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O14544

- SOCS6_HUMAN

UniProt

O14544 - SOCS6_HUMAN

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Protein

Suppressor of cytokine signaling 6

Gene

SOCS6

Organism
Homo sapiens (Human)
Status
Reviewed - 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 (By similarity). Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor.By similarity1 Publication

Pathwayi

GO - Biological processi

  1. defense response Source: ProtInc
  2. JAK-STAT cascade Source: ProtInc
  3. negative regulation of signal transduction Source: UniProtKB-KW
  4. negative regulation of T cell activation Source: Ensembl
  5. proteasomal protein catabolic process Source: MGI
  6. protein ubiquitination Source: UniProtKB-UniPathway
  7. 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

ReactomeiREACT_111225. Regulation of KIT signaling.
SignaLinkiO14544.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of cytokine signaling 6
Short name:
SOCS-6
Alternative name(s):
Cytokine-inducible SH2 protein 4
Short name:
CIS-4
Suppressor of cytokine signaling 4
Short name:
SOCS-4
Gene namesi
Name:SOCS6
Synonyms:CIS4, SOCS4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:16833. SOCS6.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: ProtInc
  2. immunological synapse Source: MGI
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134917653.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 535535Suppressor of cytokine signaling 6PRO_0000181251Add
BLAST

Proteomic databases

MaxQBiO14544.
PaxDbiO14544.
PRIDEiO14544.

PTM databases

PhosphoSiteiO14544.

Expressioni

Gene expression databases

BgeeiO14544.
CleanExiHS_SOCS4.
HS_SOCS6.
ExpressionAtlasiO14544. baseline and differential.
GenevestigatoriO14544.

Organism-specific databases

HPAiCAB010189.
HPA035477.

Interactioni

Subunit structurei

Interacts with RBCK1. Interacts with phosphorylated IRS4 (By similarity). Interacts with PIM3 (By similarity). Interacts with KIT (phosphorylated).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102754EBI-3929549,EBI-608057
GAB1Q134809EBI-3929549,EBI-517684
KITP1072112EBI-3929549,EBI-1379503
METP085814EBI-3929549,EBI-1039152

Protein-protein interaction databases

BioGridi114719. 34 interactions.
IntActiO14544. 13 interactions.
MINTiMINT-4821450.
STRINGi9606.ENSP00000306939.

Structurei

Secondary structure

1
535
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi372 – 38211Combined sources
Helixi391 – 3977Combined sources
Turni398 – 4003Combined sources
Beta strandi406 – 4105Combined sources
Beta strandi417 – 4248Combined sources
Beta strandi427 – 43610Combined sources
Beta strandi439 – 4424Combined sources
Beta strandi451 – 4533Combined sources
Helixi454 – 46714Combined sources
Beta strandi471 – 4744Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2VIFX-ray1.45A361-499[»]
ProteinModelPortaliO14544.
SMRiO14544. Positions 367-535.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14544.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini384 – 491108SH2PROSITE-ProRule annotationAdd
BLAST
Domaini486 – 53550SOCS boxPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi105 – 1084Poly-Ser

Domaini

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.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.
HOGENOMiHOG000027792.
HOVERGENiHBG057479.
InParanoidiO14544.
KOiK10322.
OMAiTTGVMLQ.
OrthoDBiEOG7SXW3G.
PhylomeDBiO14544.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028413. SOCS.
IPR028421. SOCS6.
IPR001496. SOCS_C.
[Graphical view]
PANTHERiPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF25. PTHR10385:SF25. 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]

Sequencei

Sequence statusi: Complete.

