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Protein Page:
PDHA1 (human)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
PDHA1 a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate, producing acetyl-CoA and CO2. A key enzyme in controlling the balance between lipid and glucose oxidation depending on substrate availability. The pyruvate dehydrogenase (PDH) holoenzyme is a multi-enzyme complex (PDHC) that contains 20-30 copies of pyruvate decarboxylase tetramers (2 alpha:2 beta)(E1), 60 copies of dihydrolipoamide acetyltransferase (E2), six homodimers of dihydrolipoamide dehydrogenase (E3), plus E3 binding proteins. The activity of PDH is tightly regulated by phosphorylation. The phosphorylation of at least one of three specific serine residues in E1 subunit by PDHK inactivates the PDHC, while dephosphorylation by PDP restores its activity. Sites 1, 2, and 3 of PDHA1 are S293, S300, and S232, respectively. Four PDHK isoenzymes have been described, each with different site specificity: all four phosphorylate sites 1 and 2 but at different rates; for site 1 PDHK2 >PDHK4 >PDHK1 >PDHK3; for site 2, PDHK3> PDHK4 > PDHK2 > PDHK1. Only PDHK1 phosphorylates site 3. PDHA1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. Note: This description may include information from UniProtKB.
Protein type: Mitochondrial; Amino Acid Metabolism - valine, leucine and isoleucine biosynthesis; Oxidoreductase; Carbohydrate Metabolism - pyruvate; EC 1.2.4.1; Carbohydrate Metabolism - citrate (TCA) cycle; Carbohydrate Metabolism - butanoate; Carbohydrate Metabolism - glycolysis and gluconeogenesis
Cellular Component: mitochondrion; mitochondrial matrix; pyruvate dehydrogenase complex; nucleus
Molecular Function: pyruvate dehydrogenase activity; pyruvate dehydrogenase (acetyl-transferring) activity
Biological Process: acetyl-CoA biosynthetic process from pyruvate; cellular metabolic process; glycolysis; tricarboxylic acid cycle; glucose metabolic process; regulation of acetyl-CoA biosynthetic process from pyruvate; pyruvate metabolic process
Reference #:  P08559 (UniProtKB)
Alt. Names/Synonyms: ODPA; PDHA; PDHA1; PDHCE1A; PDHE1-A type I; PHE1A; pyruvate dehydrogenase (lipoamide) alpha 1; pyruvate dehydrogenase complex, E1-alpha polypeptide 1; pyruvate dehydrogenase E1 alpha 1; Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
Gene Symbols: PDHA1
Molecular weight: 43,296 Da
Basal Isoelectric point: 8.35  Predict pI for various phosphorylation states
CST Pathways:  Warburg Effect
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

PDHA1

Protein Structure Not Found.


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Sites Implicated In
enzymatic activity, inhibited: S232‑p, S293‑p, S300‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 K18-a VLSGASQkPASRVLV
1 23 K39-a NDATFEIkKCDLHRL
0 13 K77-a TVRRMELkADQLYkQ
0 10 K83-a LkADQLYkQKIIRGF
0 8 Y227-p FICENNRyGMGtsVE
0 28 T231-p NNRyGMGtsVERAAA
18 51 S232-p NRyGMGtsVERAAAS
0 51 Y242-p RAAASTDyykRGDFI
0 4 Y243-p AAASTDyykRGDFIP
1 85 K244-a AASTDyykRGDFIPG
0 26 K277-a AAYCRSGkGPILMEL
0 488 Y289-p MELQTYRyHGHsMsD
32 709 S293-p TYRyHGHsMsDPGVs
1 252 S295-p RyHGHsMsDPGVsyR
22 512 S300-p sMsDPGVsyRtREEI
0 1446 Y301-p MsDPGVsyRtREEIQ
0 46 T303-p DPGVsyRtREEIQEV
0 22 K313-a EIQEVRSkSDPIMLL
0 1 S314 IQEVRSkSDPIMLLk
1 78 K321-a SDPIMLLkDRMVNSN
0 1 K321 SDPIMLLKDRMVNSN
0 1 S331 MVNSNLASVEELkEI
1 3 K336-a LASVEELkEIDVEVR
0 1 K385 RGANQWIKFKSVS__
  mouse

 
K18 VLAGSAQKPASRVLV
K39-a NDATFEIkKCDLHRL
K77-a TVRRMELkADQLYkQ
K83-a LkADQLYkQKIIRGF
Y227 FICENNRYGMGtsVE
T231-p NNRYGMGtsVERAAA
S232-p NRYGMGtsVERAAAS
Y242-p RAAASTDyykRGDFI
Y243-p AAASTDyykRGDFIP
K244-a AASTDyykRGDFIPG
K277-a AAYCRSGkGPILMEL
Y289-p MELQTYRyHGHsMsD
S293-p TYRyHGHsMsDPGVs
S295-p RyHGHsMsDPGVsyR
S300-p sMsDPGVsyRtREEI
Y301-p MsDPGVsyRtREEIQ
T303-p DPGVsyRtREEIQEV
K313-a EIQEVRSksDPIMLL
S314-p IQEVRSksDPIMLLk
K321-a sDPIMLLkDRMVNSN
K321-u sDPIMLLkDRMVNSN
S331-p MVNSNLAsVEELkEI
K336-a LAsVEELkEIDVEVR
K385-u RGANQWIkFKSVS__
  rat

 
K18 VLAGAAQKPASRVLV
K39 NDATFEIKKCDLHRL
K77 TVRRMELKADQLYkQ
K83-a LKADQLYkQKIIRGF
Y227-p FICENNRyGMGtsVE
T231-p NNRyGMGtsVERAAA
S232-p NRyGMGtsVERAAAS
Y242 RAAASTDYYKRGDFI
Y243 AAASTDYYKRGDFIP
K244 AASTDYYKRGDFIPG
K277 AAYCRSGKGPILMEL
Y289-p MELQTYRyHGHsMsD
S293-p TYRyHGHsMsDPGVs
S295-p RyHGHsMsDPGVsyR
S300-p sMsDPGVsyRTREEI
Y301-p MsDPGVsyRTREEIQ
T303 DPGVsyRTREEIQEV
K313-a EIQEVRSkSDPIMLL
S314 IQEVRSkSDPIMLLk
K321-a SDPIMLLkDRMVNSN
K321 SDPIMLLKDRMVNSN
S331 MVNSNLASVEELKEI
K336 LASVEELKEIDVEVR
K385 RGANQWIKFKSVS__
  pig

 
K17 VLSGVAQKPASRVLV
K38 NDATFEIKKCDLHRL
K76 TVRRMELKADQLYKQ
K82 LKADQLYKQKIIRGF
Y226 FICENNRYGMGTsVE
T230 NNRYGMGTsVERAAA
S231-p NRYGMGTsVERAAAS
Y241 RAAASTDYYKRGDFI
Y242 AAASTDYYKRGDFIP
K243 AASTDYYKRGDFIPG
K276 AAYCRSGKGPILMEL
Y288 MELQTYRYHGHsMSD
S292-p TYRYHGHsMSDPGVs
S294 RYHGHsMSDPGVsYR
S299-p sMSDPGVsYRTREEI
Y300 MSDPGVsYRTREEIQ
T302 DPGVsYRTREEIQEV
K312 EIQEVRSKSDPIMLL
S313 IQEVRSKSDPIMLLK
K320 SDPIMLLKDRMVNSN
K320 SDPIMLLKDRMVNSN
S330 MVNSNLASVEELKEI
K335 LASVEELKEIDVEVR
K384 RGANQWIKFKSIS__
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