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UniProtKB/Swiss-Prot entry P38936


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CDN1A_HUMAN
Primary accession number P38936
Secondary accession numbers Q14010 Q9BUT4
Integrated into Swiss-Prot on February 1, 1995
Sequence was last modified on January 23, 2007 (Sequence version 3)
Annotations were last modified on    July 22, 2008 (Entry version 98)
Name and origin of the protein
Protein name Cyclin-dependent kinase inhibitor 1
Synonyms p21
CDK-interacting protein 1
Melanoma differentiation-associated protein 6
MDA-6
Gene name
Name: CDKN1A
Synonyms: CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/0092-8674(93)90499-G; PubMed=8242751 [NCBI, ExPASy, EBI, Israel, Japan]
Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J.;
"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.";
Cell 75:805-816(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/0092-8674(93)90500-P; PubMed=8242752 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"WAF1, a potential mediator of p53 tumor suppression.";
Cell 75:817-825(1993).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1038/366701a0; PubMed=8259214 [NCBI, ExPASy, EBI, Israel, Japan]
Xiong Y., Hannon G.J., Zhang H., Casso D., Kobayashi R., Beach D.;
"p21 is a universal inhibitor of cyclin kinases.";
Nature 366:701-704(1993).
[4]
NUCLEOTIDE SEQUENCE [MRNA].
Jiang H., Fisher P.B.;
"Use of a sensitive and efficient subtraction hybridization protocol for the identification of genes differentially regulated during the induction of differentiation in human melanoma cells.";
Mol. Cell. Differ. 1:285-299(1993).
[5]
NUCLEOTIDE SEQUENCE.
Jiang H., Lin J., Herlyn M., Kerbel R.S., Weissman B.E., Welch D.R., Fisher P.B.;
Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1006/excr.1994.1063; PubMed=8125163 [NCBI, ExPASy, EBI, Israel, Japan]
Noda A., Ning Y., Venable S.F., Pereira-Smith O.M., Smith J.R.;
"Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen.";
Exp. Cell Res. 211:90-98(1994).
[7]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-31.
DOI=10.1093/hmg/4.6.1089; PubMed=7655464 [NCBI, ExPASy, EBI, Israel, Japan]
Mousses S., Oezcelik H., Lee P.D., Malkin D., Bull S.B., Andrulis I.L.;
"Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer.";
Hum. Mol. Genet. 4:1089-1092(1995).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-31.
Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P., Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature02055; PubMed=14574404 [NCBI, ExPASy, EBI, Israel, Japan]
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-31.
TISSUE=Eye, and Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[11]
PROTEIN SEQUENCE OF 2-16, AND ACETYLATION AT SER-2.
DOI=10.1016/j.molcel.2004.11.011; PubMed=15574338 [NCBI, ExPASy, EBI, Israel, Japan]
Chen X., Chi Y., Bloecher A., Aebersold R., Clurman B.E., Roberts J.M.;
"N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1).";
Mol. Cell 16:839-847(2004).
[12]
PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND SER-160, AND MASS SPECTROMETRY.
DOI=10.1074/jbc.275.15.11529; PubMed=10753973 [NCBI, ExPASy, EBI, Israel, Japan]
Scott M.T., Morrice N., Ball K.L.;
"Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding.";
J. Biol. Chem. 275:11529-11537(2000).
[13]
PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, AND SUBCELLULAR LOCATION.
DOI=10.1128/MCB.21.16.5644-5657.2001; PubMed=11463845 [NCBI, ExPASy, EBI, Israel, Japan]
Roessig L., Jadidi A.S., Urbich C., Badorff C., Zeiher A.M., Dimmeler S.;
"Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells.";
Mol. Cell. Biol. 21:5644-5657(2001).
[14]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[15]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160.
DOI=10.1016/S0092-8674(00)81347-1; PubMed=8861913 [NCBI, ExPASy, EBI, Israel, Japan]
Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.;
"Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA.";
Cell 87:297-306(1996).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L25610; AAA16109.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S67388; AAB29246.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U09579; AAA85641.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U03106; AAC04313.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L26165; AAA19811.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L47232; AAB59559.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L47233; AAB59560.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF497972; AAM11787.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z85996; CAB06656.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000275; AAH00275.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000312; AAH00312.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC001935; AAH01935.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC013967; AAH13967.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR I54380; I54380.
