Reviewed, UniProtKB/Swiss-Prot P42771 (CD2A1_HUMAN)

Names and origin

Protein names

Recommended name:
    Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3
Alternative name(s):
    Cyclin-dependent kinase 4 inhibitor A
      Short name=CDK4I
    p16-INK4a
      Short name=p16INK4A
      Short name=p16-INK4
    Multiple tumor suppressor 1
      Short name=MTS-1

Gene names

Name:	CDKN2A
Synonyms:	CDKN2, MTS1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	156 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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. Ref.10
Subunit structure	Heterodimer with CDK4 or CDK6. Isoform 3 does not bind to CDK4.
Tissue specificity	Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific. Ref.2
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.
Involvement in disease	Defects in CDKN2A are involved in tumor formation in a wide range of tissues. 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. Ref.18 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.30 Ref.32 Ref.33 Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719]. 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. Ref.29 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. Ref.31
Sequence similarities	Belongs to the CDKN2 cyclin-dependent kinase inhibitor family. Contains 4 ANK repeats.

Ontologies

Keywords
Biological process	Cell cycle
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Li-Fraumeni syndrome
Domain	ANK repeat Repeat
Molecular function	Anti-oncogene
Technical term	3D-structure
Gene Ontology (GO)
Biological process	G1/S transition of mitotic cell cycle Inferred from direct assay. Source: UniProtKB cell cycle arrest Inferred from mutant phenotype. Source: HGNC cell cycle checkpoint Inferred from mutant phenotype. Source: HGNC induction of apoptosis Inferred from direct assay. Source: UniProtKB negative regulation of NF-kappaB transcription factor activity Inferred from direct assay. Source: UniProtKB negative regulation of cell growth Inferred from direct assay. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype. Source: UniProtKB negative regulation of cell-matrix adhesion Inferred from mutant phenotype. Source: UniProtKB negative regulation of cyclin-dependent protein kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB negative regulation of phosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB senescence Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HGNC
Molecular function	NF-kappaB binding Inferred from direct assay. Source: UniProtKB cyclin-dependent protein kinase inhibitor activity Ref.1 Inferred from direct assay. Source: UniProtKB protein kinase binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AURKA	O14965	1	EBI-375053,EBI-448680
CDC45L	O75419	1	EBI-375053,EBI-374969
CDC6	Q99741	1	EBI-375053,EBI-374862
CDC7	O00311	1	EBI-375053,EBI-374980
CDK4	P11802	5	EBI-375053,EBI-295644
CDK6	Q00534	5	EBI-375053,EBI-295663
GMNN	O75496	1	EBI-375053,EBI-371669
MCM10	Q7L590	1	EBI-375053,EBI-374912
MCM2	P49736	1	EBI-375053,EBI-374819
MCM5	P33992	1	EBI-375053,EBI-359410
MCM6	Q14566	1	EBI-375053,EBI-374900
ORC4L	O43929	1	EBI-375053,EBI-374889
ORC5L	O43913	1	EBI-375053,EBI-374928
PCNA	P12004	3	EBI-375053,EBI-358311

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: 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.

Isoform 1 (identifier: P42771-1)

Also known as: p16INK4a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P42771-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.

Isoform 3 (identifier: P42771-3)

Also known as: p12;

The sequence of this isoform differs from the canonical sequence as follows:
     52-116: MMMGSARVAE...RDAWGRLPVD → GRRSAAGAGD...LGAWETKEEE
     117-156: Missing.

Isoform 4 (identifier: Q8N726-1)

Also known as: p14ARF; p19ARF; ARF;

The sequence of this isoform can be found in the external entry Q8N726-1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 156

156

Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3

PRO_0000144177

Regions

Repeat

11 – 40

30

ANK 1

Repeat

44 – 72

29

ANK 2

Repeat

77 – 106

30

ANK 3

Repeat

110 – 139

30

ANK 4

Natural variations

Alternative sequence

1 – 51

51

Missing in isoform 2.

VSP_015864

Alternative sequence

52 – 116

65

MMMGS…RLPVD → GRRSAAGAGDGGRLWRTKFA GELESGSASILRKKGRLPGE FSEGVCNHRPPPGDALGAWE TKEEE in isoform 3.

