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P42773

- CDN2C_HUMAN

UniProt

P42773 - CDN2C_HUMAN

Protein

Cyclin-dependent kinase 4 inhibitor C

Gene

CDKN2C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB.

    GO - Molecular functioni

    1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: BHF-UCL
    2. protein binding Source: IntAct
    3. protein kinase binding Source: BHF-UCL

    GO - Biological processi

    1. cell cycle arrest Source: BHF-UCL
    2. G1/S transition of mitotic cell cycle Source: BHF-UCL
    3. mitotic cell cycle Source: Reactome
    4. negative regulation of cell growth Source: BHF-UCL
    5. negative regulation of cell proliferation Source: BHF-UCL
    6. negative regulation of phosphorylation Source: BHF-UCL
    7. negative regulation of protein serine/threonine kinase activity Source: GOC
    8. oligodendrocyte differentiation Source: Ensembl
    9. regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL

    Keywords - Biological processi

    Cell cycle

    Enzyme and pathway databases

    ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 4 inhibitor C
    Alternative name(s):
    Cyclin-dependent kinase 6 inhibitor
    p18-INK4c
    p18-INK6
    Gene namesi
    Name:CDKN2C
    Synonyms:CDKN6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:1789. CDKN2C.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. cytosol Source: Reactome
    3. nucleus Source: BHF-UCL

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti652. Multiple endocrine neoplasia type 1.
    PharmGKBiPA26322.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 168168Cyclin-dependent kinase 4 inhibitor CPRO_0000144186Add
    BLAST

    Proteomic databases

    MaxQBiP42773.
    PaxDbiP42773.
    PRIDEiP42773.

    PTM databases

    PhosphoSiteiP42773.

    Expressioni

    Tissue specificityi

    Highest levels found in skeletal muscle. Also found in pancreas and heart.

    Gene expression databases

    ArrayExpressiP42773.
    BgeeiP42773.
    CleanExiHS_CDKN2C.
    GenevestigatoriP42773.

    Organism-specific databases

    HPAiCAB005303.
    CAB018398.
    HPA019057.
    HPA019764.

    Interactioni

    Subunit structurei

    Heterodimer of p18 with CDK6.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDK4P118023EBI-711290,EBI-295644
    CDK6Q005343EBI-711290,EBI-295663

    Protein-protein interaction databases

    BioGridi107465. 22 interactions.
    IntActiP42773. 16 interactions.
    MINTiMINT-1372629.
    STRINGi9606.ENSP00000262662.

    Structurei

    Secondary structure

    1
    168
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi6 – 1510
    Helixi18 – 247
    Turni36 – 383
    Helixi41 – 444
    Turni45 – 484
    Helixi50 – 589
    Helixi73 – 808
    Helixi83 – 919
    Beta strandi101 – 1033
    Helixi106 – 1127
    Helixi116 – 12510
    Beta strandi135 – 1373
    Helixi140 – 1467
    Helixi150 – 1589

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1BU9NMR-A1-168[»]
    1G3NX-ray2.90B/F1-168[»]
    1IHBX-ray1.95A/B1-162[»]
    1MX2X-ray2.25A/B1-168[»]
    1MX4X-ray2.00A/B1-168[»]
    1MX6X-ray2.00A/B1-168[»]
    ProteinModelPortaliP42773.
    SMRiP42773. Positions 5-160.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP42773.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati4 – 3330ANK 1Add
    BLAST
    Repeati37 – 6529ANK 2Add
    BLAST
    Repeati69 – 9830ANK 3Add
    BLAST
    Repeati102 – 13231ANK 4Add
    BLAST

    Sequence similaritiesi

    Contains 4 ANK repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    ANK repeat, Repeat

    Phylogenomic databases

    eggNOGiCOG0666.
    HOGENOMiHOG000290191.
    HOVERGENiHBG050870.
    InParanoidiP42773.
    KOiK06622.
    OMAiKDQTGFA.
    OrthoDBiEOG7ZSHVC.
    PhylomeDBiP42773.
    TreeFamiTF333311.

    Family and domain databases

    Gene3Di1.25.40.20. 2 hits.
    InterProiIPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view]
    PfamiPF00023. Ank. 3 hits.
    [Graphical view]
    SMARTiSM00248. ANK. 4 hits.
    [Graphical view]
    SUPFAMiSSF48403. SSF48403. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P42773-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEPWGNELA SAAARGDLEQ LTSLLQNNVN VNAQNGFGRT ALQVMKLGNP    50
    EIARRLLLRG ANPDLKDRTG FAVIHDAARA GFLDTLQTLL EFQADVNIED 100
    NEGNLPLHLA AKEGHLRVVE FLVKHTASNV GHRNHKGDTA CDLARLYGRN 150
    EVVSLMQANG AGGATNLQ 168
    Length:168
    Mass (Da):18,127
    Last modified:November 1, 1995 - v1
    Checksum:i5D66AFA715186E9A
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti72 – 721A → P in breast cancer; loss of CDK6 interaction. 2 Publications
    VAR_001490
    Natural varianti126 – 1261T → M.1 Publication
    Corresponds to variant rs17851380 [ dbSNP | Ensembl ].
    VAR_038604

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17074 mRNA. Translation: AAC50074.1.
    AF041248 mRNA. Translation: AAC39782.1.
    AF041250, AF041249 Genomic DNA. Translation: AAC39783.1.
    AY094608 Genomic DNA. Translation: AAM11873.1.
    BC000598 mRNA. Translation: AAH00598.1.
    BC005041 mRNA. Translation: AAH05041.1.
    BC016173 mRNA. Translation: AAH16173.1.
    CCDSiCCDS555.1.
    PIRiA55479.
    RefSeqiNP_001253.1. NM_001262.2.
    NP_523240.1. NM_078626.2.
    UniGeneiHs.525324.