I68674; I68674.
RefSeq NP_000380.1; -.
NP_510867.1; -.
UniGene Hs.370771
3D structure databases
PDB
1AXC; X-ray; 2.60 A; B/D/F=139-160.[ExPASy / RCSB / EBI]
PDBsum 1AXC; -.
DisProt DP00016; -.
ModBase P38936.
Protein-protein interaction databases
DIP DIP:246N; -.
IntAct P38936; -.
PTM databases
PhosphoSite P38936; -.
Enzyme and pathway databases
Reactome REACT_152; Cell Cycle, Mitotic.
REACT_1538; Cell Cycle Checkpoints.
REACT_383; DNA Replication.
Polymorphism databases
NIEHS-SNPs CDKN1A.
2D gel databases
SWISS-2DPAGE P38936; -.
Organism-specific databases
H-InvDB HIX0005824; -.
HGNC HGNC:1784; CDKN1A.
GenAtlas CDKN1A.
HPA CAB000064; -.
MIM 116899; gene. [NCBI / EBI]
PharmGKB PA104; -.
GeneCards P38936.
Gene expression databases
ArrayExpress P38936; -.
CleanEx HS_CDKN1A; -.
GermOnline ENSG00000124762; Homo sapiens.
Ontologies
GO
GO:0000307; Cellular component: cyclin-dependent protein kinase holoenzyme complex (inferred from direct assay from UniProtKB).
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005654; Cellular component: nucleoplasm (inferred from experiment from Reactome).
GO:0004861; Molecular function: cyclin-dependent protein kinase inhibitor activity (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0007050; Biological process: cell cycle arrest (inferred from mutant phenotype from UniProtKB).
GO:0031668; Biological process: cellular response to extracellular stimulus (inferred from mutant phenotype from UniProtKB).
GO:0000082; Biological process: G1/S transition of mitotic cell cycle (inferred from direct assay from UniProtKB).
GO:0000086; Biological process: G2/M transition of mitotic cell cycle (inferred from mutant phenotype from UniProtKB).
GO:0008629; Biological process: induction of apoptosis by intracellular signals (traceable author statement from ProtInc).
GO:0030308; Biological process: negative regulation of cell growth (inferred from direct assay from UniProtKB).
GO:0008285; Biological process: negative regulation of cell proliferation (inferred from direct assay from UniProtKB).
GO:0042326; Biological process: negative regulation of phosphorylation (inferred from direct assay from UniProtKB).
GO:0048146; Biological process: positive regulation of fibroblast proliferation (inferred from mutant phenotype from UniProtKB).
GO:0000079; Biological process: regulation of cyclin-dependent protein kinase activity (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR003175; CDI.
Graphical view of domain structure.
PANTHER PTHR10265; CDI; 1.
Pfam PF02234; CDI; 1.
Pfam graphical view of domain structure.
BLOCKS P38936.
Genome annotation databases
Ensembl ENSG00000124762; Homo sapiens. [Contig view]
GeneID 1026; -.
KEGG hsa:1026; -.
Phylogenomic databases
HOVERGEN P38936; -.
Other
LinkHub P38936; -.
SOURCE CDKN1A; Homo sapiens.
ProtoNet P38936.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Cell cycle; Cytoplasm; Direct protein sequencing; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Protein kinase inhibitor; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
INIT_MET   1     1        Removed. 
CHAIN   2   164  163     Cyclin-dependent kinase inhibitor 1. PRO_0000190079
ZN_FING   13    41  29     C4-type (Potential). 
MOTIF   141   156  16     Nuclear localization signal (Potential). 
MOD_RES   2     2        N-acetylserine. 
MOD_RES   130   130        Phosphoserine. 
MOD_RES   145   145        Phosphothreonine; by PKA and PKB/AKT1. 
MOD_RES   146   146        Phosphoserine; by PKC. 
MOD_RES   160   160        Phosphoserine; by PKC; in vitro. 
VARIANT   31    31  1     S -> R (in dbSNP:rs1801270 [NCBI]). VAR_011870 
VARIANT   149   149  1     D -> G (in dbSNP:rs1801724 [NCBI]). VAR_014875 
MUTAGEN   145   145        T->A: Reduces phosphorylation by Akt; no change in interaction with PCNA, CDK2 or CDK4; no change in subcellular location. 
MUTAGEN   145   145        T->D: No interaction with PCNA; 59% inhibition of CDK2 binding; modest inhibition of CDK4 binding; no change in subcellular location. 
MUTAGEN   146   146        S->A: No change in interaction with PCNA. 
MUTAGEN   146   146        S->D: Reduces interaction with PCNA. 
HELIX   147   149  3      
STRAND   151   158  8      
Sequence information
Length: 164 AA [This is the length of the unprocessed precursor] Molecular weight: 18119 Da [This is the MW of the unprocessed precursor] CRC64: 98D1E7C519ADFCA9 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSEPAGDVRQ NPCGSKACRR LFGPVDSEQL SRDCDALMAG CIQEARERWN FDFVTETPLE 

        70         80         90        100        110        120 
GDFAWERVRG LGLPKLYLPT GPRRGRDELG GGRRPGTSPA LLQGTAEEDH VDLSLSCTLV 

       130        140        150        160 
PRSGEQAEGS PGGPGDSQGR KRRQTSMTDF YHSKRRLIFS KRKP 

P38936 in FASTA format

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View entry in raw text format (no links)
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