[1]	NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 28-79 AND 104-152. TISSUE=Kidney; DOI=10.1016/0092-8674(94)90572-X; PubMed=8033212 [NCBI, ExPASy, EBI, Israel, Japan] Polyak K., Lee M.-H., Erdjument-Bromage H., Koff A., Roberts J.M., Tempst P., Massague J.; "Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals."; Cell 78:59-66(1994).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=7882309 [NCBI, ExPASy, EBI, Israel, Japan] Pietenpol J.A., Bohlander S.K., Sato Y., Papadopoulos N., Liu B., Friedman C., Trask B.J., Roberts J.M., Kinzler K.W., Rowley J.D.; "Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias."; Cancer Res. 55:1206-1210(1995).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-15 AND GLY-109. Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P., Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.; "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109. TISSUE=Cervix; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	INTERACTION WITH UHMK1, PHOSPHORYLATION AT SER-10, AND MUTAGENESIS OF SER-10 AND THR-187. DOI=10.1093/emboj/cdf343; PubMed=12093740 [NCBI, ExPASy, EBI, Israel, Japan] Boehm M., Yoshimoto T., Crook M.F., Nallamshetty S., True A., Nabel G.J., Nabel E.G.; "A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression."; EMBO J. 21:3390-3401(2002).
[6]	INTERACTION WITH SPDYA. DOI=10.1091/mbc.E02-12-0820; PubMed=12972555 [NCBI, ExPASy, EBI, Israel, Japan] Porter L.A., Kong-Beltran M., Donoghue D.J.; "Spy1 interacts with p27Kip1 to allow G1/S progression."; Mol. Biol. Cell 14:3664-3674(2003).
[7]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND MASS SPECTROMETRY. TISSUE=Epithelium; DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan] Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.; "Large-scale characterization of HeLa cell nuclear phosphoproteins."; Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[8]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND MASS SPECTROMETRY. DOI=10.1126/science.1140321; PubMed=17525332 [NCBI, ExPASy, EBI, Israel, Japan] Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."; Science 316:1160-1166(2007).
[9]	X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-106 OF COMPLEX WITH CDK2 AND CG2A. DOI=10.1038/382325a0; PubMed=8684460 [NCBI, ExPASy, EBI, Israel, Japan] Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.; "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex."; Nature 382:325-331(1996).
[10]	INVOLVEMENT IN MEN4. DOI=10.1073/pnas.0603877103; PubMed=17030811 [NCBI, ExPASy, EBI, Israel, Japan] Pellegata N.S., Quintanilla-Martinez L., Siggelkow H., Samson E., Bink K., Hoefler H., Fend F., Graw J., Atkinson M.J.; "Germ-line mutations in p27(Kip1) cause a multiple endocrine neoplasia syndrome in rats and humans."; Proc. Natl. Acad. Sci. U.S.A. 103:15558-15563(2006).

Comments

FUNCTION: Involved in G1 arrest. May mediate TGF beta-induced G1 arrest. Binds to and inhibits complexes formed by cyclin E-CDK2, cyclin A-CDK2, and cyclin D1-CDK4. Interaction with nucleoporin NUP50 is required for nuclear import and for degradation of phosphorylated p27Kip1 after nuclear import (By similarity).
SUBUNIT: Interacts with NUP50 and with UHMK1. Interacts with COPS5 subunit of COP9 signalosome complex, leading to its subsequent degradation (By similarity). Interacts with SPDYA and is found in a complex with both SPDYA and CDK2.
INTERACTION:
P00520:Abl1 (xeno); NbExp=1; IntAct=EBI-519280, EBI-914519;
P20248:CCNA2; NbExp=4; IntAct=EBI-519280, EBI-457097;
P14635:CCNB1; NbExp=1; IntAct=EBI-519280, EBI-495332;
P24385:CCND1; NbExp=2; IntAct=EBI-519280, EBI-375001;
P24864:CCNE1; NbExp=2; IntAct=EBI-519280, EBI-519526;
O96020:CCNE2; NbExp=1; IntAct=EBI-519280, EBI-375033;
P24941:CDK2; NbExp=6; IntAct=EBI-519280, EBI-375096;
P11802:CDK4; NbExp=2; IntAct=EBI-519280, EBI-295644;
Q00535:CDK5; NbExp=2; IntAct=EBI-519280, EBI-1041567;
Q92905:COPS5; NbExp=1; IntAct=EBI-519280, EBI-594661;
O00505:KPNA3; NbExp=1; IntAct=EBI-519280, EBI-358297;
O15131:KPNA5; NbExp=3; IntAct=EBI-519280, EBI-540602;
P07948:LYN; NbExp=2; IntAct=EBI-519280, EBI-79452;
P12931:SRC; NbExp=1; IntAct=EBI-519280, EBI-621482;
P16949:STMN1; NbExp=1; IntAct=EBI-519280, EBI-445909;
P09936:UCHL1; NbExp=1; IntAct=EBI-519280, EBI-714860;
P07947:YES1; NbExp=1; IntAct=EBI-519280, EBI-515331;
P31946:YWHAB; NbExp=1; IntAct=EBI-519280, EBI-359815;
P62258:YWHAE; NbExp=1; IntAct=EBI-519280, EBI-356498;
P61981:YWHAG; NbExp=1; IntAct=EBI-519280, EBI-359832;
SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By similarity). Note=Nuclear and cytoplasmic in quiescent cells. Upon cell cycle progression, mostly cytoplasmic (By similarity).
TISSUE SPECIFICITY: Expressed in all tissues tested. Highest levels in skeletal muscle, lowest in liver and kidney.
DOMAIN: A peptide sequence containing only AA 28-79 retains substantial KIP1 cyclin A/CDK2 inhibitory activity.
PTM: Phosphorylation on Ser-10 leads to nuclear export to the cytoplasm and promotes cell cycle progression (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in CDKN1B are the cause of multiple endocrine neoplasia type 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.
SIMILARITY: Belongs to the CDI family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDKN1BID116.html";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U10906; AAA20240.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S76988; AAD14244.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S76986; AAD14244.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF480891; AAL78041.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC001971; AAH01971.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_004055.1; -.

