HUMAN:CD2A1

Species (Taxon ID)	Homo sapiens (Human). (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	P42771
EMBL	L27211 AF115544 AB060808 AF527803 DQ318021 AL449423 CH471071 CH471071 X94154 AH007355 S69804 U12820 U12818 U12819
CCDS	CCDS56565.1 CCDS6510.1
PIR	JE0141
RefSeq	NP_000068.1 NP_001182061.1 NP_478104.2 XP_005251400.1
UniGene	Hs.512599
PDB	1A5E 1BI7 1DC2 2A5E
PDBsum	1A5E 1BI7 1DC2 2A5E
ProteinModelPortal	P42771
SMR	P42771
BioGrid	107463
DIP	DIP-6108N
IntAct	P42771
MINT	MINT-1201444
STRING	9606.ENSP00000355153
PhosphoSite	P42771
DMDM	3041660
MaxQB	P42771
PaxDb	P42771
PRIDE	P42771
DNASU	1029
Ensembl	ENST00000304494 ENST00000494262 ENST00000498124 ENST00000498628 ENST00000578845
GeneID	1029
KEGG	hsa:1029
UCSC	uc003zpk.3 uc010miu.3
CTD	1029
GeneCards	GC09M021957
HGNC	HGNC:1787
HPA	CAB000093 CAB000445 CAB018232
MIM	151623 155601 155755 600160 606719
neXtProt	NX_P42771
Orphanet	618 1333 252206 51013 99860 99861
PharmGKB	PA106
eggNOG	NOG42176
GeneTree	ENSGT00390000004527
HOGENOM	HOG000290191
HOVERGEN	HBG050870
InParanoid	P42771
KO	K06621
OMA	IGNHLWV
OrthoDB	EOG7TTQ94
TreeFam	TF352389
Reactome	REACT_169168 REACT_169325 REACT_169436 REACT_821
ChiTaRS	CDKN2A
EvolutionaryTrace	P42771
GeneWiki	P16_(gene)
GenomeRNAi	1029
NextBio	4323
PRO	PR:P42771
Proteomes	UP000005640
Bgee	P42771
CleanEx	HS_CDKN2A
ExpressionAtlas	P42771
Genevestigator	P42771
GO	GO:0005737 GO:0005829 GO:0005634 GO:0035985 GO:0004861 GO:0051059 GO:0044822 GO:0019901 GO:0007050 GO:0090398 GO:0000082 GO:0000278 GO:0030308 GO:0008285 GO:0001953 GO:0045736 GO:0032088 GO:0042326 GO:0045892 GO:2000774 GO:2000111 GO:0034393 GO:0007265 GO:0090399 GO:0035986
Gene3D	1.25.40.20
InterPro	IPR002110 IPR020683
Pfam	PF00023 PF12796
SMART	SM00248
SUPFAM	SSF48403
PROSITE	PS50297