    Genome annotation databases

    EnsembliENST00000262662; ENSP00000262662; ENSG00000123080.
    ENST00000371761; ENSP00000360826; ENSG00000123080.
    ENST00000396148; ENSP00000379452; ENSG00000123080.
    GeneIDi1031.
    KEGGihsa:1031.
    UCSCiuc001csf.3. human.

    Polymorphism databases

    DMDMi1168870.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U17074 mRNA. Translation: AAC50074.1 .
    AF041248 mRNA. Translation: AAC39782.1 .
    AF041250 , AF041249 Genomic DNA. Translation: AAC39783.1 .
    AY094608 Genomic DNA. Translation: AAM11873.1 .
    BC000598 mRNA. Translation: AAH00598.1 .
    BC005041 mRNA. Translation: AAH05041.1 .
    BC016173 mRNA. Translation: AAH16173.1 .
    CCDSi CCDS555.1.
    PIRi A55479.
    RefSeqi NP_001253.1. NM_001262.2.
    NP_523240.1. NM_078626.2.
    UniGenei Hs.525324.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1BU9 NMR - A 1-168 [» ]
    1G3N X-ray 2.90 B/F 1-168 [» ]
    1IHB X-ray 1.95 A/B 1-162 [» ]
    1MX2 X-ray 2.25 A/B 1-168 [» ]
    1MX4 X-ray 2.00 A/B 1-168 [» ]
    1MX6 X-ray 2.00 A/B 1-168 [» ]
    ProteinModelPortali P42773.
    SMRi P42773. Positions 5-160.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107465. 22 interactions.
    IntActi P42773. 16 interactions.
    MINTi MINT-1372629.
    STRINGi 9606.ENSP00000262662.

    PTM databases

    PhosphoSitei P42773.

    Polymorphism databases

    DMDMi 1168870.

    Proteomic databases

    MaxQBi P42773.
    PaxDbi P42773.
    PRIDEi P42773.

    Protocols and materials databases

    DNASUi 1031.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262662 ; ENSP00000262662 ; ENSG00000123080 .
    ENST00000371761 ; ENSP00000360826 ; ENSG00000123080 .
    ENST00000396148 ; ENSP00000379452 ; ENSG00000123080 .
    GeneIDi 1031.
    KEGGi hsa:1031.
    UCSCi uc001csf.3. human.

    Organism-specific databases

    CTDi 1031.
    GeneCardsi GC01P051427.
    HGNCi HGNC:1789. CDKN2C.
    HPAi CAB005303.
    CAB018398.
    HPA019057.
    HPA019764.
    MIMi 603369. gene.
    neXtProti NX_P42773.
    Orphaneti 652. Multiple endocrine neoplasia type 1.
    PharmGKBi PA26322.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0666.
    HOGENOMi HOG000290191.
    HOVERGENi HBG050870.
    InParanoidi P42773.
    KOi K06622.
    OMAi KDQTGFA.
    OrthoDBi EOG7ZSHVC.
    PhylomeDBi P42773.
    TreeFami TF333311.

    Enzyme and pathway databases

    Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_821. Cyclin D associated events in G1.

    Miscellaneous databases

    EvolutionaryTracei P42773.
    GeneWikii CDKN2C.
    GenomeRNAii 1031.
    NextBioi 4337.
    PROi P42773.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42773.
    Bgeei P42773.
    CleanExi HS_CDKN2C.
    Genevestigatori P42773.

    Family and domain databases

    Gene3Di 1.25.40.20. 2 hits.
    InterProi IPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    [Graphical view ]
    Pfami PF00023. Ank. 3 hits.
    [Graphical view ]
    SMARTi SM00248. ANK. 4 hits.
    [Graphical view ]
    SUPFAMi SSF48403. SSF48403. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function."
      Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L., Matera G.A., Xiong Y.
      Genes Dev. 8:2939-2952(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer."
      Blais A., Labrie Y., Pouliot F., Lachance Y., Labrie C.
      Biochem. Biophys. Res. Commun. 247:146-153(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT BREAST CANCER PRO-72.
      Tissue: Mammary gland.
    3. NIEHS SNPs program
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-126.
      Tissue: Brain, Kidney and Uterus.
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    6. "Crystal structure of the CDK4/6 inhibitory protein p18INK4c provides insights into ankyrin-like repeat structure/function and tumor-derived p16INK4 mutations."
      Venkataramani R., Swaminathan K., Marmorstein R.
      Nat. Struct. Biol. 5:74-81(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
    7. "Tumor suppressor INK4: determination of the solution structure of p18INK4C and demonstration of the functional significance of loops in p18INK4C and p16INK4A."
      Li J., Byeon I.-J.L., Ericson K., Poi M.-J., O'Maille P., Selby T., Tsai M.-D.
      Biochemistry 38:2930-2940(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    8. "A p18 mutant defective in CDK6 binding in human breast cancer cells."
      Lapointe J., Lachance Y., Labrie Y., Labrie C.
      Cancer Res. 56:4586-4589(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT BREAST CANCER PRO-72.

    Entry informationi

    Entry nameiCDN2C_HUMAN
    AccessioniPrimary (citable) accession number: P42773
    Secondary accession number(s): Q8TB83
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 142 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3