CDN2B_HUMAN
ID CDN2B_HUMAN Reviewed; 138 AA.
AC P42772; O15125; Q6FI09;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Cyclin-dependent kinase 4 inhibitor B;
DE AltName: Full=Multiple tumor suppressor 2;
DE Short=MTS-2;
DE AltName: Full=p14-INK4b;
DE AltName: Full=p15-INK4b;
DE Short=p15INK4B;
GN Name=CDKN2B; Synonyms=MTS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8001816; DOI=10.1101/gad.8.24.2939;
RA Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L.,
RA Matera G.A., Xiong Y.;
RT "Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6
RT inhibitor, correlates with wild-type pRb function.";
RL Genes Dev. 8:2939-2952(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8078588; DOI=10.1038/371257a0;
RA Hannon G.J., Beach D.;
RT "p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest.";
RL Nature 371:257-261(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9230210;
RA Tsubari M., Tiihonen E., Laiho M.;
RT "Cloning and characterization of p10, an alternatively spliced form of p15
RT cyclin-dependent kinase inhibitor.";
RL Cancer Res. 57:2966-2973(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-138.
RX PubMed=8153634; DOI=10.1126/science.8153634;
RA Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K.,
RA Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnick M.H.;
RT "A cell cycle regulator potentially involved in genesis of many tumor
RT types.";
RL Science 264:436-440(1994).
RN [9]
RP STRUCTURE BY NMR.
RX PubMed=10892805; DOI=10.1110/ps.9.6.1120;
RA Yuan C., Selby T.L., Li J., Byeon I.J., Tsai M.D.;
RT "Tumor suppressor INK4: refinement of p16INK4A structure and determination
RT of p15INK4B structure by comparative modeling and NMR data.";
RL Protein Sci. 9:1120-1128(2000).
RN [10]
RP VARIANTS LUNG ADENOCARCINOMA GLU-47 AND VAL-50.
RX PubMed=7882351;
RA Okamoto A., Hussain S.P., Hagiwara K., Spillare E.A., Rusin M.R.,
RA Demetrick D.J., Serrano M., Hannon G.J., Shiseki M., Zariwala M., Xiong Y.,
RA Beach D.H., Yokota J., Harris C.C.;
RT "Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in
RT primary and metastatic lung cancer.";
RL Cancer Res. 55:1448-1451(1995).
CC -!- FUNCTION: Interacts strongly with CDK4 and CDK6. Potent inhibitor.
CC Potential effector of TGF-beta induced cell cycle arrest.
CC -!- SUBUNIT: Heterodimer of CDKN2B with CDK4 or CDK6. Isoform 2 does not
CC interact with CDK4 nor CDK6.
CC -!- INTERACTION:
CC P42772; Q9UI12: ATP6V1H; NbExp=3; IntAct=EBI-711280, EBI-724719;
CC P42772; P24863: CCNC; NbExp=3; IntAct=EBI-711280, EBI-395261;
CC P42772; Q00537: CDK17; NbExp=3; IntAct=EBI-711280, EBI-624648;
CC P42772; P11802: CDK4; NbExp=20; IntAct=EBI-711280, EBI-295644;
CC P42772; Q00534: CDK6; NbExp=16; IntAct=EBI-711280, EBI-295663;
CC P42772; Q6P9H4: CNKSR3; NbExp=3; IntAct=EBI-711280, EBI-10253274;
CC P42772; Q0VD86: INCA1; NbExp=3; IntAct=EBI-711280, EBI-6509505;
CC P42772; P43364: MAGEA11; NbExp=4; IntAct=EBI-711280, EBI-739552;
CC P42772; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-711280, EBI-740897;
CC P42772; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-711280, EBI-79165;
CC P42772; Q53H96: PYCR3; NbExp=3; IntAct=EBI-711280, EBI-2959680;
CC P42772; A6ZKI3: RTL8C; NbExp=3; IntAct=EBI-711280, EBI-10174072;
CC P42772; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-711280, EBI-6257312;
CC P42772; Q9NZD8: SPG21; NbExp=6; IntAct=EBI-711280, EBI-742688;
CC P42772; Q13077: TRAF1; NbExp=7; IntAct=EBI-711280, EBI-359224;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9230210}. Note=Also
CC found in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p15;
CC IsoId=P42772-1; Sequence=Displayed;
CC Name=2; Synonyms=p10;
CC IsoId=P42772-2; Sequence=VSP_043898;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in normal (keratinocytes,
CC fibroblasts) and tumor cell lines. {ECO:0000269|PubMed:9230210}.
CC -!- SIMILARITY: Belongs to the CDKN2 cyclin-dependent kinase inhibitor
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdkn2b/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDKN2BID187ch9p21.html";
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DR EMBL; U17075; AAC50075.1; -; mRNA.
DR EMBL; L36844; AAA50282.1; -; mRNA.
DR EMBL; AF004819; AAB69989.1; -; mRNA.
DR EMBL; CR536529; CAG38766.1; -; mRNA.
DR EMBL; AF513858; AAM44859.1; -; Genomic_DNA.
DR EMBL; AL449423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014469; AAH14469.1; -; mRNA.
DR EMBL; S69805; AAD14049.1; -; Genomic_DNA.
