Human Gene SOCS6 (ENST00000397942.4) Description and Page Index
  Description: Homo sapiens suppressor of cytokine signaling 6 (SOCS6), mRNA. (from RefSeq NM_004232)
RefSeq Summary (NM_004232): The protein encoded by this gene contains a SH2 domain and a CIS homolog domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by GM-CSF and EPO in hematopoietic cells. A high expression level of this gene was found in factor-independent chronic myelogenous leukemia (CML) and erythroleukemia (HEL) cell lines. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660807.214235.1, SRR1660807.205991.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000397942.4/ ENSP00000381034.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000397942.4
Gencode Gene: ENSG00000170677.6
Transcript (Including UTRs)
   Position: hg38 chr18:70,289,045-70,330,199 Size: 41,155 Total Exon Count: 2 Strand: +
Coding Region
   Position: hg38 chr18:70,324,669-70,326,276 Size: 1,608 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsCTDRNA-Seq ExpressionMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr18:70,289,045-70,330,199)mRNA (may differ from genome)Protein (535 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Suppressor of cytokine signaling 6; Short=SOCS-6; AltName: Full=Cytokine-inducible SH2 protein 4; Short=CIS-4; AltName: Full=Suppressor of cytokine signaling 4; Short=SOCS-4;
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 (By similarity). Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts with RBCK1. Interacts with phosphorylated IRS4 (By similarity). Interacts with PIM3 (By similarity). Interacts with KIT (phosphorylated).
DOMAIN: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity).
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 1 SOCS box domain.

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.85 RPKM in Cells - Transformed fibroblasts
Total median expression: 207.02 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -53.90172-0.313 Picture PostScript Text
3' UTR -878.903923-0.224 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000980 - SH2
IPR001496 - SOCS_C

Pfam Domains:
PF00017 - SH2 domain
PF07525 - SOCS box

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on O14544
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004860 protein kinase inhibitor activity
GO:0005515 protein binding

Biological Process:
GO:0006469 negative regulation of protein kinase activity
GO:0006952 defense response
GO:0007259 JAK-STAT cascade
GO:0009968 negative regulation of signal transduction
GO:0010498 proteasomal protein catabolic process
GO:0016567 protein ubiquitination
GO:0019221 cytokine-mediated signaling pathway
GO:0035556 intracellular signal transduction
GO:0040008 regulation of growth
GO:0043687 post-translational protein modification
GO:0046426 negative regulation of JAK-STAT cascade
GO:0050868 negative regulation of T cell activation

Cellular Component:
GO:0001772 immunological synapse
GO:0005737 cytoplasm
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  JD204525 - Sequence 185549 from Patent EP1572962.
BC020082 - Homo sapiens suppressor of cytokine signaling 6, mRNA (cDNA clone MGC:9529 IMAGE:3917519), complete cds.
AF161545 - Homo sapiens HSPC060 mRNA, complete cds.
JD355694 - Sequence 336718 from Patent EP1572962.
JD110374 - Sequence 91398 from Patent EP1572962.
JD187356 - Sequence 168380 from Patent EP1572962.
AB464722 - Synthetic construct DNA, clone: pF1KB8846, Homo sapiens SOCS6 gene for suppressor of cytokine signaling 6, without stop codon, in Flexi system.
KJ892738 - Synthetic construct Homo sapiens clone ccsbBroadEn_02132 SOCS6 gene, encodes complete protein.
AB006968 - Homo sapiens mRNA for CIS4, complete cds.
LF369428 - JP 2014500723-A/176931: Polycomb-Associated Non-Coding RNAs.
MA605005 - JP 2018138019-A/176931: Polycomb-Associated Non-Coding RNAs.
LF369427 - JP 2014500723-A/176930: Polycomb-Associated Non-Coding RNAs.
MA605004 - JP 2018138019-A/176930: Polycomb-Associated Non-Coding RNAs.
LF369426 - JP 2014500723-A/176929: Polycomb-Associated Non-Coding RNAs.
MA605003 - JP 2018138019-A/176929: Polycomb-Associated Non-Coding RNAs.
LF369425 - JP 2014500723-A/176928: Polycomb-Associated Non-Coding RNAs.
MA605002 - JP 2018138019-A/176928: Polycomb-Associated Non-Coding RNAs.
LF369424 - JP 2014500723-A/176927: Polycomb-Associated Non-Coding RNAs.
MA605001 - JP 2018138019-A/176927: Polycomb-Associated Non-Coding RNAs.
JD091799 - Sequence 72823 from Patent EP1572962.
JD440329 - Sequence 421353 from Patent EP1572962.
JD084861 - Sequence 65885 from Patent EP1572962.
JD563584 - Sequence 544608 from Patent EP1572962.
JD559165 - Sequence 540189 from Patent EP1572962.
JD281576 - Sequence 262600 from Patent EP1572962.
JD289461 - Sequence 270485 from Patent EP1572962.
JD402618 - Sequence 383642 from Patent EP1572962.
AK024356 - Homo sapiens cDNA FLJ14294 fis, clone PLACE1008181.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O14544 (Reactome details) participates in the following event(s):

R-HSA-1470011 Downregulation of c-Kit signaling by SOCS6
R-HSA-8952039 NEDD8:AcM-UBE2F binds CRL5 E3 ubiquitin ligase complex
R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases
R-HSA-8952044 AcM-UBE2F transfers NEDD8 to CRL5 E3 ubiquitin ligase complex
R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
R-HSA-1433559 Regulation of KIT signaling
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-8951664 Neddylation
R-HSA-162582 Signal Transduction
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: CIS4, NM_004232, O14544, Q8WUM3, SOCS4, SOCS6_HUMAN, uc002lkr.1, uc002lkr.2, uc002lkr.3
UCSC ID: uc002lkr.3
RefSeq Accession: NM_004232
Protein: O14544 (aka SOCS6_HUMAN or SOC6_HUMAN)
CCDS: CCDS11998.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.