P29803 (ODPAT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial
EC=1.2.4.1

Alternative name(s):
PDHE1-A type II

Gene names

Name:	PDHA2
Synonyms:	PDHAL

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	388 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	The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and thereby links the glycolytic pathway to the tricarboxylic cycle. Ref.5
Catalytic activity	Pyruvate + [dihydrolipoyllysine-residue acetyltransferase] lipoyllysine = [dihydrolipoyllysine-residue acetyltransferase] S-acetyldihydrolipoyllysine + CO2. Ref.5
Cofactor	Thiamine pyrophosphate.
Enzyme regulation	Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA2; it is reactivated by dephosphorylation.
Subunit structure	Heterotetramer of two PDHA2 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules. Ref.4
Subcellular location	Mitochondrion matrix.
Tissue specificity	Testis. Expressed in postmeiotic spermatogenic cells. Ref.7
Post-translational modification	Phosphorylation at Ser-205, Ser-266 and Ser-273 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Phosphorylation at Ser-266 interferes with access to active site, and thereby inactivates the enzyme. Dephosphorylation at all three sites, i.e. at Ser-205, Ser-266 and Ser-273, is required for reactivation.
Sequence caution	The sequence AAH94760.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism Tricarboxylic acid cycle
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transit peptide
Ligand	Pyruvate Thiamine pyrophosphate
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycolysis Inferred from electronic annotation. Source: InterPro pyruvate metabolic process Inferred from direct assay Ref.5. Source: UniProtKB tricarboxylic acid cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	pyruvate dehydrogenase (acetyl-transferring) activity Inferred from direct assay Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 27	27	Mitochondrion By similarity
	Chain	28 – 388	361	Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial		PRO_0000020447
Amino acid modifications
	Modified residue	291	1	Phosphoserine; by PDK1, PDK2, PDK3 and PDK4 Ref.5
	Modified residue	298	1	Phosphoserine; by PDK3 Ref.5
Natural variations
	Natural variant	280	1	M → L. Corresponds to variant rs2229137 [ dbSNP | Ensembl ].		VAR_034358
	Natural variant	376	1	R → G. Corresponds to variant rs17024795 [ dbSNP | Ensembl ].		VAR_034359
Experimental info
	Mutagenesis	230	1	S → A: Slightly reduces enzyme activity. Ref.5
	Mutagenesis	291	1	S → A: Strongly reduces enzyme activity. Ref.5
	Mutagenesis	291	1	S → E: Abolishes enzyme activity. Ref.5
	Mutagenesis	298	1	S → A: Slightly reduces enzyme activity. Ref.5
	Sequence conflict	127	1	L → P in AAH66953. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P29803 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 075B6CFF6DC73CC5	FASTA	388	42,933
	10 20 30 40 50 60 MLAAFISRVL RRVAQKSARR VLVASRNSSN DATFEIKKCD LYLLEEGPPV TTVLTRAEGL 70 80 90 100 110 120 KYYRMMLTVR RMELKADQLY KQKFIRGFCH LCDGQEACCV GLEAGINPSD HVITSYRAHG 130 140 150 160 170 180 VCYTRGLSVR SILAELTGRR GGCAKGKGGS MHMYTKNFYG GNGIVGAQGP LGAGIALACK 190 200 210 220 230 240 YKGNDEICLT LYGDGAANQG QIAEAFNMAA LWKLPCVFIC ENNLYGMGTS TERAAASPDY 250 260 270 280 290 300 YKRGNFIPGL KVDGMDVLCV REATKFAANY CRSGKGPILM ELQTYRYHGH SMSDPGVSYR 310 320 330 340 350 360 TREEIQEVRS KRDPIIILQD RMVNSKLATV EELKEIGAEV RKEIDDAAQF ATTDPEPHLE 370 380 ELGHHIYSSD SSFEVRGANP WIKFKSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A testis-specific form of the human pyruvate dehydrogenase E1 alpha subunit is coded for by an intronless gene on chromosome 4." Dahl H.-H.M., Brown R.M., Hutchison W.M., Maragos C., Brown G.K. Genomics 8:225-232(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Testis.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components." Hiromasa Y., Fujisawa T., Aso Y., Roche T.E. J. Biol. Chem. 279:6921-6933(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[5]	"Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase." Korotchkina L.G., Sidhu S., Patel M.S. J. Biol. Chem. 281:9688-9696(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION, PHOSPHORYLATION AT SER-291 AND SER-298, MUTAGENESIS OF SER-230; SER-291 AND SER-298.
[6]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Pyruvate dehydrogenase complex: mRNA and protein expression patterns of E1alpha subunit genes in human spermatogenesis." Pinheiro A., Silva M.J., Graca I., Silva J., Sa R., Sousa M., Barros A., Tavares de Almeida I., Rivera I. Gene 506:173-178(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M86808 Genomic DNA. Translation: AAA60232.1. AK313872 mRNA. Translation: BAG36600.1. BC030697 mRNA. Translation: AAH30697.3. BC066953 mRNA. Translation: AAH66953.2. BC094760 mRNA. Translation: AAH94760.1. Different initiation. BC119656 mRNA. Translation: AAI19657.1. BC119657 mRNA. Translation: AAI19658.1. BC127637 mRNA. Translation: AAI27638.1. BC127638 mRNA. Translation: AAI27639.1.
IPI	IPI00024087.
PIR	DEHUPT. A37104.
RefSeq	NP_005381.1. NM_005390.4.
UniGene	Hs.131361.
3D structure databases
ProteinModelPortal	P29803.
ModBase	Search...
Protein-protein interaction databases
IntAct	P29803. 1 interaction.
STRING	9606.ENSP00000295266.
PTM databases
PhosphoSite	P29803.
Polymorphism databases
DMDM	266687.
Proteomic databases
PaxDb	P29803.
PRIDE	P29803.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295266; ENSP00000295266; ENSG00000163114.
GeneID	5161.
KEGG	hsa:5161.
UCSC	uc003htr.4. human.
Organism-specific databases
CTD	5161.
GeneCards	GC04P096761.
HGNC	HGNC:8807. PDHA2.
MIM	179061. gene.
neXtProt	NX_P29803.
PharmGKB	PA33151.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1071.
HOGENOM	HOG000281336.
HOVERGEN	HBG001863.
InParanoid	P29803.
KO	K00161.
OMA	HLTYDDI.
OrthoDB	EOG4W0XD6.
PhylomeDB	P29803.
Gene expression databases
Bgee	P29803.
CleanEx	HS_PDHA2.
Genevestigator	P29803.
GermOnline	ENSG00000163114. Homo sapiens.
Family and domain databases
InterPro	IPR001017. DH_E1. IPR017597. Pyrv_DH_E1_asu_subgrp-y. [Graphical view]
Pfam	PF00676. E1_dh. 1 hit. [Graphical view]
TIGRFAMs	TIGR03182. PDH_E1_alph_y. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL4500.
ChiTaRS	PDHA2. human.
DrugBank	DB00157. NADH.
GenomeRNAi	5161.
NextBio	19966.
SOURCE	Search...

Entry information

Entry name

ODPAT_HUMAN

Accession

Primary (citable) accession number: P29803
Secondary accession number(s): B2R9Q3 , Q0VDI5, Q4VC02, Q6NXQ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	May 1, 2013
This is version 123 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.