CDKN1B
entrez
1027
canonical
uniprot
P46527
canonical
ensembl
ENSG00000111276
resolver
ensp
ENSP00000228872
resolver
ensp
ENSP00000507272
resolver
ensp
ENSP00000577817
resolver
enst
ENST00000228872
resolver
enst
ENST00000614874
resolver
enst
ENST00000907758
resolver
genesymbol
CDKN1B
resolver
genesymbol_syn
KIP1
resolver
genesymbol_syn
p27
resolver
hgnc
HGNC:1785
resolver
uniprot
Q16307
resolver
uniprot
Q5U0H2
resolver
uniprot
Q6I9V6
resolver
uniprot
Q9BUS6
resolver
uniprot_entry
CDN1B_HUMAN
resolver
uniprot_entry
Q6I9V6_HUMAN
resolver
uniprot_sec
Q16307
resolver
uniprot_sec
Q5U0H2
resolver
uniprot_sec
Q9BUS6
resolver
amino_acid_sequence
MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEASQRKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYYRPPRPPKGACKVPAQESQDVSGSRPAAPLIGAPANSEDTHLVDPKTDPSDSQTGLAEQCAGIRKRPATDDSSTQNKRANRTEENVSDGSPNAGSVEQTPKKPGLRRRQT
uniprot
proteins
disease_involvement
DISEASE: Multiple endocrine neoplasia 4 (MEN4) [MIM:610755]: Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2. {ECO:0000269|PubMed:17030811}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:28666995). 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 stoichiometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:28666995}.
uniprot
proteins
mass_dalton
22073
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="S->A: Loss of phosphorylation by UHMK1. No translocation to the cytoplasm. Greater cell cycle arrest."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"; MUTAGEN 10; /note="S->D: Exported to the cytoplasm. Inhibits cell cycle arrest."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"; MUTAGEN 10; /note="S->E: Increased stability in vivo and in vitro."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662"; MUTAGEN 74; /note="Y->F: No change in binding CDK4 and no inhibition of CDK4 activity. Translocates to nucleus. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7."; /evidence="ECO:0000269|PubMed:16195327, ECO:0000269|PubMed:19075005"; MUTAGEN 88; /note="Y->F: Abolishes LYN-mediated phosphorylation, reduces CDK2-mediated phosphorylation on T-187, has greater cell cycle arrest into S-phase, no effect on binding CDK2 complexes, reduced CDK4 binding and inhibits CDK4 enzyme activity. No nuclear translocation. No effect on in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-89."; /evidence="ECO:0000269|PubMed:16195327, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005"; MUTAGEN 89; /note="Y->F: No effect on binding CDK2 complexes, reduced CDK4 binding and greatly inhibits CDK4 enzyme activity. No nuclear translocation. Inhibits in vitro phosphorylation of CDK4 by CCNH-CDK7. Completely abolishes CDK4 binding; when associated with F-88."; /evidence="ECO:0000269|PubMed:16195327, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005"; MUTAGEN 157; /note="T->A: Greatly reduced PKB/AKT1-mediated phosphorylation. Nuclear location. Inhibits cyclin E/CDK2 cell cycle progression. No effect on binding AKT1. Completely abolishes PKB/AKT1-mediated phosphorylation and no cytoplasmic translocation; when associated with A-198."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:12244303, ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662"; MUTAGEN 161; /note="S->A: No change in PKB/AKT1-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:12244301"; MUTAGEN 162; /note="T->A: No change in PKB/AKT1-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:12244301"; MUTAGEN 185; /note="E->A,D,Q: Strongly reduced ubiquitination by a TRIM21-containing SCF(SKP2) complex."; /evidence="ECO:0000269|PubMed:16209941"; MUTAGEN 187; /note="T->A,D: No change in PKB/AKT1- nor UHMK1-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662, ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:16880511"; MUTAGEN 187; /note="T->A: Abolishes phosphorylation-dependent ubiquitination."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:15280662, ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:16880511"; MUTAGEN 198; /note="T->A,D: Abolishes PKB/AKT1-mediated phosphorylation. 46% cytoplasmic location. Greatly reduced binding to YWHAQ. Equally reduced binding; when associated with A-10 and A-187. No nuclear import; when associated with A-157. Completely abolishes PKB/AKT1-mediated phosphorylation and no cytoplasmic translocation; when associated with A-157."; /evidence="ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:10323868, ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12093740, ECO:0000269|PubMed:14504289, ECO:0000269|PubMed:15280662, ECO:0000269|PubMed:16195327, ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:17254967, ECO:0000269|PubMed:18593906, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23707388}.; 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. {ECO:0000269|PubMed:10323868, ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:16209941, ECO:0000269|PubMed:23478441}.; PTM: Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
CDI family
uniprot
proteins
pubmed
10323868
uniprot
proteins
pubmed
10831586
uniprot
proteins
pubmed
12042314
uniprot
proteins
pubmed
12093740
uniprot
proteins
pubmed
12244301
uniprot
proteins
pubmed
12244303
uniprot
proteins
pubmed
12972555
uniprot
proteins
pubmed
14504289
uniprot
proteins
pubmed
15280662
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15509543
uniprot
proteins
pubmed
16007079
uniprot
proteins
pubmed
16195327
uniprot
proteins
pubmed
16209941
uniprot
proteins
pubmed
16782892
uniprot
proteins
pubmed
16880511
uniprot
proteins
pubmed
17030811
uniprot
proteins
pubmed
17254966
uniprot
proteins
pubmed
17254967
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
18593906
uniprot
proteins
pubmed
19075005
uniprot
proteins
pubmed
20824794
uniprot
proteins
pubmed
21423214
uniprot
proteins
pubmed
22586611
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23478441
uniprot
proteins
pubmed
23707388
uniprot
proteins
pubmed
26775844
uniprot
proteins
pubmed
28666995
uniprot
proteins
pubmed
7882309
uniprot
proteins
pubmed
8033212
uniprot
proteins
pubmed
8684460
uniprot
proteins
sequence_length
198
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. 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. Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (By similarity). {ECO:0000250}.
uniprot
proteins