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Protein

Cyclin-dependent kinase inhibitor 2A

Gene

CDKN2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  • cyclin-dependent protein serine/threonine kinase inhibitor activity Source: BHF-UCL
  • NF-kappaB binding Source: BHF-UCL
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase binding Source: BHF-UCL

GO - Biological processi

  • cell cycle arrest Source: BHF-UCL
  • cellular senescence Source: BHF-UCL
  • G1/S transition of mitotic cell cycle Source: BHF-UCL
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of cell-matrix adhesion Source: BHF-UCL
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of phosphorylation Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of cellular senescence Source: UniProtKB
  • positive regulation of macrophage apoptotic process Source: BHF-UCL
  • positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
  • Ras protein signal transduction Source: BHF-UCL
  • replicative senescence Source: BHF-UCL
  • senescence-associated heterochromatin focus assembly Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Enzyme and pathway databases

BioCyciZFISH:HS07481-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-69231. Cyclin D associated events in G1.
SIGNORiP42771.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 2AImported
Alternative name(s):
Cyclin-dependent kinase 4 inhibitor A
Short name:
CDK4I
Multiple tumor suppressor 1
Short name:
MTS-1
p16-INK4a
Short name:
p16-INK4
Short name:
p16INK4A
Gene namesi
Name:CDKN2AImported
Synonyms:CDKN2, MTS1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:1787. CDKN2A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • nucleus Source: HGNC
  • senescence-associated heterochromatin focus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.

Melanoma, cutaneous malignant 2 (CMM2)12 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
See also OMIM:155601
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05854919A → ATA in CMM2; loss of CDK4 binding. 1
Natural variantiVAR_00141324R → C in CMM2. 1
Natural variantiVAR_00141424R → P in CMM2. 1 PublicationCorresponds to variant rs104894097dbSNPEnsembl.1
Natural variantiVAR_00141632L → P in CMM2. 1 Publication1
Natural variantiVAR_00141835G → A in CMM2; also found in a biliary tract tumor and a patient with uveal melanoma; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs746834149dbSNPEnsembl.1
Natural variantiVAR_00141935G → E in CMM2. 1 PublicationCorresponds to variant rs746834149dbSNPEnsembl.1
Natural variantiVAR_05855135G → V in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00142048P → L in CMM2; also found in head and neck tumor; somatic mutation. 1 Publication1
Natural variantiVAR_00142350Q → R in CMM2. 1 Publication1
Natural variantiVAR_00142453M → I in CMM2. 3 PublicationsCorresponds to variant rs104894095dbSNPEnsembl.1
Natural variantiVAR_00142759V → G in CMM2. 1 PublicationCorresponds to variant rs104894099dbSNPEnsembl.1
Natural variantiVAR_00143062L → P in CMM2. 1
Natural variantiVAR_05855367G → R in CMM2; partial loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00143268A → L in CMM2; requires 2 nucleotide substitutions. 1
Natural variantiVAR_00143771N → K in CMM2. 1
Natural variantiVAR_05855574D → Y in CMM2; loss of CDK4 binding. 1 PublicationCorresponds to variant rs760640852dbSNPEnsembl.1
Natural variantiVAR_05855677T → P in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_05855780R → P in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_05855881P → T in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00144984D → Y in CMM2; also found in a lung tumor and a prostate tumor. 1 PublicationCorresponds to variant rs11552822dbSNPEnsembl.1
Natural variantiVAR_00145187R → P in CMM2; impairs the function. 2 Publications1
Natural variantiVAR_01231787R → W in CMM2; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs749714198dbSNPEnsembl.1
Natural variantiVAR_00145389G → D in CMM2; somatic mutation. 1 PublicationCorresponds to variant rs137854599dbSNPEnsembl.1
Natural variantiVAR_00145489G → S in CMM2. Corresponds to variant rs137854597dbSNPEnsembl.1
Natural variantiVAR_02360494L → Q in CMM2. 1 Publication1
Natural variantiVAR_00145797L → R in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00145898H → P in CMM2. 1
Natural variantiVAR_00145998H → Q in CMM2. 1
Natural variantiVAR_00146099R → P in CMM2; loss of CDK4 binding. 1
Natural variantiVAR_001462100A → L in CMM2; requires 2 nucleotide substitutions. 1
Natural variantiVAR_001464101G → W in CMM2 and FAMMMPC; impairs the function. 3 PublicationsCorresponds to variant rs104894094dbSNPEnsembl.1
Natural variantiVAR_001466107R → C in CMM2. 1 Publication1
Natural variantiVAR_035068112R → RR in CMM2. 1 Publication1
Natural variantiVAR_001471117L → M in CMM2; somatic mutation. 1 Publication1
Natural variantiVAR_001472118A → T in CMM2. 1 Publication1
Natural variantiVAR_035069122G → R in CMM2. 1 PublicationCorresponds to variant rs113798404dbSNPEnsembl.1
Natural variantiVAR_001479126V → D in CMM2; impairs the function. 3 PublicationsCorresponds to variant rs104894098dbSNPEnsembl.1
Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn inherited cancer predisposition syndrome characterized by an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer.
See also OMIM:606719
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001464101G → W in CMM2 and FAMMMPC; impairs the function. 3 PublicationsCorresponds to variant rs104894094dbSNPEnsembl.1
Melanoma-astrocytoma syndrome (MASTS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.
See also OMIM:155755