VSP_015865

Alternative sequence

117 – 156

40

Missing in isoform 3.

VSP_015866

Natural variant

14

1

D → E in a biliary tract tumor.

VAR_001408

Natural variant

16

1

L → P in a biliary tract tumor and a familial melanoma.

VAR_001409

Natural variant

20

1

A → P in a lung tumor and melanoma. Ref.23

VAR_001410

Natural variant

20

1

A → S in a biliary tract tumor. Ref.23

VAR_001411

Natural variant

23

1

G → D in a pancreas tumor.

VAR_001412

Natural variant

24

1

R → C in melanoma. Ref.25

VAR_001413

Natural variant

24

1

R → P in CMM2 and melanoma.

VAR_001414

Natural variant

26

1

E → D in a biliary tract tumor.

VAR_001415

Natural variant

32

1

L → P in CMM2. Ref.21

VAR_001416

Natural variant

33

1

E → D in a biliary tract tumor.

VAR_001417

Natural variant

35

1

G → A in CMM2 and a biliary tract tumor.

VAR_001418

Natural variant

35

1

G → E in melanoma. Ref.21

VAR_001419

Natural variant

48

1

P → L in melanoma and a head and neck tumor; somatic mutation. Ref.28

VAR_001420

Natural variant

49

1

I → S in a biliary tract tumor. Ref.18 Ref.22

VAR_001421

Natural variant

49

1

I → T Ref.18 Ref.22

VAR_001422

Natural variant

50

1

Q → R in CMM2. Ref.21 Ref.23

VAR_001423

Natural variant

53

1

M → I in CMM2. Ref.21 Ref.24 Ref.25

VAR_001424

Natural variant

56

1

S → I Possible polymorphism.

VAR_001425

Natural variant

57

1

A → V in pancreas carcinoma; somatic mutation. Ref.28

VAR_001426

Natural variant

58

1

R → Q: dbSNP rs36204273.

VAR_053027

Natural variant

59

1

V → G in CMM2. Ref.33

VAR_001427

Natural variant

60

1

A → T Ref.23

VAR_001428

Natural variant

60

1

A → V: dbSNP rs36204594. Ref.23

VAR_053028

Natural variant

61 – 62

2

EL → DV

VAR_001429

Natural variant

62

1

L → P in familial melanoma.

VAR_001430

Natural variant

66

1

H → Y in non-small cell lung carcinoma. Ref.17

VAR_001431

Natural variant

68

1

A → L in familial melanoma; requires 2 nucleotide substitutions. Ref.24

VAR_001432

Natural variant

68

1

A → T in an esophagus tumor. Ref.24

VAR_001433

Natural variant

68

1

A → V Ref.24

VAR_001434

Natural variant

69

1

E → K in a bladder tumor.

VAR_001435

Natural variant

69

1

E → V in a lung tumor.

VAR_001436

Natural variant

71

1

N → K in familial melanoma. Ref.18 Ref.22

VAR_001437

Natural variant

71

1

N → S Ref.18 Ref.22

VAR_001438

Natural variant

72

1

C → G in an esophagus tumor.

VAR_001439

Natural variant

74

1

D → N in a bladder tumor.

VAR_001440

Natural variant

74

1

D → V in a biliary tract tumor.

VAR_001441

Natural variant

80

1

R → L in a head and neck tumor. Ref.23

VAR_001442

Natural variant

81

1

P → L in melanoma; impairs the function. dbSNP rs11552823. Ref.22

VAR_001443

Natural variant

83

1

H → N in a lung tumor.

VAR_001445

Natural variant

83

1

H → Q: dbSNP rs34968276.

VAR_053029

Natural variant

83

1

H → Y in a pancreas and a head and neck tumor.

VAR_001444

Natural variant

84

1

D → E in a bladder tumor. Ref.33 Ref.17

VAR_001446

Natural variant

84

1

D → H in non-small cell lung carcinoma. Ref.33 Ref.17

VAR_001447

Natural variant

84

1

D → N in an esophagus, a head and neck and a lung tumor. Ref.33 Ref.17

VAR_001448

Natural variant

84

1

D → Y in CMM2; also found in a lung and a prostate tumor. dbSNP rs11552822. Ref.33

VAR_001449

Natural variant

85

1

A → T Ref.24

VAR_001450

Natural variant

87

1

R → P in CMM2; impairs the function. Ref.18 Ref.33

VAR_001451

Natural variant

87

1

R → W in CMM2. Ref.18 Ref.33

VAR_012317

Natural variant

88

1

E → D in a biliary tract tumor.

