290 300 SPHSTFFDTF DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG 310 320 330 340 350 360 PKLAPGMTEI SGDSSAIPQA NCDSEEDTTT LCLQSRRQKQ RQISGDSHTH VSRQGAWKVH 370 380 390 400 410 420 TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE GTFLLRDSAQ EDYLFSVSFR 430 440 450 460 470 480 RYNRSLHARI EQWNHNFSFD AHDPCVFHSS TVTGLLEHYK DPSSCMFFEP LLTISLNRTF 490 500 510 520 530 PFSLQYICRA VICRCTTYDG IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of CIS6, chromosomal assignment to 3p22 and 2p21 by in situ hybridization." Magrangeas F., Apiou F., Denis S., Weidle U., Jacques Y., Minvielle S. Cytogenet. Cell Genet. 88:78-81(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thalamus.
[5]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Brain.
[8]	"Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling." Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N., Rechavi G., Yarden Y. J. Biol. Chem. 280:7038-7048(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN EGFR DEGRADATION, INDUCTION BY EGF, PHOSPHORYLATION, MUTAGENESIS OF ARG-406; LEU-484 AND CYS-488, INTERACTION WITH EGFR; TCEB1 AND TCEB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073958 mRNA. Translation: AAD40484.1. AB014571 mRNA. Translation: BAA31646.2. Different initiation. AL136896 mRNA. Translation: CAB66830.1. AK290194 mRNA. Translation: BAF82883.1. AC020604 Genomic DNA. Translation: AAY24289.1. CH471053 Genomic DNA. Translation: EAX00236.1. CH471053 Genomic DNA. Translation: EAX00237.1. BC032862 mRNA. Translation: AAH32862.1.
IPI	IPI00022271.
PIR	T46499.
RefSeq	NP_054730.1. NM_014011.4. NP_659198.1. NM_144949.2.
UniGene	Hs.468426.
3D structure databases
ProteinModelPortal	O75159.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75159. 2 interactions.
MINT	MINT-2835826.
STRING	9606.ENSP00000305133.
PTM databases
PhosphoSite	O75159.
Proteomic databases
PaxDb	O75159.
PRIDE	O75159.
Protocols and materials databases
DNASU	9655.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000306503; ENSP00000305133; ENSG00000171150. ENST00000394861; ENSP00000378330; ENSG00000171150.
GeneID	9655.
KEGG	hsa:9655.
UCSC	uc002rvf.3. human.
Organism-specific databases
CTD	9655.
GeneCards	GC02P046926.
HGNC	HGNC:16852. SOCS5.
HPA	CAB025510. HPA020884.
MIM	607094. gene.
neXtProt	NX_O75159.
PharmGKB	PA134884627.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG258974.
HOGENOM	HOG000027791.
HOVERGEN	HBG054138.
InParanoid	O75159.
KO	K04698.
OMA	KQRQVSG.
OrthoDB	EOG40P46R.
PhylomeDB	O75159.
Enzyme and pathway databases
Pathway_Interaction_DB	il4_2pathway. IL4-mediated signaling events.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	O75159.
Bgee	O75159.
CleanEx	HS_SOCS5.
Genevestigator	O75159.
GermOnline	ENSG00000171150. Homo sapiens.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR000980. SH2. IPR022252. SOCS. IPR001496. SOCS_C. [Graphical view]
Pfam	PF00017. SH2. 1 hit. PF12610. SOCS. 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	9655.
NextBio	36245.
SOURCE	Search...

Entry information

Entry name

SOCS5_HUMAN

Accession

Primary (citable) accession number: O75159
Secondary accession number(s): Q53SD4, Q8IYZ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 16, 2002
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 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.