[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1038/366704a0; PubMed=8259215 [NCBI, ExPASy, EBI, Israel, Japan] Serrano M., Hannon G.J., Beach D.; "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4."; Nature 366:704-707(1993).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY. DOI=10.1038/sj.onc.1202737; PubMed=10445844 [NCBI, ExPASy, EBI, Israel, Japan] Robertson K.D., Jones P.A.; "Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus."; Oncogene 18:3810-3820(1999).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1074/jbc.M208353200; PubMed=12228235 [NCBI, ExPASy, EBI, Israel, Japan] Kitagawa Y., Inoue K., Sasaki S., Hayashi Y., Matsuo Y., Lieber M.R., Mizoguchi H., Yokota J., Kohno T.; "Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia."; J. Biol. Chem. 277:46289-46297(2002).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. NIEHS SNPs program; Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. DOI=10.1038/nature02465; PubMed=15164053 [NCBI, ExPASy, EBI, Israel, Japan] Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.; "DNA sequence and analysis of human chromosome 9."; Nature 429:369-374(2004).
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). TISSUE=Skin; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[7]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20. PubMed=8622687 [NCBI, ExPASy, EBI, Israel, Japan] Hara E., Smith R., Parry D., Tahara H., Stone S., Peters G.; "Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence."; Mol. Cell. Biol. 16:859-867(1996).
[8]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 51-156. DOI=10.1038/368753a0; PubMed=8152487 [NCBI, ExPASy, EBI, Israel, Japan] Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A.; "Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers."; Nature 368:753-756(1994).
[9]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 51-152. DOI=10.1126/science.8153634; PubMed=8153634 [NCBI, ExPASy, EBI, Israel, Japan] Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnick M.H.; "A cell cycle regulator potentially involved in genesis of many tumor types."; Science 264:436-440(1994).
[10]	FUNCTION. DOI=10.1073/pnas.91.23.11045; PubMed=7972006 [NCBI, ExPASy, EBI, Israel, Japan] Okamoto A., Demetrick D.J., Spillare E.A., Hagiwara K., Hussain S.P., Bennett W.P., Forrester K., Gerwin B., Serrano M., Beach D.H., Harris C.C.; "Mutations and altered expression of p16INK4 in human cancer."; Proc. Natl. Acad. Sci. U.S.A. 91:11045-11049(1994).
[11]	IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. Colinge J., Superti-Furga G., Bennett K.L.; Submitted (OCT-2008) to UniProtKB.
[12]	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CDK6. DOI=10.1038/26155; PubMed=9751050 [NCBI, ExPASy, EBI, Israel, Japan] Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P.; "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a."; Nature 395:237-243(1998).
[13]	STRUCTURE BY NMR. DOI=10.1006/jmbi.1999.3231; PubMed=10556039 [NCBI, ExPASy, EBI, Israel, Japan] Yuan C., Li J., Selby T.L., Byeon I.-J., Tsai M.-D.; "Tumor suppressor INK4: comparisons of conformational properties between p16(INK4A) and p18(INK4C)."; J. Mol. Biol. 294:201-211(1999).
[14]	STRUCTURE BY NMR. PubMed=10892805 [NCBI, ExPASy, EBI, Israel, Japan] Yuan C., Selby T.L., Li J., Byeon I.J., Tsai M.D.; "Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data."; Protein Sci. 9:1120-1128(2000).
