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Protein

Cyclin-dependent kinase inhibitor 2A

Gene

Cdkn2a

Organism
Mus musculus (Mouse)
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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 2AImported
Alternative name(s):
Cyclin-dependent kinase 4 inhibitor A
Short name:
CDK4I
p16-INK4a
Short name:
p16-INK4
Gene namesi
Name:Cdkn2aImported
Synonyms:P16ink4a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:104738. Cdkn2a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • granular component Source: Ensembl
  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • senescence-associated heterochromatin focus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi64C → G or R: No effect on activity. 1 Publication1
Mutagenesisi76D → N: Loss of activity. 1 Publication1
Mutagenesisi84 – 85Missing : Loss of activity. 1 Publication2

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001441781 – 168Cyclin-dependent kinase inhibitor 2AAdd BLAST168

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei152PhosphoserineBy similarity1
Modified residuei164PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation seems to increase interaction with CDK4.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP51480.
PeptideAtlasiP51480.
PRIDEiP51480.

PTM databases

iPTMnetiP51480.
PhosphoSitePlusiP51480.

Expressioni

Gene expression databases

BgeeiENSMUSG00000044303.
CleanExiMM_CDKN2A.
ExpressionAtlasiP51480. baseline and differential.
GenevisibleiP51480. MM.

Interactioni

Subunit structurei

Heterodimer with CDK4 or CDK6. Predominamt 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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198654. 33 interactors.
DIPiDIP-60251N.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LNNmodel-A12-159[»]
ProteinModelPortaliP51480.
SMRiP51480.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati3 – 32ANK 1Add BLAST30
Repeati36 – 64ANK 2Add BLAST29
Repeati69 – 98ANK 3Add BLAST30
Repeati102 – 131ANK 4Add BLAST30

Sequence similaritiesi

Contains 4 ANK repeats.Curated

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

GeneTreeiENSGT00390000008249.
HOVERGENiHBG050870.
KOiK06621.
OMAiADSNCED.
TreeFamiTF352389.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 4 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 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: P51480-1) [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
MESAADRLAR AAAQGRVHDV RALLEAGVSP NAPNSFGRTP IQVMMMGNVH
60 70 80 90 100
VAALLLNYGA DSNCEDPTTF SRPVHDAARE GFLDTLVVLH GSGARLDVRD
110 120 130 140 150
AWGRLPLDLA QERGHQDIVR YLRSAGCSLC SAGWSLCTAG NVAQTDGHSF
160
SSSTPRALEL RGQSQEQS
Length:168
Mass (Da):17,941
Last modified:October 25, 2005 - v2
Checksum:i9A6B0F24F34D5FEC
GO
Isoform 2 (identifier: P51480-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-43: Missing.

Show »
Length:125
Mass (Da):13,458
Checksum:i97BE6143D7C8542D
GO
Isoform tumor suppressor ARF (identifier: Q64364-1) [UniParc]FASTAAdd to basket
Also known as: p19ARF
The sequence of this isoform can be found in the external entry Q64364.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:169
Mass (Da):19,238
GO
Isoform smARF (identifier: Q64364-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q64364.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:125
Mass (Da):14,096
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11Missing in AAA85453 (PubMed:7651726).Curated1

