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Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)

 CDN1B_FELCA             Reviewed;         198 AA.
O19001;
15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
01-JAN-1998, sequence version 1.
12-AUG-2020, entry version 120.
RecName: Full=Cyclin-dependent kinase inhibitor 1B;
AltName: Full=Cyclin-dependent kinase inhibitor p27;
AltName: Full=p27Kip1;
Name=CDKN1B; Synonyms=KIP1;
Felis catus (Cat) (Felis silvestris catus).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
NCBI_TaxID=9685;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Lymph node;
PubMed=9370275; DOI=10.1016/s0378-1119(97)00304-1;
Okuda M., Minehata K., Setoguchi A., Cho K.-W., Nakamura N., Nishigaki K.,
Watari T., Cevario S., O'Brien S.J., Tsujimoto H., Hasegawa A.;
"Cloning and chromosome mapping of the feline genes p21WAF1 and p27Kip1.";
Gene 198:141-147(1997).
-!- FUNCTION: Important regulator of cell cycle progression. Inhibits the
kinase activity of CDK2 bound to cyclin A, but has little inhibitory
activity on CDK2 bound to SPDYA. Involved in G1 arrest. Potent
inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex
with cyclin type D-CDK4 complexes and is involved in the assembly,
stability, and modulation of CCND1-CDK4 complex activation. Acts either
as an inhibitor or an activator of cyclin type D-CDK4 complexes
depending on its phosphorylation state and/or stoichometry.
{ECO:0000250|UniProtKB:P46527}.
-!- SUBUNIT: Forms a ternary complex composed of CCNE1, CDK2 and CDKN1B.
Interacts directly with CCNE1; the interaction is inhibited by CDK2-
dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of
the COP9 signalosome complex; the interaction leads to CDKN1B
degradation. Interacts with NUP50; the interaction leads to nuclear
import and degradation of phosphorylated CDKN1B. Interacts with CCND1
and SNX6 (By similarity). Interacts (Thr-198-phosphorylated form) with
14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not
YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to
the cytoplasm. Interacts with AKT1 and LYN; the interactions lead to
cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of
cell cycle arrest. Forms a ternary complex with CCNA2 and CDK2; CDKN1B
inhibits the kinase activity of CDK2 through conformational
rearrangements. Interacts (unphosphorylated form) with CDK2. Forms a
complex with CDK2 and SPDYA, but does not directly interact with SPDYA.
Forms a ternary complex composed of cyclin D, CDK4 and CDKN1B.
Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the
interaction is required for cyclin D and CDK4 complex assembly, induces
nuclear translocation and activates the CDK4 kinase activity. Interacts
with GRB2. Interacts with PIM1. Identified in a complex with SKP1, SKP2
and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic
mislocation, phosphorylation of CDKN1B and inhibition of cell cycle
arrest. Interacts also with CDK1. Dephosphorylated on Thr-187 by PPM1H,
leading to CDKN1B stability (By similarity). {ECO:0000250,
ECO:0000250|UniProtKB:P46527}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
Endosome {ECO:0000250}. Note=Nuclear and cytoplasmic in quiescent
cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3,
translocates to the cytoplasm and promotes cell cycle progression.
Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in
translocation to the cytoplasm and cell cycle progression.
Phosphorylation on Ser-10 facilitates nuclear export. Translocates to
the nucleus on phosphorylation of Tyr-88 and Tyr-89 (By similarity).
Colocalizes at the endosome with SNX6; this leads to lysosomal
degradation (By similarity). {ECO:0000250}.
-!- DOMAIN: A peptide sequence containing only AA 28-79 retains substantial
Kip1 cyclin A/CDK2 inhibitory activity. {ECO:0000250}.
-!- PTM: Phosphorylated; phosphorylation occurs on serine, threonine and
tyrosine residues. Phosphorylation on Ser-10 is the major site of
phosphorylation in resting cells, takes place at the G(0)-G(1) phase
and leads to protein stability. Phosphorylation on other sites is
greatly enhanced by mitogens, growth factors, cMYC and in certain
cancer cell lines. The phosphorylated form found in the cytoplasm is
inactivate. Phosphorylation on Thr-198 is required for interaction with
14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to
protein ubiquitination and proteasomal degradation. Tyrosine
phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can
be suppressed by LY294002, an inhibitor of the catalytic subunit of
PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding
CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine
residues by G-CSF (By similarity).Dephosphorylated on Thr-187 by PPM1H,
leading to CDKN1B stability (By similarity).
{ECO:0000250|UniProtKB:P46527}.
-!- PTM: Ubiquitinated; in the cytoplasm by the KPC complex (composed of
RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The
latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a
TRIM21-containing SCF(SKP2)-like complex; leads to its degradation (By
similarity). {ECO:0000250}.
-!- PTM: Subject to degradation in the lysosome. Interaction with SNX6
promotes lysosomal degradation (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}.
---------------------------------------------------------------------------
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---------------------------------------------------------------------------
EMBL; D84649; BAA23167.1; -; mRNA.
RefSeq; NP_001009870.1; NM_001009870.1.
SMR; O19001; -.
STRING; 9685.ENSFCAP00000023343; -.
Ensembl; ENSFCAT00000058117; ENSFCAP00000044526; ENSFCAG00000043547.
GeneID; 493958; -.
KEGG; fca:493958; -.
CTD; 1027; -.
eggNOG; KOG4743; Eukaryota.
GeneTree; ENSGT00940000159852; -.
HOGENOM; CLU_077692_2_0_1; -.
InParanoid; O19001; -.
KO; K06624; -.
OMA; EGRYEWQ; -.
OrthoDB; 1595421at2759; -.
TreeFam; TF101038; -.
Proteomes; UP000011712; Chromosome B4.
Bgee; ENSFCAG00000022816; Expressed in spleen and 10 other tissues.
GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0005829; C:cytosol; IEA:Ensembl.
GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
GO; GO:0005634; C:nucleus; IBA:GO_Central.
GO; GO:0051087; F:chaperone binding; IBA:GO_Central.
GO; GO:0030332; F:cyclin binding; IEA:Ensembl.
GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
GO; GO:0048102; P:autophagic cell death; IEA:Ensembl.
GO; GO:0007050; P:cell cycle arrest; IBA:GO_Central.
GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central.
GO; GO:0007507; P:heart development; IEA:Ensembl.
GO; GO:0048839; P:inner ear development; IEA:Ensembl.
GO; GO:0071850; P:mitotic cell cycle arrest; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
GO; GO:1905179; P:negative regulation of cardiac muscle tissue regeneration; IEA:Ensembl.
GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
GO; GO:0051271; P:negative regulation of cellular component movement; IEA:Ensembl.
GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
GO; GO:0045930; P:negative regulation of mitotic cell cycle; IBA:GO_Central.
GO; GO:0042326; P:negative regulation of phosphorylation; IBA:GO_Central.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
GO; GO:1904706; P:negative regulation of vascular smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
GO; GO:0001890; P:placenta development; IEA:Ensembl.
GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
GO; GO:0031116; P:positive regulation of microtubule polymerization; IEA:Ensembl.
GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
GO; GO:0007096; P:regulation of exit from mitosis; IEA:Ensembl.
GO; GO:1902746; P:regulation of lens fiber cell differentiation; IEA:Ensembl.
GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
InterPro; IPR003175; CDI.
InterPro; IPR029843; CDKN1B.
PANTHER; PTHR10265:SF9; PTHR10265:SF9; 1.
Pfam; PF02234; CDI; 1.
2: Evidence at transcript level;
Cell cycle; Cytoplasm; Endosome; Nucleus; Phosphoprotein;
Protein kinase inhibitor; Reference proteome; Ubl conjugation.