[15]	REVIEW ON MELANOMA VARIANTS. PubMed=8783570 [NCBI, ExPASy, EBI, Israel, Japan] Dracopoli N.C., Fountain J.W.; "CDKN2 mutations in melanoma."; Cancer Surv. 26:115-132(1996).
[16]	REVIEW ON VARIANTS. DOI=10.1002/(SICI)1098-1004(1996)7:4<294::AID-HUMU2>3.3.CO;2-I; PubMed=8723678 [NCBI, ExPASy, EBI, Israel, Japan] Smith-Soerensen B., Hovig E.; "CDKN2A (p16INK4A) somatic and germline mutations."; Hum. Mutat. 7:294-303(1996).
[17]	VARIANTS NON-SMALL CELL LUNG CARCINOMA TYR-66; HIS-84; ALA-93; ALA-95; GLN-99; LEU-114; ALA-120; LYS-120; PRO-132; VAL-134; TYR-142 AND VAL-150. DOI=10.1006/bbrc.1994.2090; PubMed=8060323 [NCBI, ExPASy, EBI, Israel, Japan] Hayashi N., Sugimoto Y., Tsuchiya E., Ogawa M., Nakamura Y.; "Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas."; Biochem. Biophys. Res. Commun. 202:1426-1430(1994).
[18]	VARIANTS CMM2 PRO-87; TRP-101 AND ASP-126, AND VARIANTS THR-49; SER-71 AND THR-148. DOI=10.1038/ng0994-15; PubMed=7987387 [NCBI, ExPASy, EBI, Israel, Japan] Hussussian C.J., Struewing J.P., Goldstein A.M., Higgins P.A.T., Ally D.S., Sheahan M.D., Clark W.H. Jr., Tucker M.A., Dracopoli N.C.; "Germline p16 mutations in familial melanoma."; Nat. Genet. 8:15-21(1994).
[19]	VARIANTS SQUAMOUS CELL CARCINOMA SER-127 AND CYS-144. PubMed=7970734 [NCBI, ExPASy, EBI, Israel, Japan] Zhou X., Tarmin L., Yin J., Jiang H.-Y., Suzuki H., Rhyu M.-G., Abraham J.M., Meltzer S.J.; "The MTS1 gene is frequently mutated in primary human esophageal tumors."; Oncogene 9:3737-3741(1994).
[20]	VARIANTS. PubMed=7882351 [NCBI, ExPASy, EBI, Israel, Japan] Okamoto A., Hussain S.P., Hagiwara K., Spillare E.A., Rusin M.R., Demetrick D.J., Serrano M., Hannon G.J., Shiseki M., Zariwala M., Xiong Y., Beach D.H., Yokota J., Harris C.C.; "Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer."; Cancer Res. 55:1448-1451(1995).
[21]	VARIANTS CMM2 PRO-32; ALA-35; ARG-50 AND ILE-53, VARIANT MELANOMA GLU-35, AND VARIANT THR-148. DOI=10.1093/hmg/4.10.1845; PubMed=8595405 [NCBI, ExPASy, EBI, Israel, Japan] Walker G.J., Hussussian C.J., Flores J.F., Glendening J.M., Haluska F.G., Dracopoli N.C., Hayward N.K., Fountain J.W.; "Mutations of the CDKN2/p16INK4 gene in Australian melanoma kindreds."; Hum. Mol. Genet. 4:1845-1852(1995).
[22]	CHARACTERIZATION OF VARIANTS THR-49; SER-71; LEU-81; PRO-87; TRP-101; ASP-126 AND THR-148. DOI=10.1038/ng0595-114; PubMed=7647780 [NCBI, ExPASy, EBI, Israel, Japan] Ranade K., Hussussian C.J., Sikorski R.S., Varmus H.E., Goldstein A.M., Tucker M.A., Serrano M., Hannon G.J., Beach D., Dracopoli N.C.; "Mutations associated with familial melanoma impair p16INK4 function."; Nat. Genet. 10:114-116(1995).
[23]	VARIANT CMM2 ARG-112 INS, AND VARIANT THR-148. PubMed=8653684 [NCBI, ExPASy, EBI, Israel, Japan] Borg A., Johannsson U., Johannsson O., Haakansson S., Westerdahl J., Maasbaeck A., Olsson H., Ingvar C.; "Novel germline p16 mutation in familial malignant melanoma in southern Sweden."; Cancer Res. 56:2497-2500(1996).
[24]	VARIANTS CMM2 ILE-53 AND CYS-107, AND VARIANTS VAL-68; THR-85 AND THR-148. DOI=10.1073/pnas.93.16.8541; PubMed=8710906 [NCBI, ExPASy, EBI, Israel, Japan] Fitzgerald M.G., Harkin D.P., Silva-Arrieta S., Macdonald D.J., Lucchina L.C., Unsal H., O'Neill E., Koh J., Finkelstein D.M., Isselbacher K.J., Sober A.J., Haber D.A.; "Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population."; Proc. Natl. Acad. Sci. U.S.A. 93:8541-8545(1996).
