P49753 (ACOT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acyl-coenzyme A thioesterase 2, mitochondrial
Short name=Acyl-CoA thioesterase 2
EC=3.1.2.2

Alternative name(s):
Acyl-coenzyme A thioester hydrolase 2a
CTE-Ia
Long-chain acyl-CoA thioesterase 2
ZAP128

Gene names

Name:	ACOT2
Synonyms:	PTE2, PTE2A

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	483 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	Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Displays high levels of activity on medium- and long chain acyl CoAs. Ref.6
Catalytic activity	Palmitoyl-CoA + H2O = CoA + palmitate.
Subcellular location	Mitochondrion Ref.2.
Tissue specificity	Strongest expression in heart, liver, muscle and kidney. Weak in placenta and pancreas. Ref.2
Sequence similarities	Belongs to the C/M/P thioester hydrolase family.
Caution	Was originally (Ref.6) thought to be peroxisomal but was later shown (Ref.2) to be mitochondrial.
Biophysicochemical properties	Kinetic parameters: KM=40.3 µM for C10-acyl-CoA Ref.2 KM=8.9 µM for C12-acyl-CoA KM=1.6 µM for C14-acyl-CoA KM=2.0 µM for C16-acyl-CoA KM=2.8 µM for C18-acyl-CoA KM=4.8 µM for C20-acyl-CoA KM=4.5 µM for C16:1-acyl-CoA KM=6.1 µM for C18:1-acyl-CoA KM=4.3 µM for C18:1-trans-acyl-CoA Vmax=212 nmol/min/mg enzyme toward C10-acyl-CoA Vmax=681 nmol/min/mg enzyme toward C12-acyl-CoA Vmax=766 nmol/min/mg enzyme toward C14-acyl-CoA Vmax=656 nmol/min/mg enzyme toward C16-acyl-CoA Vmax=488 nmol/min/mg enzyme toward C18-acyl-CoA Vmax=408 nmol/min/mg enzyme toward C20-acyl-CoA Vmax=661 nmol/min/mg enzyme toward C16:1-acyl-CoA Vmax=304 nmol/min/mg enzyme toward C18:1-acyl-CoA Vmax=418 nmol/min/mg enzyme toward C18:1-trans-acyl-CoA
Sequence caution	The sequence AAC42007.1 differs from that shown. Reason: Frameshift at positions 215 and 226.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Molecular function	Hydrolase Serine esterase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acyl-CoA metabolic process Inferred from direct assay Ref.6Ref.2. Source: HGNC long-chain fatty acid metabolic process Inferred from direct assay Ref.2. Source: HGNC very long-chain fatty acid metabolic process Inferred from direct assay Ref.2. Source: HGNC
Cellular_component	mitochondrion Inferred from direct assay Ref.2. Source: HGNC
Molecular_function	acyl-CoA hydrolase activity Inferred from direct assay Ref.6Ref.2. Source: HGNC carboxylesterase activity Inferred from electronic annotation. Source: UniProtKB-KW palmitoyl-CoA hydrolase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P49753-1)

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 2 (identifier: P49753-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     53-214: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 483

Acyl-coenzyme A thioesterase 2, mitochondrial

PRO_0000202147

Regions

Motif

481 – 483

3

Microbody targeting signal Potential

Sites

Active site

294

1

Charge relay system By similarity

Active site

388

1

Charge relay system By similarity

Active site

422

1

Charge relay system By similarity

Natural variations

Alternative sequence

1 – 20

20

Missing in isoform 2.

VSP_012225

Alternative sequence

53 – 214

162

Missing in isoform 2.

VSP_012226

Natural variant

16

1

R → S.
Corresponds to variant rs11545741 [ dbSNP | Ensembl ].

VAR_057271

Natural variant

475

1

H → R. Ref.3 Ref.4 Ref.5 Ref.6
Corresponds to variant rs7494 [ dbSNP | Ensembl ].

