Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SOCS6

contributors: mct - updated : 08-02-2016

HGNC name	suppressor of cytokine signaling 6
HGNC id	16833

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	18q22.2      Physical location : 67.956.136 - 67.997.434
Synonym name	STAT induced STAT inhibitory 4
	cytokine inducible SH2 protein 4
	suppressor of cytokine signaling 4
Synonym symbol(s)	CIS4, SSI4, STAI4, STAT4, STATI4, HSPC060, SOCS4, CISH4

DNA

TYPE	functioning gene
STRUCTURE	41.30 kb     2 Exon(s)

regulatory sequence	Binding site   transcription factor
text structure	major transcription initiation site is located 469 bp upstream the ATG codon
	5prime-flanking region is able to drive transcription, and the CpG-rich sequences near the transcription initiation site are important for the TATA-less SOCS6 promoter activity
	consensus binding sequences for several transcription factors including AP1, AP2, AP4, BRE, C/EBP, CREB, E2F, GATA-1, OCT1, p53, SP1, NFAT, c-Myb, MZF

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	two SOCS6 transcripts were generated from the major transcription initiation site due to the usage of the two alternative polyadenylation sites (PMID: 19716864)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004232 2 - 5846 NP_004223 59.5 535 - 2009 19716864 variant 2 - - 2919 isoform 2 59.5 535 - 2009 19716864

EXPRESSION

Rna function	skeletal muscle, placenta, tongue
Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Digestive salivary gland       highly   stomach       moderately Endocrine parathyroid       highly   thyroid       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic mature hematopoietic Skin/Tegument melanocyte

cell lineage
cell lines	factor independent CML, erythroleukemia
fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	umbilical cord, embryonic tissue

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal amino acids 1-210 sufficient to locate the protein into the nucleus solitary in both the cytoplasm and the nucleus, and the KID domain (AA 47–218) provides an interface for binding the kinase domain of LCK
	a central Src homology SH2 domain
	at least two functional domains required for its biological role in localizing and degrading STAT3 in the nucleus
	a C terminal conserved SOCS box, acting as a common binding domain for a large family of E3 ubiquitin protein ligases
	an SH2 domain, in the cytoplasm

HOMOLOGY

interspecies	homolog to rattus Socs6 (84.91 pc)
	homolog to murine Socs6 (85.66 pc)

Homologene

FAMILY	SOCS protein family
	CIS family

CATEGORY

regulatory , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	primarily located and regulated in the cytoplasm, and in the nucleus
	localizes to the nucleus where it reduces STAT3

basic FUNCTION	part of a classical negative feedback system that regulates cytokine signal transduction
	having a putative function as a negative regulator of receptor tyrosine kinases
	having at least two functional domains required for its biological role in localizing and degrading STAT3 in the nucleus
	negative regulator of cytokine signaling pathways
	negative regulator of LCK
	in response to TCR stimulation, associates with and negatively regulates LCK
	important role for SOCS6 in cellular homeostasis
	acting as a negative regulator of T cell activation by promoting ubiquitin-dependent proteolysis

CELLULAR PROCESS	nucleotide, transcription, regulation
	protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	binding to elongin B and C through its SOCS box
	interacting with IRS4 and IRS2
	binds to KIT juxtamembrane region, which affects upstream signaling components leading to MAPK activation
	interacts with RBCK1, a type of E3 ubiquitin ligase involved in proteasome-mediated degradation
	targeting LCK to proteasome-dependent degradation in response to T cell activation and negative regulation of LCK by SOCS6 may in part prevent uncontrolled T cell activation
	SOCS6 negatively regulates FLT3 activation, the downstream Erk signaling pathway, and cell proliferation
	by terminating RELN signaling, SOCS6 and SOCS7 may allow new cycles of RELN signaling to occur and these may be essential for cortical neuron migration

cell & other

REGULATION

induced by

induced by erythropoietin (EPO) and granulocyte macrophage CSF (CSF2) in hematopoietic cell lines

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     frequent event in gastric tumorigenesis tumoral     --low   in carcinomas of stomach and colon

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS