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CNKSR1 connector enhancer of kinase suppressor of Ras 1 [ Homo sapiens (human) ]

Gene ID: 10256, updated on 11-Apr-2024

Summary

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Official Symbol
CNKSR1provided by HGNC
Official Full Name
connector enhancer of kinase suppressor of Ras 1provided by HGNC
Primary source
HGNC:HGNC:19700
See related
Ensembl:ENSG00000142675 MIM:603272; AllianceGenome:HGNC:19700
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CNK; CNK1
Summary
This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Expression
Broad expression in skin (RPKM 7.6), thyroid (RPKM 6.2) and 20 other tissues See more
Orthologs
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Genomic context

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Location:
1p36.11
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (26177491..26189884)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (26014921..26027308)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (26503982..26516375)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:26490758-26491327 Neighboring gene chromosome 1 open reading frame 230 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:26494780-26494935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 481 Neighboring gene ZNF593 opposite strand Neighboring gene zinc finger protein 593 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:26508561-26509062 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:26516979-26517796 Neighboring gene cation channel sperm associated 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:26524463-26524962 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:26527946-26528918 Neighboring gene ADP ribosylation factor like GTPase 16 pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer. Quadri HS, et al. BMC Cancer, 2017 Jul 21. PMID 28732488, Free PMC Article
  2. Differential tyrosine phosphorylation controls the function of CNK1 as a molecular switch in signal transduction. Fischer A, et al. Biochim Biophys Acta, 2015 Nov. PMID 26319181
  3. The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling. Lim J, et al. Genes Dev, 2010 Jul 15. PMID 20634316, Free PMC Article
  4. CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling. Fritz RD, et al. Mol Cancer Res, 2010 Mar. PMID 20197385
  5. Systemic analysis of TGFbeta proteomics revealed involvement of Plag1/CNK1/RASSF1A/Src network in TGFbeta1-dependent activation of Erk1/2 and cell proliferation. Bhaskaran N, et al. Proteomics, 2008 Nov. PMID 18821524

See all (43) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.
    Title: CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.
  2. RNAi-mediated knockdown of cnk, the CNKSR1 orthologue in Drosophila melanogaster brain, led to defects in eye and mushroom body (MB) structures. Findings support the possible role of CNKSR1 in brain development which can lead to cognitive impairment.
    Title: CNKSR1 gene defect can cause syndromic autosomal recessive intellectual disability.
  3. CNKSR1 expression is increased in pancreatic cancer specimens and was found to be an independent prognostic marker of overall survival.
    Title: Expression of the scaffold connector enhancer of kinase suppressor of Ras 1 (CNKSR1) is correlated with clinical outcome in pancreatic cancer.
  4. Data indicate connector enhancer of kinase suppressor of Ras 1 protein (CNK1) as a molecular platform that controls c-raf protein (RAF) and c-akt protein (AKT) signalling and determines cell fate decisions in a cell type- and cell stage-dependent manner.
    Title: Optogenetic clustering of CNK1 reveals mechanistic insights in RAF and AKT signalling controlling cell fate decisions.
  5. The findings reveal SAM domain-dependent oligomerization by AKT as a switch for CNK1 activation.
    Title: AKT-dependent phosphorylation of the SAM domain induces oligomerization and activation of the scaffold protein CNK1.
  6. tyrosine phosphorylation is an important mechanism to control the subcellular localization of CNK1 and its distinct biological functions.
    Title: Differential tyrosine phosphorylation controls the function of CNK1 as a molecular switch in signal transduction.
  7. CNK1 mediates ephrinB1 signaling that promotes cell migration through RhoA and JNK activity.
    Title: EphrinB1 interacts with CNK1 and promotes cell migration through c-Jun N-terminal kinase (JNK) activation.
  8. Studies indicate that CNK1-driven proliferation relies on Akt-dependent phosphorylation and inactivation of FoxO proteins.
    Title: CNK1 and other scaffolds for Akt/FoxO signaling.
  9. These findings identify CNK1 as a new positive regulator of insulin signaling.
    Title: The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling.
  10. Thus, CNK1 is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy.
    Title: CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling.
Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: IPCEF1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-macromolecule adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell surface receptor protein tyrosine kinase signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cell cortex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cell-cell junction TAS
Traceable Author Statement
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
connector enhancer of kinase suppressor of ras 1
Names
CNK homolog protein 1
connector enhancer of KSR 1
connector enhancer of KSR-like

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047117.1 RefSeqGene

    Range
    5002..17395
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001297647.2 → NP_001284576.1  connector enhancer of kinase suppressor of ras 1 isoform 2

    See identical proteins and their annotated locations for NP_001284576.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate in-frame splice site, compared to variant 1. The encoded isoform (2) is longer than isoform 1.
    Source sequence(s)
    AK296814, BC011604
    Consensus CDS
    CCDS72732.1
    UniProtKB/Swiss-Prot
    B1AMW9, O95381, Q969H4
    UniProtKB/TrEMBL
    A8K9D1, Q53GW4
    Related
    ENSP00000363371.5, ENST00000374253.9
    Conserved Domains (3) summary
    cd09511
    Location:4 → 70
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd01260
    Location:392 → 505
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam10534
    Location:78 → 162
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  2. NM_001297648.2 → NP_001284577.1  connector enhancer of kinase suppressor of ras 1 isoform 3

    See identical proteins and their annotated locations for NP_001284577.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate splice site in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1.
    Source sequence(s)
    AF100153, AK001900, AK296814, BC011604
    Consensus CDS
    CCDS76124.1
    UniProtKB/TrEMBL
    G3V160, Q59FX4
    Related
    ENSP00000431817.1, ENST00000531191.5
    Conserved Domains (2) summary
    cd01260
    Location:127 → 240
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam00169
    Location:141 → 237
    PH; PH domain

  3. NM_006314.3 → NP_006305.2  connector enhancer of kinase suppressor of ras 1 isoform 1

    See identical proteins and their annotated locations for NP_006305.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AF100153, BC011604, DA445069
    Consensus CDS
    CCDS276.1
    UniProtKB/TrEMBL
    A8K9D1, Q53GM7, Q53GW4
    Related
    ENSP00000354609.6, ENST00000361530.11
    Conserved Domains (6) summary
    cd09511
    Location:4 → 70
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    smart00454
    Location:4 → 69
    SAM; Sterile alpha motif
    cd00136
    Location:206 → 275
    PDZ; PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). Many PDZ domains bind C-terminal polypeptides, though binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. ...
    cd01260
    Location:385 → 498
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam00169
    Location:399 → 495
    PH; PH domain
    pfam10534
    Location:78 → 162
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    26177491..26189884
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    26014921..26027308
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NR_023345.1: Suppressed sequence

    Description
    NR_023345.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q969H4.1 GenPept UniProtKB/Swiss-Prot:Q969H4

Gene LinkOut

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