Cyclin-dependent kinase inhibitor 2A

<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

Caution

<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-dependent protein serine/threonine kinase inhibitor activity Source: MGI <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
  • "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]
  • Ref.1

    "Cloning and characterization of murine p16INK4a and p15INK4b genes."
    Quelle D.E., Ashmun R.A., Hannon G.J., Rehberger P.A., Trono D., Richter K.H., Walker C., Beach D., Sherr C.J., Serrano M.
    Oncogene 11:635-645(1995) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
• disordered domain specific binding Source: MGI
• MDM2/MDM4 family protein binding Source: MGI
• NF-kappaB binding Source: MGI
• p53 binding Source: MGI
• protein kinase binding Source: MGI
• protein N-terminus binding Source: MGI <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Structural polymorphism in the N-terminal oligomerization domain of NPM1."
    Mitrea D.M., Grace C.R., Buljan M., Yun M.K., Pytel N.J., Satumba J., Nourse A., Park C.G., Madan Babu M., White S.W., Kriwacki R.W.
    Proc Natl Acad Sci U S A 111:4466-4471(2014) [PubMed] [Europe PMC] [Abstract]
• SUMO transferase activity Source: MGI
• transcription factor binding Source: MGI
• ubiquitin ligase inhibitor activity Source: MGI

GO - Biological processⁱ

• activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
• aging Source: MGI <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
  • "The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis."
    Paramio J.M., Segrelles C., Ruiz S., Martin-Caballero J., Page A., Martinez J., Serrano M., Jorcano J.L.
    J Biol Chem 276:44203-44211(2001) [PubMed] [Europe PMC] [Abstract]
• amyloid fibril formation Source: MGI
• apoptotic mitochondrial changes Source: MGI
• autophagy of mitochondrion Source: MGI
• cell aging Source: MGIInferred from direct assayⁱ
  • "TBX-3, the gene mutated in Ulnar-Mammary Syndrome, is a negative regulator of p19ARF and inhibits senescence."
    Brummelkamp T.R., Kortlever R.M., Lingbeek M., Trettel F., MacDonald M.E., van Lohuizen M., Bernards R.
    J Biol Chem 277:6567-6572(2002) [PubMed] [Europe PMC] [Abstract]
• cell cycle arrest Source: MGIInferred from direct assayⁱ
  • Ref.1

