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P49918

- CDN1C_HUMAN

UniProt

P49918 - CDN1C_HUMAN

Protein

Cyclin-dependent kinase inhibitor 1C

Gene

CDKN1C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non-proliferative state throughout life.

    GO - Molecular functioni

    1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: ProtInc
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell cycle arrest Source: ProtInc
    2. mitotic G1 phase Source: ProtInc
    3. negative regulation of cell proliferation Source: ProtInc
    4. negative regulation of epithelial cell proliferation Source: BHF-UCL
    5. negative regulation of kinase activity Source: UniProtKB
    6. negative regulation of phosphorylation Source: UniProtKB
    7. negative regulation of protein serine/threonine kinase activity Source: GOC
    8. negative regulation of transcription, DNA-templated Source: UniProtKB
    9. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    10. neuron maturation Source: Ensembl
    11. placenta development Source: Ensembl
    12. positive regulation of transcription, DNA-templated Source: UniProtKB
    13. positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
    14. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc

    Keywords - Molecular functioni

    Protein kinase inhibitor

    Keywords - Biological processi

    Cell cycle

    Enzyme and pathway databases

    SignaLinkiP49918.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase inhibitor 1C
    Alternative name(s):
    Cyclin-dependent kinase inhibitor p57
    p57Kip2
    Gene namesi
    Name:CDKN1C
    Synonyms:KIP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1786. CDKN1C.

    Subcellular locationi

    Nucleus By similarity

    GO - Cellular componenti

    1. cytoplasm Source: BHF-UCL
    2. nucleus Source: BHF-UCL

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies (IMAGE) [MIM:614732]: A rare condition characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and commenced on steroid replacement therapy. Other reported features in this condition include, hypercalciuria and/or hypercalcemia, craniosynostosis, cleft palate, and scoliosis.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti274 – 2741D → N in IMAGE. 1 Publication
    VAR_068848
    Natural varianti276 – 2761F → S in IMAGE; PCNA binding is disrupted. 1 Publication
    VAR_068849
    Natural varianti276 – 2761F → V in IMAGE. 1 Publication
    VAR_068850
    Natural varianti278 – 2781K → E in IMAGE; PCNA binding is disrupted. 1 Publication
    VAR_068851
    Natural varianti279 – 2791R → P in IMAGE. 1 Publication
    VAR_068852
    Defects in CDKN1C are involved in tumor formation.

    Keywords - Diseasei

    Disease mutation, Tumor suppressor

    Organism-specific databases

    MIMi130650. phenotype.
    614732. phenotype.
    Orphaneti231120. Beckwith-Wiedemann syndrome due to CDKN1C mutation.
    85173. IMAGe syndrome.
    397590. Silver-Russell syndrome due to a point mutation.
    PharmGKBiPA26320.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 316316Cyclin-dependent kinase inhibitor 1CPRO_0000190087Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei268 – 2681Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP49918.
    PaxDbiP49918.
    PRIDEiP49918.

    PTM databases

    PhosphoSiteiP49918.

    Expressioni

    Tissue specificityi

    Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. Expressed in the eye. High levels are seen in the placenta while low levels are seen in the liver.1 Publication

    Developmental stagei

    Expressed within a subset of cells in the subcapsular or developing definitive zone of the adrenal gland.1 Publication

    Gene expression databases

    ArrayExpressiP49918.
    BgeeiP49918.
    CleanExiHS_CDKN1C.
    GenevestigatoriP49918.

    Organism-specific databases

    HPAiHPA002924.

    Interactioni

    Subunit structurei

    Interacts with PCNA.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FBXL12Q9NXK86EBI-519256,EBI-719790
    MCM7P339932EBI-519256,EBI-355924

    Protein-protein interaction databases

    BioGridi107462. 15 interactions.
    IntActiP49918. 7 interactions.
    MINTiMINT-128985.
    STRINGi9606.ENSP00000413720.