VAR_001452

Natural variant

89

1

G → D in melanoma; somatic mutation. Ref.28

VAR_001453

Natural variant

89

1

G → S in melanoma. Ref.28

VAR_001454

Natural variant

93

1

T → A in non-small cell lung carcinoma. Ref.17

VAR_001455

Natural variant

94

1

L → Q in melanoma. Ref.35

VAR_023604

Natural variant

95

1

V → A in non-small cell lung carcinoma. Ref.17

VAR_001456

Natural variant

97

1

L → R Possible polymorphism.

VAR_001457

Natural variant

98

1

H → P in melanoma.

VAR_001458

Natural variant

98

1

H → Q in melanoma.

VAR_001459

Natural variant

99

1

R → P in familial melanoma. Ref.17

VAR_001460

Natural variant

99

1

R → Q in non-small cell lung carcinoma. Ref.17

VAR_001461

Natural variant

99

1

R → W: dbSNP rs34886500. Ref.17

VAR_053030

Natural variant

100

1

A → L in melanoma; requires 2 nucleotide substitutions. Ref.23

VAR_001462

Natural variant

100

1

A → P Ref.23

VAR_001463

Natural variant

101

1

G → W in CMM2 and FAMMMPC; impairs the function.

VAR_001464

Natural variant

102

1

A → E in LFS; somatic mutation. Ref.29

VAR_015818

Natural variant

102

1

A → T: dbSNP rs35741010. Ref.29

VAR_053031

Natural variant

104 – 105

2

Missing

VAR_001465

Natural variant

107

1

R → C in CMM2. Ref.24

VAR_001466

Natural variant

107

1

R → H Ref.24

VAR_001467

Natural variant

108

1

D → H in a bladder tumor.

VAR_001469

Natural variant

108

1

D → Y in a head and neck tumor.

VAR_001468

Natural variant

112

1

R → RR in CMM2. Ref.23

VAR_035068

Natural variant

114

1

P → L in non-small cell lung carcinoma. Ref.17

VAR_001470

Natural variant

117

1

L → M in melanoma; somatic mutation. Ref.28

VAR_001471

Natural variant

118

1

A → T in CMM2. Ref.25

VAR_001472

Natural variant

119

1

E → Q in a biliary tract tumor.

VAR_001473

Natural variant

120

1

E → A in non-small cell lung carcinoma. Ref.23 Ref.17

VAR_001474

Natural variant

120

1

E → K in non-small cell lung carcinoma. Ref.23 Ref.17

VAR_001475

Natural variant

122

1

G → R in CMM2. Ref.32

VAR_035069

Natural variant

122

1

G → S in a biliary tract tumor. Ref.32

VAR_001476

Natural variant

123

1

H → Q in leukemia. dbSNP rs6413463.

VAR_001477

Natural variant

124

1

R → C: dbSNP rs34170727.

VAR_053032

Natural variant

124

1

R → H in an esophagus tumor.

VAR_001478

Natural variant

126

1

V → D in CMM2; impairs the function. Ref.18 Ref.30

VAR_001479

Natural variant

127

1

A → S in squamous cell carcinoma. dbSNP rs6413464. Ref.19

VAR_001480

Natural variant

132

1

A → P in non-small cell lung carcinoma. Ref.17

VAR_001481

Natural variant

134

1

A → V in non-small cell lung carcinoma. Ref.17

VAR_001482

Natural variant

142

1

H → Y in non-small cell lung carcinoma. Ref.17

VAR_001483

Natural variant

144

1

R → C in squamous cell carcinoma. Ref.19

VAR_001484

Natural variant

148

1

A → T: dbSNP rs3731249. Ref.18 Ref.21 Ref.23 Ref.24 Ref.25 Ref.28 Ref.22

VAR_001486

Natural variant

150

1

G → V in non-small cell lung carcinoma. Ref.23 Ref.17

VAR_001487

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

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156

Helix Strand Turn

Details...

