Reviewed, UniProtKB/Swiss-Prot Q16654 (PDK4_HUMAN)

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.
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
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glucose metabolic process Ref.1 Traceable author statement. Source: ProtInc peptidyl-histidine phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro 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 – ?

Mitochondrion Potential

Chain

? – 411

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

PRO_0000023445

Regions

Domain

138 – 368

231

Histidine kinase

Amino acid modifications

Modified residue

127

1

Phosphohistidine; by autocatalysis By similarity

Natural variations

Natural variant

17

1

A → V

VAR_042298

Natural variant

19

1

L → M

VAR_042299

Natural variant

109

1

D → G

VAR_042300

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)
	Q16654-1 [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]	"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

EMBLGenBankDDBJ

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.

RefSeq

NP_002603.1.

UniGene

Hs.8364

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E0A	X-ray	1.86	A/B	18-411	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000004799. Homo sapiens. [Contig view]

GeneID

5166.

KEGG

hsa:5166.

Organism-specific databases

H-InvDB

HIX0006864.

HGNC

HGNC:8812. PDK4.

MIM

602527. gene.

PharmGKB

PA33157.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q16654.

HOVERGEN

Q16654.

Gene expression databases

ArrayExpress

Q16654.

CleanEx

HS_PDK4.

GermOnline

ENSG00000004799. Homo sapiens.

Family and domain databases

InterPro

IPR003594. ATP_bd_ATPase.
IPR004358. Sig_transdc_His_kin-like_C.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]

Gene3D

G3DSA:3.30.565.10. ATP_bd_ATPase. 1 hit.

Pfam

PF02518. HATPase_c. 1 hit.
[Graphical view]

PRINTS

PR00344. BCTRLSENSOR.

SMART

SM00387. HATPase_c. 1 hit.
[Graphical view]

PROSITE

PS50109. HIS_KIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	November 25, 2008
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)