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

    Gene ID: 10256, updated on 9-Dec-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
    mouse all
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    Genomic context

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    See CNKSR1 in Genome Data Viewer
    Location:
    1p36.11
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (26177491..26189884)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (26014921..26027308)
    RS_2024_09 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 ARF 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. The CNK1 scaffold binds cytohesins and promotes insulin pathway signaling. Lim J, et al. Genes Dev, 2010 Jul 15. PMID 20634316, Free PMC Article
    2. 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
    3. CNK1 promotes invasion of cancer cells through NF-kappaB-dependent signaling. Fritz RD, et al. Mol Cancer Res, 2010 Mar. PMID 20197385
    4. 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
    5. 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

    See all (44) 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)

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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