    Structurei

    3D structure databases

    DisProtiDP00017.
    ProteinModelPortaliP49918.
    SMRiP49918. Positions 26-91.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati156 – 15941
    Repeati160 – 16342
    Repeati180 – 18343
    Repeati184 – 18744
    Repeati188 – 19145
    Repeati198 – 20146
    Repeati202 – 20547
    Repeati206 – 20948
    Repeati210 – 21349

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni156 – 213589 X 4 AA repeats of P-A-P-AAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi278 – 2814Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Belongs to the CDI family.Curated

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG245842.
    HOGENOMiHOG000294081.
    HOVERGENiHBG107407.
    InParanoidiP49918.
    KOiK09993.
    OMAiEQGANQG.
    OrthoDBiEOG7GJ6HD.
    PhylomeDBiP49918.
    TreeFamiTF101111.

    Family and domain databases

    InterProiIPR003175. CDI.
    [Graphical view]
    PANTHERiPTHR10265. PTHR10265. 1 hit.
    PfamiPF02234. CDI. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: P49918-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSDASLRSTS TMERLVARGT FPVLVRTSAC RSLFGPVDHE ELSRELQARL    50
    AELNAEDQNR WDYDFQQDMP LRGPGRLQWT EVDSDSVPAF YRETVQVGRC 100
    RLLLAPRPVA VAVAVSPPLE PAAESLDGLE EAPEQLPSVP VPAPASTPPP 150
    VPVLAPAPAP APAPVAAPVA APVAVAVLAP APAPAPAPAP APAPVAAPAP 200
    APAPAPAPAP APAPAPDAAP QESAEQGANQ GQRGQEPLAD QLHSGISGRP 250
    AAGTAAASAN GAAIKKLSGP LISDFFAKRK RSAPEKSSGD VPAPCPSPSA 300
    APGVGSVEQT PRKRLR 316
    Length:316
    Mass (Da):32,177
    Last modified:October 1, 1996 - v1
    Checksum:iA94CCBF09F8CB3E4
    GO
    Isoform Short (identifier: P49918-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-11: Missing.

    Show »
    Length:305
    Mass (Da):31,040
    Checksum:iC4C82AF45384A1CC
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti171 – 1744Missing in several cancers.
    VAR_001404
    Natural varianti181 – 1844Missing in hepatocellular carcinomas.
    VAR_001405
    Natural varianti200 – 2034Missing in a bladder cancer.
    VAR_001406
    Natural varianti206 – 2094Missing in a breast cancer.
    VAR_001407
    Natural varianti274 – 2741D → N in IMAGE. 1 Publication
    VAR_068848
    Natural varianti276 – 2761F → S in IMAGE; PCNA binding is disrupted. 1 Publication
    VAR_068849
    Natural varianti276 – 2761F → V in IMAGE. 1 Publication
    VAR_068850
    Natural varianti278 – 2781K → E in IMAGE; PCNA binding is disrupted. 1 Publication
    VAR_068851
    Natural varianti279 – 2791R → P in IMAGE. 1 Publication
    VAR_068852

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1111Missing in isoform Short. CuratedVSP_000867Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U22398 mRNA. Translation: AAA85095.1.
    U48869 Genomic DNA. Translation: AAB05896.1.
    BC067842 mRNA. Translation: AAH67842.1.
    D64137 Genomic DNA. Translation: BAA11014.1.
    D64137 Genomic DNA. Translation: BAA11015.1.
    CCDSiCCDS44519.1. [P49918-2]
    CCDS7738.1. [P49918-1]
    PIRiG02424.
    RefSeqiNP_000067.1. NM_000076.2. [P49918-1]
    NP_001116102.1. NM_001122630.1. [P49918-2]
    NP_001116103.1. NM_001122631.1. [P49918-2]
    XP_005252788.1. XM_005252731.1. [P49918-1]
    UniGeneiHs.106070.

    Genome annotation databases

    EnsembliENST00000414822; ENSP00000413720; ENSG00000129757. [P49918-1]
    ENST00000430149; ENSP00000411552; ENSG00000129757. [P49918-1]
    ENST00000440480; ENSP00000411257; ENSG00000129757. [P49918-2]
    GeneIDi1028.
    KEGGihsa:1028.
    UCSCiuc001lwr.4. human. [P49918-1]

    Polymorphism databases

    DMDMi1705731.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U22398 mRNA. Translation: AAA85095.1 .
    U48869 Genomic DNA. Translation: AAB05896.1 .
    BC067842 mRNA. Translation: AAH67842.1 .
    D64137 Genomic DNA. Translation: BAA11014.1 .
    D64137 Genomic DNA. Translation: BAA11015.1 .
    CCDSi CCDS44519.1. [P49918-2 ]
    CCDS7738.1. [P49918-1 ]
    PIRi G02424.
    RefSeqi NP_000067.1. NM_000076.2. [P49918-1 ]
    NP_001116102.1. NM_001122630.1. [P49918-2 ]
    NP_001116103.1. NM_001122631.1. [P49918-2 ]
    XP_005252788.1. XM_005252731.1. [P49918-1 ]
    UniGenei Hs.106070.