Polymorphismi

Strain BALB/c displays a significantly reduced ability to inhibit phosphorylation of the retinoblastoma protein.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti12A → V in some liver tumors. 1 Publication1
Natural varianti18H → P in strain: 020, BALB/c, BALB/cJ, C3H/21BG, C3H/HeJ, CBA/J, MA/M4J and PL/J. 3 Publications1
Natural varianti27G → E in some liver tumors. 1 Publication1
Natural varianti51V → I in strain: BALB/c and BALB/cJ. 2 Publications1
Natural varianti73P → L in some liver tumors. 1 Publication1
Natural varianti74V → M in plasmacytoma cell lines. 1 Publication1
Natural varianti75H → Y in plasmacytoma cell lines. 1 Publication1
Natural varianti90H → Q in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication1
Natural varianti90H → R in plasmacytoma cell lines. 1 Publication1
Natural varianti127C → S in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0158671 – 43Missing in isoform 2. CuratedAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76150 mRNA. Translation: AAA85453.1.
AF044335 mRNA. Translation: AAC08962.1.
AF044336 mRNA. Translation: AAC08963.1.
AF332190 Genomic DNA. Translation: AAK83159.1.
AK155307 mRNA. Translation: BAE33180.1.
AL831719 Genomic DNA. Translation: CAM16002.1.
AL831719 Genomic DNA. Translation: CAM16003.1.
U66087, U66086 Genomic DNA. Translation: AAB39600.1.
U79625 Genomic DNA. Translation: AAD00223.1.
U79626 Genomic DNA. Translation: AAD00224.1.
U79627 Genomic DNA. Translation: AAD00225.1.
U79628 Genomic DNA. Translation: AAD00226.1.
U79630 Genomic DNA. Translation: AAD00227.1.
U79631 Genomic DNA. Translation: AAD00228.1.
U79632 Genomic DNA. Translation: AAD00229.1.
U49279 Genomic DNA. Translation: AAC00051.1.
U49280 Genomic DNA. Translation: AAC00052.1.
AF004588 Genomic DNA. Translation: AAB61416.1.
CCDSiCCDS38812.1. [P51480-1]
RefSeqiNP_001035744.1. NM_001040654.1. [P51480-1]
UniGeneiMm.4733.

Genome annotation databases

EnsembliENSMUST00000060501; ENSMUSP00000061847; ENSMUSG00000044303. [P51480-1]
GeneIDi12578.
KEGGimmu:12578.
UCSCiuc008toh.1. mouse. [P51480-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76150 mRNA. Translation: AAA85453.1.
AF044335 mRNA. Translation: AAC08962.1.
AF044336 mRNA. Translation: AAC08963.1.
AF332190 Genomic DNA. Translation: AAK83159.1.
AK155307 mRNA. Translation: BAE33180.1.
AL831719 Genomic DNA. Translation: CAM16002.1.
AL831719 Genomic DNA. Translation: CAM16003.1.
U66087, U66086 Genomic DNA. Translation: AAB39600.1.
U79625 Genomic DNA. Translation: AAD00223.1.
U79626 Genomic DNA. Translation: AAD00224.1.
U79627 Genomic DNA. Translation: AAD00225.1.
U79628 Genomic DNA. Translation: AAD00226.1.
U79630 Genomic DNA. Translation: AAD00227.1.
U79631 Genomic DNA. Translation: AAD00228.1.
U79632 Genomic DNA. Translation: AAD00229.1.
U49279 Genomic DNA. Translation: AAC00051.1.
U49280 Genomic DNA. Translation: AAC00052.1.
AF004588 Genomic DNA. Translation: AAB61416.1.
CCDSiCCDS38812.1. [P51480-1]
RefSeqiNP_001035744.1. NM_001040654.1. [P51480-1]
UniGeneiMm.4733.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LNNmodel-A12-159[»]
ProteinModelPortaliP51480.
SMRiP51480.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198654. 33 interactors.
DIPiDIP-60251N.

PTM databases

iPTMnetiP51480.
PhosphoSitePlusiP51480.

Proteomic databases

MaxQBiP51480.
PeptideAtlasiP51480.
PRIDEiP51480.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000060501; ENSMUSP00000061847; ENSMUSG00000044303. [P51480-1]
GeneIDi12578.
KEGGimmu:12578.
UCSCiuc008toh.1. mouse. [P51480-1]

Organism-specific databases

CTDi1029.
MGIiMGI:104738. Cdkn2a.

Phylogenomic databases

GeneTreeiENSGT00390000008249.
HOVERGENiHBG050870.
KOiK06621.
OMAiADSNCED.
TreeFamiTF352389.

Miscellaneous databases

SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044303.
CleanExiMM_CDKN2A.
ExpressionAtlasiP51480. baseline and differential.
GenevisibleiP51480. MM.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
[Graphical view]
SMARTiSM00248. ANK. 4 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDN2A_MOUSE
AccessioniPrimary (citable) accession number: P51480
Secondary accession number(s): A2ANM1
, A2ANM2, O89088, P97510, P97937, Q6PEA2, Q78E39, Q78E57, Q792X7, Q9QWH6, Q9QWH7, Q9QWH8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 25, 2005
Last modified: November 30, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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 Q64364) which is encoded by the same gene.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.