LOCUS NP_510867 164 aa linear PRI 16-NOV-2008
DEFINITION cyclin-dependent kinase inhibitor 1A [Homo sapiens].
ACCESSION NP_510867
VERSION NP_510867.1 GI:17978495
DBSOURCE REFSEQ: accession NM_078467.1
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 164)
AUTHORS Ye,Y., Lippman,S.M., Lee,J.J., Chen,M., Frazier,M.L., Spitz,M.R.
and Wu,X.
TITLE Genetic variations in cell-cycle pathway and the risk of oral
premalignant lesions
JOURNAL Cancer 113 (9), 2488-2495 (2008)
PUBMED 18823025
REMARK GeneRIF: Observational study of gene-disease association, gene-gene
interaction, and gene-environment interaction. (HuGE Navigator)
REFERENCE 2 (residues 1 to 164)
AUTHORS Vega,A., Salas,A., Milne,R.L., Carracedo,B., Ribas,G., Ruibal,A.,
de Leon,A.C., Gonzalez-Hernandez,A., Benitez,J. and Carracedo,A.
TITLE Evaluating new candidate SNPs as low penetrance risk factors in
sporadic breast cancer: A two-stage Spanish case-control study
JOURNAL Gynecol. Oncol. (2008) In press
PUBMED 18950845
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
Publication Status: Available-Online prior to print
REFERENCE 3 (residues 1 to 164)
AUTHORS Qiu,Y.L., Wang,W., Wang,T., Liu,J., Sun,P., Qian,J., Jin,L. and
Xia,Z.L.
TITLE Genetic polymorphisms, messenger RNA expression of p53, p21, and
CCND1, and possible links with chromosomal aberrations in Chinese
vinyl chloride-exposed workers
JOURNAL Cancer Epidemiol. Biomarkers Prev. 17 (10), 2578-2584 (2008)
PUBMED 18842998
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
REFERENCE 4 (residues 1 to 164)
AUTHORS Lazzarini,R., Moretti,S., Orecchia,S., Betta,P.G., Procopio,A. and
Catalano,A.
TITLE Enhanced antitumor therapy by inhibition of p21waf1 in human
malignant mesothelioma
JOURNAL Clin. Cancer Res. 14 (16), 5099-5107 (2008)
PUBMED 18698027
REMARK GeneRIF: p21 might play an important role in chemosensitivity to
anticancer agents
REFERENCE 5 (residues 1 to 164)
AUTHORS Jin,X., Kang,S., Wang,N., Xing,Y.P. and Li,Y.
TITLE [Single nucleotide polymorphisms in cell cycle regulator p21 and
p27 genes are associated with susceptibility to epithelial ovarian
cancer]
JOURNAL Zhonghua Fu Chan Ke Za Zhi 43 (3), 209-212 (2008)
PUBMED 18788572
REMARK GeneRIF: Observational study of gene-disease association. (HuGE
Navigator)
REFERENCE 6 (sites)
AUTHORS Burch,L.R., Scott,M., Pohler,E., Meek,D. and Hupp,T.
TITLE Phage-peptide display identifies the interferon-responsive,
death-activated protein kinase family as a novel modifier of MDM2
and p21WAF1
JOURNAL J. Mol. Biol. 337 (1), 115-128 (2004)
PUBMED 15001356
REFERENCE 7 (sites)
AUTHORS Wang,Z., Bhattacharya,N., Mixter,P.F., Wei,W., Sedivy,J. and
Magnuson,N.S.
TITLE Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1
kinase
JOURNAL Biochim. Biophys. Acta 1593 (1), 45-55 (2002)
PUBMED 12431783
REFERENCE 8 (sites)
AUTHORS Kim,G.Y., Mercer,S.E., Ewton,D.Z., Yan,Z., Jin,K. and Friedman,E.
TITLE The stress-activated protein kinases p38 alpha and JNK1 stabilize
p21(Cip1) by phosphorylation
JOURNAL J. Biol. Chem. 277 (33), 29792-29802 (2002)
PUBMED 12058028
REFERENCE 9 (sites)
AUTHORS Li,Y., Dowbenko,D. and Lasky,L.A.
TITLE AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability
of p21Cip/WAF1 and promotes cell survival
JOURNAL J. Biol. Chem. 277 (13), 11352-11361 (2002)
PUBMED 11756412
REFERENCE 10 (sites)
AUTHORS Zhang,Y., Fujita,N. and Tsuruo,T.
TITLE Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells
from growth arrest to undergoing apoptosis
JOURNAL Oncogene 18 (5), 1131-1138 (1999)
PUBMED 10022118
REFERENCE 11 (sites)
AUTHORS Park,J.A., Kim,K.W., Kim,S.I. and Lee,S.K.
TITLE Caspase 3 specifically cleaves p21WAF1/CIP1 in the earlier stage of
apoptosis in SK-HEP-1 human hepatoma cells
JOURNAL Eur. J. Biochem. 257 (1), 242-248 (1998)
PUBMED 9799125
REFERENCE 12 (sites)
AUTHORS Levkau,B., Koyama,H., Raines,E.W., Clurman,B.E., Herren,B.,
Orth,K., Roberts,J.M. and Ross,R.