Helix

15 – 22

8

Helix

25 – 32

8

Turn

33 – 35

3

Beta 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

Beta strand

150 – 153

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p16INK4a) [UniParc]. Last modified July 15, 1998. Version 2. Checksum: E59C0E6174B48255	FASTA	156	16,533
	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
	Isoform 2. Checksum: 7F3FA00737E14285	FASTA	105	11,215
	10 20 30 40 50 60 MMMGSARVAE LLLLHGAEPN CADPATLTRP VHDAAREGFL DTLVVLHRAG ARLDVRDAWG 70 80 90 100 RLPVDLAEEL GHRDVARYLR AAAGGTRGSN HARIDAAEGP SDIPD
	Isoform 3 (p12). Checksum: F44DBC8E0EB3A7C8	FASTA	116	12,213
	10 20 30 40 50 60 MEPAAGSSME PSADWLATAA ARGRVEEVRA LLEAGALPNA PNSYGRRPIQ VGRRSAAGAG 70 80 90 100 110 DGGRLWRTKF AGELESGSAS ILRKKGRLPG EFSEGVCNHR PPPGDALGAW ETKEEE
	Isoform 4 (p14ARF) (p19ARF) (ARF). See Q8N726.	FASTA	–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4." Serrano M., Hannon G.J., Beach D. Nature 366:704-707(1993) [PubMed: 8259215] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus." Robertson K.D., Jones P.A. Oncogene 18:3810-3820(1999) [PubMed: 10445844] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
[3]	"Prevalent involvement of illegitimate V(D)J recombination in chromosome 9p21 deletions in lymphoid leukemia." Kitagawa Y., Inoue K., Sasaki S., Hayashi Y., Matsuo Y., Lieber M.R., Mizoguchi H., Yokota J., Kohno T. J. Biol. Chem. 277:46289-46297(2002) [PubMed: 12228235] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"DNA sequence and analysis of human chromosome 9." 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. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skin.
[7]	"Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence." Hara E., Smith R., Parry D., Tahara H., Stone S., Peters G. Mol. Cell. Biol. 16:859-867(1996) [PubMed: 8622687] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
[8]	"Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers." Nobori T., Miura K., Wu D.J., Lois A., Takabayashi K., Carson D.A. Nature 368:753-756(1994) [PubMed: 8152487] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 51-156.
[9]	"A cell cycle regulator potentially involved in genesis of many tumor types." 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. Science 264:436-440(1994) [PubMed: 8153634] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 51-152.
[10]	"Mutations and altered expression of p16INK4 in human cancer." 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. Proc. Natl. Acad. Sci. U.S.A. 91:11045-11049(1994) [PubMed: 7972006] [Abstract] Cited for: FUNCTION.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a." Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P. Nature 395:237-243(1998) [PubMed: 9751050] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CDK6.
[13]	"Tumor suppressor INK4: comparisons of conformational properties between p16(INK4A) and p18(INK4C)." Yuan C., Li J., Selby T.L., Byeon I.-J., Tsai M.-D. J. Mol. Biol. 294:201-211(1999) [PubMed: 10556039] [Abstract] Cited for: STRUCTURE BY NMR.
[14]	"Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data." Yuan C., Selby T.L., Li J., Byeon I.J., Tsai M.D. Protein Sci. 9:1120-1128(2000) [PubMed: 10892805] [Abstract] Cited for: STRUCTURE BY NMR.
[15]	"CDKN2 mutations in melanoma." Dracopoli N.C., Fountain J.W. Cancer Surv. 26:115-132(1996) [PubMed: 8783570] [Abstract] Cited for: REVIEW ON MELANOMA VARIANTS.
[16]	"CDKN2A (p16INK4A) somatic and germline mutations." Smith-Soerensen B., Hovig E. Hum. Mutat. 7:294-303(1996) [PubMed: 8723678] [Abstract] Cited for: REVIEW ON VARIANTS.
[17]	"Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas." Hayashi N., Sugimoto Y., Tsuchiya E., Ogawa M., Nakamura Y. Biochem. Biophys. Res. Commun. 202:1426-1430(1994) [PubMed: 8060323] [Abstract] Cited for: 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.
[18]	"Germline p16 mutations in familial melanoma." 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. Nat. Genet. 8:15-21(1994) [PubMed: 7987387] [Abstract] Cited for: VARIANTS CMM2 PRO-87; TRP-101 AND ASP-126, VARIANTS THR-49; SER-71 AND THR-148.
[19]	"The MTS1 gene is frequently mutated in primary human esophageal tumors." Zhou X., Tarmin L., Yin J., Jiang H.-Y., Suzuki H., Rhyu M.-G., Abraham J.M., Meltzer S.J. Oncogene 9:3737-3741(1994) [PubMed: 7970734] [Abstract] Cited for: VARIANTS SQUAMOUS CELL CARCINOMA SER-127 AND CYS-144.
