P42772 (CDN2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 4 inhibitor B

Alternative name(s):
Multiple tumor suppressor 2
Short name=MTS-2
p14-INK4b
p15-INK4b
Short name=p15INK4B

Gene names

Name:	CDKN2B
Synonyms:	MTS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	138 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.
Subunit structure	Heterodimer of CDKN2B with CDK4 or CDK6. Isoform 2 does not interact with CDK4 nor CDK6.
Subcellular location	Cytoplasm. Note: Also found in the nucleus. Ref.3
Tissue specificity	Isoform 2 is expressed in normal (keratinocytes, fibroblasts) and tumor cell lines. Ref.3
Sequence similarities	Belongs to the CDKN2 cyclin-dependent kinase inhibitor family. Contains 4 ANK repeats.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Domain	ANK repeat Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1 phase of mitotic cell cycle Traceable author statement. Source: Reactome G2/M transition of mitotic cell cycle Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL cell cycle arrest Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL cellular response to nutrient Inferred from mutant phenotype PubMed 17597576. Source: BHF-UCL megakaryocyte differentiation Inferred from expression pattern PubMed 10812241. Source: UniProtKB mitotic cell cycle checkpoint Inferred from mutant phenotype PubMed 17553787. Source: BHF-UCL negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL positive regulation of epithelial cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome positive regulation of transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype PubMed 16943770. Source: BHF-UCL regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay Ref.2. Source: BHF-UCL response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay PubMed 18564286Ref.3. Source: UniProtKB
Molecular_function	cyclin-dependent protein serine/threonine kinase inhibitor activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK4	P11802	4	EBI-711280,EBI-295644

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42772-1)

Also known as: p15;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P42772-2)

Also known as: p10;

The sequence of this isoform differs from the canonical sequence as follows:
     54-138: MMMGSARVAE...AGYLRTATGD → AGAPGPRRQGARERGARPRRIGAGT

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 138	138	Cyclin-dependent kinase 4 inhibitor B		PRO_0000144184
Regions
	Repeat	13 – 39	27	ANK 1; truncated
	Repeat	46 – 74	29	ANK 2
	Repeat	79 – 108	30	ANK 3
	Repeat	112 – 138	27	ANK 4
Natural variations
	Alternative sequence	54 – 138	85	MMMGS…TATGD → AGAPGPRRQGARERGARPRR IGAGT in isoform 2.		VSP_043898
	Natural variant	47	1	G → E in lung adenocarcinoma. Ref.10		VAR_001488
	Natural variant	50	1	A → V in lung adenocarcinoma. Ref.10		VAR_001489
Experimental info
	Sequence conflict	20 – 22	3	SAA → TP in AAA50282. Ref.2
	Sequence conflict	32 – 34	3	QLL → HSW in AAA50282. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p15) [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 0D6FFBDFA6FEAD21	FASTA	138	14,722
	10 20 30 40 50 60 MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA IQVMMMGSAR 70 80 90 100 110 120 VAELLLLHGA EPNCADPATL TRPVHDAARE GFLDTLVVLH RAGARLDVRD AWGRLPVDLA 130 EERGHRDVAG YLRTATGD
	Isoform 2 (p10) [UniParc]. Checksum: 3EB74DDEC36E674D	FASTA	78	8,078
	10 20 30 40 50 60 MREENKGMPS GGGSDEGLAS AAARGLVEKV RQLLEAGADP NGVNRFGRRA IQVAGAPGPR 70 RQGARERGAR PRRIGAGT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function." Guan K.-L., Jenkins C.W., Li Y., Nichols M.A., Wu X., O'Keefe C.L., Matera G.A., Xiong Y. Genes Dev. 8:2939-2952(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest." Hannon G.J., Beach D. Nature 371:257-261(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Cloning and characterization of p10, an alternatively spliced form of p15 cyclin-dependent kinase inhibitor." Tsubari M., Tiihonen E., Laiho M. Cancer Res. 57:2966-2973(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	NIEHS SNPs program Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skin.
[8]	"A cell cycle regulator potentially involved in genesis of many tumor types." Kamb A., Gruis N.A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S.V., Stockert E., Day R.S. III, Johnson B.E., Skolnick M.H. Science 264:436-440(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 53-138.
[9]	"Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data." Yuan C., Selby T.L., Li J., Byeon I.J., Tsai M.D. Protein Sci. 9:1120-1128(2000) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[10]	"Mutations in the p16INK4/MTS1/CDKN2, p15INK4B/MTS2, and p18 genes in primary and metastatic lung cancer." Okamoto A., Hussain S.P., Hagiwara K., Spillare E.A., Rusin M.R., Demetrick D.J., Serrano M., Hannon G.J., Shiseki M., Zariwala M., Xiong Y., Beach D.H., Yokota J., Harris C.C. Cancer Res. 55:1448-1451(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LUNG ADENOCARCINOMA GLU-47 AND VAL-50.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	U17075 mRNA. Translation: AAC50075.1. L36844 mRNA. Translation: AAA50282.1. AF004819 mRNA. Translation: AAB69989.1. CR536529 mRNA. Translation: CAG38766.1. AF513858 Genomic DNA. Translation: AAM44859.1. AL449423 Genomic DNA. Translation: CAH70602.1. AL449423 Genomic DNA. Translation: CAH70603.1. BC014469 mRNA. Translation: AAH14469.1. S69805 Genomic DNA. Translation: AAD14049.1.
IPI	IPI00001563.
PIR	B55479.
RefSeq	NP_004927.2. NM_004936.3. NP_511042.1. NM_078487.2.
UniGene	Hs.72901.
3D structure databases
ProteinModelPortal	P42772.
ModBase	Search...
Protein-protein interaction databases
IntAct	P42772. 9 interactions.
STRING	9606.ENSP00000276925.
PTM databases
PhosphoSite	P42772.
Polymorphism databases
DMDM	1168869.
Proteomic databases
PaxDb	P42772.
PRIDE	P42772.
Protocols and materials databases
DNASU	1030.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000276925; ENSP00000276925; ENSG00000147883. ENST00000380142; ENSP00000369487; ENSG00000147883. ENST00000539462; ENSP00000445136; ENSG00000147883.
GeneID	1030.
KEGG	hsa:1030.
UCSC	uc003zpo.3. human.
Organism-specific databases
CTD	1030.
GeneCards	GC09M021992.
HGNC	HGNC:1788. CDKN2B.
HPA	CAB000349.
MIM	600431. gene.
neXtProt	NX_P42772.
Orphanet	652. Multiple endocrine neoplasia type 1.
PharmGKB	PA26321.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG287192.
HOGENOM	HOG000290191.
HOVERGEN	HBG050870.
InParanoid	P42772.
KO	K04685.
OMA	MMGSTSV.
OrthoDB	EOG49KFS3.
PhylomeDB	P42772.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Reactome	REACT_111102. Signal Transduction. REACT_115566. Cell Cycle. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P42772.
Bgee	P42772.
CleanEx	HS_CDKN2B.
Genevestigator	P42772.
GermOnline	ENSG00000147883. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. [Graphical view]
Pfam	PF12796. Ank_2. 1 hit. [Graphical view]
SMART	SM00248. ANK. 3 hits. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	1030.
NextBio	4331.
SOURCE	Search...

Entry information

Entry name

CDN2B_HUMAN

Accession

Primary (citable) accession number: P42772
Secondary accession number(s): O15125, Q6FI09

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.