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P51480

- CD2A1_MOUSE

UniProt

P51480 - CD2A1_MOUSE

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Protein

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

Gene

Cdkn2a

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGI
  2. sequence-specific DNA binding transcription factor activity Source: MGI

GO - Biological processi

  1. aging Source: MGI
  2. cell aging Source: MGI
  3. cell cycle arrest Source: MGI
  4. cellular response to hydrogen peroxide Source: MGI
  5. cellular senescence Source: MGI
  6. epidermis development Source: MGI
  7. glucose homeostasis Source: MGI
  8. negative regulation of cell cycle Source: MGI
  9. negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
  10. negative regulation of mammary gland epithelial cell proliferation Source: MGI
  11. positive regulation of apoptotic process involved in mammary gland involution Source: MGI
  12. positive regulation of macrophage apoptotic process Source: BHF-UCL
  13. positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
  14. regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
  15. regulation of gene expression Source: MGI
  16. regulation of nucleocytoplasmic transport Source: MGI
  17. regulation of transcription, DNA-templated Source: MGI
  18. rRNA transcription Source: MGI
  19. somatic stem cell maintenance Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 2A, isoforms 1/2
Alternative name(s):
Cyclin-dependent kinase 4 inhibitor A
Short name:
CDK4I
p16-INK4a
Short name:
p16-INK4
Gene namesi
Name:Cdkn2a
Synonyms:P16ink4a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:104738. Cdkn2a.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nucleolus Source: MGI
  3. nucleoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi64 – 641C → G or R: No effect on activity. 1 Publication
Mutagenesisi76 – 761D → N: Loss of activity. 1 Publication
Mutagenesisi84 – 852Missing: Loss of activity. 1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 168168Cyclin-dependent kinase inhibitor 2A, isoforms 1/2PRO_0000144178Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei152 – 1521PhosphoserineBy similarity
Modified residuei164 – 1641PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation seems to increase interaction with CDK4.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP51480.

PTM databases

PhosphoSiteiP51480.

Expressioni

Gene expression databases

BgeeiP51480.
CleanExiMM_CDKN2A.
ExpressionAtlasiP51480. baseline and differential.
GenevestigatoriP51480.

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

BioGridi198654. 34 interactions.
DIPiDIP-60251N.

Structurei

Secondary structure

1
168
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni13 – 153
Helixi17 – 259
Helixi40 – 434
Helixi49 – 5810
Helixi72 – 809
Helixi83 – 919
Helixi106 – 1138
Helixi116 – 1238
Turni124 – 1263
Helixi139 – 1457
Helixi149 – 1579

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LNNmodel-A12-159[»]
ProteinModelPortaliP51480.
SMRiP51480. Positions 2-126.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati3 – 3230ANK 1Add
BLAST
Repeati36 – 6429ANK 2Add
BLAST
Repeati69 – 9830ANK 3Add
BLAST
Repeati102 – 13130ANK 4Add
BLAST

Sequence similaritiesi

Contains 4 ANK repeats.Curated

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiNOG42176.
GeneTreeiENSGT00390000008249.
HOVERGENiHBG050870.
KOiK06621.
OMAiPLRRERY.
OrthoDBiEOG7TTQ94.
TreeFamiTF352389.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. 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. Align

Note: Isoform 1 and isoform 3 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 3 (identifier: Q64364-1) [UniParc]FASTAAdd to Basket

Also known as: p19ARF, ARF

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 4 (identifier: Q64364-2) [UniParc]FASTAAdd to Basket

Also known as: smARF

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 111Missing in AAA85453. (PubMed:7651726)Curated

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121A → V in some liver tumors. 1 Publication
Natural varianti18 – 181H → P in strain: 020, BALB/c, BALB/cJ, C3H/21BG, C3H/HeJ, CBA/J, MA/M4J and PL/J. 3 Publications
Natural varianti27 – 271G → E in some liver tumors. 1 Publication
Natural varianti51 – 511V → I in strain: BALB/c and BALB/cJ. 2 Publications
Natural varianti73 – 731P → L in some liver tumors. 1 Publication
Natural varianti74 – 741V → M in plasmacytoma cell lines. 1 Publication
Natural varianti75 – 751H → Y in plasmacytoma cell lines. 1 Publication
Natural varianti90 – 901H → Q in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication
Natural varianti90 – 901H → R in plasmacytoma cell lines. 1 Publication
Natural varianti127 – 1271C → S in strain: BALB/cJ, C57BL/6J and MOLF/Ei. 1 Publication

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4343Missing in isoform 2. CuratedVSP_015867Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS38812.1. [P51480-1 ]
RefSeqi NP_001035744.1. NM_001040654.1. [P51480-1 ]
UniGenei Mm.4733.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1LNN model - A 12-159 [» ]
ProteinModelPortali P51480.
SMRi P51480. Positions 2-126.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198654. 34 interactions.
DIPi DIP-60251N.

