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Protein

Acyl-coenzyme A thioesterase 8

Gene

ACOT8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acyl-coenzyme A (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 (PubMed:9299485, PubMed:9153233, PubMed:15194431). Competes with bile acid CoA:amino acid N-acyltransferase (BAAT) for bile acid-CoA substrate (such as chenodeoxycholoyl-CoA). Shows a preference for medium-length fatty acyl-CoAs (C2 to C20) (PubMed:9299485, PubMed:9153233). Inactive towards substrates with more than C20 aliphatic chains (PubMed:9153233). Involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431).3 Publications
(Microbial infection) May mediate Nef-induced down-regulation of CD4 cell-surface expression (PubMed:9153233).1 Publication

Catalytic activityi

Choloyl-CoA + H2O = cholate + CoA.2 Publications

Enzyme regulationi

Inhibited by CoASH (IC50=10-15 µM). Also inhibited by cysteine-reactive agents.By similarity

Kineticsi

  1. KM=10.1 µM for decanoyl-CoA1 Publication
  1. Vmax=7.1 µmol/min/mg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei232Charge relay systemBy similarity1
Active sitei254Charge relay systemBy similarity1
Active sitei304Charge relay systemBy similarity1

GO - Molecular functioni

  • acetyl-CoA hydrolase activity Source: Reactome
  • acyl-CoA hydrolase activity Source: UniProtKB
  • carboxylic ester hydrolase activity Source: UniProtKB-KW
  • choloyl-CoA hydrolase activity Source: UniProtKB-EC
  • CoA hydrolase activity Source: Reactome
  • medium-chain acyl-CoA hydrolase activity Source: UniProtKB
  • palmitoyl-CoA hydrolase activity Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • acyl-CoA metabolic process Source: UniProtKB
  • alpha-linolenic acid metabolic process Source: Reactome
  • bile acid biosynthetic process Source: Reactome
  • dicarboxylic acid catabolic process Source: UniProtKB
  • fatty acid beta-oxidation using acyl-CoA oxidase Source: Reactome
  • fatty acid catabolic process Source: GO_Central
  • negative regulation of CD4 biosynthetic process Source: UniProtKB
  • peroxisome fission Source: UniProtKB
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionHydrolase, Serine esterase
Biological processHost-virus interaction, Peroxisome biogenesis

Enzyme and pathway databases

BRENDAi3.1.2.2. 2681.
3.1.2.20. 2681.
ReactomeiR-HSA-193368. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
R-HSA-2046106. alpha-linolenic acid (ALA) metabolism.
R-HSA-389887. Beta-oxidation of pristanoyl-CoA.
R-HSA-390247. Beta-oxidation of very long chain fatty acids.

Chemistry databases

SwissLipidsiSLP:000000591.

Names & Taxonomyi

Protein namesi
Recommended name:
Acyl-coenzyme A thioesterase 8 (EC:3.1.2.272 Publications)
Short name:
Acyl-CoA thioesterase 8
Alternative name(s):
Choloyl-coenzyme A thioesterase
HIV-Nef-associated acyl-CoA thioesterase
PTE-2
Peroxisomal acyl-coenzyme A thioester hydrolase 1
Short name:
PTE-1
Peroxisomal long-chain acyl-CoA thioesterase 1
Thioesterase II
Short name:
hACTE-III
Short name:
hACTEIII
Short name:
hTE
Gene namesi
Name:ACOT8
Synonyms:ACTEIII, PTE1, PTE2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000101473.16.
HGNCiHGNC:15919. ACOT8.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Peroxisome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78H → A: Reduces Acyl-CoA thioesterase activity and peroxisome proliferation. 1 Publication1

Organism-specific databases

DisGeNETi10005.
OpenTargetsiENSG00000101473.
PharmGKBiPA33941.

Polymorphism and mutation databases

BioMutaiACOT8.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002021521 – 319Acyl-coenzyme A thioesterase 8Add BLAST319

Proteomic databases

EPDiO14734.
MaxQBiO14734.
PaxDbiO14734.
PeptideAtlasiO14734.
PRIDEiO14734.

PTM databases

iPTMnetiO14734.
PhosphoSitePlusiO14734.
SwissPalmiO14734.