    "Cloning and characterization of murine p16INK4a and p15INK4b genes."
    Quelle D.E., Ashmun R.A., Hannon G.J., Rehberger P.A., Trono D., Richter K.H., Walker C., Beach D., Sherr C.J., Serrano M.
    Oncogene 11:635-645(1995) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
• cellular response to hydrogen peroxide Source: MGIInferred from direct assayⁱ
  • "A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1."
    Negishi M., Saraya A., Mochizuki S., Helin K., Koseki H., Iwama A.
    PLoS One 5:e12373-e12373(2010) [PubMed] [Europe PMC] [Abstract]
• cellular senescence Source: MGIInferred from direct assayⁱ
  • "c-Abl promotes osteoblast expansion by differentially regulating canonical and non-canonical BMP pathways and p16INK4a expression."
    Kua H.Y., Liu H., Leong W.F., Li L., Jia D., Ma G., Hu Y., Wang X., Chau J.F., Chen Y.G., Mishina Y., Boast S., Yeh J., Xia L., Chen G.Q., He L., Goff S.P., Li B.
    Nat Cell Biol 14:727-737(2012) [PubMed] [Europe PMC] [Abstract]
• epidermis development Source: MGIInferred from mutant phenotypeⁱ
  • "The ink4a/arf tumor suppressors cooperate with p21cip1/waf in the processes of mouse epidermal differentiation, senescence, and carcinogenesis."
    Paramio J.M., Segrelles C., Ruiz S., Martin-Caballero J., Page A., Martinez J., Serrano M., Jorcano J.L.
    J Biol Chem 276:44203-44211(2001) [PubMed] [Europe PMC] [Abstract]
• G1/S transition of mitotic cell cycle Source: MGI
• glucose homeostasis Source: MGIInferred from mutant phenotypeⁱ
  • "Effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice."
    Kim J.B., Deluna A., Mungrue I.N., Vu C., Pouldar D., Civelek M., Orozco L., Wu J., Wang X., Charugundla S., Castellani L.W., Rusek M., Jakubowski H., Jakobowski H., Lusis A.J.
    Circulation 126:1896-1906(2012) [PubMed] [Europe PMC] [Abstract]
• mitochondrial depolarization Source: MGI
• negative regulation of cell cycle Source: MGIInferred from direct assayⁱ
  • "ARF impedes NPM/B23 shuttling in an Mdm2-sensitive tumor suppressor pathway."
    Brady S.N., Yu Y., Maggi L.B. Jr., Weber J.D.
    Mol Cell Biol 24:9327-9338(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell growth Source: MGI
• negative regulation of cell-matrix adhesion Source: MGI
• negative regulation of cell population proliferation 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 hepatocyte proliferation Source: MGI
• negative regulation of mammary gland epithelial cell proliferation Source: MGIInferred from mutant phenotypeⁱ
  • "p19ARF determines the balance between normal cell proliferation rate and apoptosis during mammary gland development."
    Yi Y., Shepard A., Kittrell F., Mulac-Jericevic B., Medina D., Said T.K.
    Mol. Biol. Cell 15:2302-2311(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of NF-kappaB transcription factor activity Source: MGI
• negative regulation of phosphorylation Source: MGI
• negative regulation of protein binding Source: MGIInferred from direct assayⁱ
  • "Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity."
    Zhang Q., Spears E., Boone D.N., Li Z., Gregory M.A., Hann S.R.
    Proc Natl Acad Sci U S A 110:978-983(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of protein kinase activity Source: MGI
• negative regulation of protein neddylation Source: MGI
• negative regulation of proteolysis involved in cellular protein catabolic process Source: MGIInferred from direct assayⁱ
  • "Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity."
    Zhang Q., Spears E., Boone D.N., Li Z., Gregory M.A., Hann S.R.
    Proc Natl Acad Sci U S A 110:978-983(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: MGI
• negative regulation of ubiquitin-dependent protein catabolic process Source: MGIInferred from direct assayⁱ
  • "Domain-specific c-Myc ubiquitylation controls c-Myc transcriptional and apoptotic activity."
    Zhang Q., Spears E., Boone D.N., Li Z., Gregory M.A., Hann S.R.
    Proc Natl Acad Sci U S A 110:978-983(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of ubiquitin protein ligase activity Source: MGI
• positive regulation of apoptotic process Source: MGI
• positive regulation of apoptotic process involved in mammary gland involution Source: MGIInferred from mutant phenotypeⁱ
  • "p19ARF determines the balance between normal cell proliferation rate and apoptosis during mammary gland development."
    Yi Y., Shepard A., Kittrell F., Mulac-Jericevic B., Medina D., Said T.K.
    Mol. Biol. Cell 15:2302-2311(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell cycle arrest Source: MGI
• positive regulation of cellular senescence Source: MGI
• positive regulation of DNA damage response, signal transduction by p53 class mediator Source: MGI
• positive regulation of gene expression Source: MGI
• positive regulation of macrophage apoptotic process Source: BHF-UCL <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
  • "p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis."
    Gonzalez-Navarro H., Abu Nabah Y.N., Vinue A., Andres-Manzano M.J., Collado M., Serrano M., Andres V.
    J Am Coll Cardiol 55:2258-2268(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein localization to nucleus Source: MGI
• positive regulation of protein sumoylation Source: MGI
• positive regulation of signal transduction by p53 class mediator Source: MGI
• positive regulation of smooth muscle cell apoptotic process Source: BHF-UCLInferred from genetic interactionⁱ
  • "p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis."
    Gonzalez-Navarro H., Abu Nabah Y.N., Vinue A., Andres-Manzano M.J., Collado M., Serrano M., Andres V.
    J Am Coll Cardiol 55:2258-2268(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: MGI
• positive regulation of transcription by RNA polymerase II Source: MGI
• protein destabilization Source: MGI
• protein K63-linked ubiquitination Source: MGI
• protein polyubiquitination Source: MGI
• protein stabilization Source: MGI
• regulation of apoptotic DNA fragmentation Source: MGI
• regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGIInferred from direct assayⁱ
  • Ref.1

