Cyclin-dependent kinase inhibitor 1

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• cyclin binding Source: BHF-UCL <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes."
    Tane S., Ikenishi A., Okayama H., Iwamoto N., Nakayama K.I., Takeuchi T.
    Biochem Biophys Res Commun 443:1105-1109(2014) [PubMed] [Europe PMC] [Abstract]
• cyclin-dependent protein kinase activating kinase activity Source: MGI
• cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGIInferred from direct assayⁱ
  • "Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation."
    Lazaro J.B., Bailey P.J., Lassar A.B.
    Genes Dev 16:1792-1805(2002) [PubMed] [Europe PMC] [Abstract]
• metal ion binding Source: UniProtKB-KW
• protein-containing complex binding Source: MGI
• protein kinase binding Source: MGI
• protein kinase inhibitor activity Source: MGI
• protein sequestering activity Source: MGI
• ubiquitin protein ligase binding Source: MGI

GO - Biological processⁱ

• animal organ regeneration Source: Ensembl
• cell cycle arrest Source: MGIInferred from direct assayⁱ
  • "Inactivation of CtIP leads to early embryonic lethality mediated by G1 restraint and to tumorigenesis by haploid insufficiency."
    Chen P.L., Liu F., Cai S., Lin X., Li A., Chen Y., Gu B., Lee E.Y., Lee W.H.
    Mol Cell Biol 25:3535-3542(2005) [PubMed] [Europe PMC] [Abstract]
• cellular response to amino acid starvation Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress."
    Lehman S.L., Cerniglia G.J., Johannes G.J., Ye J., Ryeom S., Koumenis C.
    PLoS Genet. 11:E1005212-E1005212(2015) [PubMed] [Europe PMC] [Abstract]
• cellular response to DNA damage stimulus Source: MGIInferred from mutant phenotypeⁱ
  • "Integral role of Noxa in p53-mediated apoptotic response."
    Shibue T., Takeda K., Oda E., Tanaka H., Murasawa H., Takaoka A., Morishita Y., Akira S., Taniguchi T., Tanaka N.
    Genes Dev 17:2233-2238(2003) [PubMed] [Europe PMC] [Abstract]
• cellular response to extracellular stimulus Source: MGI
• cellular response to gamma radiation Source: MGIInferred from direct assayⁱ
  • "DNA damage-induced activation of p53 by the checkpoint kinase Chk2."
    Hirao A., Kong Y.Y., Matsuoka S., Wakeham A., Ruland J., Yoshida H., Liu D., Elledge S.J., Mak T.W.
    Science 287:1824-1827(2000) [PubMed] [Europe PMC] [Abstract]
• cellular response to heat Source: Ensembl
• cellular response to ionizing radiation Source: MGI
• cellular response to UV-B Source: UniProtKBInferred from direct assayⁱ
  • Ref.6