Keywords - Diseasei

Disease mutation, Li-Fraumeni syndrome, Tumor suppressor

Organism-specific databases

DisGeNETi1029.
MalaCardsiCDKN2A.
MIMi155601. phenotype.
155755. phenotype.
606719. phenotype.
OpenTargetsiENSG00000147889.
Orphaneti404560. Familial atypical multiple mole melanoma syndrome.
618. Familial melanoma.
1333. Familial pancreatic carcinoma.
252206. Melanoma and neural system tumor syndrome.
51013. Melanoma-pancreatic cancer syndrome.
99860. Precursor B-cell acute lymphoblastic leukemia.
99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA106.

Polymorphism and mutation databases

BioMutaiMTAP.
DMDMi3041660.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001441771 – 156Cyclin-dependent kinase inhibitor 2AAdd BLAST156

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei7Phosphoserine1 Publication1
Modified residuei8Phosphoserine1 Publication1
Modified residuei140Phosphoserine1 Publication1
Modified residuei152Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation seems to increase interaction with CDK4.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP42771.
PaxDbiP42771.
PeptideAtlasiP42771.
PRIDEiP42771.
TopDownProteomicsiP42771-1. [P42771-1]

PTM databases

iPTMnetiP42771.
PhosphoSitePlusiP42771.

Expressioni

Tissue specificityi

Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific.1 Publication

Gene expression databases

BgeeiENSG00000147889.
CleanExiHS_CDKN2A.
ExpressionAtlasiP42771. baseline and differential.
GenevisibleiP42771. HS.

Organism-specific databases

HPAiCAB000093.
CAB000445.
CAB018232.

Interactioni

Subunit structurei

Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity. Interacts with ISCO2.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK4P1180213EBI-375053,EBI-295644
CDK6Q0053414EBI-375053,EBI-295663
CRELD2Q6UXH12EBI-375053,EBI-3935314
DEAF1O753982EBI-375053,EBI-718185
HNRNPUQ008392EBI-375053,EBI-351126
MCM6Q145664EBI-375053,EBI-374900
PCNAP120048EBI-375053,EBI-358311
TDRD7Q8NHU62EBI-375053,EBI-624505

GO - Molecular functioni

  • NF-kappaB binding Source: BHF-UCL
  • protein kinase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107463. 156 interactors.
DIPiDIP-6108N.
IntActiP42771. 59 interactors.
MINTiMINT-1201444.
STRINGi9606.ENSP00000394932.