PTM databases

PhosphoSitei P51480.

Proteomic databases

PRIDEi P51480.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000060501 ; ENSMUSP00000061847 ; ENSMUSG00000044303 . [P51480-1 ]
GeneIDi 12578.
KEGGi mmu:12578.
UCSCi uc008toh.1. mouse. [P51480-1 ]

Organism-specific databases

CTDi 1029.
MGIi MGI:104738. Cdkn2a.

Phylogenomic databases

eggNOGi NOG42176.
GeneTreei ENSGT00390000008249.
HOVERGENi HBG050870.
KOi K06621.
OMAi PLRRERY.
OrthoDBi EOG7TTQ94.
TreeFami TF352389.

Miscellaneous databases

NextBioi 281698.
SOURCEi Search...

Gene expression databases

Bgeei P51480.
CleanExi MM_CDKN2A.
ExpressionAtlasi P51480. baseline and differential.
Genevestigatori P51480.

Family and domain databases

Gene3Di 1.25.40.20. 1 hit.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
[Graphical view ]
Pfami PF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
[Graphical view ]
SMARTi SM00248. ANK. 4 hits.
[Graphical view ]
SUPFAMi SSF48403. SSF48403. 1 hit.
PROSITEi PS50297. ANK_REP_REGION. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of murine p16INK4a and p15INK4b genes."
    Quelle D.E., Ashmun R.A., Hannon G.J., Rehberger P.A., Trono D., Richter K.H., Walker C., Beach D., Sherr C.J., Serrano M.
    Oncogene 11:635-645(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16(INK4a) and p19(ARF), is a candidate for the plasmacytoma susceptibility locus, Pctr1."
    Zhang S., Ramsay E.S., Mock B.A.
    Proc. Natl. Acad. Sci. U.S.A. 95:2429-2434(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS PRO-18; ILE-51; MET-74; TYR-75 AND ARG-90.
    Strain: BALB/c and DBA/2N.
    Tissue: Spleen.
  3. "Cloning and structure analysis of murine p16INK4a."
    Gong Z., Li J., Fu J.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/SvJ.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  6. "Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de novo methylation with independence of p16INK4a alterations in murine primary T-cell lymphomas."
    Malumbres M., de Castro I.P., Santos J., Melendez B., Mangues R., Serrano M., Pellicer A., Fernandez-Piqueras J.
    Oncogene 14:1361-1370(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-155.
    Strain: C57BL/6J X DBA.
  7. "Comparative analysis of the p16(INK4a) and p15(INK4b) DNA sequences in mouse inbred strains."
    Santos J., Melendez B., Perez de Castro I., Malumbres M., Serrano M., Pellicer A., Fernandez-Piqueras J.
    Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-155, VARIANTS PRO-18; ILE-51; GLN-90 AND SER-127.
    Strain: BALB/cJ, C57BL/6J, CAST/Ei, MOLF/Ei and RF/J.
  8. "Sequence variation and chromosomal mapping of the murine Cdkn2a tumor suppressor gene."
    Herzog C.R., You M.
    Mamm. Genome 8:65-66(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-42 (ISOFORM 1), VARIANT PRO-18.
    Strain: 020, 129/J, A/J, A/Wy, AKR/J, B10.A, B10.D2(58N), BALB/c, C3H/21BG, C3H/HeJ, C57BL/10SCN, C57BL/10SN, C57BL/6By, C57BL/6J, C57BR/cdJ, CBA/J, DBA/2J, HS/IBG, LP/J, LS/IBG, MA/M4J, PL/J, RF/J, Sencar, SJL/J, SM/J, ST/J and SWR/J.
    Tissue: Lung.
  9. "Induction of mutations in Ki-ras and INK4a in liver tumors of mice exposed in utero to 3-methylcholanthrene."
    Gressani K.M., Rollins L.A., Leone-Kabler S., Cline J.M., Miller M.S.
    Carcinogenesis 19:1045-1052(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42, VARIANTS VAL-12; GLU-27 AND LEU-73.
  10. "Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16INK4a but not by the alternative reading frame protein p19ARF."
    Quelle D.E., Cheng M., Ashmun R.A., Sherr C.J.
    Proc. Natl. Acad. Sci. U.S.A. 94:669-673(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF CYS-64; ASP-76 AND 84-ASP-THR-85.

Entry informationi

Entry nameiCD2A1_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: October 29, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

External Data

Dasty 3