Reviewed, UniProtKB/Swiss-Prot Q15118 (PDK1_HUMAN)

Names and origin

Protein names

Recommended name:
    [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial
    EC=2.7.11.2
Alternative name(s):
    Pyruvate dehydrogenase kinase isoform 1

Gene names

Name:

PDK1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	436 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.
Enzyme regulation	Inhibited by AZD7545, dichloroacetate and radicicol.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Expressed predominantly in the heart.
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
Gene Ontology (GO)
Biological process	glucose metabolic process Ref.1 Traceable author statement. Source: ProtInc peptidyl-histidine phosphorylation Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Traceable author statement. Source: ProtInc
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW pyruvate dehydrogenase (acetyl-transferring) kinase activity Ref.1 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 – 28

28

Mitochondrion Potential

Chain

29 – 436

408

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial

PRO_0000023437

Regions

Domain

163 – 393

231

Histidine kinase

Nucleotide binding

279 – 286

8

ATP By similarity

Nucleotide binding

337 – 338

2

ATP By similarity

Nucleotide binding

354 – 359

6

ATP By similarity

Sites

Binding site

318

1

ATP By similarity

Natural variations

Natural variant

134

1

A → T: dbSNP rs35661499.

VAR_050477

Natural variant

412

1

N → T: dbSNP rs34250425. Ref.7

VAR_042295

Secondary structure

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436

Helix Strand Turn

Details...

Helix

42 – 50

9

Helix

59 – 66

8

Helix

72 – 94

23

Helix

99 – 102

4

Helix

105 – 121

17

Helix

122 – 124

3

Helix

132 – 148

17

Turn

149 – 151

3

Helix

152 – 166

15

Helix

172 – 202

31

Beta strand

219 – 224

6

Helix

225 – 244

20

Beta strand

250 – 259

10

Beta strand

265 – 268

4

Helix

270 – 291

22

Turn

293 – 296

4

Beta strand

301 – 307

7

Beta strand

309 – 318

10

Helix

325 – 328

4

Helix

329 – 332

4

Turn

334 – 337

4

Helix

358 – 368

11

Beta strand

372 – 378

7

Turn

379 – 381

3

Beta strand

382 – 392

11

Turn

393 – 395

3

Helix

405 – 411

7

Sequences

	Sequence		Length	Mass (Da)
	Q15118-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: D14CD594E0EA45A2	FASTA	436	49,244
	10 20 30 40 50 60 MRLARLLRGA ALAGPGPGLR AAGFSRSFSS DSGSSPASER GVPGQVDFYA RFSPSPLSMK 70 80 90 100 110 120 QFLDFGSVNA CEKTSFMFLR QELPVRLANI MKEISLLPDN LLRTPSVQLV QSWYIQSLQE 130 140 150 160 170 180 LLDFKDKSAE DAKAIYDFTD TVIRIRNRHN DVIPTMAQGV IEYKESFGVD PVTSQNVQYF 190 200 210 220 230 240 LDRFYMSRIS IRMLLNQHSL LFGGKGKGSP SHRKHIGSIN PNCNVLEVIK DGYENARRLC 250 260 270 280 290 300 DLYYINSPEL ELEELNAKSP GQPIQVVYVP SHLYHMVFEL FKNAMRATME HHANRGVYPP 310 320 330 340 350 360 IQVHVTLGNE DLTVKMSDRG GGVPLRKIDR LFNYMYSTAP RPRVETSRAV PLAGFGYGLP 370 380 390 400 410 420 ISRLYAQYFQ GDLKLYSLEG YGTDAVIYIK ALSTDSIERL PVYNKAAWKH YNTNHEADDW 430 CVPSREPKDM TTFRSA

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].
[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]. Tissue: Skin.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol." Kato M., Li J., Chuang J.L., Chuang D.T. Structure 15:992-1004(2007) [PubMed: 17683942] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-436 IN COMPLEX WITH THE INHIBITORS AZD7545 AND DICHLOROACETATE, FUNCTION, ENZYME REGULATION.
[7]	"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] THR-412.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L42450 mRNA. Translation: AAC42009.1.
AK312700 mRNA. Translation: BAG35578.1.
CH471058 Genomic DNA. Translation: EAX11173.1.
BC039158 mRNA. Translation: AAH39158.1.

IPI

IPI00014831.

PIR

I55465.

RefSeq

NP_002601.1.

UniGene

Hs.470633

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q8F	X-ray	2.03	A	30-436	[»]
2Q8G	X-ray	1.90	A	30-436	[»]
2Q8H	X-ray	2.00	A	30-436	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29497N.

STRING

Q15118.

PTM databases

PhosphoSite

Q15118.

Proteomic databases

PRIDE

Q15118.

Genome annotation databases

Ensembl

ENST00000282077; ENSP00000282077; ENSG00000152256; Homo sapiens. [Genome view]
ENST00000410055; ENSP00000386985; ENSG00000152256; Homo sapiens. [Genome view]

GeneID

5163.

KEGG

hsa:5163.

UCSC

uc002uhr.2. human.

Organism-specific databases

CTD

5163.

GeneCards

GC02P173129.

H-InvDB

HIX0002597.

HGNC

HGNC:8809. PDK1.

HPA

CAB017554.
HPA027376.

MIM

602524. gene.

PharmGKB

PA33154.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08616.

HOVERGEN

Q15118.

PhylomeDB

Q15118.

Enzyme and pathway databases

BRENDA

2.7.11.2. 247.

Reactome

REACT_1505. Integration of energy metabolism.

Gene expression databases

ArrayExpress

Q15118.

Bgee

Q15118.

CleanEx

HS_PDK1.

Genevestigator

Q15118.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit.

Pfam

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

SMART

SM00387. HATPase_c. 1 hit.
[Graphical view]

PROSITE

PS50109. HIS_KIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

19974.

SOURCE

Search...

Entry information

Entry name

PDK1_HUMAN

Accession

Primary (citable) accession number: Q15118
Secondary accession number(s): B2R6T1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.