Structurei

Secondary structure

1156
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 6Combined sources3
Helixi15 – 22Combined sources8
Helixi25 – 32Combined sources8
Turni33 – 35Combined sources3
Beta strandi43 – 45Combined sources3
Turni48 – 50Combined sources3
Helixi57 – 64Combined sources8
Turni65 – 67Combined sources3
Turni75 – 77Combined sources3
Helixi81 – 88Combined sources8
Helixi91 – 100Combined sources10
Beta strandi109 – 111Combined sources3
Helixi114 – 121Combined sources8
Helixi124 – 130Combined sources7
Turni133 – 135Combined sources3
Turni141 – 143Combined sources3
Beta strandi145 – 147Combined sources3
Beta strandi150 – 153Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A5ENMR-A1-156[»]
1BI7X-ray3.40B1-156[»]
1DC2NMR-A1-156[»]
2A5ENMR-A1-156[»]
ProteinModelPortaliP42771.
SMRiP42771.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42771.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati11 – 40ANK 1Add BLAST30
Repeati44 – 72ANK 2Add BLAST29
Repeati77 – 106ANK 3Add BLAST30
Repeati110 – 139ANK 4Add BLAST30

Sequence similaritiesi

Contains 4 ANK repeats.Curated

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00390000004527.
HOGENOMiHOG000290191.
HOVERGENiHBG050870.
InParanoidiP42771.
KOiK06621.
OMAiVNCYGRR.
TreeFamiTF352389.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoform 1 and isoform tumor suppressor ARF 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) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MEPAAGSSME PSADWLATAA ARGRVEEVRA LLEAGALPNA PNSYGRRPIQ
60 70 80 90 100
VMMMGSARVA ELLLLHGAEP NCADPATLTR PVHDAAREGF LDTLVVLHRA
110 120 130 140 150
GARLDVRDAW GRLPVDLAEE LGHRDVARYL RAAAGGTRGS NHARIDAAEG

PSDIPD
Length:156
Mass (Da):16,533
Last modified:July 15, 1998 - v2
Checksum:iE59C0E6174B48255
GO
Isoform 2 (identifier: P42771-2) [UniParc]FASTAAdd to basket

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

Show »
Length:105
Mass (Da):11,215
Checksum:i7F3FA00737E14285
GO
Isoform 3 (identifier: P42771-3) [UniParc]FASTAAdd to basket
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.

Show »
Length:116
Mass (Da):12,213
Checksum:iF44DBC8E0EB3A7C8
GO
Isoform tumor suppressor ARF (identifier: Q8N726-1) [UniParc]FASTAAdd to basket
Also known as: p14ARF, p19ARF
The sequence of this isoform can be found in the external entry Q8N726.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:132
Mass (Da):13,903
GO
Isoform 5 (identifier: P42771-4) [UniParc]FASTAAdd to basket
Also known as: p16gamma

The sequence of this isoform differs from the canonical sequence as follows:
     153-156: DIPD → EMIGNHLWVCRSRHA

Note: Barely detectable in non-tumor cells.
Show »
Length:167
Mass (Da):17,883
Checksum:i07328B24CC7ECC61
GO
Isoform smARF (identifier: Q8N726-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q8N726.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:85
Mass (Da):8,731
GO