DR CCDS; CCDS6512.1; -. [P42772-1]
DR CCDS; CCDS6513.1; -. [P42772-2]
DR PIR; B55479; B55479.
DR RefSeq; NP_004927.2; NM_004936.3. [P42772-1]
DR RefSeq; NP_511042.1; NM_078487.2. [P42772-2]
DR AlphaFoldDB; P42772; -.
DR SMR; P42772; -.
DR BioGRID; 107464; 71.
DR IntAct; P42772; 23.
DR MINT; P42772; -.
DR STRING; 9606.ENSP00000276925; -.
DR iPTMnet; P42772; -.
DR PhosphoSitePlus; P42772; -.
DR BioMuta; CDKN2B; -.
DR DMDM; 1168869; -.
DR jPOST; P42772; -.
DR MassIVE; P42772; -.
DR MaxQB; P42772; -.
DR PaxDb; P42772; -.
DR PeptideAtlas; P42772; -.
DR PRIDE; P42772; -.
DR ProteomicsDB; 55555; -. [P42772-1]
DR ProteomicsDB; 55556; -. [P42772-2]
DR Antibodypedia; 3605; 635 antibodies from 38 providers.
DR DNASU; 1030; -.
DR Ensembl; ENST00000276925.7; ENSP00000276925.6; ENSG00000147883.12. [P42772-1]
DR Ensembl; ENST00000380142.5; ENSP00000369487.4; ENSG00000147883.12. [P42772-2]
DR GeneID; 1030; -.
DR KEGG; hsa:1030; -.
DR MANE-Select; ENST00000276925.7; ENSP00000276925.6; NM_004936.4; NP_004927.2.
DR UCSC; uc003zpn.4; human. [P42772-1]
DR CTD; 1030; -.
DR DisGeNET; 1030; -.
DR GeneCards; CDKN2B; -.
DR HGNC; HGNC:1788; CDKN2B.
DR HPA; ENSG00000147883; Tissue enhanced (esophagus, intestine).
DR MalaCards; CDKN2B; -.
DR MIM; 600431; gene.
DR neXtProt; NX_P42772; -.
DR OpenTargets; ENSG00000147883; -.
DR Orphanet; 618; Familial melanoma.
DR Orphanet; 652; Multiple endocrine neoplasia type 1.
DR PharmGKB; PA26321; -.
DR VEuPathDB; HostDB:ENSG00000147883; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000162423; -.
DR HOGENOM; CLU_000134_37_1_1; -.
DR InParanoid; P42772; -.
DR OMA; QQGHHQV; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; P42772; -.
DR TreeFam; TF352389; -.
DR PathwayCommons; P42772; -.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR SignaLink; P42772; -.
DR SIGNOR; P42772; -.
DR BioGRID-ORCS; 1030; 16 hits in 1086 CRISPR screens.
DR GeneWiki; CDKN2B; -.
DR GenomeRNAi; 1030; -.
DR Pharos; P42772; Tbio.
DR PRO; PR:P42772; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P42772; protein.
DR Bgee; ENSG00000147883; Expressed in jejunal mucosa and 149 other tissues.
DR ExpressionAtlas; P42772; baseline and differential.
DR Genevisible; P42772; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IMP:BHF-UCL.
DR GO; GO:0031670; P:cellular response to nutrient; IMP:BHF-UCL.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0030219; P:megakaryocyte differentiation; IEP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0070316; P:regulation of G0 to G1 transition; IMP:BHF-UCL.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cell cycle; Cytoplasm;
KW Reference proteome; Repeat; Tumor suppressor.
FT CHAIN 1..138
FT /note="Cyclin-dependent kinase 4 inhibitor B"
FT /id="PRO_0000144184"
FT REPEAT 13..39
FT /note="ANK 1; truncated"
FT REPEAT 46..74
FT /note="ANK 2"
FT REPEAT 79..108
FT /note="ANK 3"
FT REPEAT 112..138
FT /note="ANK 4"
FT VAR_SEQ 54..138
FT /note="MMMGSARVAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGAR
FT LDVRDAWGRLPVDLAEERGHRDVAGYLRTATGD -> AGAPGPRRQGARERGARPRRIG
FT AGT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9230210"
FT /id="VSP_043898"
FT VARIANT 47
FT /note="G -> E (in lung adenocarcinoma)"
FT /evidence="ECO:0000269|PubMed:7882351"
FT /id="VAR_001488"
FT VARIANT 50
FT /note="A -> V (in lung adenocarcinoma; dbSNP:rs1423790481)"
FT /evidence="ECO:0000269|PubMed:7882351"
FT /id="VAR_001489"
FT CONFLICT 20..22
FT /note="SAA -> TP (in Ref. 2; AAA50282)"
FT /evidence="ECO:0000305"
FT CONFLICT 32..34
FT /note="QLL -> HSW (in Ref. 2; AAA50282)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 138 AA; 14722 MW; 0D6FFBDFA6FEAD21 CRC64;
MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA IQVMMMGSAR
VAELLLLHGA EPNCADPATL TRPVHDAARE GFLDTLVVLH RAGARLDVRD AWGRLPVDLA
EERGHRDVAG YLRTATGD
