P55273 (CDN2D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-dependent kinase 4 inhibitor D

Alternative name(s):
p19-INK4d

Gene names

Name:

CDKN2D

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	166 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interacts strongly with CDK4 and CDK6 and inhibits them. Ref.2 Ref.3
Subunit structure	Interacts with CDK6. Ref.10
Subcellular location	Nucleus. Cytoplasm Ref.10.
Sequence similarities	Belongs to the CDKN2 cyclin-dependent kinase inhibitor family. Contains 4 ANK repeats.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Disease	Tumor suppressor
Domain	ANK repeat Repeat
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA synthesis involved in DNA repair Inferred from mutant phenotype PubMed 15750620. Source: BHF-UCL G1 phase of mitotic cell cycle Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Inferred from direct assay PubMed 10208428. Source: BHF-UCL autophagic cell death Inferred from mutant phenotype PubMed 16322758. Source: BHF-UCL cell cycle arrest Inferred from direct assay PubMed 10208428. Source: BHF-UCL negative regulation of apoptotic process Inferred from mutant phenotype PubMed 15750620. Source: BHF-UCL negative regulation of cell growth Inferred from direct assay PubMed 10208428. Source: BHF-UCL negative regulation of cell proliferation Inferred from direct assay PubMed 10208428. Source: BHF-UCL negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 15750620. Source: BHF-UCL regulation of cyclin-dependent protein serine/threonine kinase activity Inferred from direct assay Ref.3. Source: BHF-UCL response to UV Inferred from mutant phenotype PubMed 15750620. Source: BHF-UCL response to retinoic acid Inferred from mutant phenotype PubMed 16322758. Source: BHF-UCL response to vitamin D Inferred from mutant phenotype PubMed 16322758. Source: BHF-UCL sensory perception of sound Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay PubMed 15750620Ref.3. Source: BHF-UCL
Molecular_function	cyclin-dependent protein serine/threonine kinase inhibitor activity Inferred from direct assay Ref.3. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 166

166

Cyclin-dependent kinase 4 inhibitor D

PRO_0000144188

Regions

Repeat

41 – 69

29

ANK 1

Repeat

73 – 102

30

ANK 2

Repeat

106 – 135

30

ANK 3

Repeat

138 – 166

29

ANK 4

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.9

Experimental info

Sequence conflict

159

1

Q → P in AAA85436. Ref.2

Secondary structure

1

.

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.

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166

Helix Strand Turn

Details...

Helix

8 – 18

11

Helix

21 – 29

9

Helix

45 – 48

4

Helix

54 – 62

9

Helix

77 – 83

7

Helix

87 – 95

9

Helix

110 – 117

8

Helix

120 – 127

8

Helix

142 – 148

7

Helix

152 – 159

8

Sequences

	Sequence		Length	Mass (Da)
	P55273 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2FACD11CF56340DC	FASTA	166	17,700
	10 20 30 40 50 60 MLLEEVRAGD RLSGAAARGD VQEVRRLLHR ELVHPDALNR FGKTALQVMM FGSTAIALEL 70 80 90 100 110 120 LKQGASPNVQ DTSGTSPVHD AARTGFLDTL KVLVEHGADV NVPDGTGALP IHLAVQEGHT 130 140 150 160 AVVSFLAAES DLHRRDARGL TPLELALQRG AQDLVDILQG HMVAPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases." Okuda T., Hirai H., Valentine V.A., Shurtleff S.A., Kidd V.J., Lahti J.M., Sherr C.J., Downing J.R. Genomics 29:623-630(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone marrow.
[2]	"Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4." Chan F.K.M., Zhang J., Cheng L., Shapiro D.N., Winoto A. Mol. Cell. Biol. 15:2682-2688(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Thymus.
[3]	"Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4." Guan K.L., Jenkins C.W., Li Y., O'Keefe C.L., Noh S., Wu X., Zariwala M., Matera A.G., Xiong Y. Mol. Biol. Cell 7:57-70(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[4]	"Mutation testing in melanoma families: INK4A, CDK4 and INK4D." Newton Bishop J.A., Harland M., Bennett D.C., Bataille V., Goldstein A.M., Tucker M.A., Ponder B.A.J., Cuzick J., Selby P., Bishop D.T. Br. J. Cancer 80:295-300(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	NIEHS SNPs program Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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]. Tissue: Muscle.
[8]	Murthy S.K., Demetrick D.J. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
[9]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-7, ACETYLATION AT MET-1. Tissue: Platelet.
[10]	"Active cdk6 complexes are predominantly nuclear and represent only a minority of the cdk6 in T cells." Mahony D., Parry D.A., Lees E. Oncogene 16:603-611(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH CDK6.
[11]	"Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a." Russo A.A., Tong L., Lee J.O., Jeffrey P.D., Pavletich N.P. Nature 395:237-243(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF COMPLEX WITH CDK6.
[12]	"Structure of human cyclin-dependent kinase inhibitor p19(INK4d): comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16(INK4a)." Baumgartner R., Fernandez-Catalan C., Winoto A., Huber R., Engh R.A., Holak T.A. Structure 6:1279-1290(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U49399 mRNA. Translation: AAB03772.1.
U20498 mRNA. Translation: AAA85436.1.
U40343 mRNA. Translation: AAB18139.1.
AF061327 Genomic DNA. Translation: AAC27450.1.
CR542158 mRNA. Translation: CAG46955.1.
AF518878 Genomic DNA. Translation: AAM54045.1.
BC001822 mRNA. Translation: AAH01822.1.
AF044171 Genomic DNA. Translation: AAD02320.1.

IPI

IPI00024008.

PIR

A57378.

RefSeq

NP_001791.1. NM_001800.3.
NP_524145.1. NM_079421.2.

UniGene

Hs.435051.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BD8	X-ray	1.80	A	7-162	[»]
1BI8	X-ray	2.80	B/D	1-166	[»]

ProteinModelPortal

P55273.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6109N.

IntAct

P55273. 3 interactions.

MINT

MINT-1475963.

STRING

9606.ENSP00000337056.

PTM databases

PhosphoSite

P55273.

Polymorphism databases

DMDM

1705730.

Proteomic databases

PaxDb

P55273.

PRIDE

P55273.

Protocols and materials databases

DNASU

1032.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000335766; ENSP00000337056; ENSG00000129355.
ENST00000393599; ENSP00000377224; ENSG00000129355.

GeneID

1032.

KEGG

hsa:1032.

UCSC

uc002mpa.3. human.

Organism-specific databases

CTD

1032.

GeneCards

GC19M010677.

HGNC

HGNC:1790. CDKN2D.

HPA

CAB011201.

MIM

600927. gene.

neXtProt

NX_P55273.

PharmGKB

PA26323.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0666.

HOGENOM

HOG000290191.

HOVERGEN

HBG050870.

InParanoid

P55273.

KO

K06623.

OMA

PIHIAIR.

OrthoDB

EOG4G7C0Q.

PhylomeDB

P55273.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.

Gene expression databases

Bgee

P55273.

CleanEx

HS_CDKN2D.

Genevestigator

P55273.

GermOnline

ENSG00000129355. 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

PF00023. Ank. 2 hits.
PF12796. Ank_2. 1 hit.
[Graphical view]

SMART

SM00248. ANK. 4 hits.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P55273.

GenomeRNAi

1032.

NextBio

4343.

SOURCE

Search...

Entry information

Entry name

CDN2D_HUMAN

Accession

Primary (citable) accession number: P55273
Secondary accession number(s): Q13102, Q6FGE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 122 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.