Sequence cautioni

The sequence AAB60645 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00140814D → E in a biliary tract tumor. 1
Natural variantiVAR_00140916L → P in a biliary tract tumor and a familial melanoma. 1
Natural variantiVAR_05854919A → ATA in CMM2; loss of CDK4 binding. 1
Natural variantiVAR_00141020A → P in a lung tumor and melanoma. 1
Natural variantiVAR_00141120A → S in a biliary tract tumor. Corresponds to variant rs760065045dbSNPEnsembl.1
Natural variantiVAR_00141223G → D in a pancreas tumor and a melanoma; loss of CDK4 binding. 1
Natural variantiVAR_00141324R → C in CMM2. 1
Natural variantiVAR_00141424R → P in CMM2. 1 PublicationCorresponds to variant rs104894097dbSNPEnsembl.1
Natural variantiVAR_05855024R → Q Found in a patient with multiple primary melanoma; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs104894097dbSNPEnsembl.1
Natural variantiVAR_00141526E → D in a biliary tract tumor. 1
Natural variantiVAR_00141632L → P in CMM2. 1 Publication1
Natural variantiVAR_00141733E → D in a biliary tract tumor. 1
Natural variantiVAR_00141835G → A in CMM2; also found in a biliary tract tumor and a patient with uveal melanoma; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs746834149dbSNPEnsembl.1
Natural variantiVAR_00141935G → E in CMM2. 1 PublicationCorresponds to variant rs746834149dbSNPEnsembl.1
Natural variantiVAR_05855135G → V in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00142048P → L in CMM2; also found in head and neck tumor; somatic mutation. 1 Publication1
Natural variantiVAR_00142149I → S in a biliary tract tumor. 1
Natural variantiVAR_00142249I → T.2 PublicationsCorresponds to variant rs199907548dbSNPEnsembl.1
Natural variantiVAR_00142350Q → R in CMM2. 1 Publication1
Natural variantiVAR_00142453M → I in CMM2. 3 PublicationsCorresponds to variant rs104894095dbSNPEnsembl.1
Natural variantiVAR_00142556S → I Possible polymorphism. Corresponds to variant rs104894109dbSNPEnsembl.1
Natural variantiVAR_00142657A → V in pancreas carcinoma; somatic mutation; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs372266620dbSNPEnsembl.1
Natural variantiVAR_05302758R → Q.Corresponds to variant rs36204273dbSNPEnsembl.1
Natural variantiVAR_00142759V → G in CMM2. 1 PublicationCorresponds to variant rs104894099dbSNPEnsembl.1
Natural variantiVAR_00142860A → T.Corresponds to variant rs769382085dbSNPEnsembl.1
Natural variantiVAR_05302860A → V in melanoma; loss of CDK4 binding. Corresponds to variant rs36204594dbSNPEnsembl.1
Natural variantiVAR_00142961 – 62EL → DV.2
Natural variantiVAR_00143062L → P in CMM2. 1
Natural variantiVAR_00143166H → Y in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_05855267 – 71Missing in melanoma; loss of CDK4 binding. 1 Publication5
Natural variantiVAR_05855367G → R in CMM2; partial loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00143268A → L in CMM2; requires 2 nucleotide substitutions. 1
Natural variantiVAR_00143368A → T in an esophagus tumor. 1
Natural variantiVAR_00143468A → V.1 Publication1
Natural variantiVAR_05855469E → G Found in some patients with melanoma; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs372670098dbSNPEnsembl.1
Natural variantiVAR_00143569E → K in a bladder tumor. 1
Natural variantiVAR_00143669E → V in a lung tumor. 1
Natural variantiVAR_00143771N → K in CMM2. 1
Natural variantiVAR_00143871N → S.2 PublicationsCorresponds to variant rs559848002dbSNPEnsembl.1