    "Cloning and characterization of murine p16INK4a and p15INK4b genes."
    Quelle D.E., Ashmun R.A., Hannon G.J., Rehberger P.A., Trono D., Richter K.H., Walker C., Beach D., Sherr C.J., Serrano M.
    Oncogene 11:635-645(1995) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
• regulation of DNA-binding transcription factor activity Source: MGIInferred from genetic interactionⁱ
  • "CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53."
    Hasan M.K., Yaguchi T., Sugihara T., Kumar P.K.R., Taira K., Reddel R.R., Kaul S.C., Wadhwa R.
    J. Biol. Chem. 277:37765-37770(2002) [PubMed] [Europe PMC] [Abstract]
• regulation of G2/M transition of mitotic cell cycle Source: MGI
• regulation of gene expression Source: MGIInferred from mutant phenotypeⁱ
  • "Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis."
    Eischen C.M., Woo D., Roussel M.F., Cleveland J.L.
    Mol Cell Biol 21:5063-5070(2001) [PubMed] [Europe PMC] [Abstract]
• regulation of nucleocytoplasmic transport Source: MGIInferred from genetic interactionⁱ
  • "ARF impedes NPM/B23 shuttling in an Mdm2-sensitive tumor suppressor pathway."
    Brady S.N., Yu Y., Maggi L.B. Jr., Weber J.D.
    Mol Cell Biol 24:9327-9338(2004) [PubMed] [Europe PMC] [Abstract]
• regulation of protein export from nucleus Source: MGI
• regulation of protein targeting to mitochondrion Source: MGI
• replicative senescence Source: MGI
• response to drug Source: MGI
• response to organic cyclic compound Source: MGI
• response to organonitrogen compound Source: MGI
• rRNA transcription Source: MGIInferred from genetic interactionⁱ
  • "Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome."
    Maggi L.B. Jr., Kuchenruether M., Dadey D.Y., Schwope R.M., Grisendi S., Townsend R.R., Pandolfi P.P., Weber J.D.
    Mol. Cell. Biol. 28:7050-7065(2008) [PubMed] [Europe PMC] [Abstract]
• senescence-associated heterochromatin focus assembly Source: MGI
• somatic stem cell population maintenance Source: MGIInferred from genetic interactionⁱ
  • "Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression."
    Nishino J., Kim I., Chada K., Morrison S.J.
    Cell 135:227-239(2008) [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

<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

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Mutagenesis

Keywords - Diseaseⁱ

<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

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

GO - Molecular functionⁱ

• disordered domain specific binding Source: MGI
• MDM2/MDM4 family protein binding Source: MGI
• NF-kappaB binding Source: MGI
• p53 binding Source: MGI
• protein kinase binding Source: MGI
• protein N-terminus binding Source: MGIInferred from physical interactionⁱ
  • "Structural polymorphism in the N-terminal oligomerization domain of NPM1."
    Mitrea D.M., Grace C.R., Buljan M., Yun M.K., Pytel N.J., Satumba J., Nourse A., Park C.G., Madan Babu M., White S.W., Kriwacki R.W.
    Proc Natl Acad Sci U S A 111:4466-4471(2014) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: MGI

Protein-protein interaction 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

Domains and Repeats

<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

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>Sequences (4)ⁱ

<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.

        10         20         30         40         50
MESAADRLAR AAAQGRVHDV RALLEAGVSP NAPNSFGRTP IQVMMMGNVH 
        60         70         80         90        100
VAALLLNYGA DSNCEDPTTF SRPVHDAARE GFLDTLVVLH GSGARLDVRD 
       110        120        130        140        150
AWGRLPLDLA QERGHQDIVR YLRSAGCSLC SAGWSLCTAG NVAQTDGHSF 
       160 
SSSTPRALEL RGQSQEQS                                    

        10         20         30         40         50
MMMGNVHVAA LLLNYGADSN CEDPTTFSRP VHDAAREGFL DTLVVLHGSG 
        60         70         80         90        100
ARLDVRDAWG RLPLDLAQER GHQDIVRYLR SAGCSLCSAG WSLCTAGNVA 
       110        120 
QTDGHSFSSS TPRALELRGQ SQEQS                            

Experimental Info

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismⁱ

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<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

Genome annotation databases

Organism-specific databases

Phylogenomic 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. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references
3. SIMILARITY comments
   Index of protein domains and families