VAR_016136

Experimental info

Sequence conflict

167

1

E → V in AAZ31237. Ref.2

Sequence conflict

167

1

E → V in BAA91989. Ref.3

Sequence conflict

328

1

H → R in AAZ31237. Ref.2

Sequence conflict

328

1

H → R in BAA91989. Ref.3

Sequence conflict

328

1

H → R in BAD97355. Ref.4

Sequence conflict

328

1

H → R in AAH04436. Ref.5

Sequence conflict

328

1

H → R in AAH06335. Ref.5

Sequence conflict

328

1

H → R in AAH06500. Ref.5

Sequence conflict

328

1

H → R in AAF97985. Ref.6

Sequence conflict

454

1

A → V in AAH06335. Ref.5

Secondary structure

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483

Helix Strand Turn

Details...

Beta strand

66 – 71

6

Beta strand

82 – 87

6

Beta strand

93 – 101

9

Beta strand

107 – 115

9

Turn

124 – 126

3

Beta strand

131 – 133

3

Helix

141 – 144

4

Beta strand

147 – 150

4

Beta strand

164 – 174

11

Beta strand

181 – 192

12

Beta strand

197 – 203

7

Beta strand

206 – 212

7

Beta strand

214 – 216

3

Beta strand

221 – 225

5

Helix

235 – 241

7

Turn

242 – 244

3

Beta strand

246 – 250

5

Beta strand

253 – 255

3

Beta strand

263 – 266

4

Helix

267 – 278

12

Beta strand

286 – 293

8

Helix

295 – 306

12

Beta strand

310 – 317

8

Beta strand

324 – 329

6

Beta strand

332 – 334

3

Helix

341 – 343

3

Beta strand

348 – 350

3

Helix

364 – 369

6

Helix

373 – 375

3

Beta strand

378 – 385

8

Helix

393 – 406

14

Beta strand

413 – 417

5

Helix

450 – 471

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 6. Checksum: FAEDD42BBBD935E4	FASTA	483	53,218
	10 20 30 40 50 60 MSNKLLSPHP HSVVLRSEFK MASSPAVLRA SRLYQWSLKS SAQFLGSPQL RQVGQIIRVP 70 80 90 100 110 120 ARMAATLILE PAGRCCWDEP VRIAVRGLAP EQPVTLRASL RDEKGALFQA HARYRADTLG 130 140 150 160 170 180 ELDLERAPAL GGSFAGLEPM GLLWALEPEK PLVRLVKRDV RTPLAVELEV LDGHDPDPGR 190 200 210 220 230 240 LLCQTRHERY FLPPGVRREP VRVGRVRGTL FLPPEPGPFP GIVDMFGTGG GLLEYRASLL 250 260 270 280 290 300 AGKGFAVMAL AYYNYEDLPK TMETLHLEYF EEAMNYLLSH PEVKGPGVGL LGISKGGELC 310 320 330 340 350 360 LSMASFLKGI TAAVVINGSV ANVGGTLHYK GETLPPVGVN RNRIKVTKDG YADIVDVLNS 370 380 390 400 410 420 PLEGPDQKSF IPVERAESTF LFLVGQDDHN WKSEFYANEA CKRLQAHGRR KPQIICYPET 430 440 450 460 470 480 GHYIEPPYFP LCRASLHALV GSPIIWGGEP RAHAMAQVDA WKQLQTFFHK HLGGHEGTIP SKV
	Isoform 2 [UniParc]. Checksum: D157DF13EAF26EC6	FASTA	301	32,959
	10 20 30 40 50 60 MASSPAVLRA SRLYQWSLKS SAQFLGSPQL RQEPGPFPGI VDMFGTGGGL LEYRASLLAG 70 80 90 100 110 120 KGFAVMALAY YNYEDLPKTM ETLHLEYFEE AMNYLLSHPE VKGPGVGLLG ISKGGELCLS 130 140 150 160 170 180 MASFLKGITA AVVINGSVAN VGGTLHYKGE TLPPVGVNRN RIKVTKDGYA DIVDVLNSPL 190 200 210 220 230 240 EGPDQKSFIP VERAESTFLF LVGQDDHNWK SEFYANEACK RLQAHGRRKP QIICYPETGH 250 260 270 280 290 300 YIEPPYFPLC RASLHALVGS PIIWGGEPRA HAMAQVDAWK QLQTFFHKHL GGHEGTIPSK V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease." Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H. Nature 375:754-760(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[2]	"Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs." Hunt M.C., Rautanen A., Westin M.A.K., Svensson L.T., Alexson S.E.H. FASEB J. 20:1855-1864(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-475. Tissue: Placenta.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-475. Tissue: Spleen.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ARG-475. Tissue: Lung and Uterus.
[6]	"Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase." Jones J.M., Gould S.J. Biochem. Biophys. Res. Commun. 275:233-240(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-483 (ISOFORM 1), FUNCTION, VARIANT ARG-475.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L40401 mRNA. Translation: AAC42007.1. Frameshift.
DQ082755 mRNA. Translation: AAZ31237.1.
AK001939 mRNA. Translation: BAA91989.1.
AK223635 mRNA. Translation: BAD97355.1.
BC004436 mRNA. Translation: AAH04436.2.
BC006335 mRNA. Translation: AAH06335.1.
BC006500 mRNA. Translation: AAH06500.4.
AY005822 mRNA. Translation: AAF97985.1.

IPI

IPI00220906.
IPI00513928.

PIR

JC7367.

RefSeq

NP_006812.3. NM_006821.5.

UniGene

Hs.446685.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HLK	X-ray	2.10	A/B	46-483	[»]

ProteinModelPortal

P49753.

SMR

P49753. Positions 57-472.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000238651.

Protein family/group databases

MEROPS

S09.028.

PTM databases

PhosphoSite

P49753.

Polymorphism databases

DMDM

269849771.

Proteomic databases

PRIDE

P49753.

Protocols and materials databases

DNASU

10965.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000238651; ENSP00000238651; ENSG00000119673.

GeneID

10965.

KEGG

hsa:10965.

UCSC

uc001xon.4. human.

Organism-specific databases

CTD

10965.

GeneCards

GC14P074036.

H-InvDB

HIX0011795.
HIX0172385.

HGNC

HGNC:18431. ACOT2.

HPA

HPA043705.

MIM

609972. gene.

neXtProt

NX_P49753.

PharmGKB

PA142672653.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000116219.

HOVERGEN

HBG000331.

InParanoid

P49753.

KO

K01068.

OMA

LPEYRAC.

OrthoDB

EOG4QC15F.

PhylomeDB

P49753.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04318-MONOMER.

BRENDA

3.1.2.2. 2681.

SABIO-RK

P49753.

Gene expression databases

ArrayExpress

P49753.

Bgee

P49753.

CleanEx

HS_ACOT2.

Genevestigator

P49753.

GermOnline

ENSG00000119673. Homo sapiens.

Family and domain databases

InterPro

IPR016662. Acyl-CoA_thioEstase_long-chain.
IPR014940. BAAT_C.
IPR006862. Thio_Ohase/aa_AcTrfase.
[Graphical view]

Pfam

PF08840. BAAT_C. 1 hit.
PF04775. Bile_Hydr_Trans. 1 hit.
[Graphical view]

PIRSF

PIRSF016521. Acyl-CoA_hydro. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P49753.

GenomeRNAi

10965.

NextBio

41670.

SOURCE

Search...

Entry information

Entry name

ACOT2_HUMAN

Accession

Primary (citable) accession number: P49753
Secondary accession number(s): Q3I5F8, Q53EK4, Q9NUX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 24, 2009
Last modified:	April 3, 2013
This is version 126 of the entry and version 6 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.