Reviewed, UniProtKB/Swiss-Prot P08461 (ODP2_RAT)

Names and origin

Protein names

Recommended name:
    Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial
    EC=2.3.1.12
Alternative name(s):
    Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
    PDC-E2
      Short name=E2
    70 kDa mitochondrial autoantigen of primary biliary cirrhosis
      Short name=PBC

Gene names

Name:

Dlat

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	632 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. It contains multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3).
Catalytic activity	Acetyl-CoA + enzyme N(6)-(dihydrolipoyl)lysine = CoA + enzyme N(6)-(S-acetyldihydrolipoyl)lysine.
Cofactor	Binds 1 lipoyl cofactor covalently.
Subunit structure	20 to 30 alpha(2)-beta2 tetramers of E1 + 6 homodimers of E3 + 60 copies of E2.
Subcellular location	Mitochondrion matrix.
Tissue specificity	Expressed in flagella of epididymal sperm. Ref.5
Involvement in disease	Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. The E2 component of pyruvate dehydrogenase complex is the autoantigen for PBC.
Sequence similarities	Belongs to the 2-oxoacid dehydrogenase family. Contains 2 lipoyl-binding domains.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Mitochondrion
Domain	Lipoyl Repeat Transit peptide
Molecular function	Acyltransferase Transferase
PTM	Acetylation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	acetyl-CoA biosynthetic process from pyruvate Inferred from direct assay. Source: RGD glycolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell pyruvate dehydrogenase complex Ref.2 Inferred from direct assay. Source: RGD
Molecular function	dihydrolipoyllysine-residue acetyltransferase activity Ref.2 Inferred from direct assay. Source: RGD lipoic acid binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Ref.2 Traceable author statement. Source: RGD protein binding 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 – 77	77	Mitochondrion Ref.2
	Chain	78 – 632	555	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial		PRO_0000162298
Regions
	Domain	83 – 157	75	Lipoyl-binding 1
	Domain	209 – 283	75	Lipoyl-binding 2
	Region	344 – 375	32	E3- and/or E1-component binding domain Potential
	Region	456 – 632	177	Catalytic By similarity
	Region	600 – 611	12	CoA-binding By similarity
Sites
	Active site	605	1	Potential
	Active site	609	1	Potential
Amino acid modifications
	Modified residue	249	1	N6-lipoyllysine
	Modified residue	451	1	N6-acetyllysine By similarity
Experimental info
	Sequence conflict	150 – 152	3	VGS → IGC in BAA01504. Ref.2
	Sequence conflict	163 – 164	2	DI → GP in BAA20956. Ref.3
	Sequence conflict	163 – 164	2	DI → GP in AAA41813. Ref.3
	Sequence conflict	601 – 632	32	LSCDH…VTMLL → HSAVIIELWMEQLEPSGLL in BAA20956. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P08461-1 [UniParc]. Last modified December 12, 2006. Version 3. Checksum: 3F0EDBD44D93EB68	FASTA	632	67,166
