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CNKSR2 connector enhancer of kinase suppressor of Ras 2 [ Homo sapiens (human) ]

Gene ID: 22866, updated on 2-Nov-2024

Summary

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Official Symbol
CNKSR2provided by HGNC
Official Full Name
connector enhancer of kinase suppressor of Ras 2provided by HGNC
Primary source
HGNC:HGNC:19701
See related
Ensembl:ENSG00000149970 MIM:300724; AllianceGenome:HGNC:19701
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
CNK2; KSR2; MAGUIN; MRXSHG
Summary
This gene encodes a multidomain protein that functions as a scaffold protein to mediate the mitogen-activated protein kinase pathways downstream from Ras. This gene product is induced by vitamin D and inhibits apoptosis in certain cancer cells. It may also play a role in ternary complex assembly of synaptic proteins at the postsynaptic membrane and coupling of signal transduction to membrane/cytoskeletal remodeling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
Expression
Biased expression in brain (RPKM 9.7), adrenal (RPKM 1.3) and 2 other tissues See more
Orthologs
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Genomic context

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See CNKSR2 in Genome Data Viewer
Location:
Xp22.12
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (21374418..21654689)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (20957756..21238011)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (21392536..21672807)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124905258 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:20991102-20991662 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:21007714-21008913 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:21064982-21065616 Neighboring gene NANOG hESC enhancer GRCh37_chrX:21176863-21177381 Neighboring gene RNA, U6 small nuclear 133, pseudogene Neighboring gene uncharacterized LOC105373146 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:21357913-21358412 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:21391460-21391960 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:21391961-21392461 Neighboring gene retinoic acid receptor responder 2 pseudogene 3 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:21704726-21705925 Neighboring gene kelch like family member 34 Neighboring gene small muscle protein X-linked

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 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. hKSR-2, a vitamin D-regulated gene, inhibits apoptosis in arabinocytosine-treated HL60 leukemia cells. Wang X, et al. Mol Cancer Ther, 2008 Sep. PMID 18790760, Free PMC Article
  2. Functions of CNKSR2 and Its Association with Neurodevelopmental Disorders. Ito H, et al. Cells, 2022 Jan 17. PMID 35053419, Free PMC Article
  3. Absent CNKSR2 causes seizures and intellectual, attention, and language deficits. Vaags AK, et al. Ann Neurol, 2014 Nov. PMID 25223753
  4. CNKSR2 deletions: a novel cause of X-linked intellectual disability and seizures. Aypar U, et al. Am J Med Genet A, 2015 Jul. PMID 25754917
  5. Psychomotor development and attention problems caused by a splicing variant of CNKSR2. Zhang Y, et al. BMC Med Genomics, 2020 Dec 9. PMID 33298018, Free PMC Article

See all (42) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Functions of CNKSR2 and Its Association with Neurodevelopmental Disorders.
    Title: Functions of CNKSR2 and Its Association with Neurodevelopmental Disorders.
  2. Finding underlying genetic mechanisms of two patients with autism spectrum disorder carrying familial apparently balanced chromosomal translocations.
    Title: Finding underlying genetic mechanisms of two patients with autism spectrum disorder carrying familial apparently balanced chromosomal translocations.
  3. Psychomotor development and attention problems caused by a splicing variant of CNKSR2.
    Title: Psychomotor development and attention problems caused by a splicing variant of CNKSR2.
  4. Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES).
    Title: Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES).
  5. This study enhances our knowledge of the CNKSR2 gene mutation spectrum and provides further information about the phenotypic characteristics of X-linked syndromic intellectual disability.
    Title: Exons deletion of CNKSR2 gene identified in X-linked syndromic intellectual disability.
  6. High CNKSR2 expression is associated with breast cancer progression.
    Title: Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.
  7. CNKSR2 deletions: a novel cause of X-linked intellectual disability and seizures.
    Title: CNKSR2 deletions: a novel cause of X-linked intellectual disability and seizures.
  8. This study describes the phenotype of CNKSR2 deficiency and its involvement in systems underlying common neurological
    Title: Absent CNKSR2 causes seizures and intellectual, attention, and language deficits.
  9. CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
    Title: CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
  10. CNK2 through interaction with Raf and Rlf may function as a regulator of Ras signaling.
    Title: Human homologue of Drosophila CNK interacts with Ras effector proteins Raf and Rlf.
Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual disability, X-linked, syndromic, Houge type
MedGen: C4538788 OMIM: 301008 GeneReviews: Not available
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Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2021-01-12)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-12)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci.
EBI GWAS Catalog

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

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0902

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
acts_upstream_of_or_within intracellular signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in postsynaptic specialization organization IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of signal transduction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in extrinsic component of postsynaptic density membrane IEA
Inferred from Electronic Annotation
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
connector enhancer of kinase suppressor of ras 2
Names
CNK homolog protein 2
connector enhancer of KSR2
membrane-associated guanylate kinase-interacting protein

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_016266.1 RefSeqGene

    Range
    5001..285272
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001168647.3 → NP_001162118.1  connector enhancer of kinase suppressor of ras 2 isoform 2

    See identical proteins and their annotated locations for NP_001162118.1

    Status: REVIEWED

    Source sequence(s)
    AL772392, AL807781, BC143839
    Consensus CDS
    CCDS55388.1
    UniProtKB/TrEMBL
    A0A2R8YED7
    Related
    ENSP00000397906.2, ENST00000425654.7
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 294
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:529 → 642
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:339 → 484
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  2. NM_001168648.3 → NP_001162119.1  connector enhancer of kinase suppressor of ras 2 isoform 3

