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Protein

Suppressor of cytokine signaling 5

Gene

SOCS5

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

Functioni

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.1 Publication

Pathwayi

GO - Molecular functioni

  • protein kinase inhibitor activity Source: GO_Central
  • receptor tyrosine kinase 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

SignaLinkiO75159.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:SOCS5
Synonyms:CIS6, CISH5, CISH6, KIAA0671
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:16852. SOCS5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi406 – 4061R → K: Abrogates the ability to induce EGFR degradation. 1 Publication
Mutagenesisi484 – 4841L → P: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with F-488. 1 Publication
Mutagenesisi488 – 4881C → F: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with P-484. 1 Publication

Organism-specific databases

PharmGKBiPA134884627.

Polymorphism and mutation databases

BioMutaiSOCS5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 536536Suppressor of cytokine signaling 5PRO_0000181249Add
BLAST

Post-translational modificationi

Phosphorylated. Phosphorylation is induced by EGF.1 Publication

Proteomic databases

MaxQBiO75159.
PaxDbiO75159.
PRIDEiO75159.

PTM databases

PhosphoSiteiO75159.

Expressioni

Inductioni

Up-regulated by EGF (at protein level).1 Publication

Gene expression databases

BgeeiO75159.
CleanExiHS_SOCS5.
GenevestigatoriO75159.

Organism-specific databases

HPAiCAB025510.
HPA020884.

Interactioni

Subunit structurei

Interacts with IL4R; inhibits IL4 signaling (By similarity). Interacts with EGFR. Interacts with TCEB1 AND TCEB2; mediates EGFR ubiquitination and degradation.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
METP085812EBI-970130,EBI-1039152

Protein-protein interaction databases

BioGridi115013. 9 interactions.
IntActiO75159. 6 interactions.
MINTiMINT-2835826.
STRINGi9606.ENSP00000305133.

Structurei

3D structure databases

ProteinModelPortaliO75159.
SMRiO75159. Positions 369-524.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini381 – 47696SH2PROSITE-ProRule annotationAdd
BLAST
Domaini471 – 52050SOCS boxPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5050Required for interaction with IL4RBy similarityAdd
BLAST

Domaini

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

Sequence similaritiesi

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

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG258974.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000027791.
HOVERGENiHBG054138.
InParanoidiO75159.
KOiK04698.
OMAiQVSGDSH.
OrthoDBiEOG7XH6QR.
PhylomeDBiO75159.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR022252. SOCS4/SOCS5_dom.
IPR028420. SOCS5.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF28. PTHR10385:SF28. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF12610. SOCS. 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]

Sequencei

Sequence statusi: Complete.

O75159-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKVGKMWNN FKYRCQNLFG HEGGSRSENV DMNSNRCLSV KEKNISIGDS
60 70 80 90 100
TPQQQSSPLR ENIALQLGLS PSKNSSRRNQ NCATEIPQIV EISIEKDNDS
110 120 130 140 150
CVTPGTRLAR RDSYSRHAPW GGKKKHSCST KTQSSLDADK KFGRTRSGLQ
160 170 180 190 200
RRERRYGVSS VHDMDSVSSR TVGSRSLRQR LQDTVGLCFP MRTYSKQSKP
210 220 230 240 250
LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV SPHSTFFDTF
260 270 280 290 300
DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG
310 320 330 340 350
PKLAPGMTEI SGDSSAIPQA NCDSEEDTTT LCLQSRRQKQ RQISGDSHTH
360 370 380 390 400
VSRQGAWKVH TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE
410 420 430 440 450
GTFLLRDSAQ EDYLFSVSFR RYNRSLHARI EQWNHNFSFD AHDPCVFHSS
460 470 480 490 500
TVTGLLEHYK DPSSCMFFEP LLTISLNRTF PFSLQYICRA VICRCTTYDG
510 520 530
IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK
Length:536
Mass (Da):61,246
Last modified:November 1, 1998 - v1
Checksum:i0629CDCF2A97E9D8
GO

Sequence cautioni

The sequence BAA31646.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti478 – 4781R → M in AAH32862 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1830.1.
PIRiT46499.
RefSeqiNP_054730.1. NM_014011.4.
NP_659198.1. NM_144949.2.
UniGeneiHs.468426.

Genome annotation databases

EnsembliENST00000306503; ENSP00000305133; ENSG00000171150.
ENST00000394861; ENSP00000378330; ENSG00000171150.
GeneIDi9655.
KEGGihsa:9655.
UCSCiuc002rvf.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1830.1.
PIRiT46499.
RefSeqiNP_054730.1. NM_014011.4.
NP_659198.1. NM_144949.2.
UniGeneiHs.468426.

3D structure databases

ProteinModelPortaliO75159.
SMRiO75159. Positions 369-524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115013. 9 interactions.
IntActiO75159. 6 interactions.
MINTiMINT-2835826.
STRINGi9606.ENSP00000305133.

PTM databases

PhosphoSiteiO75159.

Polymorphism and mutation databases

BioMutaiSOCS5.

Proteomic databases

MaxQBiO75159.
PaxDbiO75159.
PRIDEiO75159.

Protocols and materials databases

DNASUi9655.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306503; ENSP00000305133; ENSG00000171150.
ENST00000394861; ENSP00000378330; ENSG00000171150.
GeneIDi9655.
KEGGihsa:9655.
UCSCiuc002rvf.3. human.

Organism-specific databases

CTDi9655.
GeneCardsiGC02P046926.
HGNCiHGNC:16852. SOCS5.
HPAiCAB025510.
HPA020884.
MIMi607094. gene.
neXtProtiNX_O75159.
PharmGKBiPA134884627.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG258974.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000027791.
HOVERGENiHBG054138.
InParanoidiO75159.
KOiK04698.
OMAiQVSGDSH.
OrthoDBiEOG7XH6QR.
PhylomeDBiO75159.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
SignaLinkiO75159.

Miscellaneous databases

GeneWikiiSOCS5.
GenomeRNAii9655.
NextBioi36245.
PROiO75159.
SOURCEiSearch...

Gene expression databases

BgeeiO75159.
CleanExiHS_SOCS5.
GenevestigatoriO75159.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR022252. SOCS4/SOCS5_dom.
IPR028420. SOCS5.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF28. PTHR10385:SF28. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF12610. SOCS. 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. "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. 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. 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.

Entry informationi

Entry nameiSOCS5_HUMAN
AccessioniPrimary (citable) accession number: O75159
Secondary accession number(s): Q53SD4, Q8IYZ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: November 1, 1998
Last modified: May 27, 2015
This is version 132 of the entry and version 1 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 2
    Human chromosome 2: 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.