Reviewed, UniProtKB/Swiss-Prot P49753 (ACOT2_HUMAN)

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
    Long-chain acyl-CoA thioesterase 2
    ZAP128
    CTE-Ia

Gene names

Name:	ACOT2
Synonyms:	PTE2, PTE2A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 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
PTM	Acetylation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	acyl-CoA metabolic process Ref.2 Ref.6 Inferred from direct assay. Source: HGNC long-chain fatty acid metabolic process Ref.2 Inferred from direct assay. Source: HGNC very-long-chain fatty acid metabolic process Ref.2 Inferred from direct assay. Source: HGNC
Cellular component	mitochondrion Ref.2 Inferred from direct assay. Source: HGNC
Molecular function	carboxylesterase activity Inferred from electronic annotation. Source: UniProtKB-KW palmitoyl-CoA hydrolase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ZNF277	Q9NRM2	1	EBI-1052865,EBI-949305

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
Amino acid modifications
	Modified residue	104	1	N6-acetyllysine Ref.7
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: dbSNP rs11545741.		VAR_057271
	Natural variant	475	1	H → R: dbSNP rs7494. Ref.6 Ref.3 Ref.4 Ref.5		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	R → H in AAC42007. Ref.1
	Sequence conflict	454	1	A → V in AAH06335. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 13, 2007. Version 5. Checksum: FAF96B6F4533745E	FASTA	483	53,238
	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 ANVGGTLRYK 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. Checksum: D143605714182F7C	FASTA	301	32,978
	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 VGGTLRYKGE 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: 7596406] [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: 16940157] [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: 14702039] [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: 15489334] [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: 10944470] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 35-483 (ISOFORM 1), FUNCTION, VARIANT ARG-475.
[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-104, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

UniGene

Hs.446685
Hs.710625

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

IntAct

P49753. 1 interaction.

STRING

P49753.

Proteomic databases

PRIDE

P49753.

Genome annotation databases

Ensembl

ENST00000238651; ENSP00000238651; ENSG00000119673; Homo sapiens. [Genome view]

GeneID

10965.

KEGG

hsa:10965.

UCSC

uc001xon.2. human.

Organism-specific databases

CTD

10965.

GeneCards

GC14P073106.

H-InvDB

HIX0037756.

HGNC

HGNC:18431. ACOT2.

MIM

609972. gene.

PharmGKB

PA142672653.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P49753.

HOVERGEN

P49753.

Enzyme and pathway databases

BRENDA

3.1.2.2. 247.

Gene expression databases

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 Resources

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 13, 2007
Last modified:	October 13, 2009
This is version 94 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.