[25]	VARIANTS CMM2 PRO-24; ILE-53 AND THR-118, AND VARIANT THR-148. DOI=10.1093/hmg/6.12.2061; PubMed=9328469 [NCBI, ExPASy, EBI, Israel, Japan] Harland M., Meloni R., Gruis N., Pinney E., Brookes S., Spurr N.K., Frischauf A.-M., Bataille V., Peters G., Cuzick J., Selby P., Bishop D.T., Bishop J.N.; "Germline mutations of the CDKN2 gene in UK melanoma families."; Hum. Mol. Genet. 6:2061-2067(1997).
[26]	VARIANTS CMM2. DOI=10.1093/hmg/7.2.209; PubMed=9425228 [NCBI, ExPASy, EBI, Israel, Japan] Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.; "Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France."; Hum. Mol. Genet. 7:209-216(1998).
[27]	ERRATUM. Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.; Hum. Mol. Genet. 7:941-941(1998).
[28]	VARIANTS MELANOMA LEU-48; ASP-89 AND MET-117, VARIANT PANCREAS CARCINOMA VAL-57, AND VARIANT THR-148. PubMed=10651484 [NCBI, ExPASy, EBI, Israel, Japan] Gretarsdottir S., Olafsdottir G.H., Borg A.; "Five novel somatic CDKN2/p16 mutations identified in melanoma, glioma and carcinoma of the pancreas."; Hum. Mutat. 12:212-212(1998).
[29]	VARIANT LFS GLU-102. DOI=10.1016/S0165-4608(98)00276-3; PubMed=10484981 [NCBI, ExPASy, EBI, Israel, Japan] Gueran S., Tunca Y., Imirzalioglu N.; "Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family."; Cancer Genet. Cytogenet. 113:145-151(1999).
[30]	VARIANT CMM2 ASP-126. DOI=10.1054/bjoc.2001.1944; PubMed=11506491 [NCBI, ExPASy, EBI, Israel, Japan] Goldstein A.M., Liu L., Shennan M.G., Hogg D., Tucker M.A., Struewing J.P.; "A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families."; Br. J. Cancer 85:527-530(2001).
[31]	INVOLVEMENT IN MELANOMA-ASTROCYTOMA SYNDROME. DOI=10.1093/hmg/10.1.55; PubMed=11136714 [NCBI, ExPASy, EBI, Israel, Japan] Randerson-Moor J.A., Harland M., Williams S., Cuthbert-Heavens D., Sheridan E., Aveyard J., Sibley K., Whitaker L., Knowles M., Bishop J.N., Bishop D.T.; "A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family."; Hum. Mol. Genet. 10:55-62(2001).
[32]	VARIANT CMM2 ARG-122. DOI=10.1093/hmg/11.11.1273; PubMed=12019208 [NCBI, ExPASy, EBI, Israel, Japan] Hewitt C., Lee Wu C., Evans G., Howell A., Elles R.G., Jordan R., Sloan P., Read A.P., Thakker N.; "Germline mutation of ARF in a melanoma kindred."; Hum. Mol. Genet. 11:1273-1279(2002).
[33]	VARIANTS CMM2 GLY-59; TYR-84; TRP-87 AND TRP-101. PubMed=10874641 [NCBI, ExPASy, EBI, Israel, Japan] Ruiz A., Puig S., Malvehy J., Lazaro C., Lynch M., Gimenez-Arnau A.M., Puig L., Sanchez-Conejo J., Estivill X., Castel T.; "CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia."; J. Med. Genet. 36:490-493(1999).
[34]	POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO UVEAL MELANOMA. DOI=10.1167/iovs.02-0026; PubMed=12556369 [NCBI, ExPASy, EBI, Israel, Japan] Hearle N., Damato B.E., Humphreys J., Wixey J., Green H., Stone J., Easton D.F., Houlston R.S.; "Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma."; Invest. Ophthalmol. Vis. Sci. 44:458-462(2003).
[35]	VARIANT MELANOMA GLN-94. DOI=10.1097/00008390-200312000-00005; PubMed=14646619 [NCBI, ExPASy, EBI, Israel, Japan] Avbelj M., Hocevar M., Trebusak-Podkrajsek K., Krzisnik C., Battelino T.; "A novel L94Q mutation in the CDKN2A gene in a melanoma kindred."; Melanoma Res. 13:567-570(2003).