    See identical proteins and their annotated locations for NP_001162119.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as CNK2B and MAGUIN-2) differs in the 3' UTR and 3' coding region, compared to variant 1. It encodes isoform 3 which has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AF418270, AK056549, AL772392, BM692904, DA067208, F09543, T65396, Z40257
    Consensus CDS
    CCDS55387.1
    UniProtKB/TrEMBL
    A0A2R8YGJ7
    Related
    ENSP00000496709.1, ENST00000642359.1
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 294
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:559 → 672
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:339 → 514
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  3. NM_001168649.3 → NP_001162120.1  connector enhancer of kinase suppressor of ras 2 isoform 4

    See identical proteins and their annotated locations for NP_001162120.1

    Status: REVIEWED

    Source sequence(s)
    AK056549, AK294728, AL772392, AL807781, F09543, T65396, Z40257
    Consensus CDS
    CCDS55389.1
    UniProtKB/TrEMBL
    A0A2R8YGJ7
    Related
    ENSP00000444633.1, ENST00000543067.6
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 270
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:510 → 623
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:290 → 465
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  4. NM_001330770.2 → NP_001317699.1  connector enhancer of kinase suppressor of ras 2 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AL772392, AL807781, AL928874
    Consensus CDS
    CCDS87729.1
    UniProtKB/TrEMBL
    A0A2R8Y7A1, A0A2R8YED7
    Related
    ENSP00000495954.1, ENST00000644585.1
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 270
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:510 → 623
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:290 → 465
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  5. NM_001330771.2 → NP_001317700.1  connector enhancer of kinase suppressor of ras 2 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AL772392, AL807781, AL928874
    Consensus CDS
    CCDS87730.1
    UniProtKB/TrEMBL
    A0A2R8Y5S6, A0A2R8Y622
    Related
    ENSP00000494906.1, ENST00000645791.1
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 270
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:480 → 593
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:290 → 408
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  6. NM_001330772.2 → NP_001317701.1  connector enhancer of kinase suppressor of ras 2 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AL772392, AL807781, AL928874
    Consensus CDS
    CCDS87731.1
    UniProtKB/TrEMBL
    A0A2R8Y700, A0A2R8YED7
    Related
    ENSP00000495695.1, ENST00000645245.1
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 270
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:480 → 593
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:290 → 435
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  7. NM_001330773.2 → NP_001317702.1  connector enhancer of kinase suppressor of ras 2 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AL772392, AL807781, AL928874
    Consensus CDS
    CCDS87728.1
    UniProtKB/TrEMBL
    A0A2R8Y5S6, A0A2U3TZH5
    Related
    ENSP00000279451.5, ENST00000279451.9
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 294
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:529 → 642
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:339 → 457
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras

  8. NM_014927.5 → NP_055742.2  connector enhancer of kinase suppressor of ras 2 isoform 1

    See identical proteins and their annotated locations for NP_055742.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1, also known as CNK2A and MAGUIN-1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL772392, AL807781, BC136289
    Consensus CDS
    CCDS14198.1
    UniProtKB/Swiss-Prot
    B4DGR4, B7ZLJ1, B9EG83, E7ESA4, O94976, Q5JPK4, Q5JPN0, Q8WXI1, Q8WXI2
    UniProtKB/TrEMBL
    A0A2R8YED7
    Related
    ENSP00000368824.3, ENST00000379510.5
    Conserved Domains (5) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    cd00992
    Location:222 → 294
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:559 → 672
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam06663
    Location:339 → 514
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    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_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    21374418..21654689
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011545471.4 → XP_011543773.1  connector enhancer of kinase suppressor of ras 2 isoform X1

    UniProtKB/TrEMBL
    A0A2R8Y5S6
    Conserved Domains (8) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    smart00454
    Location:8 → 73
    SAM; Sterile alpha motif
    cd00992
    Location:222 → 294
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:529 → 642
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam00169
    Location:543 → 639
    PH; PH domain
    pfam06663
    Location:341 → 531
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras
    pfam15499
    Location:139 → 218
    Peptidase_C98; Ubiquitin-specific peptidase-like, SUMO isopeptidase

  2. XM_011545472.4 → XP_011543774.1  connector enhancer of kinase suppressor of ras 2 isoform X2

    See identical proteins and their annotated locations for XP_011543774.1

    UniProtKB/TrEMBL
    A0A2R8YGJ7
    Conserved Domains (8) summary
    cd09511
    Location:8 → 76
    SAM_CNK1,2,3-suppressor; SAM domain of CNK1,2,3-suppressor subfamily
    smart00454
    Location:8 → 73
    SAM; Sterile alpha motif
    cd00992
    Location:222 → 270
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cd01260
    Location:510 → 623
    PH_CNK_mammalian-like; Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain
    pfam00169
    Location:524 → 620
    PH; PH domain
    pfam06663
    Location:292 → 512
    DUF1170; Protein of unknown function (DUF1170)
    pfam10534
    Location:84 → 176
    CRIC_ras_sig; Connector enhancer of kinase suppressor of ras
    pfam15499
    Location:139 → 218
    Peptidase_C98; Ubiquitin-specific peptidase-like, SUMO isopeptidase

  3. XM_017029358.3 → XP_016884847.1  connector enhancer of kinase suppressor of ras 2 isoform X3

    UniProtKB/TrEMBL
    A0A2R8Y5S6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    20957756..21238011
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WXI2.1 GenPept UniProtKB/Swiss-Prot:Q8WXI2

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