    "A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor mediating CDKN1A (p21WAF1/CIP1) degradation."
    Esteve-Puig R., Gil R., Gonzalez-Sanchez E., Bech-Serra J.J., Grueso J., Hernandez-Losa J., Moline T., Canals F., Ferrer B., Cortes J., Bastian B., Cajal S.R.Y., Martin-Caballero J., Flores J.M., Vivancos A., Garcia-Patos V., Recio J.A.
    PLoS Genet. 10:E1004721-E1004721(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH STK11, PHOSPHORYLATION AT SER-78 AND SER-141.
• cellular senescence Source: MGI
• DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: MGI
• DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: MGIInferred from direct assayⁱ
  • "DNA damage-induced activation of p53 by the checkpoint kinase Chk2."
    Hirao A., Kong Y.Y., Matsuoka S., Wakeham A., Ruland J., Yoshida H., Liu D., Elledge S.J., Mak T.W.
    Science 287:1824-1827(2000) [PubMed] [Europe PMC] [Abstract]
• G1/S transition of mitotic cell cycle Source: MGI
• G2/M transition of mitotic cell cycle Source: MGI
• heart development Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes."
    Tane S., Ikenishi A., Okayama H., Iwamoto N., Nakayama K.I., Takeuchi T.
    Biochem Biophys Res Commun 443:1105-1109(2014) [PubMed] [Europe PMC] [Abstract]
• intestinal epithelial cell maturation Source: Ensembl
• intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGIInferred from mutant phenotypeⁱ
  • "Integral role of Noxa in p53-mediated apoptotic response."
    Shibue T., Takeda K., Oda E., Tanaka H., Murasawa H., Takaoka A., Morishita Y., Akira S., Taniguchi T., Tanaka N.
    Genes Dev 17:2233-2238(2003) [PubMed] [Europe PMC] [Abstract]
• mitotic cell cycle arrest Source: MGIInferred from direct assayⁱ
  • "noxin, a novel stress-induced gene involved in cell cycle and apoptosis."
    Nakaya N., Hemish J., Krasnov P., Kim S.Y., Stasiv Y., Michurina T., Herman D., Davidoff M.S., Middendorff R., Enikolopov G.
    Mol. Cell. Biol. 27:5430-5444(2007) [PubMed] [Europe PMC] [Abstract]
• mitotic G2 DNA damage checkpoint Source: UniProtKB
• negative regulation of apoptotic process Source: MGI
• negative regulation of cardiac muscle tissue regeneration Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes."
    Tane S., Ikenishi A., Okayama H., Iwamoto N., Nakayama K.I., Takeuchi T.
    Biochem Biophys Res Commun 443:1105-1109(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell growth Source: MGI
• negative regulation of cell population proliferation Source: MGIInferred from mutant phenotypeⁱ
  • "The Cdk inhibitor p21 is required for necrosis, but it inhibits apoptosis following toxin-induced liver injury."
    Kwon Y.H., Jovanovic A., Serfas M.S., Tyner A.L.
    J Biol Chem 278:30348-30355(2003) [PubMed] [Europe PMC] [Abstract]
  • "Absence of p21 partially rescues Mdm4 loss and uncovers an antiproliferative effect of Mdm4 on cell growth."
    Steinman H.A., Sluss H.K., Sands A.T., Pihan G., Jones S.N.
    Oncogene 23:303-306(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cyclin-dependent protein kinase activity Source: MGI
• negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGIInferred from direct assayⁱ
  • "Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation."
    Lazaro J.B., Bailey P.J., Lassar A.B.
    Genes Dev 16:1792-1805(2002) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA biosynthetic process Source: MGI
• negative regulation of G1/S transition of mitotic cell cycle Source: MGI
• negative regulation of gene expression Source: MGIInferred from mutant phenotypeⁱ
  • "The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers."
    Jaime M., Pujol M.J., Serratosa J., Pantoja C., Canela N., Casanovas O., Serrano M., Agell N., Bachs O.
    Hepatology 35:1063-1071(2002) [PubMed] [Europe PMC] [Abstract]
• negative regulation of phosphorylation Source: MGI
• negative regulation of protein binding Source: MGI
• negative regulation of vascular associated smooth muscle cell proliferation Source: MGI
• positive regulation of B cell proliferation Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity."
    Woo M., Hakem R., Furlonger C., Hakem A., Duncan G.S., Sasaki T., Bouchard D., Lu L., Wu G.E., Paige C.J., Mak T.W.
    Nat Immunol 4:1016-1022(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell death Source: MGI
• positive regulation of fibroblast proliferation Source: MGI
• positive regulation of programmed cell death Source: MGIInferred from mutant phenotypeⁱ
  • "The Cdk inhibitor p21 is required for necrosis, but it inhibits apoptosis following toxin-induced liver injury."
    Kwon Y.H., Jovanovic A., Serfas M.S., Tyner A.L.
    J Biol Chem 278:30348-30355(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein kinase activity Source: MGIInferred from sequence orthologyⁱ
  • "Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities."
    Porter D.C., Farmaki E., Altilia S., Schools G.P., West D.K., Chen M., Chang B.D., Puzyrev A.T., Lim C.U., Rokow-Kittell R., Friedhoff L.T., Papavassiliou A.G., Kalurupalle S., Hurteau G., Shi J., Baran P.S., Gyorffy B., Wentland M.P.