TITLE Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in
endothelial cells through activation of Cdk2: role of a caspase
cascade
JOURNAL Mol. Cell 1 (4), 553-563 (1998)
PUBMED 9660939
REFERENCE 13 (residues 1 to 164)
AUTHORS Kearsey,J.M., Coates,P.J., Prescott,A.R., Warbrick,E. and Hall,P.A.
TITLE Gadd45 is a nuclear cell cycle regulated protein which interacts
with p21Cip1
JOURNAL Oncogene 11 (9), 1675-1683 (1995)
PUBMED 7478594
REFERENCE 14 (residues 1 to 164)
AUTHORS Hall,M., Bates,S. and Peters,G.
TITLE Evidence for different modes of action of cyclin-dependent kinase
inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to
cyclins
JOURNAL Oncogene 11 (8), 1581-1588 (1995)
PUBMED 7478582
REFERENCE 15 (residues 1 to 164)
AUTHORS Mousses,S., Ozcelik,H., Lee,P.D., Malkin,D., Bull,S.B. and
Andrulis,I.L.
TITLE Two variants of the CIP1/WAF1 gene occur together and are
associated with human cancer
JOURNAL Hum. Mol. Genet. 4 (6), 1089-1092 (1995)
PUBMED 7655464
REFERENCE 16 (residues 1 to 164)
AUTHORS Jiang,H., Lin,J., Su,Z.Z., Herlyn,M., Kerbel,R.S., Weissman,B.E.,
Welch,D.R. and Fisher,P.B.
TITLE 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
JOURNAL Oncogene 10 (9), 1855-1864 (1995)
PUBMED 7753561
REFERENCE 17 (residues 1 to 164)
AUTHORS Demetrick,D.J., Matsumoto,S., Hannon,G.J., Okamoto,K., Xiong,Y.,
Zhang,H. and Beach,D.H.
TITLE Chromosomal mapping of the genes for the human cell cycle proteins
cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3)
JOURNAL Cytogenet. Cell Genet. 69 (3-4), 190-192 (1995)
PUBMED 7698009
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from BC000312.2 and U09579.1.
Summary: This gene encodes a potent cyclin-dependent kinase
inhibitor. The encoded protein binds to and inhibits the activity
of cyclin-CDK2 or -CDK4 complexes, and thus functions as a
regulator of cell cycle progression at G1. The expression of this
gene is tightly controlled by the tumor suppressor protein p53,
through which this protein mediates the p53-dependent cell cycle G1
phase arrest in response to a variety of stress stimuli. This
protein can interact with proliferating cell nuclear antigen
(PCNA), a DNA polymerase accessory factor, and plays a regulatory
role in S phase DNA replication and DNA damage repair. This protein
was reported to be specifically cleaved by CASP3-like caspases,
which thus leads to a dramatic activation of CDK2, and may be
instrumental in the execution of apoptosis following caspase
activation. Two alternatively spliced variants, which encode an
identical protein, have been reported. [provided by RefSeq].
Transcript Variant: This variant (2) contains an extra internal
sequence segment in the 5' UTR region. Variants 1 and 2 encode the
same protein.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the
Entrez Gene record to access additional publications.
FEATURES Location/Qualifiers
source 1..164
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="6"
/map="6p21.2"
Protein 1..164
/product="cyclin-dependent kinase inhibitor 1A"
/note="melanoma differentiation associated protein 6;
CDK-interaction protein 1; wild-type p53-activated
fragment 1; DNA synthesis inhibitor"
/calculated_mol_wt=17988
Site 57
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[8]
/db_xref="HPRD:03100"
Site 112
/site_type="modified"
/experiment="experimental evidence, no additional details
recorded"
/note="proteolytic cleavage site"
/citation=[10]
/citation=[12]
/db_xref="HPRD:02799"
Site 112
/site_type="modified"
/experiment="experimental evidence, no additional details
recorded"
/note="proteolytic cleavage site"
/citation=[12]
Site 130
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[8]
/db_xref="HPRD:03100"
Site 145
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[9]
/db_xref="HPRD:01261"
Site 145
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[6]
/db_xref="HPRD:04478"
Site 145
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[7]
/db_xref="HPRD:01292"
Site 146
/site_type="phosphorylation"
/experiment="experimental evidence, no additional details
recorded"
/citation=[9]
/db_xref="HPRD:01261"
Site 149
/site_type="modified"
/experiment="experimental evidence, no additional details
recorded"
/note="proteolytic cleavage site"
/citation=[11]
/db_xref="HPRD:02799"
CDS 1..164
/gene="CDKN1A"
/gene_synonym="P21"
/gene_synonym="CIP1"
/gene_synonym="SDI1"
/gene_synonym="WAF1"
/gene_synonym="CAP20"
/gene_synonym="CDKN1"
/gene_synonym="MDA-6"
/gene_synonym="p21CIP1"
/coded_by="NM_078467.1:236..730"
/db_xref="CCDS:CCDS4824.1"
/db_xref="GeneID:1026"
/db_xref="HGNC:1784"
/db_xref="HPRD:00298"
/db_xref="MIM:116899"
ORIGIN
1 msepagdvrq npcgskacrr lfgpvdseql srdcdalmag ciqearerwn fdfvtetple
61 gdfawervrg lglpklylpt gprrgrdelg ggrrpgtspa llqgtaeedh vdlslsctlv
121 prsgeqaegs pggpgdsqgr krrqtsmtdf yhskrrlifs krkp
//