CDN1B_NEOVI
ID CDN1B_NEOVI Reviewed; 178 AA.
AC P46529;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Cyclin-dependent kinase inhibitor 1B;
DE AltName: Full=Cyclin-dependent kinase inhibitor p27;
DE AltName: Full=p27Kip1;
DE Flags: Fragment;
GN Name=CDKN1B;
OS Neovison vison (American mink) (Mustela vison).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Mustelidae; Mustelinae;
OC Neogale.
OX NCBI_TaxID=452646;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8033212; DOI=10.1016/0092-8674(94)90572-x;
RA Polyak K., Lee M.-H., Erdjument-Bromage H., Koff A., Roberts J.M.,
RA Tempst P., Massague J.;
RT "Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential
RT mediator of extracellular antimitogenic signals.";
RL Cell 78:59-66(1994).
RN [2]
RP FUNCTION.
RX PubMed=8288131; DOI=10.1101/gad.8.1.9;
RA Polyak K., Kato J.-Y., Solomon M.J., Sherr C.J., Massague J., Roberts J.M.,
RA Koff A.;
RT "p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and
RT contact inhibition to cell cycle arrest.";
RL Genes Dev. 8:9-22(1994).
CC -!- FUNCTION: Important regulator of cell cycle progression
CC (PubMed:8288131). Inhibits the kinase activity of CDK2 bound to cyclin
CC A, but has little inhibitory activity on CDK2 bound to SPDYA (By
CC similarity). Involved in G1 arrest (PubMed:8288131). Potent inhibitor
CC of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin
CC type D-CDK4 complexes and is involved in the assembly, stability, and
CC modulation of CCND1-CDK4 complex activation. Acts either as an
CC inhibitor or an activator of cyclin type D-CDK4 complexes depending on
CC its phosphorylation state and/or stoichometry (By similarity).
CC {ECO:0000250|UniProtKB:P46527, ECO:0000269|PubMed:8288131}.
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. Interacts with COPS5, subunit of the COP9
CC signalosome complex; the interaction leads to CDKN1B degradation.
CC Interacts with NUP50; the interaction leads to nuclear import and
CC degradation of phosphorylated CDKN1B. Interacts with CCND1 and SNX6 (By
CC similarity). Interacts (Thr-198-phosphorylated form) with 14-3-3
CC proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not YWHAB
CC nor YWHAZ; the interaction with YWHAQ results in translocation to the
CC 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 by PPM1H, leading to
CC 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. Mitogen-activated UHMK1 phosphorylation on Ser-10 results in
CC translocation to the cytoplasm and cell cycle progression.
CC Phosphorylation on Ser-10 facilitates nuclear export (By similarity).
CC Colocalizes at the endosome with SNX6; this leads to lysosomal
CC degradation (By similarity). {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, MYC and in certain cancer
CC cell lines. The phosphorylated form found in the cytoplasm is
CC inactivate. Phosphorylation on Tyr-88 has no effect on binding CDK
CC complexes (By similarity). {ECO:0000250}.
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; U09966; AAA20234.1; -; mRNA.
DR AlphaFoldDB; P46529; -.
DR SMR; P46529; -.
DR CORUM; P46529; -.
DR Proteomes; UP000694425; Unplaced.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:InterPro.
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..>178
FT /note="Cyclin-dependent kinase inhibitor 1B"
FT /id="PRO_0000190086"
FT REGION 1..31
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..178
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..178
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, SRC and JAK2"
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, RPS6KA1,
FT RPS6KA3 and PIM1"
FT /evidence="ECO:0000250|UniProtKB:P46527"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46414"
FT NON_TER 178
SQ SEQUENCE 178 AA; 20129 MW; D1B61C84AD1D473E CRC64;
MSNVRVSNGS PSLERMDARQ AEYPKPSACR NLFGPVNHEE LTRDLEKHRR DMEEASQRKW
NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GTRQAVPLMG
SQANSEDTHL VDQKTDTADN QAGLAEQCTG IRKRPATDDS SPQNKRANRT EENVSDGS
