ID   CDN1B_HUMAN             Reviewed;         198 AA.
AC   P46527; Q16307; Q9BUS6;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   29-MAY-2007, entry version 80.
DE   Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase
DE   inhibitor p27) (p27Kip1).
GN   Name=CDKN1B; Synonyms=KIP1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 28-79 AND 104-152.
RC   TISSUE=Kidney;
RX   MEDLINE=94306518; 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
RT   potential mediator of extracellular antimitogenic signals.";
RL   Cell 78:59-66(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=95188144; PubMed=7882309;
RA   Pietenpol J.A., Bohlander S.K., Sato Y., Papadopoulos N., Liu B.,
RA   Friedman C., Trask B.J., Roberts J.M., Kinzler K.W., Rowley J.D.;
RT   "Assignment of the human p27Kip1 gene to 12p13 and its analysis in
RT   leukemias.";
RL   Cancer Res. 55:1206-1210(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-15 AND GLY-109.
RA   Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P.,
RA   Nguyen D.A., Livingston R.J., Poel C.L., Robertson P.D.,
RA   Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT   "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT   of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-109.
RC   TISSUE=Cervix;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   INTERACTION WITH UHMK1, PHOSPHORYLATION AT SER-10, AND MUTAGENESIS OF
RP   SER-10 AND THR-187.
RX   PubMed=12093740; DOI=10.1093/emboj/cdf343;
RA   Boehm M., Yoshimoto T., Crook M.F., Nallamshetty S., True A.,
RA   Nabel G.J., Nabel E.G.;
RT   "A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and
RT   regulates cell cycle progression.";
RL   EMBO J. 21:3390-3401(2002).
RN   [6]
RP   INTERACTION WITH SPDYA.
RX   PubMed=12972555; DOI=10.1091/mbc.E02-12-0820;
RA   Porter L.A., Kong-Beltran M., Donoghue D.J.;
RT   "Spy1 interacts with p27Kip1 to allow G1/S progression.";
RL   Mol. Biol. Cell 14:3664-3674(2003).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA   Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA   Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT   "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 23-106 OF COMPLEX WITH CDK2
RP   AND CG2A.
RX   MEDLINE=96300318; PubMed=8684460; DOI=10.1038/382325a0;
RA   Russo A.A., Jeffrey P.D., Patten A.K., Massague J., Pavletich N.P.;
RT   "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor
RT   bound to the cyclin A-Cdk2 complex.";
RL   Nature 382:325-331(1996).
CC   -!- FUNCTION: Involved in G1 arrest. May mediate TGF beta-induced G1
CC       arrest. Binds to and inhibits complexes formed by cyclin E-CDK2,
CC       cyclin A-CDK2, and cyclin D1-CDK4. Interaction with nucleoporin
CC       NUP50 is required for nuclear import and for degradation of
CC       phosphorylated p27Kip1 after nuclear import (By similarity).
CC   -!- SUBUNIT: Interacts with NUP50 and with UHMK1. Interacts with COPS5
CC       subunit of COP9 signalosome complex, leading to its subsequent
CC       degradation (By similarity). Interacts with SPDYA and is found in
CC       a complex with both SPDYA and CDK2.
CC   -!- INTERACTION:
CC       P00520:Abl1 (xeno); NbExp=1; IntAct=EBI-519280, EBI-914519;
CC       P20248:CCNA2; NbExp=4; IntAct=EBI-519280, EBI-457097;
CC       P14635:CCNB1; NbExp=1; IntAct=EBI-519280, EBI-495332;
CC       P24385:CCND1; NbExp=2; IntAct=EBI-519280, EBI-375001;
CC       P24864:CCNE1; NbExp=2; IntAct=EBI-519280, EBI-519526;
CC       O96020:CCNE2; NbExp=1; IntAct=EBI-519280, EBI-375033;
CC       P24941:CDK2; NbExp=6; IntAct=EBI-519280, EBI-375096;
CC       P11802:CDK4; NbExp=2; IntAct=EBI-519280, EBI-295644;
CC       Q00535:CDK5; NbExp=2; IntAct=EBI-519280, EBI-1041567;
CC       Q92905:COPS5; NbExp=1; IntAct=EBI-519280, EBI-594661;
CC       O00505:KPNA3; NbExp=1; IntAct=EBI-519280, EBI-358297;
CC       O15131:KPNA5; NbExp=3; IntAct=EBI-519280, EBI-540602;
CC       P07948:LYN; NbExp=2; IntAct=EBI-519280, EBI-79452;
CC       P12931:SRC; NbExp=1; IntAct=EBI-519280, EBI-621482;
CC       P16949:STMN1; NbExp=1; IntAct=EBI-519280, EBI-445909;
CC       P09936:UCHL1; NbExp=1; IntAct=EBI-519280, EBI-714860;
CC       P07947:YES1; NbExp=1; IntAct=EBI-519280, EBI-515331;
CC       P31946:YWHAB; NbExp=1; IntAct=EBI-519280, EBI-359815;
CC       P62258:YWHAE; NbExp=1; IntAct=EBI-519280, EBI-356498;
CC       P61981:YWHAG; NbExp=1; IntAct=EBI-519280, EBI-359832;
CC   -!- SUBCELLULAR LOCATION: Nucleus (By similarity). Cytoplasm (By
CC       similarity). Note=Nuclear and cytoplasmic in quiescent cells. Upon
CC       cell cycle progression, mostly cytoplasmic (By similarity).
