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Protein

Cyclin-dependent kinase inhibitor 2A

Gene

Cdkn2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cerebellum development Source: RGD
  • positive regulation of apoptotic process Source: RGD
  • response to drug Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to organonitrogen compound Source: RGD
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
Short name:
p16-INK4
Gene namesi
Name:Cdkn2aImported
Synonyms:P16ink4aBy similarity
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2323. Cdkn2a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 159159Cyclin-dependent kinase inhibitor 2APRO_0000144179Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei143 – 1431PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation seems to increase interaction with CDK4.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R0Z3.
PRIDEiQ9R0Z3.

Expressioni

Tissue specificityi

Expressed in spleen, liver and lung. Not detected in kidney, colon, stomach or brain.1 Publication

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000061040.

Structurei

3D structure databases

ProteinModelPortaliQ9R0Z3.
SMRiQ9R0Z3. Positions 1-123.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati3 – 3533ANK 1Sequence analysisAdd
BLAST
Repeati36 – 6429ANK 2Sequence analysisAdd
BLAST
Repeati69 – 9830ANK 3Sequence analysisAdd
BLAST
Repeati102 – 13433ANK 4Sequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.Sequence analysis
Contains 4 ANK repeats.Sequence analysis

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
HOGENOMiHOG000290191.
HOVERGENiHBG050870.
KOiK06621.

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 (2)i

Sequence statusi: Complete.

This entry describes 2 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.By similarity
Isoform 11 Publication (identifier: Q9R0Z3-1) [UniParc]FASTAAdd to basket
Also known as: p16INK4aBy similarity

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
MESSADRLAR AAALGREHEV RALLEAGASP NAPNTFGRTP IQVMMMGNVK
60 70 80 90 100
VAALLLSYGA DSNCEDPTTL SRPVHDAARE GFLDTLVVLH QAGARLDVRD
110 120 130 140 150
AWGRLPLDLA LERGHHDVVR YLRYLLSSAG NVSRVTDRHN FCSSTPRCLG

LRGQPPKQR
Length:159
Mass (Da):17,366
Last modified:May 1, 2000 - v1
Checksum:i3C4CA920A1FEAEB6
GO
Isoform tumor suppressor ARFCurated (identifier: Q8QZZ9-1) [UniParc]FASTAAdd to basket
Also known as: p19ARFCurated
The sequence of this isoform can be found in the external entry Q8QZZ9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:160
Mass (Da):17,307
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L81167 mRNA. Translation: AAD48924.1.
AF474976 mRNA. Translation: AAL76338.1.
AF474977 mRNA. Translation: AAL76339.1.
AY679728 mRNA. Translation: AAT92510.1.
RefSeqiNP_113738.1. NM_031550.1. [Q9R0Z3-1]
UniGeneiRn.48717.

Genome annotation databases

GeneIDi25163.
KEGGirno:25163.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L81167 mRNA. Translation: AAD48924.1.
AF474976 mRNA. Translation: AAL76338.1.
AF474977 mRNA. Translation: AAL76339.1.
AY679728 mRNA. Translation: AAT92510.1.
RefSeqiNP_113738.1. NM_031550.1. [Q9R0Z3-1]
UniGeneiRn.48717.

3D structure databases

ProteinModelPortaliQ9R0Z3.
SMRiQ9R0Z3. Positions 1-123.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000061040.

Proteomic databases

PaxDbiQ9R0Z3.
PRIDEiQ9R0Z3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25163.
KEGGirno:25163.

Organism-specific databases

CTDi1029.
RGDi2323. Cdkn2a.

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
HOGENOMiHOG000290191.
HOVERGENiHBG050870.
KOiK06621.

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_RAT
AccessioniPrimary (citable) accession number: Q9R0Z3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Down-regulated in a number of tumor cell lines in response to methylation of the CpG island in exon 1.1 Publication

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 Q8QZZ9) which is encoded by the same gene.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.