P39689 (CDN1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 123. History...
Names and origin
|Protein names||Recommended name:|
Cyclin-dependent kinase inhibitor 1
CDK-interacting protein 1
Melanoma differentiation-associated protein
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||159 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex By similarity.
Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair By similarity. Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21. Interacts with PIM1 By similarity. Ref.5
By p53, mezerein (antileukemic compound) and interferon beta.
The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex By similarity.
The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination By similarity.
Phosphorylation of Thr-140 or Ser-141 impairs binding to PCNA. Phosphorylation at Ser-112 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex By similarity. Phosphorylation of Thr-140 by PIM2 enhances its stability and inhibits cell proliferation. Phosphorylation of Thr-140 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability.
Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation By similarity.
Acetylation leads to protein stability. Acetylated in vitro on Lys-136, Lys-149, Lys-156 and Lys-158. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1. Ref.5
Belongs to the CDI family.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 159||158||Cyclin-dependent kinase inhibitor 1||PRO_0000190080|
|Zinc finger||12 – 40||29||C4-type Potential|
|Region||17 – 24||8||Required for binding cyclins By similarity|
|Region||53 – 58||6||Required for binding CDKs By similarity|
|Motif||135 – 159||25||PIP-box K+4 motif|
Amino acid modifications
|Modified residue||2||1||N-acetylserine By similarity|
|Modified residue||112||1||Phosphoserine; by GSK3-beta By similarity|
|Modified residue||125||1||Phosphoserine By similarity|
|Modified residue||140||1||Phosphothreonine; by PKA; PKB/AKT1; PIM1 and PIM2 By similarity|
|Modified residue||141||1||Phosphoserine By similarity|
|Cross-link||2||Glycyl serine ester (Ser-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Sequence conflict||30||1||R → S no nucleotide entry Ref.4|
|Sequence conflict||56 – 57||2||TP → RQ no nucleotide entry Ref.4|
|||"Molecular cloning, sequencing, chromosomal localization and expression of mouse p21 (Waf1)."|
Huppi K., Siwarski D., Dosik J., Michieli P., Chedid M., Reed S., Mock B., Givol D., Mushinski J.F.
Oncogene 9:3017-3020(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues."|
El-Deiry W.S., Tokino T., Waldman T., Velculescu V.E., Oliner J.D., Burell M., Hill D.E., Rees J.L., Hamilton S.R., Kinzler K.W., Vogelstein B.
Cancer Res. 55:2910-2919(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
|||"WAF1, a potential mediator of p53 tumor suppression."|
El-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R., Trent J.M., Lin D., Mercer W.E., Kinzler K.W., Vogelstein B.
Cell 75:817-825(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-143.
|||"An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis."|
Li Z., Zhang Q., Mao J.H., Weise A., Mrasek K., Fan X., Zhang X., Liehr T., Lu K.H., Balmain A., Cai W.W.
Oncogene 29:2659-2671(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC1, SUBCELLULAR LOCATION, ACETYLATION.
|+||Additional computationally mapped references.|
|U09507 mRNA. Translation: AAB60456.1.|
U24173 mRNA. Translation: AAC52220.1.
BC002043 mRNA. Translation: AAH02043.1.
|RefSeq||NP_001104569.1. NM_001111099.1. |
3D structure databases
|SMR||P39689. Positions 13-79. |
Protein-protein interaction databases
|BioGrid||198651. 12 interactions.|
|IntAct||P39689. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000023829; ENSMUSP00000023829; ENSMUSG00000023067. |
ENSMUST00000119901; ENSMUSP00000113150; ENSMUSG00000023067.
ENSMUST00000122348; ENSMUSP00000112411; ENSMUSG00000023067.
|UCSC||uc008bsg.2. mouse. |
|MGI||MGI:104556. Cdkn1a. |
Gene expression databases
Family and domain databases
|InterPro||IPR003175. CDI. |
|PANTHER||PTHR10265. PTHR10265. 1 hit. |
|Pfam||PF02234. CDI. 1 hit. |
|ChiTaRS||CDKN1A. mouse. |
|Accession||Primary (citable) accession number: P39689|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|