UniGene

Hs.238990

3D structure databases

PDB

1H27; X-ray; 2.20 A; E=25-35.	[ExPASy / RCSB / EBI]
1JSU; X-ray; 2.30 A; C=23-106.	[ExPASy / RCSB / EBI]
2AST; X-ray; 2.30 A; D=181-190.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1H27; -.
1JSU; -.
2AST; -.

DisProt

DP00018; -.

ModBase

P46527.

Protein-protein interaction databases

IntAct

P46527; -.

PTM databases

PhosphoSite

P46527; -.

Polymorphism databases

NIEHS-SNPs

CDKN1B.

2D gel databases

SWISS-2DPAGE

P46527; -.

Organism-specific databases

H-InvDB

HIX0010441; -.

HGNC

HGNC:1785; CDKN1B.

GeneLynx

CDKN1B; Homo sapiens.

CAB003691; -.

600778; gene. [NCBI / EBI]
610755; phenotype. [NCBI / EBI]

PharmGKB

PA105; -.

GeneCards

P46527.

Gene expression databases

ArrayExpress

P46527; -.

CleanEx

HS_CDKN1B; -.

GermOnline

ENSG00000111276; Homo sapiens.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005634;	Cellular component: nucleus (inferred from direct assay from HGNC).
GO:0004861;	Molecular function: cyclin-dependent protein kinase inhibitor activity (traceable author statement from ProtInc).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0005072;	Molecular function: transforming growth factor beta receptor, cytoplasmic mediator activity (traceable author statement from ProtInc).
GO:0048102;	Biological process: autophagic cell death (inferred from direct assay from UniProtKB).
GO:0007050;	Biological process: cell cycle arrest (inferred from mutant phenotype from HGNC).
GO:0000082;	Biological process: G1/S transition of mitotic cell cycle (inferred from direct assay from UniProtKB).
GO:0006917;	Biological process: induction of apoptosis (inferred from direct assay from UniProtKB).
GO:0030308;	Biological process: negative regulation of cell growth (inferred from direct assay from UniProtKB).
GO:0008285;	Biological process: negative regulation of cell proliferation (traceable author statement from ProtInc).
GO:0042326;	Biological process: negative regulation of phosphorylation (inferred from direct assay from UniProtKB).
GO:0000079;	Biological process: regulation of cyclin-dependent protein kinase activity (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR003175; CDI.
IPR015456; Cyclin_inhib_p27.
Graphical view of domain structure.

PANTHER

PTHR10265; CDI; 1.
PTHR10265:SF4; p27_Kip1; 1.

Pfam

PF02234; CDI; 1.
Pfam graphical view of domain structure.

BLOCKS

P46527.

Genome annotation databases

Ensembl

ENSG00000111276; Homo sapiens. [Contig view]

GeneID

1027; -.

KEGG

hsa:1027; -.

Phylogenomic databases

HOGENOM

P46527; -.

HOVERGEN

P46527; -.

Other

LinkHub

P46527; -.

SOURCE

CDKN1B; Homo sapiens.

ProtoNet

P46527.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Cell cycle; Cytoplasm; Direct protein sequencing; Nucleus; Phosphoprotein; Polymorphism; Protein kinase inhibitor; Proto-oncogene.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 198`	`198`	`Cyclin-dependent kinase inhibitor 1B.`	`PRO_0000190084`
`MOTIF`	`153 169`	`17`	`Nuclear localization signal (Potential).`
`MOD_RES`	`10 10`		`Phosphoserine; by UHMK1.`
`MOD_RES`	`140 140`		`Phosphoserine.`
`VARIANT`	`15 15`	`1`	`R -> W (in dbSNP:rs2066828 [NCBI]).`	`VAR_011871`
`VARIANT`	`109 109`	`1`	`V -> G (in dbSNP:rs2066827 [NCBI]).`	`VAR_011872`
`MUTAGEN`	`10 10`		`S->A: Loss of phosphorylation by UHMK1; causes cell cycle arrest.`
`MUTAGEN`	`187 187`		`T->A: No effect on phosphorylation by UHMK1.`
`CONFLICT`	`22 22`		`E -> D (in Ref. 2; AAD14244).`
`HELIX`	`38 49`	`12`
`TURN`	`50 53`	`4`
`HELIX`	`54 60`	`7`
`TURN`	`64 67`	`4`
`STRAND`	`71 74`	`4`
`STRAND`	`77 80`	`4`
`HELIX`	`86 89`	`4`

Sequence information

Length: 198 AA [This is the length of the unprocessed precursor]

Molecular weight: 22073 Da [This is the MW of the unprocessed precursor]

CRC64: 1118D58901CDF3FC [This is a checksum on the sequence]

        10         20         30         40         50         60 
MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR DMEEASQRKW 

        70         80         90        100        110        120 
NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GSRPAAPLIG 

       130        140        150        160        170        180 
APANSEDTHL VDPKTDPSDS QTGLAEQCAG IRKRPATDDS STQNKRANRT EENVSDGSPN 

       190 
AGSVEQTPKK PGLRRRQT

P46527 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools