CPLM-007062

Genbank Nucleotide ID

Cyclin-dependent kinase inhibitor 1

Protein Synonyms/Alias

CDK-interacting protein 1; Melanoma differentiation-associated protein 6; MDA-6; p21

CAP20; CDKN1; CIP1; MDA6; PIC1; SDI1; WAF1

Homo sapiens (Human)

Position	Peptide	Type	References
75	VRGLGLPKLYLPTGP	ubiquitination	[1, 2, 3, 4, 5, 6]
154	MTDFYHSKRRLIFSK	ubiquitination	[5]
161	KRRLIFSKRKP****	ubiquitination	[5]

[1] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

ZN_FING 13 41 C4-type (Potential).
REGION 17 24 Required for binding cyclins.
REGION 53 58 Required for binding CDKs.
MOTIF 140 164 PIP-box K+4 motif.
MOTIF 141 156 Nuclear localization signal (Potential).
MOD_RES 2 2 N-acetylserine.
MOD_RES 114 114 Phosphoserine; by GSK3-beta.
MOD_RES 130 130 Phosphoserine.
MOD_RES 145 145 Phosphothreonine; by PKA; PKB/AKT1, PIM1
MOD_RES 146 146 Phosphoserine; by PKC.
MOD_RES 160 160 Phosphoserine; by PKC; in vitro.

3D-structure; Acetylation; Cell cycle; Complete proteome; Cytoplasm; Direct protein sequencing; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Protein kinase inhibitor; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL.
GO:0005829; C:cytosol; TAS:Reactome.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0070557; C:PCNA-p21 complex; IDA:UniProtKB.
GO:0019912; F:cyclin-dependent protein kinase activating kinase activity; IDA:UniProtKB.
GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; TAS:ProtInc.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0007050; P:cell cycle arrest; IDA:BHF-UCL.
GO:0031668; P:cellular response to extracellular stimulus; IMP:BHF-UCL.
GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL.
GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IDA:BHF-UCL.
GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:BHF-UCL.
GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc.
GO:0071850; P:mitotic cell cycle arrest; IEA:Compara.
GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL.
GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Compara.
GO:0010629; P:negative regulation of gene expression; IEA:Compara.
GO:0031100; P:organ regeneration; IEA:Compara.
GO:0030890; P:positive regulation of B cell proliferation; IEA:Compara.
GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL.
GO:0043068; P:positive regulation of programmed cell death; IEA:Compara.
GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL.
GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
GO:2000278; P:regulation of DNA biosynthetic process; IEA:Compara.
GO:0033158; P:regulation of protein import into nucleus, translocation; IEA:Compara.
GO:0046685; P:response to arsenic-containing substance; IEA:Compara.
GO:0051412; P:response to corticosterone stimulus; IEA:Compara.
GO:0042493; P:response to drug; IEA:Compara.
GO:0055093; P:response to hyperoxia; IEA:Compara.
GO:0010243; P:response to organic nitrogen; IEA:Compara.
GO:0009636; P:response to toxic substance; IEA:Compara.
GO:0009411; P:response to UV; IEA:Compara.
GO:0090400; P:stress-induced premature senescence; TAS:BHF-UCL.