HUMAN:CD2A1

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Species (Taxon ID)	Homo sapiens (Human). (taxon:9606)
Gene Name(s)	CDKN2A ( synonyms: CDKN2, MTS1 )
Protein Name(s)	Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 Cyclin-dependent kinase 4 inhibitor A CDK4I Multiple tumor suppressor 1 MTS-1 p16-INK4a p16-INK4 p16INK4A
External Links
UniProt Identifier	CD2A1_HUMAN
UniProt Accessions	P42771, D3DRK1, O95440, Q15191, Q5VVJ5, Q96B52, Q9NP05,
EMBL	L27211, AB060808, AF527803, AF115544, AL449423, CH471071, CH471071, X94154, S69824, S69822, S69804, U12820, U12818, U12819,
PIR	JE0141,
RefSeq	NP_000068.1, NP_478104.2,
PDB	1A5E, 1BI7, 1DC2, 2A5E,
IntAct	P42771,
Ensembl	ENST00000304494,

Annotations

Qualifier	GO ID	GO term name	Reference	Evidence Code	with/from	Aspect	Notes
	GO:0005737	cytoplasm		IDA: Inferred from Direct Assay		C	Source: HGNC
	GO:0005634	nucleus		IDA: Inferred from Direct Assay		C	Source: HGNC
	GO:0004861	cyclin-dependent protein kinase inhibitor a...		IDA: Inferred from Direct Assay		F	Source: BHF-UCL
	GO:0051059	NF-kappaB binding		IDA: Inferred from Direct Assay		F	Source: BHF-UCL
	GO:0005515	protein binding		IPI: Inferred from Physical Interaction		F	Source: BHF-UCL
	GO:0005515	protein binding		IPI: Inferred from Physical Interaction		F	Source: UniProtKB
	GO:0019901	protein kinase binding		IPI: Inferred from Physical Interaction		F	Source: BHF-UCL
	GO:0007050	cell cycle arrest		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0000075	cell cycle checkpoint		IMP: Inferred from Mutant Phenotype		P	Source: HGNC
	GO:0000082	G1/S transition of mitotic cell cycle		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0006917	induction of apoptosis		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0030308	negative regulation of cell growth		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0008285	negative regulation of cell proliferation		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0001953	negative regulation of cell-matrix adhesion		IMP: Inferred from Mutant Phenotype		P	Source: BHF-UCL
	GO:0045736	negative regulation of cyclin-dependent pro...		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0032088	negative regulation of NF-kappaB transcript...		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0033034	positive regulation of myeloid cell apoptosis		ISS: Inferred from Sequence or Structural Similarity		P	Source: BHF-UCL
	GO:0034393	positive regulation of smooth muscle cell a...		ISS: Inferred from Sequence or Structural Similarity		P	Source: BHF-UCL
	GO:0007265	Ras protein signal transduction		IEP: Inferred from Expression Pattern		P	Source: BHF-UCL
	GO:0010149	senescence		IDA: Inferred from Direct Assay		P	Source: BHF-UCL
	GO:0000075	cell cycle checkpoint	PMID:16243918^[1]	IMP: Inferred from Mutant Phenotype		P
	GO:0000080	G1 phase of mitotic cell cycle	Reactome:REACT_1590	TAS: Traceable Author Statement		P
	GO:0000082	G1/S transition of mitotic cell cycle	PMID:10208428^[2]	IDA: Inferred from Direct Assay		P
	GO:0000278	mitotic cell cycle	Reactome:REACT_152	TAS: Traceable Author Statement		P
	GO:0001953	negative regulation of cell-matrix adhesion	PMID:10205165^[3]	IMP: Inferred from Mutant Phenotype		P
	GO:0004861	cyclin-dependent protein kinase inhibitor activity	PMID:8259215^[4]	IDA: Inferred from Direct Assay		F
	GO:0005515	protein binding	PMID:11278317^[5]	IPI: Inferred from Physical Interaction	UniProtKB:Q96SB3	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:O00311	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:O43913	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:O43929	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:O75419	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:O75496	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:P33992	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:P49736	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:Q7L590	F
	GO:0005515	protein binding	PMID:15232106^[6]	IPI: Inferred from Physical Interaction	UniProtKB:Q99741	F
	GO:0005515	protein binding	PMID:17110379^[7]	IPI: Inferred from Physical Interaction	UniProtKB:Q3YBR2	F
	GO:0005515	protein binding	PMID:17353931^[8]	IPI: Inferred from Physical Interaction	UniProtKB:O14965	F
	GO:0005515	protein binding	PMID:17353931^[8]	IPI: Inferred from Physical Interaction	UniProtKB:P11802	F
	GO:0005515	protein binding	PMID:17658461^[9]	IPI: Inferred from Physical Interaction	UniProtKB:Q96AB3	F
	GO:0005515	protein binding	PMID:17909018^[10]	IPI: Inferred from Physical Interaction	UniProtKB:Q00534	F
	GO:0005515	protein binding	PMID:17955473^[11]	IPI: Inferred from Physical Interaction	UniProtKB:P12004	F
	GO:0005515	protein binding	PMID:17955473^[11]	IPI: Inferred from Physical Interaction	UniProtKB:Q14566	F
	GO:0005515	protein binding	PMID:19149898^[12]	IPI: Inferred from Physical Interaction	UniProtKB:P51532	F
	GO:0005515	protein binding	PMID:9529249^[13]	IPI: Inferred from Physical Interaction	UniProtKB:P11802	F
	GO:0005634	nucleus	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0539	C