Natural variantiVAR_00143972C → G in an esophagus tumor. 1
Natural variantiVAR_00144074D → N in a bladder tumor. 1
Natural variantiVAR_00144174D → V in a biliary tract tumor. 1
Natural variantiVAR_05855574D → Y in CMM2; loss of CDK4 binding. 1 PublicationCorresponds to variant rs760640852dbSNPEnsembl.1
Natural variantiVAR_05855677T → P in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00144280R → L in a head and neck tumor. 1
Natural variantiVAR_05855780R → P in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00144381P → L in some patients with melanoma; impairs the function. 1 PublicationCorresponds to variant rs11552823dbSNPEnsembl.1
Natural variantiVAR_05855881P → T in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00144583H → N in a lung tumor. 1
Natural variantiVAR_05302983H → Q.Corresponds to variant rs34968276dbSNPEnsembl.1
Natural variantiVAR_00144483H → Y in a pancreas tumor; also found in head and neck tumor. Corresponds to variant rs121913385dbSNPEnsembl.1
Natural variantiVAR_00144684D → E in a bladder tumor. 1
Natural variantiVAR_00144784D → H in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_00144884D → N in an esophagus tumor; also found in head and neck tumor; also found in a lung tumor. 1
Natural variantiVAR_00144984D → Y in CMM2; also found in a lung tumor and a prostate tumor. 1 PublicationCorresponds to variant rs11552822dbSNPEnsembl.1
Natural variantiVAR_00145085A → T.1 Publication1
Natural variantiVAR_00145187R → P in CMM2; impairs the function. 2 Publications1
Natural variantiVAR_01231787R → W in CMM2; partial loss of CDK4 binding. 1 PublicationCorresponds to variant rs749714198dbSNPEnsembl.1
Natural variantiVAR_00145288E → D in a biliary tract tumor. 1
Natural variantiVAR_00145389G → D in CMM2; somatic mutation. 1 PublicationCorresponds to variant rs137854599dbSNPEnsembl.1
Natural variantiVAR_00145489G → S in CMM2. Corresponds to variant rs137854597dbSNPEnsembl.1
Natural variantiVAR_00145593T → A in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_02360494L → Q in CMM2. 1 Publication1
Natural variantiVAR_00145695V → A in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_00145797L → R in CMM2; loss of CDK4 binding. 1 Publication1
Natural variantiVAR_00145898H → P in CMM2. 1
Natural variantiVAR_00145998H → Q in CMM2. 1
Natural variantiVAR_00146099R → P in CMM2; loss of CDK4 binding. 1
Natural variantiVAR_00146199R → Q in non-small cell lung carcinoma. 1 PublicationCorresponds to variant rs754806883dbSNPEnsembl.1
Natural variantiVAR_05303099R → W.Corresponds to variant rs34886500dbSNPEnsembl.1
Natural variantiVAR_001462100A → L in CMM2; requires 2 nucleotide substitutions. 1
Natural variantiVAR_001463100A → P.1
Natural variantiVAR_001464101G → W in CMM2 and FAMMMPC; impairs the function. 3 PublicationsCorresponds to variant rs104894094dbSNPEnsembl.1
Natural variantiVAR_015818102A → E Found in seminoma and medulloblastoma tissues from Li-Fraumeni syndrome patients carrying a mutation in TP53; somatic mutation. 1 PublicationCorresponds to variant rs137854598dbSNPEnsembl.1
Natural variantiVAR_053031102A → T.Corresponds to variant rs35741010dbSNPEnsembl.1
Natural variantiVAR_001465104 – 105Missing .2
Natural variantiVAR_001466107R → C in CMM2. 1 Publication1
Natural variantiVAR_001467107R → H.Corresponds to variant rs370823171dbSNPEnsembl.1
Natural variantiVAR_001469108D → H in a bladder tumor. 1
