CDN1B_FELCA
ID CDN1B_FELCA Reviewed; 198 AA.
AC O19001;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1B;
DE AltName: Full=Cyclin-dependent kinase inhibitor p27;
DE AltName: Full=p27Kip1;
GN Name=CDKN1B; Synonyms=KIP1;
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: Important regulator of cell cycle progression. Inhibits the
CC kinase activity of CDK2 bound to cyclin A, but has little inhibitory
CC activity on CDK2 bound to SPDYA. Involved in G1 arrest. Potent
CC inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex
CC with cyclin type D-CDK4 complexes and is involved in the assembly,
CC stability, and modulation of CCND1-CDK4 complex activation. Acts either
CC as an inhibitor or an activator of cyclin type D-CDK4 complexes
CC depending on its phosphorylation state and/or stoichometry.
CC {ECO:0000250|UniProtKB:P46527}.
CC -!- SUBUNIT: Forms a ternary complex composed of CCNE1, CDK2 and CDKN1B.
CC Interacts directly with CCNE1; the interaction is inhibited by CDK2-
CC dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of
CC the COP9 signalosome complex; the interaction leads to CDKN1B
CC degradation. Interacts with NUP50; the interaction leads to nuclear
CC import and degradation of phosphorylated CDKN1B. Interacts with CCND1
CC and SNX6 (By similarity). Interacts (Thr-198-phosphorylated form) with
CC 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not
CC YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to
CC the cytoplasm. Interacts with AKT1 and LYN; the interactions lead to
CC cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of
CC cell cycle arrest. Forms a ternary complex with CCNA2 and CDK2; CDKN1B
CC inhibits the kinase activity of CDK2 through conformational
CC rearrangements. Interacts (unphosphorylated form) with CDK2. Forms a
CC complex with CDK2 and SPDYA, but does not directly interact with SPDYA.
CC Forms a ternary complex composed of cyclin D, CDK4 and CDKN1B.
CC Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the
CC interaction is required for cyclin D and CDK4 complex assembly, induces
CC nuclear translocation and activates the CDK4 kinase activity. Interacts
CC with GRB2. Interacts with PIM1. Identified in a complex with SKP1, SKP2
CC and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic
CC mislocation, phosphorylation of CDKN1B and inhibition of cell cycle
CC arrest. Interacts also with CDK1. Dephosphorylated on Thr-187 by PPM1H,
CC leading to CDKN1B stability (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P46527}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Endosome {ECO:0000250}. Note=Nuclear and cytoplasmic in quiescent
CC cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3,
CC translocates to the cytoplasm and promotes cell cycle progression.
CC Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in
CC translocation to the cytoplasm and cell cycle progression.
CC Phosphorylation on Ser-10 facilitates nuclear export. Translocates to
CC the nucleus on phosphorylation of Tyr-88 and Tyr-89 (By similarity).
CC Colocalizes at the endosome with SNX6; this leads to lysosomal
CC degradation (By similarity). {ECO:0000250}.
CC -!- DOMAIN: A peptide sequence containing only AA 28-79 retains substantial
CC Kip1 cyclin A/CDK2 inhibitory activity. {ECO:0000250}.
CC -!- PTM: Phosphorylated; phosphorylation occurs on serine, threonine and
CC tyrosine residues. Phosphorylation on Ser-10 is the major site of
CC phosphorylation in resting cells, takes place at the G(0)-G(1) phase
CC and leads to protein stability. Phosphorylation on other sites is
CC greatly enhanced by mitogens, growth factors, cMYC and in certain
CC cancer cell lines. The phosphorylated form found in the cytoplasm is
CC inactivate. Phosphorylation on Thr-198 is required for interaction with
CC 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to
CC protein ubiquitination and proteasomal degradation. Tyrosine
CC phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can
CC be suppressed by LY294002, an inhibitor of the catalytic subunit of
CC PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding
CC CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine
CC residues by G-CSF (By similarity).Dephosphorylated on Thr-187 by PPM1H,
CC leading to CDKN1B stability (By similarity).
CC {ECO:0000250|UniProtKB:P46527}.
CC -!- PTM: Ubiquitinated; in the cytoplasm by the KPC complex (composed of
CC RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The
CC latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a
CC TRIM21-containing SCF(SKP2)-like complex; leads to its degradation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Subject to degradation in the lysosome. Interaction with SNX6
CC promotes lysosomal degradation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
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DR EMBL; D84649; BAA23167.1; -; mRNA.
DR RefSeq; NP_001009870.1; NM_001009870.1.
DR AlphaFoldDB; O19001; -.
DR SMR; O19001; -.
DR STRING; 9685.ENSFCAP00000023343; -.
DR Ensembl; ENSFCAT00000058117; ENSFCAP00000044526; ENSFCAG00000043547.
DR GeneID; 493958; -.
DR KEGG; fca:493958; -.
DR CTD; 1027; -.
DR eggNOG; KOG4743; Eukaryota.
DR GeneTree; ENSGT00940000159852; -.
DR HOGENOM; CLU_077692_2_0_1; -.
DR InParanoid; O19001; -.
DR OMA; QCAGMRK; -.
DR OrthoDB; 1595421at2759; -.
DR TreeFam; TF101038; -.
DR Proteomes; UP000011712; Chromosome B4.
DR Bgee; ENSFCAG00000043547; Expressed in uterus and 9 other tissues.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central.
DR GO; GO:0030332; F:cyclin binding; IEA:Ensembl.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0048102; P:autophagic cell death; IEA:Ensembl.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; IEA:Ensembl.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0007096; P:regulation of exit from mitosis; IEA:Ensembl.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:1902746; P:regulation of lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR Gene3D; 4.10.365.10; -; 1.
DR InterPro; IPR003175; CDI_dom.
DR InterPro; IPR044898; CDI_dom_sf.
DR InterPro; IPR029843; CDKN1B.
DR PANTHER; PTHR10265:SF9; PTHR10265:SF9; 1.
DR Pfam; PF02234; CDI; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cytoplasm; Endosome; Nucleus; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome; Ubl conjugation.
FT CHAIN 1..198
FT /note="Cyclin-dependent kinase inhibitor 1B"
FT /id="PRO_0000190083"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..91
FT /note="Interaction with CDK2"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT REGION 87..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 153..169
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 105..128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine; by UHMK1"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 74
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 88
FT /note="Phosphotyrosine; by ABL, LYN and SRC"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 89
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 157
FT /note="Phosphothreonine; by CaMK1, PKB/AKT1 and PIM1"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46414"
FT MOD_RES 187
FT /note="Phosphothreonine; by PKB/AKT1, CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 198
FT /note="Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1,
FT RPS6KA3 and PIM1"
FT /evidence="ECO:0000250|UniProtKB:P46527"
SQ SEQUENCE 198 AA; 22330 MW; 5A652F81462938D4 CRC64;
MSNVRVSNGS PSLERMDARQ AEYPKPSACR NLFGPVNHEE LTRDLEKHCR DMEEASQRKW
NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GNRQAVPLIG
SQANTEDTHL VDQKTDTSDN QTGLAEQCPG IRKRPATDDS SPQNKRANRT EENVSDGSPN
AGSVEQTPKK PGLRRRQT
