Q16654 (PDK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
EC=2.7.11.2

Alternative name(s):
Pyruvate dehydrogenase kinase isoform 4

Gene names

Name:

PDK4

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	411 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. Ref.4
Catalytic activity	ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Ubiquitous; highest levels of expression in heart and skeletal muscle.
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
PTM	Phosphoprotein
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
Molecular function	ATP binding Inferred from direct assay Ref.4. 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

? – 411

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial

PRO_0000023445

Regions

Domain

138 – 368

231

Histidine kinase

Nucleotide binding

254 – 261

8

ATP

Nucleotide binding

312 – 313

2

ATP

Nucleotide binding

329 – 334

6

ATP

Sites

Binding site

293

1

ATP

Amino acid modifications

Modified residue

127

1

Phosphohistidine; by autocatalysis By similarity

Natural variations

Natural variant

17

1

A → V. [dbSNP:rs56391840] Ref.6

VAR_042298

Natural variant

19

1

L → M. [dbSNP:rs55761955] Ref.6

VAR_042299

Natural variant

109

1

D → G. [dbSNP:rs34898343] Ref.6

VAR_042300

Experimental info

Mutagenesis

157

1

Y → F: Loss of activity. Ref.4

Mutagenesis

161

1

R → A: Loss of activity. Ref.4

Mutagenesis

394

1

D → A: Loss of activity; when associated with A-395. Ref.4

Mutagenesis

395

1

W → A: Loss of activity; when associated with A-394. Ref.4

Secondary structure

1

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411

Helix Strand Turn

Details...

Helix

22 – 27

6

Helix

37 – 42

6

Helix

50 – 72

23

Helix

77 – 80

4

Helix

83 – 100

18

Beta strand

103 – 105

3

Helix

110 – 127

18

Helix

130 – 142

13

Turn

149 – 151

3

Helix

153 – 180

28

Beta strand

194 – 199

6

Helix

200 – 219

20

Beta strand

225 – 234

10

Beta strand

240 – 243

4

Helix

245 – 266

22

Turn

267 – 269

3

Beta strand

270 – 272

3

Beta strand

276 – 282

7

Beta strand

284 – 293

10

Helix

300 – 302

3

Helix

303 – 306

4

Helix

333 – 343

11

Beta strand

347 – 353

7

Turn

354 – 356

3

Beta strand

357 – 367

11

Turn

368 – 370

3

Helix

380 – 385

6

Sequences

	Sequence		Length	Mass (Da)
	Q16654 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: C17B78B6057000E9	FASTA	411	46,469
	10 20 30 40 50 60 MKAARFVLRS AGSLNGAGLV PREVEHFSRY SPSPLSMKQL LDFGSENACE RTSFAFLRQE 70 80 90 100 110 120 LPVRLANILK EIDILPTQLV NTSSVQLVKS WYIQSLMDLV EFHEKSPDDQ KALSDFVDTL 130 140 150 160 170 180 IKVRNRHHNV VPTMAQGIIE YKDACTVDPV TNQNLQYFLD RFYMNRISTR MLMNQHILIF 190 200 210 220 230 240 SDSQTGNPSH IGSIDPNCDV VAVVQDAFEC SRMLCDQYYL SSPELKLTQV NGKFPDQPIH 250 260 270 280 290 300 IVYVPSHLHH MLFELFKNAM RATVEHQENQ PSLTPIEVIV VLGKEDLTIK ISDRGGGVPL 310 320 330 340 350 360 RIIDRLFSYT YSTAPTPVMD NSRNAPLAGF GYGLPISRLY AKYFQGDLNL YSLSGYGTDA 370 380 390 400 410 IIYLKALSSE SIEKLPVFNK SAFKHYQMSS EADDWCIPSR EPKNLAKEVA M

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human." Rowles J., Scherer S.W., Xi T., Majer M., Nickle D.C., Rommens J.M., Popov K.M., Harris R.A., Riebow N.L., Xia J., Tsui L.-C., Bogardus C., Prochazka M. J. Biol. Chem. 271:22376-22382(1996) [PubMed: 8798399] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: Cervix.
[4]	"Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity." Wynn R.M., Kato M., Chuang J.L., Tso S.C., Li J., Chuang D.T. J. Biol. Chem. 283:25305-25315(2008) [PubMed: 18658136] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 20-411 IN COMPLEX WITH ATP, FUNCTION, ENZYME REGULATION, MUTAGENESIS OF TYR-157; ARG-161; ASP-394 AND TRP-395.
[5]	"Crystal structure of human pyruvate dehydrogenase kinase 4 in complex with AMPPNP." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 20-411 IN COMPLEX WITH ATP ANALOG.
[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: VARIANTS [LARGE SCALE ANALYSIS] VAL-17; MET-19 AND GLY-109.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U54628 , U54618, U54619, U54620, U54621, U54622, U54623, U54624, U54625, U54626, U54627 Genomic DNA. Translation: AAC50670.1.
U54617 mRNA. Translation: AAC50669.1.
AC002451 Genomic DNA. Translation: AAB67048.1.
BC040239 mRNA. Translation: AAH40239.1.

IPI

IPI00003425.

RefSeq

NP_002603.1. NM_002612.3.

UniGene

Hs.8364.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E0A	X-ray	1.86	A/B	20-411	[»]
2ZDX	X-ray	2.54	A/B	20-411	[»]
2ZDY	X-ray	2.40	A/B	20-411	[»]
2ZKJ	X-ray	2.00	A/B	20-411	[»]
3D2R	X-ray	2.03	A/B	20-411	[»]

ProteinModelPortal

Q16654.

SMR

Q16654. Positions 20-386.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16654. 1 interaction.

STRING

Q16654.

Polymorphism databases

DMDM

3183120.

Proteomic databases

PRIDE

Q16654.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000005178; ENSP00000005178; ENSG00000004799.

GeneID

5166.

KEGG

hsa:5166.

UCSC

uc003uoa.1. human.

Organism-specific databases

CTD

5166.

GeneCards

GC07M095212.

H-InvDB

HIX0006864.

HGNC

HGNC:8812. PDK4.

MIM

602527. gene.

neXtProt

NX_Q16654.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG382024.

HOVERGEN

HBG000511.

InParanoid

Q16654.

OMA

YFQGDLN.

OrthoDB

EOG4G1MGF.

PhylomeDB

Q16654.

Enzyme and pathway databases

BRENDA

2.7.11.2. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q16654.

Bgee

Q16654.

CleanEx

HS_PDK4.

Genevestigator

Q16654.

GermOnline

ENSG00000004799. 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

19986.

SOURCE

Search...

Entry information

Entry name

PDK4_HUMAN

Accession

Primary (citable) accession number: Q16654

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 111 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.