Annotations

Qualifier	GO ID	GO term name	Reference	ECO ID	ECO term name	with/from	Aspect	Notes	Status
involved_in	GO:2000111	positive regulation of macrophage apoptotic process	PMID:20381282^[1]	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P51480	P	Seeded From UniProt	complete
involved_in	GO:0090399	replicative senescence	PMID:14720514^[2]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0051059	NF-kappaB binding	PMID:10353611^[3]	ECO:0000314	direct assay evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity	PMID:8259215^[4]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0042326	negative regulation of phosphorylation	PMID:8259215^[4]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0042326	negative regulation of phosphorylation	PMID:10208428^[5]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0034393	positive regulation of smooth muscle cell apoptotic process	PMID:20381282^[1]	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:P51480	P	Seeded From UniProt	complete
involved_in	GO:0032088	negative regulation of NF-kappaB transcription factor activity	PMID:10353611^[3]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0030308	negative regulation of cell growth	PMID:10208428^[5]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0019901	protein kinase binding	PMID:8259215^[4]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:P11802	F	Seeded From UniProt	complete
involved_in	GO:0008285	negative regulation of cell population proliferation	PMID:7603984^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0008285	negative regulation of cell population proliferation	PMID:15149599^[7]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0007265	Ras protein signal transduction	PMID:9054499^[8]	ECO:0000270	expression pattern evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0007050	cell cycle arrest	PMID:15149599^[7]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity	PMID:8259215^[4]	ECO:0000314	direct assay evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:0001953	negative regulation of cell-matrix adhesion	PMID:10205165^[9]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0000082	G1/S transition of mitotic cell cycle	PMID:10208428^[5]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0008285	negative regulation of cell population proliferation	PMID:16243918^[10]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0007050	cell cycle arrest	PMID:16243918^[10]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	PMID:16243918^[10]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005634	nucleus	PMID:16243918^[10]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
involved_in	GO:0090398	cellular senescence	PMID:16243918^[10]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:2000774	positive regulation of cellular senescence	PMID:16901784^[11]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
involved_in	GO:0045892	negative regulation of transcription, DNA-templated	PMID:16901784^[11]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0003723	RNA binding	PMID:22681889^[12]	ECO:0007005	high throughput direct assay evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:0035986	senescence-associated heterochromatin focus assembly	PMID:16901784^[11]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0035985	senescence-associated heterochromatin focus	PMID:16901784^[11]	ECO:0000314	direct assay evidence used in manual assertion		C	Seeded From UniProt	complete
involved_in	GO:0008285	negative regulation of cell population proliferation	PMID:16901784^[11]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0005634	nucleus	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	PANTHER:PTN001948826 RGD:2324 UniProtKB:P42771 UniProtKB:P42772 UniProtKB:P55273	C	Seeded From UniProt	complete
enables	GO:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity	PMID:21873635^[13]	ECO:0000318	biological aspect of ancestor evidence used in manual assertion	PANTHER:PTN001948826 UniProtKB:P42771 UniProtKB:P42772 UniProtKB:P55273	F	Seeded From UniProt	complete
involved_in	GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity	PMID:7739547^[14]	ECO:0000314	direct assay evidence used in manual assertion		P	Seeded From UniProt	complete
enables	GO:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity	PMID:7739547^[14]	ECO:0000314	direct assay evidence used in manual assertion		F	Seeded From UniProt	complete
involved_in	GO:2000134	negative regulation of G1/S transition of mitotic cell cycle	Reactome:R-HSA-182594	ECO:0000304	author statement supported by traceable reference used in manual assertion		P	Seeded From UniProt	complete
part_of	GO:0005829	cytosol	Reactome:R-HSA-3209114 Reactome:R-HSA-182594	ECO:0000304	author statement supported by traceable reference used in manual assertion		C	Seeded From UniProt	complete
part_of	GO:0005634	nucleus	GO_REF:0000037 GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0539 UniProtKB-SubCell:SL-0191	C	Seeded From UniProt	complete
involved_in	GO:0007049	cell cycle	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0131	P	Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	GO_REF:0000037 GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0963 UniProtKB-SubCell:SL-0086	C	Seeded From UniProt	complete
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Notes

References

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

↑ ^1.0 ^1.1 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
↑ ^3.0 ^3.1 Wolff, B & Naumann, M (1999) INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 18 2663-6 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
↑ ^5.0 ^5.1 ^5.2 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
↑ 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
↑ ^7.0 ^7.1 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
↑ 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
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 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
↑ ^11.0 ^11.1 ^11.2 ^11.3 ^11.4 Narita, M et al. (2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 126 503-14 PubMed GONUTS page
↑ Baltz, AG et al. (2012) The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol. Cell 46 674-90 PubMed GONUTS page
↑ ^13.0 ^13.1 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page
↑ ^14.0 ^14.1 Hirai, H et al. (1995) Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol. Cell. Biol. 15 2672-81 PubMed GONUTS page

[PMID:20381282-1] 1.0 ^1.1 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:14720514-2] 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:10353611-3] 3.0 ^3.1 Wolff, B & Naumann, M (1999) INK4 cell cycle inhibitors direct transcriptional inactivation of NF-kappaB. Oncogene 18 2663-6 PubMed GONUTS page

[PMID:8259215-4] 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:10208428-5] 5.0 ^5.1 ^5.2 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:7603984-6] 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:15149599-7] 7.0 ^7.1 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:9054499-8] 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:10205165-9] 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:16243918-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 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:16901784-11] 11.0 ^11.1 ^11.2 ^11.3 ^11.4 Narita, M et al. (2006) A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell 126 503-14 PubMed GONUTS page

[PMID:22681889-12] Baltz, AG et al. (2012) The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Mol. Cell 46 674-90 PubMed GONUTS page

[PMID:21873635-13] 13.0 ^13.1 Gaudet, P et al. (2011) Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Brief. Bioinformatics 12 449-62 PubMed GONUTS page

[PMID:7739547-14] 14.0 ^14.1 Hirai, H et al. (1995) Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. Mol. Cell. Biol. 15 2672-81 PubMed GONUTS page

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HUMAN:CD2A1

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Annotations

Notes

References

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