	10 20 30 40 50 60 MWRVCARRVQ SAVPRAGFRA RWATLKGPRT GPAAVRCGSG IPSYGVRSLC GWSYGSATVP 70 80 90 100 110 120 RNRILQQLLG SPSRRSYSLP PHQKVPLPSL SPTMQAGTIA RWEKKEGEKI SEGDLIAEVE 130 140 150 160 170 180 TDKATVGFES LEECYMAKIL VPEGTRDVPV GSIICITVEK PQDIEAFKNY TLDSATAATQ 190 200 210 220 230 240 AAPAPAAAPA AAPAAPSASA PGSSYPVHMQ IVLPALSPTM TMGTVQRWEK KVGEKLSEGD 250 260 270 280 290 300 LLAEIETDKA TIGFEVQEEG YLAKILVPEG TRDVPLGTPL CIIVEKQEDI AAFADYRPTE 310 320 330 340 350 360 VTSLKPQAPP PVPPPVAAVP PIPQPLAPTP SAAPAGPKGR VFVSPLAKKL AAEKGIDLTQ 370 380 390 400 410 420 VKGTGPEGRI IKKDIDSFVP TKAAPAAAAA APPGPRVAPT PAGVFIDIPI SNIRRVIAQR 430 440 450 460 470 480 LMQSKQTIPH YYLSVDVNMG EVLLVRKELN KMLEGKGKIS VNDFIIKASA LACLKVPEAN 490 500 510 520 530 540 SSWMDTVIRQ NHVVDVSVAV STPAGLITPI VFNAHIKGLE TIASDVVSLA SKAREGKLQP 550 560 570 580 590 600 HEFQGGTFTI SNLGMFGIKN FSAIINPPQA CILAIGASED KLIPADNEKG FDVASVMSVT 610 620 630 LSCDHRVVDG AVGAQWLAEF KKYLEKPVTM LL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: Testis.
[2]	"Molecular cloning of dihydrolipoamide acetyltransferase of the rat pyruvate dehydrogenase complex: sequence comparison and evolutionary relationship to other dihydrolipoamide acyltransferases." Matuda S., Nakano K., Ohta S., Shimura M., Yamanaka T., Nakagawa S., Titani K., Miyata T. Biochim. Biophys. Acta 1131:114-118(1992) [PubMed: 1581353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 92-632, PROTEIN SEQUENCE OF 78-91. Tissue: Heart.
[3]	"Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis." Gershwin M.E., McKay I.R., Sturgess A., Coppel R.L. J. Immunol. 138:3525-3531(1987) [PubMed: 3571977] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 163-632. Tissue: Liver.
[4]	Lubec G., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 397-414, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
[5]	"Identification of novel immunodominant epididymal sperm proteins using combinatorial approach." Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V. Reproduction 138:81-93(2009) [PubMed: 19423663] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC107440 mRNA. Translation: AAI07441.1. D10655 mRNA. Translation: BAA01504.1. D00092 mRNA. Translation: BAA20956.1. M16075 mRNA. Translation: AAA41813.1.
IPI	IPI00231714.
PIR	S21766.
RefSeq	NP_112287.1.
UniGene	Rn.15413
3D structure databases
HSSP	HSSP built from PDB template 1FYC based on UniProtKB P10515.
SMR	P08461. Positions 83-173, 204-296.
ModBase	Search...
Protein-protein interaction databases
STRING	P08461.
Proteomic databases
PRIDE	P08461.
Genome annotation databases
Ensembl	ENSRNOT00000032152; ENSRNOP00000032890; ENSRNOG00000009994; Rattus norvegicus. [Genome view]
GeneID	81654.
KEGG	rno:81654.
NMPDR	fig|10116.3.peg.28575.
UCSC	NM_031025. rat.
Organism-specific databases
CTD	81654.
RGD	619859. Dlat.
Phylogenomic databases
HOVERGEN	P08461.
OMA	ISNLGMN.
Enzyme and pathway databases
BRENDA	2.3.1.12. 248.
Gene expression databases
ArrayExpress	P08461.
Genevestigator	P08461.
GermOnline	ENSRNOG00000009994. Rattus norvegicus.
Family and domain databases
InterPro	IPR003016. 2-oxoA_DH_lipoyl-BS. IPR001078. 2-oxoacid_DH_actylTfrase. IPR006257. AcTrfase_Pyrv_DH_cplx_L. IPR000089. Biotin_lipoyl. IPR004167. E3_bd. [Graphical view]
Gene3D	G3DSA:4.10.320.10. E3_bd. 1 hit.
Pfam	PF00198. 2-oxoacid_dh. 1 hit. PF00364. Biotin_lipoyl. 2 hits. PF02817. E3_binding. 1 hit. [Graphical view]
ProDom	PD001115. 2Oxoacid_dh. 1 hit. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR01349. PDHac_trf_mito. 1 hit.
PROSITE	PS50968. BIOTINYL_LIPOYL. 2 hits. PS00189. LIPOYL. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	615200.

Entry information

Entry name

ODP2_RAT

Accession

Primary (citable) accession number: P08461
Secondary accession number(s): Q3B7V7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	December 12, 2006
Last modified:	November 3, 2009
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)