Comments

FUNCTION: Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
SUBUNIT: Heterodimer with CDK4 or CDK6. Isoform 3 does not bind to CDK4.
INTERACTION:
O14965:AURKA; NbExp=1; IntAct=EBI-375053, EBI-448680;
O75419:CDC45L; NbExp=1; IntAct=EBI-375053, EBI-374969;
Q99741:CDC6; NbExp=1; IntAct=EBI-375053, EBI-374862;
O00311:CDC7; NbExp=1; IntAct=EBI-375053, EBI-374980;
P11802:CDK4; NbExp=5; IntAct=EBI-375053, EBI-295644;
Q00534:CDK6; NbExp=5; IntAct=EBI-375053, EBI-295663;
O75496:GMNN; NbExp=1; IntAct=EBI-375053, EBI-371669;
Q7L590:MCM10; NbExp=1; IntAct=EBI-375053, EBI-374912;
P49736:MCM2; NbExp=1; IntAct=EBI-375053, EBI-374819;
P33992:MCM5; NbExp=1; IntAct=EBI-375053, EBI-359410;
Q14566:MCM6; NbExp=1; IntAct=EBI-375053, EBI-374900;
O43929:ORC4L; NbExp=1; IntAct=EBI-375053, EBI-374889;
O43913:ORC5L; NbExp=1; IntAct=EBI-375053, EBI-374928;
P12004:PCNA; NbExp=3; IntAct=EBI-375053, EBI-358311;

ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing. Isoform 1 and isoform 4 arise due to the use of two alternative first exons joined to a common exon 2 at the same acceptor site but in different reading frames, resulting in two completely different isoforms.

Name	1
Synonyms	p16INK4a
Isoform ID	P42771-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	P42771-2
Features which should be applied to build the isoform sequence: VSP_015864.

Name	3
Synonyms	p12
Isoform ID	P42771-3
Features which should be applied to build the isoform sequence: VSP_015865, VSP_015866.

Name	4
Synonyms	p14ARF, p19ARF, ARF
Isoform ID	Q8N726-1
This isoform is stored in UniProtKB/Swiss-Prot entry Q8N726.

TISSUE SPECIFICITY: Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific.
POLYMORPHISM: Genetic variations in CDKN2A may underlie susceptibility to uveal melanoma [MIM:155720]. Uveal melanoma is the most common type of ocular malignant tumor, consisting of overgrowth of uveal melanocytes and often preceded by a uveal nevus.
DISEASE: Defects in CDKN2A are involved in tumor formation in a wide range of tissues.
DISEASE: Defects in CDKN2A are the cause of cutaneous malignant melanoma 2 (CMM2) [MIM:155601]. Inheritance is autosomal dominant. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a preexisting benign nevus, which occurs most often in the skin but also may involve other sites.
DISEASE: Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719].
DISEASE: Defects in CDKN2A are a cause of Li-Fraumeni syndrome (LFS) [MIM:151623]. LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.
DISEASE: Defects in CDKN2A are the cause of melanoma-astrocytoma syndrome [MIM:155755]. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.
SIMILARITY: Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.
SIMILARITY: Contains 4 ANK repeats.
WEB RESOURCE: Name=CDKN2A Database; Note=Database of CDKN2A germline and somatic variants; URL="https://biodesktop.uvm.edu/perl/p16";.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDKN2aID146.html";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CDKN2A";.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdkn2a/";.
WEB RESOURCE: Name=Wikipedia; Note=P16INK4a entry; URL="http://en.wikipedia.org/wiki/P16INK4a";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

L27211; AAA92554.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB060808; BAB91133.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF527803; AAR05391.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF115544; AAD11437.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL449423; CAH70600.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC015960; AAH15960.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC021998; AAH21998.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X94154; CAA63870.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S69824; AAD14050.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S69822; AAD14050.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S69804; AAD14048.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U12820; AAB60645.1; ALT_INIT; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U12818; AAB60645.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U12819; AAB60645.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00001560; -.
IPI00030733; -.
IPI00651662; -.