[20]	"Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer." 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. Cancer Res. 55:1448-1451(1995) [PubMed: 7882351] [Abstract] Cited for: VARIANTS.
[21]	"Mutations of the CDKN2/p16INK4 gene in Australian melanoma kindreds." Walker G.J., Hussussian C.J., Flores J.F., Glendening J.M., Haluska F.G., Dracopoli N.C., Hayward N.K., Fountain J.W. Hum. Mol. Genet. 4:1845-1852(1995) [PubMed: 8595405] [Abstract] Cited for: VARIANTS CMM2 PRO-32; ALA-35; ARG-50 AND ILE-53, VARIANT MELANOMA GLU-35, VARIANT THR-148.
[22]	"Mutations associated with familial melanoma impair p16INK4 function." 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. Nat. Genet. 10:114-116(1995) [PubMed: 7647780] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS THR-49; SER-71; LEU-81; PRO-87; TRP-101; ASP-126 AND THR-148.
[23]	"Novel germline p16 mutation in familial malignant melanoma in southern Sweden." Borg A., Johannsson U., Johannsson O., Haakansson S., Westerdahl J., Maasbaeck A., Olsson H., Ingvar C. Cancer Res. 56:2497-2500(1996) [PubMed: 8653684] [Abstract] Cited for: VARIANT CMM2 ARG-112 INS, VARIANT THR-148.
[24]	"Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: analysis of a clinic-based population." 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. Proc. Natl. Acad. Sci. U.S.A. 93:8541-8545(1996) [PubMed: 8710906] [Abstract] Cited for: VARIANTS CMM2 ILE-53 AND CYS-107, VARIANTS VAL-68; THR-85 AND THR-148.
[25]	"Germline mutations of the CDKN2 gene in UK melanoma families." 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. Hum. Mol. Genet. 6:2061-2067(1997) [PubMed: 9328469] [Abstract] Cited for: VARIANTS CMM2 PRO-24; ILE-53 AND THR-118, VARIANT THR-148.
[26]	"Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France." 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. 7:209-216(1998) [PubMed: 9425228] [Abstract] Cited for: VARIANTS CMM2.
[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]	"Five novel somatic CDKN2/p16 mutations identified in melanoma, glioma and carcinoma of the pancreas." Gretarsdottir S., Olafsdottir G.H., Borg A. Hum. Mutat. 12:212-212(1998) [PubMed: 10651484] [Abstract] Cited for: VARIANTS MELANOMA LEU-48; ASP-89 AND MET-117, VARIANT PANCREAS CARCINOMA VAL-57, VARIANT THR-148.
[29]	"Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family." Gueran S., Tunca Y., Imirzalioglu N. Cancer Genet. Cytogenet. 113:145-151(1999) [PubMed: 10484981] [Abstract] Cited for: VARIANT LFS GLU-102.
[30]	"A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families." Goldstein A.M., Liu L., Shennan M.G., Hogg D., Tucker M.A., Struewing J.P. Br. J. Cancer 85:527-530(2001) [PubMed: 11506491] [Abstract] Cited for: VARIANT CMM2 ASP-126.
[31]	"A germline deletion of p14(ARF) but not CDKN2A in a melanoma-neural system tumour syndrome family." 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. Hum. Mol. Genet. 10:55-62(2001) [PubMed: 11136714] [Abstract] Cited for: INVOLVEMENT IN MELANOMA-ASTROCYTOMA SYNDROME.
[32]	"Germline mutation of ARF in a melanoma kindred." Hewitt C., Lee Wu C., Evans G., Howell A., Elles R.G., Jordan R., Sloan P., Read A.P., Thakker N. Hum. Mol. Genet. 11:1273-1279(2002) [PubMed: 12019208] [Abstract] Cited for: VARIANT CMM2 ARG-122.
[33]	"CDKN2A mutations in Spanish cutaneous malignant melanoma families and patients with multiple melanomas and other neoplasia." Ruiz A., Puig S., Malvehy J., Lazaro C., Lynch M., Gimenez-Arnau A.M., Puig L., Sanchez-Conejo J., Estivill X., Castel T. J. Med. Genet. 36:490-493(1999) [PubMed: 10874641] [Abstract] Cited for: VARIANTS CMM2 GLY-59; TYR-84; TRP-87 AND TRP-101.
[34]	"Contribution of germline mutations in BRCA2, P16(INK4A), P14(ARF) and P15 to uveal melanoma." Hearle N., Damato B.E., Humphreys J., Wixey J., Green H., Stone J., Easton D.F., Houlston R.S. Invest. Ophthalmol. Vis. Sci. 44:458-462(2003) [PubMed: 12556369] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO UVEAL MELANOMA.
[35]	"A novel L94Q mutation in the CDKN2A gene in a melanoma kindred." Avbelj M., Hocevar M., Trebusak-Podkrajsek K., Krzisnik C., Battelino T. Melanoma Res. 13:567-570(2003) [PubMed: 14646619] [Abstract] Cited for: VARIANT MELANOMA GLN-94.
+	Additional computationally mapped references.

