CDN1A_FELCA
ID CDN1A_FELCA Reviewed; 164 AA.
AC O19002;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1;
DE AltName: Full=CDK-interacting protein 1;
DE AltName: Full=p21;
GN Name=CDKN1A; Synonyms=CIP1, WAF1;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymph node;
RX PubMed=9370275; DOI=10.1016/s0378-1119(97)00304-1;
RA Okuda M., Minehata K., Setoguchi A., Cho K.-W., Nakamura N., Nishigaki K.,
RA Watari T., Cevario S., O'Brien S.J., Tsujimoto H., Hasegawa A.;
RT "Cloning and chromosome mapping of the feline genes p21WAF1 and p27Kip1.";
RL Gene 198:141-147(1997).
CC -!- FUNCTION: May be involved in p53/TP53 mediated inhibition of cellular
CC proliferation in response to DNA damage (By similarity). Binds to and
CC inhibits cyclin-dependent kinase activity, preventing phosphorylation
CC of critical cyclin-dependent kinase substrates and blocking cell cycle
CC progression (By similarity). Functions in the nuclear localization and
CC assembly of cyclin D-CDK4 complex and promotes its kinase activity
CC towards RB1 (By similarity). At higher stoichiometric ratios, inhibits
CC the kinase activity of the cyclin D-CDK4 complex (By similarity).
CC Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3
CC for PCNA binding (By similarity). Plays an important role in
CC controlling cell cycle progression and DNA damage-induced G2 arrest (By
CC similarity). {ECO:0000250|UniProtKB:P38936}.
CC -!- SUBUNIT: Interacts with HDAC1; the interaction is prevented by
CC competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation
CC and protein stabilization of CDKN1A/p21 (By similarity). Interacts with
CC MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the
CC ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal
CC domain) with CDK4; the interaction promotes the assembly of the cyclin
CC D-CDK4 complex, its nuclear translocation and promotes the cyclin D-
CC dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin
CC E inactivation at the G1-S phase DNA damage checkpoint, thereby
CC arresting cells at the G1-S transition during DNA repair. Interacts
CC with PIM1. Interacts with STK11 and NUAK1 (By similarity). Interacts
CC with DTL and TRIM39 (By similarity). {ECO:0000250|UniProtKB:P38936,
CC ECO:0000250|UniProtKB:P39689}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P38936}. Nucleus
CC {ECO:0000250|UniProtKB:P38936}.
CC -!- DOMAIN: The C-terminal is required for nuclear localization of the
CC cyclin D-CDK4 complex. {ECO:0000250}.
CC -!- DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA
CC and the recruitment of the DCX(DTL) complex: while the PIP-box
CC interacts with PCNA, the presence of the K+4 submotif, recruits the
CC DCX(DTL) complex, leading to its ubiquitination. {ECO:0000250}.
CC -!- PTM: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs
CC binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances
CC ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by
CC PIM2 enhances protein stability and inhibits cell proliferation.
CC Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A
CC to the cytoplasm and enhanced CDKN1A protein stability. UV radiation-
CC induced phosphorylation at Ser-146 by NUAK1 leads to its degradation.
CC {ECO:0000250|UniProtKB:P38936, ECO:0000250|UniProtKB:P39689}.
CC -!- PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S
CC proteasome-dependent degradation. Ubiquitinated by the DCX(DTL)
CC complex, also named CRL4(CDT2) complex, leading to its degradation
CC during S phase or following UV irradiation. Ubiquitination by the
CC DCX(DTL) complex is essential to control replication licensing and is
CC PCNA-dependent: interacts with PCNA via its PIP-box, while the presence
CC of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL)
CC complex, leading to its degradation. Ubiquitination at Ser-2 leads to
CC degradation by the proteasome pathway. Ubiquitinated by RNF114; leading
CC to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P38936}.
CC -!- PTM: Acetylation leads to protein stability. Acetylated in vitro on
CC Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is
CC prevented by competitive binding of C10orf90/FATS to HDAC1 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D84650; BAA23168.1; -; mRNA.
DR RefSeq; NP_001009865.1; NM_001009865.1.
DR RefSeq; XP_006931683.1; XM_006931621.3.
DR AlphaFoldDB; O19002; -.
DR BMRB; O19002; -.
DR SMR; O19002; -.
DR STRING; 9685.ENSFCAP00000020450; -.
DR Ensembl; ENSFCAT00000025177; ENSFCAP00000020450; ENSFCAG00000027886.
DR GeneID; 493943; -.
DR KEGG; fca:493943; -.
DR CTD; 1026; -.
DR VGNC; VGNC:60713; CDKN1A.
DR eggNOG; KOG4743; Eukaryota.
DR GeneTree; ENSGT00940000159918; -.
DR HOGENOM; CLU_077692_1_1_1; -.
DR InParanoid; O19002; -.
DR OMA; KVCRRLF; -.
DR OrthoDB; 1595421at2759; -.
DR TreeFam; TF101038; -.
DR Proteomes; UP000011712; Chromosome B2.
DR Bgee; ENSFCAG00000027886; Expressed in tip of external ear and 10 other tissues.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070557; C:PCNA-p21 complex; ISS:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl.
DR GO; GO:0019912; F:cyclin-dependent protein kinase activating kinase activity; IEA:Ensembl.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IBA:GO_Central.
DR GO; GO:0140311; F:protein sequestering activity; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0071493; P:cellular response to UV-B; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IEA:Ensembl.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0090399; P:replicative senescence; IEA:Ensembl.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR Gene3D; 4.10.365.10; -; 1.
DR InterPro; IPR003175; CDI_dom.
DR InterPro; IPR044898; CDI_dom_sf.
DR InterPro; IPR029841; CDKN1A.
DR PANTHER; PTHR46778; PTHR46778; 1.
DR Pfam; PF02234; CDI; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cell cycle; Cytoplasm; Metal-binding; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome; Ubl conjugation; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT CHAIN 2..164
FT /note="Cyclin-dependent kinase inhibitor 1"
FT /id="PRO_0000190078"
FT ZN_FING 13..41
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 17..24
FT /note="Required for binding cyclins"
FT /evidence="ECO:0000250"
FT REGION 53..58
FT /note="Required for binding CDKs"
FT /evidence="ECO:0000250"
FT REGION 80..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..164
FT /note="Interaction with TRIM39"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOTIF 140..164
FT /note="PIP-box K+4 motif"
FT MOTIF 141..156
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOD_RES 114
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOD_RES 145
FT /note="Phosphothreonine; by PKA, PKB/AKT1, PIM1 and PIM2"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOD_RES 146
FT /note="Phosphoserine; by PKC and NUAK1"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38936"
FT CROSSLNK 2
FT /note="Glycyl serine ester (Ser-Gly) (interchain with G-
FT Cter in ubiquitin)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 164 AA; 18316 MW; 0F7912A76C78BF38 CRC64;
MSEPSRDAHQ IPHGSKACRR LFGPVDSEQL RRDCDALMAG CVQEARERWN FDFVTETPLE
GDFAWERVWG LGLPKLYLPA GPRGGRDDLG GGKRPSTSST LLPGTAREDH LDLSLSCTLM
PHSPERPEAS PGAPGTSQGR KRRQTSMTDF YHSKRRLIFS KRKP