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues tested. Highest
CC       levels in skeletal muscle, lowest in liver and kidney.
CC   -!- DOMAIN: A peptide sequence containing only AA 28-79 retains
CC       substantial KIP1 cyclin A/CDK2 inhibitory activity.
CC   -!- PTM: Phosphorylation on Ser-10 leads to nuclear export to the
CC       cytoplasm and promotes cell cycle progression (By similarity).
CC   -!- SIMILARITY: Belongs to the CDI family.
CC   -!- WEB RESOURCE: NAME=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/CDKN1BID116.html".
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DR   EMBL; U10906; AAA20240.1; -; mRNA.
DR   EMBL; S76988; AAD14244.1; -; Genomic_DNA.
DR   EMBL; S76986; AAD14244.1; JOINED; Genomic_DNA.
DR   EMBL; AF480891; AAL78041.1; -; Genomic_DNA.
DR   EMBL; BC001971; AAH01971.1; -; mRNA.
DR   UniGene; Hs.238990; -.
DR   PDB; 1H27; X-ray; E=25-35.
DR   PDB; 1JSU; X-ray; C=23-106.
DR   PDB; 2AST; X-ray; D=181-190.
DR   IntAct; P46527; -.
DR   SWISS-2DPAGE; P46527; HUMAN.
DR   Ensembl; ENSG00000111276; Homo sapiens.
DR   KEGG; hsa:1027; -.
DR   H-InvDB; HIX0010441; -.
DR   HGNC; HGNC:1785; CDKN1B.
DR   HPA; CAB003691; -.
DR   MIM; 600778; gene.
DR   LinkHub; P46527; -.
DR   ArrayExpress; P46527; -.
DR   GermOnline; ENSG00000111276; Homo sapiens.
DR   RZPD-ProtExp; C0696; -.
DR   RZPD-ProtExp; RZPDo834F0810; -.
DR   GO; GO:0005737; C:cytoplasm; IDA:HGNC.
DR   GO; GO:0005634; C:nucleus; IDA:HGNC.
DR   GO; GO:0004861; F:cyclin-dependent protein kinase inhibitor a...; TAS:ProtInc.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0005072; F:transforming growth factor beta receptor, c...; TAS:ProtInc.
DR   GO; GO:0007050; P:cell cycle arrest; IMP:HGNC.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR   GO; GO:0000079; P:regulation of cyclin-dependent protein kina...; TAS:ProtInc.
DR   InterPro; IPR003175; CDI.
DR   Gene3D; G3DSA:4.10.365.10; G3DSA:4.10.365.10; 1.
DR   PANTHER; PTHR10265; CDI; 1.
DR   PANTHER; PTHR10265:SF4; PTHR10265:SF4; 1.
DR   Pfam; PF02234; CDI; 1.
KW   3D-structure; Cell cycle; Direct protein sequencing; Nuclear protein;
KW   Phosphorylation; Polymorphism; Protein kinase inhibitor.
FT   CHAIN         1    198       Cyclin-dependent kinase inhibitor 1B.
FT                                /FTId=PRO_0000190084.
FT   MOTIF       153    169       Nuclear localization signal (Potential).
FT   MOD_RES      10     10       Phosphoserine (by UHMK1).
FT   VARIANT      15     15       R -> W (in dbSNP:rs2066828).
FT                                /FTId=VAR_011871.
FT   VARIANT     109    109       V -> G (in dbSNP:rs2066827).
FT                                /FTId=VAR_011872.
FT   MUTAGEN      10     10       S->A: Loss of phosphorylation by UHMK1;
FT                                causes cell cycle arrest.
FT   MUTAGEN     187    187       T->A: No effect on phosphorylation by
FT                                UHMK1.
FT   CONFLICT     22     22       E -> D (in Ref. 2).
FT   HELIX        38     49
FT   TURN         50     53
FT   HELIX        54     60
FT   TURN         64     67
FT   STRAND       71     74
FT   STRAND       77     80
FT   HELIX        86     89
SQ   SEQUENCE   198 AA;  22073 MW;  1118D58901CDF3FC CRC64;
     MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR DMEEASQRKW
     NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GSRPAAPLIG
     APANSEDTHL VDPKTDPSDS QTGLAEQCAG IRKRPATDDS STQNKRANRT EENVSDGSPN
     AGSVEQTPKK PGLRRRQT
//