Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P38936 (CDN1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase inhibitor 1
Alternative name(s):
CDK-interacting protein 1
Melanoma differentiation-associated protein 6
Short name=MDA-6
p21
Gene names
Name:CDKN1A
Synonyms:CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1
OrganismHomo sapiens (Human) [Reference proteome]
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/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. Ref.1 Ref.17

Subunit structure

Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 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. Interacts with PIM1. Ref.17 Ref.18 Ref.20 Ref.24 Ref.26 Ref.28 Ref.29

Subcellular location

Cytoplasm. Nucleus Ref.17 Ref.19 Ref.20.

Tissue specificity

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

Induction

Activated by p53/TP53, mezerein (antileukemic compound) and IFNB1. Repressed by HDAC1. Ref.1 Ref.2

Domain

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. Ref.24 Ref.26

The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex. Ref.24 Ref.26

Post-translational modification

Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell proliferation. Phosphorylation of Thr-145 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. Ref.21 Ref.24 Ref.25 Ref.26 Ref.29 Ref.30 Ref.33

Acetylation leads to protein stability. Acetylated in vitro on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1 By similarity. Ref.15

Sequence similarities

Belongs to the CDI family.

Sequence caution

The sequence AAB59559.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAB59560.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionProtein kinase inhibitor
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest

Inferred from direct assay PubMed 15149599. Source: BHF-UCL

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

G1/S transition of mitotic cell cycle

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

G2/M transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

Ras protein signal transduction

Inferred from expression pattern PubMed 9054499. Source: BHF-UCL

cell cycle arrest

Inferred from direct assay PubMed 15149599. Source: BHF-UCL

cellular response to DNA damage stimulus

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

cellular response to extracellular stimulus

Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL

cellular response to ionizing radiation

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

cellular senescence

Inferred from mutant phenotype PubMed 15149599. Source: BHF-UCL

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway

Traceable author statement PubMed 9660939. Source: ProtInc

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic cell cycle arrest

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell growth

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from direct assay PubMed 10208428PubMed 15149599. Source: BHF-UCL

negative regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

negative regulation of phosphorylation

Inferred from direct assay PubMed 10208428. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

organ regeneration

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of fibroblast proliferation

Inferred from mutant phenotype PubMed 17420273. Source: BHF-UCL

positive regulation of programmed cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase activity

Inferred from direct assay Ref.17. Source: GOC

positive regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

protein phosphorylation

Inferred from direct assay Ref.17. Source: GOC

regulation of DNA biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of cyclin-dependent protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: ProtInc

regulation of protein import into nucleus, translocation

Inferred from electronic annotation. Source: Ensembl

response to UV

Inferred from electronic annotation. Source: Ensembl

response to arsenic-containing substance

Inferred from electronic annotation. Source: Ensembl

response to corticosterone

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hyperoxia

Inferred from electronic annotation. Source: Ensembl

response to organonitrogen compound

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

stress-induced premature senescence

Traceable author statement PubMed 20160708. Source: BHF-UCL

   Cellular_componentPCNA-p21 complex

Inferred from direct assay Ref.24. Source: UniProtKB

cyclin-dependent protein kinase holoenzyme complex

Inferred from direct assay PubMed 17420273. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 11343236. Source: BHF-UCL

   Molecular_functioncyclin-dependent protein kinase activating kinase activity

Inferred from direct assay Ref.17. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase inhibitor activity

Traceable author statement PubMed 7958916. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.24. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 164163Cyclin-dependent kinase inhibitor 1
PRO_0000190079

Regions

Zinc finger13 – 4129C4-type Potential
Region17 – 248Required for binding cyclins
Region53 – 586Required for binding CDKs
Motif140 – 16425PIP-box K+4 motif
Motif141 – 15616Nuclear localization signal Potential

Amino acid modifications

Modified residue21N-acetylserine Ref.15
Modified residue1141Phosphoserine; by GSK3-beta Ref.24
Modified residue1301Phosphoserine Ref.23 Ref.27
Modified residue1451Phosphothreonine; by PKA; PKB/AKT1, PIM1 and PIM2 Ref.16 Ref.19 Ref.20 Ref.22 Ref.31
Modified residue1461Phosphoserine; by PKC Ref.16
Modified residue1601Phosphoserine; by PKC; in vitro Ref.16
Cross-link2Glycyl serine ester (Ser-Gly) (interchain with G-Cter in ubiquitin) Probable

Natural variations

Natural variant41P → L.
Corresponds to variant rs4986866 [ dbSNP | Ensembl ].
VAR_048686
Natural variant311S → R. Ref.7 Ref.8 Ref.14
Corresponds to variant rs1801270 [ dbSNP | Ensembl ].
VAR_011870
Natural variant631F → L.
Corresponds to variant rs4986867 [ dbSNP | Ensembl ].
VAR_048687
Natural variant1491D → G.
Corresponds to variant rs1801724 [ dbSNP | Ensembl ].
VAR_014875

Experimental info

Mutagenesis1141S → E: Phosphomimetic mutant, increases ubiquitination by the DCX(DTL) complex. Ref.24
Mutagenesis144 – 1507QTSMTDF → ATSATDA: Abolishes interaction with PCNA and subsequent degradation by the proteasome. Ref.24
Mutagenesis1451T → A: Reduces phosphorylation by Akt; no change in interaction with PCNA, CDK2 or CDK4; no change in subcellular location. Ref.19
Mutagenesis1451T → D: No interaction with PCNA; 59% inhibition of CDK2 binding; modest inhibition of CDK4 binding; no change in subcellular location. Ref.19
Mutagenesis1461S → A: No change in interaction with PCNA. Ref.19
Mutagenesis1461S → D: Reduces interaction with PCNA. Ref.19
Mutagenesis147 – 1515MTDFY → ATDAAA: Abolishes interaction with PCNA and subsequent degradation by the proteasome. Ref.26
Mutagenesis154 – 1563KRR → AAA: Abolishes degradation by the proteasome without affecting the interaction with PCNA. Ref.26

Secondary structure

..... 164
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P38936 [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[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] [Europe PMC] [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]"The melanoma differentiation-associated gene mda-6, which encodes the cyclin-dependent kinase inhibitor p21, is differentially expressed during growth, differentiation and progression in human melanoma cells."
Jiang H., Lin J., Su Z.Z., Herlyn M., Kerbel R.S., Weissman B.E., Welch D.R., Fisher P.B.
Oncogene 10:1855-1864(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-31.
[8]NIEHS SNPs program
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-31.
[9]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[12]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[14]"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], VARIANT ARG-31.
Tissue: Eye and Lung.
[15]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
[16]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND SER-160, IDENTIFICATION BY MASS SPECTROMETRY.
[17]"New functional activities for the p21 family of CDK inhibitors."
LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., Chou H.S., Fattaey A., Harlow E.
Genes Dev. 11:847-862(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDK4 AND CCND1 IN THE CYCLIN D-CDK4-CDKN1A COMPLEX.
[18]"A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 alpha-subunit of the 20S proteasome."
Touitou R., Richardson J., Bose S., Nakanishi M., Rivett J., Allday M.J.
EMBO J. 20:2367-2375(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PSMA3.
[19]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, SUBCELLULAR LOCATION.
[20]"Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase."
Wang Z., Bhattacharya N., Mixter P.F., Wei W., Sedivy J., Magnuson N.S.
Biochim. Biophys. Acta 1593:45-55(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-145 BY PIM1, SUBCELLULAR LOCATION, INTERACTION WITH PIM1.
[21]"N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome."
Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.
Mol. Cell. Biol. 24:6140-6150(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT SER-2.
[22]"Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding."
Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D., Hemmings B.A., Fernandez A., Lamb N.J.
Mol. Cell. Biol. 26:8267-8280(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-145.
[23]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex."
Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.
Genes Dev. 22:2496-2506(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, INTERACTION WITH PCNA, MUTAGENESIS OF SER-114 AND 144-GLN--PHE-150, PHOSPHORYLATION AT SER-114.
[25]"The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing."
Kim Y., Starostina N.G., Kipreos E.T.
Genes Dev. 22:2507-2519(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[26]"CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation."
Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., Tsurimoto T.
J. Biol. Chem. 283:29045-29052(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, MUTAGENESIS OF 147-MET--TYR-151 AND 154-LYS--ARG-156, INTERACTION WITH PCNA.
[27]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"A dual role of Cdk2 in DNA damage response."
Satyanarayana A., Kaldis P.
Cell Div. 4:9-9(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON DNA REPAIR, INTERACTION WITH CDK2.
[29]"Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis."
Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C., Lane D.P., Song J.
EMBO J. 28:2100-2113(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH MKRN1.
[30]"Ionizing radiation induces ATM-independent degradation of p21Cip1 in transformed cells."
Stuart S.A., Wang J.Y.
J. Biol. Chem. 284:15061-15070(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[31]"Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells."
Wang Z., Zhang Y., Gu J.J., Davitt C., Reeves R., Magnuson N.S.
Int. J. Biochem. Cell Biol. 42:1030-1038(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-145 BY PIM2.
[32]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"ZNF313 is a novel cell cycle activator with an E3 ligase activity inhibiting cellular senescence by destabilizing p21(WAF1.)."
Han J., Kim Y.L., Lee K.W., Her N.G., Ha T.K., Yoon S., Jeong S.I., Lee J.H., Kang M.J., Lee M.G., Ryu B.K., Baik J.H., Chi S.G.
Cell Death Differ. 20:1055-1067(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY RNF114.
[34]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160 IN COMPLEX WITH PCNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
BT006719 mRNA. Translation: AAP35365.1.
AB451290 mRNA. Translation: BAG70104.1.
AB451422 mRNA. Translation: BAG70236.1.
CR536533 mRNA. Translation: CAG38770.1.
Z85996 Genomic DNA. Translation: CAB06656.1.
CH471081 Genomic DNA. Translation: EAX03904.1.
BC000275 mRNA. Translation: AAH00275.1.
BC000312 mRNA. Translation: AAH00312.1.
BC001935 mRNA. Translation: AAH01935.1.
BC013967 mRNA. Translation: AAH13967.1.
CCDSCCDS4824.1.
PIRI54380.
I68674.
RefSeqNP_000380.1. NM_000389.4.
NP_001207706.1. NM_001220777.1.
NP_001207707.1. NM_001220778.1.
NP_001278478.1. NM_001291549.1.
NP_510867.1. NM_078467.2.
UniGeneHs.370771.
Hs.732576.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AXCX-ray2.60B/D/F139-160[»]
2ZVVX-ray2.00X/Y139-160[»]
2ZVWX-ray2.50I/J/K/L/M/N/O/P139-160[»]
DisProtDP00016.
ProteinModelPortalP38936.
SMRP38936. Positions 17-77.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107460. 197 interactions.
DIPDIP-246N.
IntActP38936. 142 interactions.
MINTMINT-104203.
STRING9606.ENSP00000244741.