Expressioni

Tissue specificityi

Detected in a T-cell line (at protein level). Ubiquitous (PubMed:9153233, PubMed:9299485).2 Publications

Inductioni

Regulated by peroxisome proliferator (such as Clofibrate), via the peroxisome proliferator-activated receptors (PPARs).By similarity

Gene expression databases

BgeeiENSG00000101473.
CleanExiHS_ACOT8.
ExpressionAtlasiO14734. baseline and differential.
GenevisibleiO14734. HS.

Organism-specific databases

HPAiCAB010261.

Interactioni

Subunit structurei

Homodimer (By similarity).By similarity
(Microbial infection) Interacts with human immunodeficiency virus (HIV-1) Nef (via middle region); this interaction enhances ACOT8 Acyl-CoA thioesterase activity and occurs in a Nef myristoylation-independent manner (PubMed:9299485). According to a second report, the interaction with HIV-1 Nef occurs in a Nef myristoylation-independent manner but does not enhance ACOT8 Acyl-CoA thioesterase activity (PubMed:9153233).2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115323. 17 interactors.
DIPiDIP-38179N.
IntActiO14734. 9 interactors.
MINTiMINT-2998229.
STRINGi9606.ENSP00000217455.

Structurei

3D structure databases

ProteinModelPortaliO14734.
SMRiO14734.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi317 – 319Microbody targeting signalSequence analysis3

Sequence similaritiesi

Belongs to the C/M/P thioester hydrolase family.Curated

Phylogenomic databases

eggNOGiKOG3016. Eukaryota.
COG1946. LUCA.
GeneTreeiENSGT00390000004207.
HOGENOMiHOG000246495.
HOVERGENiHBG019167.
InParanoidiO14734.
KOiK11992.
OMAiRHYWVPT.
OrthoDBiEOG091G0BLB.
PhylomeDBiO14734.
TreeFamiTF315124.

Family and domain databases

InterProiView protein in InterPro
IPR003703. Acyl_CoA_thio.
IPR029069. HotDog_dom.
PANTHERiPTHR11066. PTHR11066. 1 hit.
SUPFAMiSSF54637. SSF54637. 2 hits.
TIGRFAMsiTIGR00189. tesB. 1 hit.

Sequencei

Sequence statusi: Complete.

O14734-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSPQAPEDG QGCGDRGDPP GDLRSVLVTT VLNLEPLDED LFRGRHYWVP
60 70 80 90 100
AKRLFGGQIV GQALVAAAKS VSEDVHVHSL HCYFVRAGDP KLPVLYQVER
110 120 130 140 150
TRTGSSFSVR SVKAVQHGKP IFICQASFQQ AQPSPMQHQF SMPTVPPPEE
160 170 180 190 200
LLDCETLIDQ YLRDPNLQKR YPLALNRIAA QEVPIEIKPV NPSPLSQLQR
210 220 230 240 250
MEPKQMFWVR ARGYIGEGDM KMHCCVAAYI SDYAFLGTAL LPHQWQHKVH
260 270 280 290 300
FMVSLDHSMW FHAPFRADHW MLYECESPWA GGSRGLVHGR LWRQDGVLAV
310
TCAQEGVIRV KPQVSESKL
Length:319
Mass (Da):35,914
Last modified:January 1, 1998 - v1
Checksum:i8345C6E5EABF3326
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti291 – 293LWR → VWS in CAA60024 (PubMed:9153233).Curated3
Sequence conflicti319L → R in CAA60024 (PubMed:9153233).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF014404 mRNA. Translation: AAB71665.1.
X86032 mRNA. Translation: CAA60024.1.
AF124264 mRNA. Translation: AAD27616.1.
AL008726 Genomic DNA. No translation available.
BC117155 mRNA. Translation: AAI17156.1.
BC117157 mRNA. Translation: AAI17158.1.
CCDSiCCDS13378.1.
PIRiJC5644.
RefSeqiNP_005460.2. NM_005469.3.
UniGeneiHs.444776.

Genome annotation databases

EnsembliENST00000217455; ENSP00000217455; ENSG00000101473.
GeneIDi10005.
KEGGihsa:10005.
UCSCiuc002xqa.3. human.

Similar proteinsi

Entry informationi

Entry nameiACOT8_HUMAN
AccessioniPrimary (citable) accession number: O14734
Secondary accession number(s): O15261, Q17RX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 1, 1998
Last modified: September 27, 2017
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families