O14544-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKKISLKTLR KSFNLNKSKE ETDFMVVQQP SLASDFGKDD SLFGSCYGKD
60 70 80 90 100
MASCDINGED EKGGKNRSKS ESLMGTLKRR LSAKQKSKGK AGTPSGSSAD
110 120 130 140 150
EDTFSSSSAP IVFKDVRAQR PIRSTSLRSH HYSPAPWPLR PTNSEETCIK
160 170 180 190 200
MEVRVKALVH SSSPSPALNG VRKDFHDLQS ETTCQEQANS LKSSASHNGD
210 220 230 240 250
LHLHLDEHVP VVIGLMPQDY IQYTVPLDEG MYPLEGSRSY CLDSSSPMEV
260 270 280 290 300
SAVPPQVGGR AFPEDESQVD QDLVVAPEIF VDQSVNGLLI GTTGVMLQSP
310 320 330 340 350
RAGHDDVPPL SPLLPPMQNN QIQRNFSGLT GTEAHVAESM RCHLNFDPNS
360 370 380 390 400
APGVARVYDS VQSSGPMVVT SLTEELKKLA KQGWYWGPIT RWEAEGKLAN
410 420 430 440 450
VPDGSFLVRD SSDDRYLLSL SFRSHGKTLH TRIEHSNGRF SFYEQPDVEG
460 470 480 490 500
HTSIVDLIEH SIRDSENGAF CYSRSRLPGS ATYPVRLTNP VSRFMQVRSL
510 520 530
QYLCRFVIRQ YTRIDLIQKL PLPNKMKDYL QEKHY
Length:535
Mass (Da):59,528
Last modified:September 23, 2008 - v2
Checksum:iAE513312A999B763
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti74 – 741M → I in BAA22538. (PubMed:9344848)Curated
Sequence conflicti161 – 1611S → T in BAA22538. (PubMed:9344848)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB006968 mRNA. Translation: BAA22538.1.
CH471117 Genomic DNA. Translation: EAW66522.1.
BC020082 mRNA. Translation: AAH20082.1.
CCDSiCCDS11998.1.
PIRiJC5762.
RefSeqiNP_004223.2. NM_004232.3.
XP_005266840.1. XM_005266783.1.
XP_006722640.1. XM_006722577.1.
UniGeneiHs.44439.

Genome annotation databases

EnsembliENST00000397942; ENSP00000381034; ENSG00000170677.
ENST00000582322; ENSP00000463395; ENSG00000170677.
GeneIDi9306.
KEGGihsa:9306.
UCSCiuc002lkr.1. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB006968 mRNA. Translation: BAA22538.1 .
CH471117 Genomic DNA. Translation: EAW66522.1 .
BC020082 mRNA. Translation: AAH20082.1 .
CCDSi CCDS11998.1.
PIRi JC5762.
RefSeqi NP_004223.2. NM_004232.3.
XP_005266840.1. XM_005266783.1.
XP_006722640.1. XM_006722577.1.
UniGenei Hs.44439.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2VIF X-ray 1.45 A 361-499 [» ]
ProteinModelPortali O14544.
SMRi O14544. Positions 367-535.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114719. 34 interactions.
IntActi O14544. 13 interactions.
MINTi MINT-4821450.
STRINGi 9606.ENSP00000306939.

PTM databases

PhosphoSitei O14544.

Proteomic databases

MaxQBi O14544.
PaxDbi O14544.
PRIDEi O14544.

Protocols and materials databases

DNASUi 9306.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000397942 ; ENSP00000381034 ; ENSG00000170677 .
ENST00000582322 ; ENSP00000463395 ; ENSG00000170677 .
GeneIDi 9306.
KEGGi hsa:9306.
UCSCi uc002lkr.1. human.

Organism-specific databases

CTDi 9306.
GeneCardsi GC18P067956.
HGNCi HGNC:16833. SOCS6.
HPAi CAB010189.
HPA035477.
MIMi 605118. gene.
neXtProti NX_O14544.
PharmGKBi PA134917653.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG318341.
GeneTreei ENSGT00760000119136.
HOGENOMi HOG000027792.
HOVERGENi HBG057479.
InParanoidi O14544.
KOi K10322.
OMAi TTGVMLQ.
OrthoDBi EOG7SXW3G.
PhylomeDBi O14544.
TreeFami TF321368.

Enzyme and pathway databases

UniPathwayi UPA00143 .
Reactomei REACT_111225. Regulation of KIT signaling.
SignaLinki O14544.

Miscellaneous databases

EvolutionaryTracei O14544.
GeneWikii SOCS6.
GenomeRNAii 9306.
NextBioi 34859.
PROi O14544.
SOURCEi Search...

Gene expression databases

Bgeei O14544.
CleanExi HS_SOCS4.
HS_SOCS6.
ExpressionAtlasi O14544. baseline and differential.
Genevestigatori O14544.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR000980. SH2.
IPR028413. SOCS.
IPR028421. SOCS6.
IPR001496. SOCS_C.
[Graphical view ]
PANTHERi PTHR10385. PTHR10385. 1 hit.
PTHR10385:SF25. PTHR10385:SF25. 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. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. 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].
    Tissue: Skin.
  4. "Signal transduction via the stem cell factor receptor/c-Kit."
    Ronnstrand L.
    Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION.
  5. "Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase."
    Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S., Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.
    J. Biol. Chem. 286:480-490(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 361-499 IN COMPLEX WITH KIT, FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE FOR KIT.

Entry informationi

Entry nameiSOCS6_HUMAN
AccessioniPrimary (citable) accession number: O14544
Secondary accession number(s): Q8WUM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: September 23, 2008
Last modified: October 29, 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3