PIR

JE0141; JE0141.

RefSeq

NP_000068.1; -.
NP_478104.2; -.

UniGene

Hs.512599

3D structure databases

PDB

1A5E; NMR; -; A=1-156.	[ExPASy / RCSB / EBI]
1BI7; X-ray; 3.40 A; B=1-156.	[ExPASy / RCSB / EBI]
1DC2; NMR; -; A=1-156.	[ExPASy / RCSB / EBI]
2A5E; NMR; -; A=1-156.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1A5E; -.
1BI7; -.
1DC2; -.
2A5E; -.

ModBase

P42771.

Protein-protein interaction databases

DIP

DIP:6108N; -.

IntAct

P42771; 52.

PTM databases

PhosphoSite

P42771; -.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway; Coregulation of Androgen receptor activity.

Organism-specific databases

GC09M021957; -.

HGNC:1787; CDKN2A.

CAB000093; -.
CAB018232; -.

MIM

151623; phenotype. [NCBI / EBI]
155601; phenotype. [NCBI / EBI]
155720; phenotype. [NCBI / EBI]
155755; phenotype. [NCBI / EBI]
600160; gene. [NCBI / EBI]
606719; phenotype. [NCBI / EBI]

PharmGKB

PA106; -.

Gene expression databases

P42771; -.

P42771; -.

HS_CDKN2A; -.

ENSG00000147889; Homo sapiens.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from direct assay from HGNC).
GO:0004861;	Molecular function: cyclin-dependent protein kinase inhibitor activity (inferred from direct assay from UniProtKB).
GO:0051059;	Molecular function: NF-kappaB binding (inferred from direct assay from UniProtKB).
GO:0019901;	Molecular function: protein kinase binding (inferred from physical interaction from UniProtKB).
GO:0007050;	Biological process: cell cycle arrest (inferred from mutant phenotype from HGNC).
GO:0000075;	Biological process: cell cycle checkpoint (inferred from mutant phenotype from HGNC).
GO:0000082;	Biological process: G1/S transition of mitotic cell cycle (inferred from direct assay from UniProtKB).
GO:0006917;	Biological process: induction of apoptosis (inferred from direct assay from UniProtKB).
GO:0030308;	Biological process: negative regulation of cell growth (inferred from direct assay from UniProtKB).
GO:0008285;	Biological process: negative regulation of cell proliferation (inferred from mutant phenotype from UniProtKB).
GO:0001953;	Biological process: negative regulation of cell-matrix adhesion (inferred from mutant phenotype from UniProtKB).
GO:0045736;	Biological process: negative regulation of cyclin-dependent protein kinase activity (inferred from direct assay from UniProtKB).
GO:0032088;	Biological process: negative regulation of NF-kappaB transcription factor activity (inferred from direct assay from UniProtKB).
GO:0042326;	Biological process: negative regulation of phosphorylation (inferred from direct assay from UniProtKB).
GO:0010149;	Biological process: senescence (inferred from mutant phenotype from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR002110; ANK.
Graphical view of domain structure.

Gene3D

G3DSA:1.25.40.20; ANK; 1.

Pfam

PF00023; Ank; 3.
Pfam graphical view of domain structure.

SMART

SM00248; ANK; 2.
SMART graphical view of domain structure.

PROSITE

PS50297; ANK_REP_REGION; 1.
PS50088; ANK_REPEAT; FALSE_NEG.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

P42771; -.

Genome annotation databases

Ensembl

ENSG00000147889; Homo sapiens. [Contig view]

GeneID

1029; -.

KEGG

hsa:1029; -.

Phylogenomic databases

HOVERGEN

P42771; -.

OMA

P42771; SNHARID.

Other

NextBio

4323; -.

SOURCE

CDKN2A; Homo sapiens.