    , Broude E.V., Kiaris H., Roninson I.B.
    Proc Natl Acad Sci U S A 109:13799-13804(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of reactive oxygen species metabolic process Source: MGI
• protein import into nucleus Source: MGIInferred from mutant phenotypeⁱ
  • "The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers."
    Jaime M., Pujol M.J., Serratosa J., Pantoja C., Canela N., Casanovas O., Serrano M., Agell N., Bachs O.
    Hepatology 35:1063-1071(2002) [PubMed] [Europe PMC] [Abstract]
• Ras protein signal transduction Source: Ensembl
• regulation of cell cycle Source: MGIInferred from direct assayⁱ
  • "Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase."
    Diehl J.A., Yang W., Rimerman R.A., Xiao H., Emili A.
    Mol Cell Biol 23:1764-1774(2003) [PubMed] [Europe PMC] [Abstract]
• regulation of cell cycle G1/S phase transition Source: UniProtKB
• regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGIInferred from mutant phenotypeⁱ
  • "The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers."
    Jaime M., Pujol M.J., Serratosa J., Pantoja C., Canela N., Casanovas O., Serrano M., Agell N., Bachs O.
    Hepatology 35:1063-1071(2002) [PubMed] [Europe PMC] [Abstract]
• regulation of DNA biosynthetic process Source: MGIInferred from mutant phenotypeⁱ
  • "The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers."
    Jaime M., Pujol M.J., Serratosa J., Pantoja C., Canela N., Casanovas O., Serrano M., Agell N., Bachs O.
    Hepatology 35:1063-1071(2002) [PubMed] [Europe PMC] [Abstract]
• regulation of mitotic cell cycle Source: MGIInferred from mutant phenotypeⁱ
  • "The p21(Cip1) protein, a cyclin inhibitor, regulates the levels and the intracellular localization of CDC25A in mice regenerating livers."
    Jaime M., Pujol M.J., Serratosa J., Pantoja C., Canela N., Casanovas O., Serrano M., Agell N., Bachs O.
    Hepatology 35:1063-1071(2002) [PubMed] [Europe PMC] [Abstract]
• response to arsenic-containing substance Source: Ensembl
• response to corticosterone Source: Ensembl
• response to drug Source: Ensembl
• response to hyperoxia Source: Ensembl
• response to organonitrogen compound Source: Ensembl
• response to toxic substance Source: Ensembl
• response to UV Source: MGIInferred from mutant phenotypeⁱ
  • "Integral role of Noxa in p53-mediated apoptotic response."
    Shibue T., Takeda K., Oda E., Tanaka H., Murasawa H., Takaoka A., Morishita Y., Akira S., Taniguchi T., Tanaka N.
    Genes Dev 17:2233-2238(2003) [PubMed] [Europe PMC] [Abstract]
• response to X-ray Source: Ensembl
• tissue regeneration Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Lack of p21 expression links cell cycle control and appendage regeneration in mice."
    Bedelbaeva K., Snyder A., Gourevitch D., Clark L., Zhang X.M., Leferovich J., Cheverud J.M., Lieberman P., Heber-Katz E.
    Proc Natl Acad Sci U S A 107:5845-5850(2010) [PubMed] [Europe PMC] [Abstract]
• wound healing Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Lack of p21 expression links cell cycle control and appendage regeneration in mice."
    Bedelbaeva K., Snyder A., Gourevitch D., Clark L., Zhang X.M., Leferovich J., Cheverud J.M., Lieberman P., Heber-Katz E.
    Proc Natl Acad Sci U S A 107:5845-5850(2010) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

• UniProt annotation
• GO - Cellular component

Keywords - Cellular componentⁱ

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• cyclin binding Source: BHF-UCLInferred from direct assayⁱ
  • "CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell cycle exit of mammalian cardiomyocytes."
    Tane S., Ikenishi A., Okayama H., Iwamoto N., Nakayama K.I., Takeuchi T.
    Biochem Biophys Res Commun 443:1105-1109(2014) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: MGI
• ubiquitin protein ligase binding Source: MGI

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Region

Motif

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Zinc finger

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

        10         20         30         40         50
MSNPGDVRPV PHRSKVCRCL FGPVDSEQLR RDCDALMAGC LQEARERWNF 
        60         70         80         90        100
DFVTETPLEG NFVWERVRSL GLPKVYLSPG SRSRDDLGGD KRPSTSSALL 
       110        120        130        140        150
QGPAPEDHVA LSLSCTLVSE RPEDSPGGPG TSQGRKRRQT SLTDFYHSKR 

RLVFCKRKP                                              

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. MGD cross-references
   Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
2. SIMILARITY comments
   Index of protein domains and families