Natural variantiVAR_001468108D → Y in a head and neck tumor. Corresponds to variant rs121913381dbSNPEnsembl.1
Natural variantiVAR_035068112R → RR in CMM2. 1 Publication1
Natural variantiVAR_001470114P → L in non-small cell lung carcinoma. 1 PublicationCorresponds to variant rs121913386dbSNPEnsembl.1
Natural variantiVAR_058559114P → S Found in some patients with melanoma; loss of CDK4 binding. 1 PublicationCorresponds to variant rs104894104dbSNPEnsembl.1
Natural variantiVAR_001471117L → M in CMM2; somatic mutation. 1 Publication1
Natural variantiVAR_001472118A → T in CMM2. 1 Publication1
Natural variantiVAR_001473119E → Q in a biliary tract tumor. 1
Natural variantiVAR_001474120E → A in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_001475120E → K in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_035069122G → R in CMM2. 1 PublicationCorresponds to variant rs113798404dbSNPEnsembl.1
Natural variantiVAR_001476122G → S in a biliary tract tumor. Corresponds to variant rs113798404dbSNPEnsembl.1
Natural variantiVAR_001477123H → Q in leukemia. Corresponds to variant rs6413463dbSNPEnsembl.1
Natural variantiVAR_053032124R → C.Corresponds to variant rs34170727dbSNPEnsembl.1
Natural variantiVAR_001478124R → H in an esophagus tumor. Corresponds to variant rs747621669dbSNPEnsembl.1
Natural variantiVAR_001479126V → D in CMM2; impairs the function. 3 PublicationsCorresponds to variant rs104894098dbSNPEnsembl.1
Natural variantiVAR_001480127A → S in squamous cell carcinoma. 1 PublicationCorresponds to variant rs6413464dbSNPEnsembl.1
Natural variantiVAR_001481132A → P in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_001482134A → V in non-small cell lung carcinoma. 1 PublicationCorresponds to variant rs757497674dbSNPEnsembl.1
Natural variantiVAR_001483142H → Y in non-small cell lung carcinoma. 1 Publication1
Natural variantiVAR_001484144R → C in squamous cell carcinoma. 1 PublicationCorresponds to variant rs116150891dbSNPEnsembl.1
Natural variantiVAR_001486148A → T.7 PublicationsCorresponds to variant rs3731249dbSNPEnsembl.1
Natural variantiVAR_001487150G → V in non-small cell lung carcinoma. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0158641 – 51Missing in isoform 2. CuratedAdd BLAST51
Alternative sequenceiVSP_01586552 – 116MMMGS…RLPVD → GRRSAAGAGDGGRLWRTKFA GELESGSASILRKKGRLPGE FSEGVCNHRPPPGDALGAWE TKEEE in isoform 3. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_015866117 – 156Missing in isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_043577153 – 156DIPD → EMIGNHLWVCRSRHA in isoform 5. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27211 mRNA. Translation: AAA92554.1.
AF115544 mRNA. Translation: AAD11437.1.
AB060808 Genomic DNA. Translation: BAB91133.1.
AF527803 Genomic DNA. Translation: AAR05391.1.
DQ318021 mRNA. Translation: ABC47036.1.
AL449423 Genomic DNA. Translation: CAH70600.1.
CH471071 Genomic DNA. Translation: EAW58599.1.
CH471071 Genomic DNA. Translation: EAW58603.1.
X94154 Genomic DNA. Translation: CAA63870.1.
AH007355 Genomic DNA. Translation: AAD14050.1.
S69804 Genomic DNA. Translation: AAD14048.1.
U12820, U12818, U12819 Genomic DNA. Translation: AAB60645.1. Different initiation.
CCDSiCCDS56565.1. [P42771-4]
CCDS6510.1. [P42771-1]
PIRiJE0141.
RefSeqiNP_000068.1. NM_000077.4. [P42771-1]
NP_001182061.1. NM_001195132.1. [P42771-4]
NP_478104.2. NM_058197.4.
XP_005251400.1. XM_005251343.1. [P42771-2]
XP_011515981.1. XM_011517679.1. [P42771-2]
UniGeneiHs.512599.