	GO:0005634	nucleus	GO_REF:0000023	IEA: Inferred from Electronic Annotation	SP_SL:SL-0191	C
	GO:0005634	nucleus	PMID:16243918^[1]	IDA: Inferred from Direct Assay		C
	GO:0005737	cytoplasm	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0963	C
	GO:0005737	cytoplasm	GO_REF:0000023	IEA: Inferred from Electronic Annotation	SP_SL:SL-0086	C
	GO:0005737	cytoplasm	PMID:16243918^[1]	IDA: Inferred from Direct Assay		C
	GO:0005829	cytosol	Reactome:REACT_7947	TAS: Traceable Author Statement		C
	GO:0006917	induction of apoptosis	PMID:10208428^[2]	IDA: Inferred from Direct Assay		P
	GO:0007049	cell cycle	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0131	P
	GO:0007050	cell cycle arrest	PMID:15149599^[14]	IDA: Inferred from Direct Assay		P
	GO:0007050	cell cycle arrest	PMID:16243918^[1]	IMP: Inferred from Mutant Phenotype		P
	GO:0007265	Ras protein signal transduction	PMID:9054499^[15]	IEP: Inferred from Expression Pattern		P
	GO:0008285	negative regulation of cell proliferation	PMID:15149599^[14]	IDA: Inferred from Direct Assay		P
	GO:0008285	negative regulation of cell proliferation	PMID:16243918^[1]	IMP: Inferred from Mutant Phenotype		P
	GO:0008285	negative regulation of cell proliferation	PMID:7603984^[16]	IMP: Inferred from Mutant Phenotype		P
	GO:0019901	protein kinase binding	PMID:8259215^[4]	IPI: Inferred from Physical Interaction	UniProtKB:P11802	F
	GO:0030308	negative regulation of cell growth	PMID:10208428^[2]	IDA: Inferred from Direct Assay		P
	GO:0032088	negative regulation of NF-kappaB transcription factor activity	PMID:10353611^[17]	IDA: Inferred from Direct Assay		P
	GO:0034393	positive regulation of smooth muscle cell apoptosis	PMID:20381282^[18]	ISS: Inferred from Sequence or Structural Similarity	UniProtKB:P51480	P
	GO:0042326	negative regulation of phosphorylation	PMID:10208428^[2]	IDA: Inferred from Direct Assay		P
	GO:0042326	negative regulation of phosphorylation	PMID:8259215^[4]	IDA: Inferred from Direct Assay		P
	GO:0045736	negative regulation of cyclin-dependent protein kinase activity	PMID:8259215^[4]	IDA: Inferred from Direct Assay		P
	GO:0051059	NF-kappaB binding	PMID:10353611^[17]	IDA: Inferred from Direct Assay		F
	GO:0090399	replicative senescence	PMID:14720514^[19]	IMP: Inferred from Mutant Phenotype		P
	GO:2000111	positive regulation of macrophage apoptosis	PMID:20381282^[18]	ISS: Inferred from Sequence or Structural Similarity	UniProtKB:P51480	P
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 Chen J et al. (2006) Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 290: H1575-86 PubMed GONUTS page
↑ ^2.0 ^2.1 ^2.2 ^2.3 Schreiber M et al. (1999) Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. Oncogene 18: 1663-76 PubMed GONUTS page
↑ Fåhraeus R & Lane DP (1999) The p16(INK4a) tumour suppressor protein inhibits alphavbeta3 integrin-mediated cell spreading on vitronectin by blocking PKC-dependent localization of alphavbeta3 to focal contacts. EMBO J 18: 2106-18 PubMed GONUTS page
↑ ^4.0 ^4.1 ^4.2 ^4.3 Serrano M et al. (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366: 704-7 PubMed GONUTS page
↑ Vivo M et al. (2001) The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein. J Biol Chem 276: 14161-9 PubMed GONUTS page
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 Ramachandran N et al. (2004) Self-assembling protein microarrays. Science 305: 86-90 PubMed GONUTS page
↑ Tompkins VS et al. (2007) A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability. J Biol Chem 282: 1322-33 PubMed GONUTS page
↑ ^8.0 ^8.1 Ewing RM et al. (2007) Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol 3: 89 PubMed GONUTS page
↑ Huang X et al. (2007) Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a. Biochem Biophys Res Commun 361: 287-93 PubMed GONUTS page
↑ Jones R et al. (2007) A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res 67: 9134-41 PubMed GONUTS page
↑ ^11.0 ^11.1 Souza-Rodrígues E et al. (2007) Proteomic analysis of p16ink4a-binding proteins. Proteomics 7: 4102-11 PubMed GONUTS page
↑ Becker TM et al. (2009) The chromatin remodelling factor BRG1 is a novel binding partner of the tumor suppressor p16INK4a. Mol Cancer 8: 4 PubMed GONUTS page
↑ Zhang Y et al. (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725-34 PubMed GONUTS page
↑ ^14.0 ^14.1 Herbig U et al. (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14: 501-13 PubMed GONUTS page
↑ Serrano M et al. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593-602 PubMed GONUTS page
↑ Medema RH et al. (1995) Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A 92: 6289-93 PubMed GONUTS page
↑ ^17.0 ^17.1 Wolff B & Naumann M (1999) INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 18: 2663-6 PubMed GONUTS page
↑ ^18.0 ^18.1 González-Navarro H et al. (2010) p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol 55: 2258-68 PubMed GONUTS page
↑ Bond J et al. (2004) Direct evidence from siRNA-directed "knock down" that p16(INK4a) is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation. Exp Cell Res 292: 151-6 PubMed GONUTS page