Chemistry

ChEMBLCHEMBL3038463.

PTM databases

PhosphoSiteP38936.

Polymorphism databases

DMDM729143.

2D gel databases

SWISS-2DPAGEP38936.

Proteomic databases

MaxQBP38936.
PaxDbP38936.
PRIDEP38936.

Protocols and materials databases

DNASU1026.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000244741; ENSP00000244741; ENSG00000124762.
ENST00000373711; ENSP00000362815; ENSG00000124762.
ENST00000405375; ENSP00000384849; ENSG00000124762.
GeneID1026.
KEGGhsa:1026.
UCSCuc003omm.4. human.

Organism-specific databases

CTD1026.
GeneCardsGC06P036761.
HGNCHGNC:1784. CDKN1A.
HPACAB000064.
HPA051359.
MIM116899. gene.
neXtProtNX_P38936.
Orphanet652. Multiple endocrine neoplasia type 1.
PharmGKBPA104.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG290902.
HOGENOMHOG000285999.
HOVERGENHBG050868.
InParanoidP38936.
KOK06625.
OrthoDBEOG7GJ6HD.
PhylomeDBP38936.
TreeFamTF101038.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_120956. Cellular responses to stress.
REACT_383. DNA Replication.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP38936.
BgeeP38936.
CleanExHS_CDKN1A.
GenevestigatorP38936.

Family and domain databases

InterProIPR003175. CDI.
[Graphical view]
PANTHERPTHR10265. PTHR10265. 1 hit.
PfamPF02234. CDI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDKN1A. human.
EvolutionaryTraceP38936.
GeneWikiP21.
GenomeRNAi1026.
NextBio4309.
PROP38936.
SOURCESearch...

Entry information

Entry nameCDN1A_HUMAN
AccessionPrimary (citable) accession number: P38936
Secondary accession number(s): Q14010, Q6FI05, Q9BUT4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

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