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Reviewed, UniProtKB/Swiss-Prot P38936 (CDN1A_HUMAN)

Last modified November 25, 2008. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Cyclin-dependent kinase inhibitor 1
Alternative name(s):
    p21
    CDK-interacting protein 1
    Melanoma differentiation-associated protein 6
      Short name=MDA-6
Gene names
Name: CDKN1A
Synonyms: CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length164 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

May be the important intermediate by which p53 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.

Subcellular location

Cytoplasm. Nucleus.

Tissue specificity

Expressed in all adult human tissues, with 5-fold lower levels observed in the brain.

Induction

By p53, mezerein (antileukemic compound) and interferon beta.

Post-translational modification

Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA.

Sequence similarities

Belongs to the CDI family.

Ontologies

Keywords

   Biological processCell cycle
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionProtein kinase inhibitor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processG1/S transition of mitotic cell cycle

Inferred from direct assay. Source: UniProtKB

G2/M transition of mitotic cell cycle

Inferred from mutant phenotype. Source: UniProtKB

cell cycle arrest

Inferred from electronic annotation. Source: InterPro

cellular response to extracellular stimulus

Inferred from mutant phenotype. Source: UniProtKB

induction of apoptosis by intracellular signals

Traceable author statement. Source: ProtInc

negative regulation of cell growth

Inferred from direct assay. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay. Source: UniProtKB

negative regulation of phosphorylation

Inferred from direct assay. Source: UniProtKB

positive regulation of fibroblast proliferation

Inferred from mutant phenotype. Source: UniProtKB

   Cellular componentcyclin-dependent protein kinase holoenzyme complex

Inferred from direct assay. Source: UniProtKB

cytosol

Inferred from Experiment. Source: Reactome

nucleoplasm

Inferred from Experiment. Source: Reactome

   Molecular functioncyclin-dependent protein kinase inhibitor activity Ref.1

Traceable author statement. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 164163Cyclin-dependent kinase inhibitor 1
PRO_0000190079

Regions

Zinc finger13 – 4129C4-type Potential
Motif141 – 15616Nuclear localization signal Potential

Amino acid modifications

Modified residue21N-acetylserine
Modified residue1301Phosphoserine
Modified residue1451Phosphothreonine; by PKA and PKB/AKT1
Modified residue1461Phosphoserine; by PKC
Modified residue1601Phosphoserine; by PKC; in vitro

Natural variations

Natural variant311S → R: dbSNP rs1801270.
VAR_011870
Natural variant1491D → G: dbSNP rs1801724.
VAR_014875

Experimental info

Mutagenesis1451T → A: Reduces phosphorylation by Akt; no change in interaction with PCNA, CDK2 or CDK4; no change in subcellular location
Mutagenesis1451T → D: No interaction with PCNA; 59% inhibition of CDK2 binding; modest inhibition of CDK4 binding; no change in subcellular location
Mutagenesis1461S → A: No change in interaction with PCNA
Mutagenesis1461S → D: Reduces interaction with PCNA

Secondary structure

..... 164
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P38936-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 98D1E7C519ADFCA9

FASTA16418,119
        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 

« Hide

References

« Hide 'large scale' references
[1]"The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases."
Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J.
Cell 75:805-816(1993) [PubMed: 8242751] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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: 8242752] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"p21 is a universal inhibitor of cyclin kinases."
Xiong Y., Hannon G.J., Zhang H., Casso D., Kobayashi R., Beach D.
Nature 366:701-704(1993) [PubMed: 8259214] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"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."
Jiang H., Fisher P.B.
Mol. Cell. Differ. 1:285-299(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]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
Cited for: NUCLEOTIDE SEQUENCE.
[6]"Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen."
Noda A., Ning Y., Venable S.F., Pereira-Smith O.M., Smith J.R.
Exp. Cell Res. 211:90-98(1994) [PubMed: 8125163] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]"Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer."
Mousses S., Oezcelik H., Lee P.D., Malkin D., Bull S.B., Andrulis I.L.
Hum. Mol. Genet. 4:1089-1092(1995) [PubMed: 7655464] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-31.
[8]"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."
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.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-31.
[9]"The DNA sequence and analysis of human chromosome 6."
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. expand/collapse author list , 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.
Nature 425:805-811(2003) [PubMed: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-31.
Tissue: Eye and Lung.
[11]"N-acetylation and ubiquitin-independent proteasomal degradation of p21(Cip1)."
Chen X., Chi Y., Bloecher A., Aebersold R., Clurman B.E., Roberts J.M.
Mol. Cell 16:839-847(2004) [PubMed: 15574338] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16, ACETYLATION AT SER-2.
[12]"Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding."
Scott M.T., Morrice N., Ball K.L.
J. Biol. Chem. 275:11529-11537(2000) [PubMed: 10753973] [Abstract]
Cited for: PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND SER-160, MASS SPECTROMETRY.
[13]"Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells."
Roessig L., Jadidi A.S., Urbich C., Badorff C., Zeiher A.M., Dimmeler S.
Mol. Cell. Biol. 21:5644-5657(2001) [PubMed: 11463845] [Abstract]
Cited for: PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, SUBCELLULAR LOCATION.
[14]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, MASS SPECTROMETRY.
Tissue: Epithelium.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, MASS SPECTROMETRY.
[16]"Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA."
Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.
Cell 87:297-306(1996) [PubMed: 8861913] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160.
+Additional computationally mapped references.

Cross-references

Sequence databases

L25610 mRNA. Translation: AAA16109.1.
S67388 mRNA. Translation: AAB29246.1.
U09579 mRNA. Translation: AAA85641.1.
U03106 mRNA. Translation: AAC04313.1.
L26165 mRNA. Translation: AAA19811.1.
L47232 mRNA. Translation: AAB59559.1. Different initiation.
L47233 mRNA. Translation: AAB59560.1. Different initiation.
AF497972 Genomic DNA. Translation: AAM11787.1.
Z85996 Genomic DNA. Translation: CAB06656.1.
BC000275 mRNA. Translation: AAH00275.1.
BC000312 mRNA. Translation: AAH00312.1.
BC001935 mRNA. Translation: AAH01935.1.
BC013967 mRNA. Translation: AAH13967.1.
PIRI54380.
I68674.
RefSeqNP_000380.1.
NP_510867.1.
UniGeneHs.370771

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1AXCX-ray2.60B/D/F139-160[»]
DisProtDP00016.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:246N.
IntActP38936.

PTM databases

PhosphoSiteP38936.

Polymorphism databases

NIEHS-SNPsSearch...

2-D gel databases

SWISS-2DPAGEP38936.

Genome annotation databases

EnsemblENSG00000124762. Homo sapiens. [Contig view]
GeneID1026.
KEGGhsa:1026.

Organism-specific databases

H-InvDBHIX0005824.
HGNCHGNC:1784. CDKN1A.
HPACAB000064.
MIM116899. gene.
PharmGKBPA104.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP38936.

Enzyme and pathway databases

ReactomeREACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressP38936.
CleanExHS_CDKN1A.
GermOnlineENSG00000124762. Homo sapiens.

Family and domain databases

InterProIPR003175. CDI.
[Graphical view]
PANTHERPTHR10265. CDI. 1 hit.
PfamPF02234. CDI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

LinkHubP38936.
NextBio4309.
SOURCESearch...

Entry information

Entry nameCDN1A_HUMAN
AccessionPrimary (citable) accession number: P38936
Secondary accession number(s): Q14010, Q9BUT4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: November 25, 2008
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents