O15382 (BCAT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Branched-chain-amino-acid aminotransferase, mitochondrial
Short name=BCAT(m)
EC=2.6.1.42

Alternative name(s):
Placental protein 18
Short name=PP18

Gene names

Name:	BCAT2
Synonyms:	BCATM, BCT2, ECA40

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	392 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	Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
Catalytic activity	L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate. 2-oxoglutaric acid + L-isoleucine = (S)-3-methyl-2-oxopentanoic acid + L-glutamic acid. 2-oxoglutaric acid + L-valine = 3-methyl-2-oxobutanoic acid + L-glutamic acid.
Cofactor	Pyridoxal phosphate. Ref.9 Ref.10 Ref.11 Ref.12
Subunit structure	Homodimer. Ref.9
Subcellular location	Isoform A: Mitochondrion. Isoform B: Cytoplasm.
Tissue specificity	Ubiquitous.
Sequence similarities	Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
Sequence caution	The sequence AAB53087.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Branched-chain amino acid biosynthesis
Cellular component	Cytoplasm Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Aminotransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	L-isoleucine transaminase activity Inferred from electronic annotation. Source: EC L-leucine transaminase activity Inferred from electronic annotation. Source: EC L-valine transaminase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: O15382-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: O15382-2)

The sequence of this isoform differs from the canonical sequence as follows:
     9-100: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 27

27

Mitochondrion

Chain

28 – 392

365

Branched-chain-amino-acid aminotransferase, mitochondrial

PRO_0000001271

Sites

Binding site

168

1

Substrate

Amino acid modifications

Modified residue

229

1

N6-(pyridoxal phosphate)lysine

Modified residue

321

1

N6-acetyllysine Ref.7

Modified residue

377

1

N6-acetyllysine Ref.7

Natural variations

Alternative sequence

9 – 100

92

Missing in isoform B.

VSP_000236

Natural variant

186

1

T → R. Ref.1 Ref.6
Corresponds to variant rs11548193 [ dbSNP | Ensembl ].

VAR_048234

Experimental info

Mutagenesis

342

1

C → A: Reduces activity about 6-fold. Ref.12

Mutagenesis

345

1

C → A: Slight reduction of activity. Ref.12

Sequence conflict

154

1

V → L in AAB53087. Ref.6

Sequence conflict

207

1

T → N in AAB53087. Ref.6

Sequence conflict

214 – 216

3

DPA → EPT in AAB53087. Ref.6

Sequence conflict

253

1

L → F in AAB53087. Ref.6

Sequence conflict

326

1

A → P in AAB53087. Ref.6

Sequence conflict

330

1

G → A in AAB53087. Ref.6

Sequence conflict

349

1

R → G in AAB53087. Ref.6

Sequence conflict

357

1

L → F in AAB53087. Ref.6

Sequence conflict

370

1

L → F in AAB53087. Ref.6

Secondary structure

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392

Helix Strand Turn

Details...

Turn

57 – 59

3

Beta strand

63 – 71

9

Beta strand

79 – 83

5

Beta strand

86 – 88

3

Helix

93 – 96

4

Beta strand

100 – 102

3

Beta strand

105 – 109

5

Beta strand

115 – 119

5

Helix

120 – 133

14

Helix

141 – 154

14

Helix

156 – 158

3

Beta strand

166 – 175

10

Beta strand

188 – 197

10

Beta strand

200 – 205

6

Beta strand

209 – 213

5

Helix

231 – 233

3

Turn

234 – 236

3

Helix

237 – 246

10

Beta strand

250 – 256

7

Turn

257 – 260

4

Beta strand

261 – 275

15

Beta strand

281 – 285

5

Beta strand

289 – 292

4

Helix

296 – 308

13

Beta strand

310 – 315

6

Helix

320 – 327

8

Turn

328 – 330

3

Beta strand

332 – 338

7

Beta strand

343 – 352

10

Beta strand

355 – 358

4

Helix

362 – 364

3

Helix

367 – 380

14

Beta strand

389 – 391

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified May 2, 2002. Version 2. Checksum: EC07047264B190DA	FASTA	392	44,288
	10 20 30 40 50 60 MAAAALGQIW ARKLLSVPWL LCGPRRYASS SFKAADLQLE MTQKPHKKPG PGEPLVFGKT 70 80 90 100 110 120 FTDHMLMVEW NDKGWGQPRI QPFQNLTLHP ASSSLHYSLQ LFEGMKAFKG KDQQVRLFRP 130 140 150 160 170 180 WLNMDRMLRS AMRLCLPSFD KLELLECIRR LIEVDKDWVP DAAGTSLYVR PVLIGNEPSL 190 200 210 220 230 240 GVSQPTRALL FVILCPVGAY FPGGSVTPVS LLADPAFIRA WVGGVGNYKL GGNYGPTVLV 250 260 270 280 290 300 QQEALKRGCE QVLWLYGPDH QLTEVGTMNI FVYWTHEDGV LELVTPPLNG VILPGVVRQS 310 320 330 340 350 360 LLDMAQTWGE FRVVERTITM KQLLRALEEG RVREVFGSGT ACQVCPVHRI LYKDRNLHIP 370 380 390 TMENGPELIL RFQKELKEIQ YGIRAHEWMF PV
	Isoform B [UniParc]. Checksum: 656A626FEC867073	FASTA	300	33,777
	10 20 30 40 50 60 MAAAALGQLF EGMKAFKGKD QQVRLFRPWL NMDRMLRSAM RLCLPSFDKL ELLECIRRLI 70 80 90 100 110 120 EVDKDWVPDA AGTSLYVRPV LIGNEPSLGV SQPTRALLFV ILCPVGAYFP GGSVTPVSLL 130 140 150 160 170 180 ADPAFIRAWV GGVGNYKLGG NYGPTVLVQQ EALKRGCEQV LWLYGPDHQL TEVGTMNIFV 190 200 210 220 230 240 YWTHEDGVLE LVTPPLNGVI LPGVVRQSLL DMAQTWGEFR VVERTITMKQ LLRALEEGRV 250 260 270 280 290 300 REVFGSGTAC QVCPVHRILY KDRNLHIPTM ENGPELILRF QKELKEIQYG IRAHEWMFPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the rat and human mitochondrial branched chain aminotransferases (BCATm)." Bledsoe R.K., Dawson P.A., Hutson S.M. Biochim. Biophys. Acta 1339:9-13(1997) [PubMed: 9165094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), VARIANT ARG-186.
[2]	"Molecular cloning and characterization of placental tissue protein 18 (PP18a)/human mitochondrial branched-chain aminotransferase (BCATm) and its novel alternatively spliced PP18b variant." Than N.G., Sumegi B., Than G.N., Bellyei S., Bohn H. Placenta 22:235-243(2001) [PubMed: 11170829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B). Tissue: Placenta.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). Tissue: Heart.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM A). Tissue: Lung and Skin.
[6]	"Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases." Eden A., Simchen G., Benvenisty N. J. Biol. Chem. 271:20242-20245(1996) [PubMed: 8702755] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-392 (ISOFORM A), VARIANT ARG-186. Tissue: Brain.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-321 AND LYS-377, MASS SPECTROMETRY.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"The structure of human mitochondrial branched-chain aminotransferase." Yennawar N.H., Dunbar J., Conway M.E., Hutson S.M., Farber G.K. Acta Crystallogr. D 57:506-515(2001) [PubMed: 11264579] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 28-392 IN COMPLEX WITH COFACTOR, SUBUNIT.
[10]	"Crystal structures of human mitochondrial branched chain aminotransferase reaction intermediates: ketimine and pyridoxamine phosphate forms." Yennawar N.H., Conway M.E., Yennawar H.P., Farber G.K., Hutson S.M. Biochemistry 41:11592-11601(2002) [PubMed: 12269802] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 28-392 IN COMPLEXES WITH COFACTOR AND SUBSTRATES.
[11]	"Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin." Goto M., Miyahara I., Hirotsu K., Conway M., Yennawar N., Islam M.M., Hutson S.M. J. Biol. Chem. 280:37246-37256(2005) [PubMed: 16141215] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF OF 28-392 IN COMPLEXES WITH COFACTOR AND SUBSTRATE ANALOGS.
[12]	"Human mitochondrial branched chain aminotransferase isozyme: structural role of the CXXC center in catalysis." Yennawar N.H., Islam M.M., Conway M., Wallin R., Hutson S.M. J. Biol. Chem. 281:39660-39671(2006) [PubMed: 17050531] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 28-392 IN COMPLEXES WITH COFACTOR AND SUBSTRATE ANALOGS, MUTAGENESIS OF CYS-342 AND CYS-345.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U68418 mRNA. Translation: AAB67672.1.
AF268047 mRNA. Translation: AAK38368.1.
AF268048 mRNA. Translation: AAK38369.1.
AK314548 mRNA. Translation: BAG37134.1.
CH471177 Genomic DNA. Translation: EAW52403.1.
BC001900 mRNA. Translation: AAH01900.1.
BC004243 mRNA. Translation: AAH04243.2.
U62739 mRNA. Translation: AAB53087.1. Different initiation.

IPI

IPI00396258.
IPI01009966.

RefSeq

NP_001158245.1. NM_001164773.1.
NP_001181.2. NM_001190.3.

UniGene

Hs.512670.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EKF	X-ray	1.95	A/B	28-392	[»]
1EKP	X-ray	2.50	A/B	28-392	[»]
1EKV	X-ray	2.25	A/B	28-392	[»]
1KT8	X-ray	1.90	A/B	28-392	[»]
1KTA	X-ray	1.90	A/B	28-392	[»]
2A1H	X-ray	1.80	A/B	28-392	[»]
2HDK	X-ray	2.40	A/B	28-392	[»]
2HG8	X-ray	1.80	A/B	28-392	[»]
2HGW	X-ray	1.98	A/B	28-392	[»]
2HGX	X-ray	1.80	A/B	28-392	[»]
2HHF	X-ray	1.80	A/B	28-392	[»]

ProteinModelPortal

O15382.

SMR

O15382. Positions 30-392.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15382. 3 interactions.

STRING

O15382.

PTM databases

PhosphoSite

O15382.

Proteomic databases

PRIDE

O15382.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316273; ENSP00000322991; ENSG00000105552.

GeneID

587.

KEGG

hsa:587.

NMPDR

fig|9606.3.peg.16829.

UCSC

uc002pkr.1. human.
uc002pkt.1. human.

Organism-specific databases

CTD

587.

GeneCards

GC19M049298.

H-InvDB

HIX0015301.

HGNC

HGNC:977. BCAT2.

MIM

113530. gene.

neXtProt

NX_O15382.

PharmGKB

PA25289.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13996.

HOGENOM

HBG617123.

HOVERGEN

HBG050678.

InParanoid

O15382.

OMA

CIRRLIE.

OrthoDB

EOG4BZN2N.

PhylomeDB

O15382.

Enzyme and pathway databases

BRENDA

2.6.1.42. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O15382.

Bgee

O15382.

CleanEx

HS_BCAT2.

Genevestigator

O15382.

GermOnline

ENSG00000105552. Homo sapiens.

Family and domain databases

InterPro

IPR001544. Aminotrans_IV.
IPR018300. Aminotrans_IV_CS.
IPR005786. B_amino_transII.
[Graphical view]

KO

K00826.

PANTHER

PTHR11825. Aminotrans_IV. 1 hit.
PTHR11825:SF2. B_amino_transII. 1 hit.

Pfam

PF01063. Aminotran_4. 1 hit.
[Graphical view]

PIRSF

PIRSF006468. BCAT1. 1 hit.

SUPFAM

SSF56752. Aminotrans_IV. 1 hit.

TIGRFAMs

TIGR01123. IlvE_II. 1 hit.

PROSITE

PS00770. AA_TRANSFER_CLASS_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00142. L-Glutamic Acid.
DB00167. L-Isoleucine.
DB00149. L-Leucine.
DB00114. Pyridoxal Phosphate.

NextBio

2399.

SOURCE

Search...

Entry information

Entry name

BCAT2_HUMAN

Accession

Primary (citable) accession number: O15382
Secondary accession number(s): B2RB87 , O00269, Q96KG1, Q9BTB6, Q9BUU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 2, 2002
Last modified:	January 25, 2012
This is version 120 of the entry and version 2 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.