[PMID:16243918-0] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 Chen J et al. (2006) Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 290: H1575-86 PubMed GONUTS page

[PMID:10208428-1] 2.0 ^2.1 ^2.2 ^2.3 Schreiber M et al. (1999) Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. Oncogene 18: 1663-76 PubMed GONUTS page

[PMID:10205165-2] Fåhraeus R & Lane DP (1999) The p16(INK4a) tumour suppressor protein inhibits alphavbeta3 integrin-mediated cell spreading on vitronectin by blocking PKC-dependent localization of alphavbeta3 to focal contacts. EMBO J 18: 2106-18 PubMed GONUTS page

[PMID:8259215-3] 4.0 ^4.1 ^4.2 ^4.3 Serrano M et al. (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366: 704-7 PubMed GONUTS page

[PMID:11278317-4] Vivo M et al. (2001) The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein. J Biol Chem 276: 14161-9 PubMed GONUTS page

[PMID:15232106-5] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 ^6.6 ^6.7 ^6.8 Ramachandran N et al. (2004) Self-assembling protein microarrays. Science 305: 86-90 PubMed GONUTS page

[PMID:17110379-6] Tompkins VS et al. (2007) A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability. J Biol Chem 282: 1322-33 PubMed GONUTS page

[PMID:17353931-7] 8.0 ^8.1 Ewing RM et al. (2007) Large-scale mapping of human protein-protein interactions by mass spectrometry. Mol Syst Biol 3: 89 PubMed GONUTS page

[PMID:17658461-8] Huang X et al. (2007) Identification and characterization of a novel protein ISOC2 that interacts with p16INK4a. Biochem Biophys Res Commun 361: 287-93 PubMed GONUTS page

[PMID:17909018-9] Jones R et al. (2007) A CDKN2A mutation in familial melanoma that abrogates binding of p16INK4a to CDK4 but not CDK6. Cancer Res 67: 9134-41 PubMed GONUTS page

[PMID:17955473-10] 11.0 ^11.1 Souza-Rodrígues E et al. (2007) Proteomic analysis of p16ink4a-binding proteins. Proteomics 7: 4102-11 PubMed GONUTS page

[PMID:19149898-11] Becker TM et al. (2009) The chromatin remodelling factor BRG1 is a novel binding partner of the tumor suppressor p16INK4a. Mol Cancer 8: 4 PubMed GONUTS page

[PMID:9529249-12] Zhang Y et al. (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725-34 PubMed GONUTS page

[PMID:15149599-13] 14.0 ^14.1 Herbig U et al. (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14: 501-13 PubMed GONUTS page

[PMID:9054499-14] Serrano M et al. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88: 593-602 PubMed GONUTS page

[PMID:7603984-15] Medema RH et al. (1995) Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci U S A 92: 6289-93 PubMed GONUTS page

[PMID:10353611-16] 17.0 ^17.1 Wolff B & Naumann M (1999) INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 18: 2663-6 PubMed GONUTS page

[PMID:20381282-17] 18.0 ^18.1 González-Navarro H et al. (2010) p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis. J Am Coll Cardiol 55: 2258-68 PubMed GONUTS page

[PMID:14720514-18] Bond J et al. (2004) Direct evidence from siRNA-directed "knock down" that p16(INK4a) is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation. Exp Cell Res 292: 151-6 PubMed GONUTS page

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HUMAN:CD2A1

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