Genome annotation databases

EnsembliENST00000304494; ENSP00000307101; ENSG00000147889. [P42771-1]
ENST00000494262; ENSP00000464952; ENSG00000147889. [P42771-2]
ENST00000498124; ENSP00000418915; ENSG00000147889. [P42771-4]
ENST00000498628; ENSP00000467857; ENSG00000147889. [P42771-2]
ENST00000578845; ENSP00000467390; ENSG00000147889. [P42771-2]
GeneIDi1029.
KEGGihsa:1029.
UCSCiuc003zpk.4. human. [P42771-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

CDKN2A Database

Database of CDKN2A germline and somatic variants

NIEHS-SNPs
Wikipedia

P16INK4a entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27211 mRNA. Translation: AAA92554.1.
AF115544 mRNA. Translation: AAD11437.1.
AB060808 Genomic DNA. Translation: BAB91133.1.
AF527803 Genomic DNA. Translation: AAR05391.1.
DQ318021 mRNA. Translation: ABC47036.1.
AL449423 Genomic DNA. Translation: CAH70600.1.
CH471071 Genomic DNA. Translation: EAW58599.1.
CH471071 Genomic DNA. Translation: EAW58603.1.
X94154 Genomic DNA. Translation: CAA63870.1.
AH007355 Genomic DNA. Translation: AAD14050.1.
S69804 Genomic DNA. Translation: AAD14048.1.
U12820, U12818, U12819 Genomic DNA. Translation: AAB60645.1. Different initiation.
CCDSiCCDS56565.1. [P42771-4]
CCDS6510.1. [P42771-1]
PIRiJE0141.
RefSeqiNP_000068.1. NM_000077.4. [P42771-1]
NP_001182061.1. NM_001195132.1. [P42771-4]
NP_478104.2. NM_058197.4.
XP_005251400.1. XM_005251343.1. [P42771-2]
XP_011515981.1. XM_011517679.1. [P42771-2]
UniGeneiHs.512599.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A5ENMR-A1-156[»]
1BI7X-ray3.40B1-156[»]
1DC2NMR-A1-156[»]
2A5ENMR-A1-156[»]
ProteinModelPortaliP42771.
SMRiP42771.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107463. 156 interactors.
DIPiDIP-6108N.
IntActiP42771. 59 interactors.
MINTiMINT-1201444.
STRINGi9606.ENSP00000394932.

PTM databases

iPTMnetiP42771.
PhosphoSitePlusiP42771.

Polymorphism and mutation databases

BioMutaiMTAP.
DMDMi3041660.

Proteomic databases

EPDiP42771.
PaxDbiP42771.
PeptideAtlasiP42771.
PRIDEiP42771.
TopDownProteomicsiP42771-1. [P42771-1]

Protocols and materials databases

DNASUi1029.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000304494; ENSP00000307101; ENSG00000147889. [P42771-1]
ENST00000494262; ENSP00000464952; ENSG00000147889. [P42771-2]
ENST00000498124; ENSP00000418915; ENSG00000147889. [P42771-4]
ENST00000498628; ENSP00000467857; ENSG00000147889. [P42771-2]
ENST00000578845; ENSP00000467390; ENSG00000147889. [P42771-2]
GeneIDi1029.
KEGGihsa:1029.
UCSCiuc003zpk.4. human. [P42771-1]

Organism-specific databases

CTDi1029.
DisGeNETi1029.
GeneCardsiCDKN2A.
HGNCiHGNC:1787. CDKN2A.
HPAiCAB000093.
CAB000445.
CAB018232.
MalaCardsiCDKN2A.
MIMi155601. phenotype.
155755. phenotype.
600160. gene.
606719. phenotype.
neXtProtiNX_P42771.
OpenTargetsiENSG00000147889.
Orphaneti404560. Familial atypical multiple mole melanoma syndrome.
618. Familial melanoma.
1333. Familial pancreatic carcinoma.
252206. Melanoma and neural system tumor syndrome.
51013. Melanoma-pancreatic cancer syndrome.
99860. Precursor B-cell acute lymphoblastic leukemia.
99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA106.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00390000004527.
HOGENOMiHOG000290191.
HOVERGENiHBG050870.
InParanoidiP42771.
KOiK06621.
OMAiVNCYGRR.
TreeFamiTF352389.

Enzyme and pathway databases

BioCyciZFISH:HS07481-MONOMER.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-69231. Cyclin D associated events in G1.
SIGNORiP42771.

Miscellaneous databases

ChiTaRSiCDKN2A. human.
EvolutionaryTraceiP42771.
GeneWikiiP16_(gene).
GenomeRNAii1029.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147889.
CleanExiHS_CDKN2A.
ExpressionAtlasiP42771. baseline and differential.
GenevisibleiP42771. HS.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDN2A_HUMAN
AccessioniPrimary (citable) accession number: P42771
Secondary accession number(s): A5X2G7
, D3DRK1, O95440, Q15191, Q5VVJ5, Q96B52, Q9NP05
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 15, 1998
Last modified: November 2, 2016
This is version 189 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in term of sequence and function to tumor suppressor ARF (AC Q8N726) which is encoded by the same gene.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.