Q15119 (PDK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial
EC=2.7.11.2

Alternative name(s):
Pyruvate dehydrogenase kinase isoform 2

Gene names

Name:

PDK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	407 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits the mitochondrial pyruvate dehydrogenase complex by phosphorylation of the E1 alpha subunit, thus contributing to the regulation of glucose metabolism.
Catalytic activity	ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Expressed in many tissues, with the highest level in heart and skeletal muscle, intermediate levels in brain, kidney, pancreas and liver, and low levels in placenta and lung.
Sequence similarities	Belongs to the PDK/BCKDK protein kinase family. Contains 1 histidine kinase domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glucose metabolic process Traceable author statement. Source: ProtInc peptidyl-histidine phosphorylation Inferred from electronic annotation. Source: InterPro pyruvate metabolic process Traceable author statement. Source: Reactome regulation of acetyl-CoA biosynthetic process from pyruvate Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from direct assay Ref.5. Source: UniProtKB pyruvate dehydrogenase (acetyl-transferring) kinase activity Traceable author statement. Source: ProtInc two-component sensor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 407

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial

PRO_0000023440

Regions

Domain

135 – 364

230

Histidine kinase

Nucleotide binding

251 – 258

8

ATP

Nucleotide binding

309 – 310

2

ATP By similarity

Nucleotide binding

325 – 330

6

ATP

Sites

Binding site

290

1

ATP

Natural variations

Natural variant

342

1

G → R in a glioblastoma multiforme sample; somatic mutation. Ref.4 Ref.6
Corresponds to variant rs17855787 [ dbSNP | Ensembl ].

VAR_042296

Experimental info

Sequence conflict

80

1

S → T in AAC42010. Ref.1

Sequence conflict

407

1

S → T in AAC42010. Ref.1

Secondary structure

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407

Helix Strand Turn

Details...

Helix

16 – 23

8

Helix

33 – 40

8

Beta strand

41 – 43

3

Helix

46 – 68

23

Helix

73 – 77

5

Helix

79 – 96

18

Turn

97 – 100

4

Turn

106 – 109

4

Helix

110 – 123

14

Helix

126 – 141

16

Helix

145 – 175

31

Beta strand

191 – 196

6

Helix

197 – 216

20

Beta strand

222 – 228

7

Beta strand

237 – 240

4

Helix

242 – 262

21

Turn

263 – 266

4

Beta strand

273 – 279

7

Beta strand

281 – 290

10

Helix

297 – 303

7

Turn

306 – 309

4

Helix

329 – 339

11

Beta strand

343 – 349

7

Turn

350 – 352

3

Beta strand

353 – 363

11

Turn

364 – 366

3

Helix

376 – 379

4

Helix

380 – 382

3

Sequences

	Sequence		Length	Mass (Da)
	Q15119 [UniParc]. Last modified June 6, 2002. Version 2. Checksum: 77DBA03EF922EF03	FASTA	407	46,154
	10 20 30 40 50 60 MRWVWALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF TFLRQELPVR 70 80 90 100 110 120 LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD KDPEDHRTLS QFTDALVTIR 130 140 150 160 170 180 NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN IQYFLDRFYL SRISIRMLIN QHTLIFDGST 190 200 210 220 230 240 NPAHPKHIGS IDPNCNVSEV VKDAYDMAKL LCDKYYMASP DLEIQEINAA NSKQPIHMVY 250 260 270 280 290 300 VPSHLYHMLF ELFKNAMRAT VESHESSLIL PPIKVMVALG EEDLSIKMSD RGGGVPLRKI 310 320 330 340 350 360 ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME GFGTDAVIYL 370 380 390 400 KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN TSTYRVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Diversity of the pyruvate dehydrogenase kinase gene family in humans." Gudi R., Bowker-Kinley M.M., Kedishvili N.Y., Zhao Y., Popov K.M. J. Biol. Chem. 270:28989-28994(1995) [PubMed: 7499431] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-342. Tissue: Lung, Prostate and Skin.
[5]	"Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands." Knoechel T.R., Tucker A.D., Robinson C.M., Phillips C., Taylor W., Bungay P.J., Kasten S.A., Roche T.E., Brown D.G. Biochemistry 45:402-415(2006) [PubMed: 16401071] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-407 IN COMPLEX WITH ATP AND THE INHIBITORS AZD7545; NOV3R; PFZ3 AND DICHLOROACETATE.
[6]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-342.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L42451 mRNA. Translation: AAC42010.1.
AK290522 mRNA. Translation: BAF83211.1.
CH471109 Genomic DNA. Translation: EAW94642.1.
BC005811 mRNA. Translation: AAH05811.1.
BC040478 mRNA. Translation: AAH40478.1.
BC063137 mRNA. Translation: AAH63137.1.

IPI

IPI01011342.

PIR

I70159.

RefSeq

NP_001186828.1. NM_001199899.1.
NP_002602.2. NM_002611.4.

UniGene

Hs.256667.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BTZ	X-ray	2.20	A	16-407	[»]
2BU2	X-ray	2.40	A	16-407	[»]
2BU5	X-ray	2.35	A	16-407	[»]
2BU6	X-ray	2.40	A	16-407	[»]
2BU7	X-ray	2.40	A	16-407	[»]
2BU8	X-ray	2.50	A	16-407	[»]

ProteinModelPortal

Q15119.

SMR

Q15119. Positions 16-383.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15119. 4 interactions.

MINT

MINT-1379180.

STRING

Q15119.

Polymorphism databases

DMDM

21431820.

Proteomic databases

PRIDE

Q15119.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000007708; ENSP00000007708; ENSG00000005882.

GeneID

5164.

KEGG

hsa:5164.

UCSC

uc002iqc.1. human.

Organism-specific databases

CTD

5164.

GeneCards

GC17P048172.

H-InvDB

HIX0013970.

HGNC

HGNC:8810. PDK2.

HPA

HPA008287.

MIM

602525. gene.

neXtProt

NX_Q15119.

PharmGKB

PA33155.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13973.

GeneTree

ENSGT00550000074574.

HOGENOM

HBG382024.

HOVERGEN

HBG000511.

InParanoid

Q15119.

OMA

LTTPSVQ.

PhylomeDB

Q15119.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q15119.

Bgee

Q15119.

CleanEx

HS_PDK2.

Genevestigator

Q15119.

GermOnline

ENSG00000005882. Homo sapiens.

Family and domain databases

InterPro

IPR003594. ATPase-like_ATP-bd.
IPR018955. BCDHK/PDK_N.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]

Gene3D

G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit.
G3DSA:1.20.140.20. BCDHK/PDK_N. 1 hit.

KO

K00898.

Pfam

PF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]

SMART

SM00387. HATPase_c. 1 hit.
[Graphical view]

SUPFAM

SSF55874. ATP_bd_ATPase. 1 hit.
SSF69012. BCDHK/PDK_N. 1 hit.

PROSITE

PS50109. HIS_KIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

19978.

SOURCE

Search...

Entry information

Entry name

PDK2_HUMAN

Accession

Primary (citable) accession number: Q15119
Secondary accession number(s): A8K3A7, Q6P515, Q9BS05

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 6, 2002
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 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.