CHAIN 1..198
/note="Cyclin-dependent kinase inhibitor 1B"
/id="PRO_0000190083"
REGION 51..91
/note="Interaction with CDK2"
/evidence="ECO:0000250|UniProtKB:P46527"
MOTIF 153..169
/note="Nuclear localization signal"
/evidence="ECO:0000255"
MOD_RES 10
/note="Phosphoserine; by UHMK1"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 74
/note="Phosphotyrosine; by SRC"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 88
/note="Phosphotyrosine; by ABL, LYN and SRC"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 89
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 157
/note="Phosphothreonine; by CaMK1, PKB/AKT1 and PIM1"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 170
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P46414"
MOD_RES 187
/note="Phosphothreonine; by PKB/AKT1, CDK1 and CDK2"
/evidence="ECO:0000250|UniProtKB:P46527"
MOD_RES 198
/note="Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1,
RPS6KA3 and PIM1"
/evidence="ECO:0000250|UniProtKB:P46527"
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


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WP1151: ACE Inhibitor Pathway
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Related Genes :
[CDKN1B KIP1] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
[Cdkn1b] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
[CDKN1B KIP1] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
[CDKN1B] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1) (Fragment)
[CDKN1B KIP1] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
[CDKN1B KIP1] Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
[CDKN1A CIP1 WAF1] Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (p21)
[CDK2 CDKN2] Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase)
[LAMTOR1 C11orf59 PDRO PP7157] Ragulator complex protein LAMTOR1 (Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1) (Lipid raft adaptor protein p18) (Protein associated with DRMs and endosomes) (p27Kip1-releasing factor from RhoA) (p27RF-Rho)
[CDKN1A CAP20 CDKN1 CIP1 MDA6 PIC1 SDI1 WAF1] Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21)
[CDK4] Cyclin-dependent kinase 4 (EC 2.7.11.22) (Cell division protein kinase 4) (PSK-J3)
[Cdkn1a Cip1 Waf1] Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein) (p21)
[CDKN2A CDKN2 MTS1] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (Multiple tumor suppressor 1) (MTS-1) (p16-INK4a) (p16-INK4) (p16INK4A)
[CDKN1C KIP2] Cyclin-dependent kinase inhibitor 1C (Cyclin-dependent kinase inhibitor p57) (p57Kip2)
[CCND1 BCL1 PRAD1] G1/S-specific cyclin-D1 (B-cell lymphoma 1 protein) (BCL-1) (BCL-1 oncogene) (PRAD1 oncogene)
[Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16-INK4)
[Cdkn2a P16ink4a] Cyclin-dependent kinase inhibitor 2A (Cyclin-dependent kinase 4 inhibitor A) (CDK4I) (p16-INK4a) (p16) (p16-INK4)
[CDKN3 CDI1 CIP2 KAP] Cyclin-dependent kinase inhibitor 3 (EC 3.1.3.16) (EC 3.1.3.48) (CDK2-associated dual-specificity phosphatase) (Cyclin-dependent kinase interactor 1) (Cyclin-dependent kinase-interacting protein 2) (Kinase-associated phosphatase)
[CCNA2 CCN1 CCNA] Cyclin-A2 (Cyclin-A) (Cyclin A)
[Cdkn2a] Tumor suppressor ARF (Alternative reading frame) (ARF) (Cyclin-dependent kinase inhibitor 2A) (p19ARF)
[Cdkn2a] Tumor suppressor ARF (Alternative reading frame) (ARF) (Cyclin-dependent kinase inhibitor 2A) (p19ARF)
[CDKN2A CDKN2 MLM] Tumor suppressor ARF (Alternative reading frame) (ARF) (Cyclin-dependent kinase inhibitor 2A) (p14ARF)
[KRP1 ICK1 At2g23430 F26B6.8] Cyclin-dependent kinase inhibitor 1 (Inhibitor/interactor of CDK protein 1) (KIP-related protein 1)
[CDK1 CDC2 CDC28A CDKN1 P34CDC2] Cyclin-dependent kinase 1 (CDK1) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase)
[Rps6ka3 Mapkapk1b Rps6ka-rs1 Rsk2] Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2)
[cdk1-b cdc2 cdc2x1.2] Cyclin-dependent kinase 1-B (CDK1-B) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog 2) (Cell division control protein 2-B) (Cell division protein kinase 1) (p34 protein kinase 2)
[CDKN2B MTS2] Cyclin-dependent kinase 4 inhibitor B (Multiple tumor suppressor 2) (MTS-2) (p14-INK4b) (p15-INK4b) (p15INK4B)
[Cdkn2b Ink4] Cyclin-dependent kinase 4 inhibitor B (p14-INK4b) (p15-INK4b)
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]

Bibliography :
[32963616] MicroRNA-150 suppresses p27 expression and promotes cell proliferation in HeLa human cervical cancer cells.
[32957483] Visualizing Cell Cycle Phase Organization and Control During Neural Lineage Elaboration.
[32686172] Depletion of cyclic-GMP levels and inhibition of cGMP-dependent protein kinase activate p21 /p27 pathways and lead to renal fibrosis and dysfunction.
[32628811] Cell cycle exit during bortezomib-induced osteogenic differentiation of mesenchymal stem cells was mediated by Xbp1s-upregulated p21 and p27.
[32628792] miR-196a-mediated downregulation of p27 protein promotes prostate cancer proliferation and relates to biochemical recurrence after radical prostatectomy.
[32066583] Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury.
[31959038] WIP1 dephosphorylation of p27 Serine 140 destabilizes p27 and reverses anti-proliferative effects of ATM phosphorylation.
[31929545] A non-canonical role for p27Kip1 in restricting proliferation of corneal endothelial cells during development.
[31863533] YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27 mediated by Akt.
[31754404] CACYBP Enhances Cytoplasmic Retention of P27 to Promote Hepatocellular Carcinoma Progression in the Absence of RNF41 Mediated Degradation.