ProtoNet

P42771.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; ANK repeat; Anti-oncogene; Cell cycle; Disease mutation; Li-Fraumeni syndrome; Polymorphism; Repeat.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 156`	`156`	`Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3.`	`PRO_0000144177`
`REPEAT`	`11 40`	`30`	`ANK 1.`
`REPEAT`	`44 72`	`29`	`ANK 2.`
`REPEAT`	`77 106`	`30`	`ANK 3.`
`REPEAT`	`110 139`	`30`	`ANK 4.`
`VAR_SEQ`	`1 51`		`Missing (in isoform 2).`	`VSP_015864`
`VAR_SEQ`	`52 116`		`MMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFL` `DTLVVLHRAGARLDVRDAWGRLPVD -> GRRSAAGAGDGGRLWRTKFAGELESGSASILRKKGRLPGE` `FSEGVCNHRPPPGDALGAWETKEEE (in isoform 3).`	`VSP_015865`
`VAR_SEQ`	`117 156`		`Missing (in isoform 3).`	`VSP_015866`
`VARIANT`	`14 14`	`1`	`D -> E (in a biliary tract tumor).`	`VAR_001408`
`VARIANT`	`16 16`	`1`	`L -> P (in a biliary tract tumor and a familial melanoma).`	`VAR_001409`
`VARIANT`	`20 20`	`1`	`A -> P (in a lung tumor and melanoma).`	`VAR_001410`
`VARIANT`	`20 20`	`1`	`A -> S (in a biliary tract tumor).`	`VAR_001411`
`VARIANT`	`23 23`	`1`	`G -> D (in a pancreas tumor).`	`VAR_001412`
`VARIANT`	`24 24`	`1`	`R -> C (in melanoma).`	`VAR_001413`
`VARIANT`	`24 24`	`1`	`R -> P (in CMM2 and melanoma).`	`VAR_001414`
`VARIANT`	`26 26`	`1`	`E -> D (in a biliary tract tumor).`	`VAR_001415`
`VARIANT`	`32 32`	`1`	`L -> P (in CMM2).`	`VAR_001416`
`VARIANT`	`33 33`	`1`	`E -> D (in a biliary tract tumor).`	`VAR_001417`
`VARIANT`	`35 35`	`1`	`G -> A (in CMM2 and a biliary tract tumor).`	`VAR_001418`
`VARIANT`	`35 35`	`1`	`G -> E (in melanoma).`	`VAR_001419`
`VARIANT`	`48 48`	`1`	`P -> L (in melanoma and a head and neck tumor; somatic mutation).`	`VAR_001420`
`VARIANT`	`49 49`	`1`	`I -> S (in a biliary tract tumor).`	`VAR_001421`
`VARIANT`	`49 49`	`1`	`I -> T.`	`VAR_001422`
`VARIANT`	`50 50`	`1`	`Q -> R (in CMM2).`	`VAR_001423`
`VARIANT`	`53 53`	`1`	`M -> I (in CMM2).`	`VAR_001424`
`VARIANT`	`56 56`	`1`	`S -> I (possible polymorphism).`	`VAR_001425`
`VARIANT`	`57 57`	`1`	`A -> V (in pancreas carcinoma; somatic mutation).`	`VAR_001426`
`VARIANT`	`58 58`	`1`	`R -> Q (in dbSNP:rs36204273 [NCBI]).`	`VAR_053027`
`VARIANT`	`59 59`	`1`	`V -> G (in CMM2).`	`VAR_001427`
`VARIANT`	`60 60`	`1`	`A -> T.`	`VAR_001428`
`VARIANT`	`60 60`	`1`	`A -> V (in dbSNP:rs36204594 [NCBI]).`	`VAR_053028`
`VARIANT`	`61 62`	`2`	`EL -> DV.`	`VAR_001429`
`VARIANT`	`62 62`	`1`	`L -> P (in familial melanoma).`	`VAR_001430`
`VARIANT`	`66 66`	`1`	`H -> Y (in non-small cell lung carcinoma).`	`VAR_001431`
`VARIANT`	`68 68`	`1`	`A -> L (in familial melanoma; requires 2 nucleotide substitutions).`	`VAR_001432`
`VARIANT`	`68 68`	`1`	`A -> T (in an esophagus tumor).`	`VAR_001433`