Web resources

CDKN2A Database

Database of CDKN2A germline and somatic variants

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Wikipedia

P16INK4a entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

L27211 mRNA. Translation: AAA92554.1.
AB060808 Genomic DNA. Translation: BAB91133.1.
AF527803 Genomic DNA. Translation: AAR05391.1.
AF115544 mRNA. Translation: AAD11437.1.
AL449423 Genomic DNA. Translation: CAH70600.1.
BC015960 mRNA. Translation: AAH15960.2.
BC021998 mRNA. Translation: AAH21998.2.
X94154 Genomic DNA. Translation: CAA63870.1.
S69824, S69822 Genomic DNA. Translation: AAD14050.1.
S69804 Genomic DNA. Translation: AAD14048.1.
U12820, U12818, U12819 Genomic DNA. Translation: AAB60645.1. Different initiation.

IPI

IPI00001560.
IPI00030733.
IPI00651662.

PIR

JE0141.

RefSeq

NP_000068.1.
NP_478104.2.

UniGene

Hs.512599

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A5E	NMR	-	A	1-156	[»]
1BI7	X-ray	3.40	B	1-156	[»]
1DC2	NMR	-	A	1-156	[»]
2A5E	NMR	-	A	1-156	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6108N.

IntAct

P42771. 52 interactions.

PTM databases

PhosphoSite

P42771.

Proteomic databases

PRIDE

P42771.

Genome annotation databases

Ensembl

ENSG00000147889. Homo sapiens. [Contig view]

GeneID

1029.

KEGG

hsa:1029.

Organism-specific databases

GeneCards

GC09M021957.

HGNC

HGNC:1787. CDKN2A.

HPA

CAB000093.
CAB018232.

MIM

151623. phenotype.
155601. phenotype.
155720. phenotype.
155755. phenotype.
600160. gene.
606719. phenotype.

PharmGKB

PA106.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P42771.

OMA

P42771. SNHARID.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

P42771.

Bgee

P42771.

CleanEx

HS_CDKN2A.

GermOnline

ENSG00000147889. Homo sapiens.

Family and domain databases

InterPro

IPR002110. ANK.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 1 hit.

Pfam

PF00023. Ank. 3 hits.
[Graphical view]

SMART

SM00248. ANK. 2 hits.
[Graphical view]

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4323.

SOURCE

Search...

Entry information

Entry name

CD2A1_HUMAN

Accession

Primary (citable) accession number: P42771
Secondary accession number(s): O95440 , Q15191, Q5VVJ5, Q96B52, Q9NP05

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 15, 1998
Last modified:	June 16, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)