    3D structure databases

    DisProti DP00017.
    ProteinModelPortali P49918.
    SMRi P49918. Positions 26-91.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107462. 15 interactions.
    IntActi P49918. 7 interactions.
    MINTi MINT-128985.
    STRINGi 9606.ENSP00000413720.

    PTM databases

    PhosphoSitei P49918.

    Polymorphism databases

    DMDMi 1705731.

    Proteomic databases

    MaxQBi P49918.
    PaxDbi P49918.
    PRIDEi P49918.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000414822 ; ENSP00000413720 ; ENSG00000129757 . [P49918-1 ]
    ENST00000430149 ; ENSP00000411552 ; ENSG00000129757 . [P49918-1 ]
    ENST00000440480 ; ENSP00000411257 ; ENSG00000129757 . [P49918-2 ]
    GeneIDi 1028.
    KEGGi hsa:1028.
    UCSCi uc001lwr.4. human. [P49918-1 ]

    Organism-specific databases

    CTDi 1028.
    GeneCardsi GC11M002904.
    GeneReviewsi CDKN1C.
    HGNCi HGNC:1786. CDKN1C.
    HPAi HPA002924.
    MIMi 130650. phenotype.
    600856. gene.
    614732. phenotype.
    neXtProti NX_P49918.
    Orphaneti 231120. Beckwith-Wiedemann syndrome due to CDKN1C mutation.
    85173. IMAGe syndrome.
    397590. Silver-Russell syndrome due to a point mutation.
    PharmGKBi PA26320.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG245842.
    HOGENOMi HOG000294081.
    HOVERGENi HBG107407.
    InParanoidi P49918.
    KOi K09993.
    OMAi EQGANQG.
    OrthoDBi EOG7GJ6HD.
    PhylomeDBi P49918.
    TreeFami TF101111.

    Enzyme and pathway databases

    SignaLinki P49918.

    Miscellaneous databases

    GeneWikii Cyclin-dependent_kinase_inhibitor_1C.
    GenomeRNAii 1028.
    NextBioi 4319.
    PROi P49918.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49918.
    Bgeei P49918.
    CleanExi HS_CDKN1C.
    Genevestigatori P49918.

    Family and domain databases

    InterProi IPR003175. CDI.
    [Graphical view ]
    PANTHERi PTHR10265. PTHR10265. 1 hit.
    Pfami PF02234. CDI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene."
      Matsuoka S., Edwards M.C., Bai C., Parker S., Zhang P., Baldini A., Harper J.W., Elledge S.J.
      Genes Dev. 9:650-662(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
      Tissue: Embryo.
    2. "Genomic organization of the human p57KIP2 gene and its analysis in the G401 Wilms' tumor assay."
      Reid L.H., Crider-Miller S.J., West A., Lee M.H., Massague J., Weissman B.E.
      Cancer Res. 56:1214-1218(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "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] (ISOFORM LONG).
      Tissue: Placenta.
    4. "Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis."
      Tokino T., Urano T., Furuhata T., Matsushima M., Miyatsu T., Sasaki S., Nakamura Y.
      Hum. Genet. 97:625-631(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-316, VARIANTS.
    5. "Analysis of germline CDKN1C (p57-KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation."
      Lam W.W.K., Hatada I., Ohishi S., Mukai T., Joyce J.A., Cole T.R.P., Donnai D., Reik W., Schofield P.N., Maher E.R.
      J. Med. Genet. 36:518-523(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN BWS.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH PCNA, VARIANTS IMAGE ASN-274; SER-276; VAL-276; GLU-278 AND PRO-279, CHARACTERIZATION OF VARIANTS IMAGE SER-276 AND GLU-278.

    Entry informationi

    Entry nameiCDN1C_HUMAN
    AccessioniPrimary (citable) accession number: P49918
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 131 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3