`VARIANT`	`68 68`	`1`	`A -> V.`	`VAR_001434`
`VARIANT`	`69 69`	`1`	`E -> K (in a bladder tumor).`	`VAR_001435`
`VARIANT`	`69 69`	`1`	`E -> V (in a lung tumor).`	`VAR_001436`
`VARIANT`	`71 71`	`1`	`N -> K (in familial melanoma).`	`VAR_001437`
`VARIANT`	`71 71`	`1`	`N -> S.`	`VAR_001438`
`VARIANT`	`72 72`	`1`	`C -> G (in an esophagus tumor).`	`VAR_001439`
`VARIANT`	`74 74`	`1`	`D -> N (in a bladder tumor).`	`VAR_001440`
`VARIANT`	`74 74`	`1`	`D -> V (in a biliary tract tumor).`	`VAR_001441`
`VARIANT`	`80 80`	`1`	`R -> L (in a head and neck tumor).`	`VAR_001442`
`VARIANT`	`81 81`	`1`	`P -> L (in melanoma; impairs the function; dbSNP:rs11552823 [NCBI]).`	`VAR_001443`
`VARIANT`	`83 83`	`1`	`H -> N (in a lung tumor).`	`VAR_001445`
`VARIANT`	`83 83`	`1`	`H -> Q (in dbSNP:rs34968276 [NCBI]).`	`VAR_053029`
`VARIANT`	`83 83`	`1`	`H -> Y (in a pancreas and a head and neck tumor).`	`VAR_001444`
`VARIANT`	`84 84`	`1`	`D -> E (in a bladder tumor).`	`VAR_001446`
`VARIANT`	`84 84`	`1`	`D -> H (in non-small cell lung carcinoma).`	`VAR_001447`
`VARIANT`	`84 84`	`1`	`D -> N (in an esophagus, a head and neck and a lung tumor).`	`VAR_001448`
`VARIANT`	`84 84`	`1`	`D -> Y (in CMM2; also found in a lung and a prostate tumor; dbSNP:rs11552822 [NCBI]).`	`VAR_001449`
`VARIANT`	`85 85`	`1`	`A -> T.`	`VAR_001450`
`VARIANT`	`87 87`	`1`	`R -> P (in CMM2; impairs the function).`	`VAR_001451`
`VARIANT`	`87 87`	`1`	`R -> W (in CMM2).`	`VAR_012317`
`VARIANT`	`88 88`	`1`	`E -> D (in a biliary tract tumor).`	`VAR_001452`
`VARIANT`	`89 89`	`1`	`G -> D (in melanoma; somatic mutation).`	`VAR_001453`
`VARIANT`	`89 89`	`1`	`G -> S (in melanoma).`	`VAR_001454`
`VARIANT`	`93 93`	`1`	`T -> A (in non-small cell lung carcinoma).`	`VAR_001455`
`VARIANT`	`94 94`	`1`	`L -> Q (in melanoma).`	`VAR_023604`
`VARIANT`	`95 95`	`1`	`V -> A (in non-small cell lung carcinoma).`	`VAR_001456`
`VARIANT`	`97 97`	`1`	`L -> R (possible polymorphism).`	`VAR_001457`
`VARIANT`	`98 98`	`1`	`H -> P (in melanoma).`	`VAR_001458`
`VARIANT`	`98 98`	`1`	`H -> Q (in melanoma).`	`VAR_001459`
`VARIANT`	`99 99`	`1`	`R -> P (in familial melanoma).`	`VAR_001460`
`VARIANT`	`99 99`	`1`	`R -> Q (in non-small cell lung carcinoma).`	`VAR_001461`
`VARIANT`	`99 99`	`1`	`R -> W (in dbSNP:rs34886500 [NCBI]).`	`VAR_053030`
`VARIANT`	`100 100`	`1`	`A -> L (in melanoma; requires 2 nucleotide substitutions).`	`VAR_001462`
`VARIANT`	`100 100`	`1`	`A -> P.`	`VAR_001463`
`VARIANT`	`101 101`	`1`	`G -> W (in CMM2 and FAMMMPC; impairs the function).`	`VAR_001464`
`VARIANT`	`102 102`	`1`	`A -> E (in LFS; somatic mutation).`	`VAR_015818`
`VARIANT`	`102 102`	`1`	`A -> T (in dbSNP:rs35741010 [NCBI]).`	`VAR_053031`
`VARIANT`	`104 105`	`2`	`Missing.`	`VAR_001465`
`VARIANT`	`107 107`	`1`	`R -> C (in CMM2).`	`VAR_001466`
`VARIANT`	`107 107`	`1`	`R -> H.`	`VAR_001467`
`VARIANT`	`108 108`	`1`	`D -> H (in a bladder tumor).`	`VAR_001469`
`VARIANT`	`108 108`	`1`	`D -> Y (in a head and neck tumor).`	`VAR_001468`
`VARIANT`	`112 112`	`1`	`R -> RR (in CMM2).`	`VAR_035068`
`VARIANT`	`114 114`	`1`	`P -> L (in non-small cell lung carcinoma).`	`VAR_001470`
`VARIANT`	`117 117`	`1`	`L -> M (in melanoma; somatic mutation).`	`VAR_001471`
`VARIANT`	`118 118`	`1`	`A -> T (in CMM2).`	`VAR_001472`
`VARIANT`	`119 119`	`1`	`E -> Q (in a biliary tract tumor).`	`VAR_001473`
`VARIANT`	`120 120`	`1`	`E -> A (in non-small cell lung carcinoma).`	`VAR_001474`
`VARIANT`	`120 120`	`1`	`E -> K (in non-small cell lung carcinoma).`	`VAR_001475`
`VARIANT`	`122 122`	`1`	`G -> R (in CMM2).`	`VAR_035069`
`VARIANT`	`122 122`	`1`	`G -> S (in a biliary tract tumor).`	`VAR_001476`
`VARIANT`	`123 123`	`1`	`H -> Q (in leukemia; dbSNP:rs6413463 [NCBI]).`	`VAR_001477`
`VARIANT`	`124 124`	`1`	`R -> C (in dbSNP:rs34170727 [NCBI]).`	`VAR_053032`
`VARIANT`	`124 124`	`1`	`R -> H (in an esophagus tumor).`	`VAR_001478`
`VARIANT`	`126 126`	`1`	`V -> D (in CMM2; impairs the function).`	`VAR_001479`
`VARIANT`	`127 127`	`1`	`A -> S (in squamous cell carcinoma; dbSNP:rs6413464 [NCBI]).`	`VAR_001480`
`VARIANT`	`132 132`	`1`	`A -> P (in non-small cell lung carcinoma).`	`VAR_001481`
`VARIANT`	`134 134`	`1`	`A -> V (in non-small cell lung carcinoma).`	`VAR_001482`
`VARIANT`	`142 142`	`1`	`H -> Y (in non-small cell lung carcinoma).`	`VAR_001483`
`VARIANT`	`144 144`	`1`	`R -> C (in squamous cell carcinoma).`	`VAR_001484`
`VARIANT`	`148 148`	`1`	`A -> T (in dbSNP:rs3731249 [NCBI]).`	`VAR_001486`
`VARIANT`	`150 150`	`1`	`G -> V (in non-small cell lung carcinoma).`	`VAR_001487`
`HELIX`	`15 22`	`8`
`HELIX`	`25 32`	`8`
`TURN`	`33 35`	`3`
`STRAND`	`43 45`	`3`
`TURN`	`48 50`	`3`
`HELIX`	`57 64`	`8`
`TURN`	`65 67`	`3`
`TURN`	`75 77`	`3`
`HELIX`	`81 88`	`8`
`HELIX`	`91 100`	`10`
`HELIX`	`114 121`	`8`
`HELIX`	`124 130`	`7`
`STRAND`	`150 153`	`4`

Sequence information

Length: 156 AA [This is the length of the unprocessed precursor]

Molecular weight: 16533 Da [This is the MW of the unprocessed precursor]

CRC64: E59C0E6174B48255 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEPAAGSSME PSADWLATAA ARGRVEEVRA LLEAGALPNA PNSYGRRPIQ VMMMGSARVA 

        70         80         90        100        110        120 
ELLLLHGAEP NCADPATLTR PVHDAAREGF LDTLVVLHRA GARLDVRDAW GRLPVDLAEE 

       130        140        150 
LGHRDVARYL RAAAGGTRGS NHARIDAAEG PSDIPD

P42771 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools