Reviewed, UniProtKB/Swiss-Prot Q14032 (BAAT_HUMAN)

Names and origin

Protein names

Recommended name:
    Bile acid-CoA:amino acid N-acyltransferase
      Short name=BAT
      Short name=BACAT
    EC=2.3.1.65
Alternative name(s):
    Glycine N-choloyltransferase
    Long-chain fatty-acyl-CoA hydrolase
    EC=3.1.2.2

Gene names

Name:

BAAT

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	418 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in bile acid metabolism. In liver hepatocytes catalyzes the second step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi. The major components of bile are cholic acid and chenodeoxycholic acid. In a first step the bile acids are converted to an acyl-CoA thioester, either in peroxisomes (primary bile acids deriving from the cholesterol pathway), or cytoplasmic at the endoplasmic reticulum (secondary bile acids). May catalyze the conjugation of primary or secondary bile acids, or both. The conjugation increases the detergent properties of bile acids in the intestine, which facilitates lipid and fat-soluble vitamin absorption. In turn, bile acids are deconjugated by bacteria in the intestine and are recycled back to the liver for reconjugation (secondary bile acids). May also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids. In vitro, catalyzes the hydrolysis of long- and very long-chain saturated acyl-CoAs to the free fatty acid and coenzyme A (CoASH), and conjugates glycine to these acyl-CoAs.
Catalytic activity	Choloyl-CoA + glycine = CoA + glycocholate. Ref.1 Ref.6 Ref.8 Palmitoyl-CoA + H2O = CoA + palmitate. Ref.1 Ref.6 Ref.8
Subunit structure	Monomer. Ref.6
Subcellular location	Cytoplasm Ref.8.
Tissue specificity	Expressed in liver, gallbladder mucosa and pancreas. Ref.6 Ref.8
Involvement in disease	Defects in BAAT are involved in familial hypercholanemia (FHCA) [MIM:607748]. FHCA is a disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption. Ref.9
Miscellaneous	In humans more than 95% of the biliary bile acids are N-acyl amidates with glycine and taurine. In other mammalian species large differences are observed in the relative amounts of taurine- and glycine-conjugated bile acids formed in bile.
Sequence similarities	Belongs to the C/M/P thioester hydrolase family.
Biophysicochemical properties	Kinetic parameters: KM=1.1 mM for taurine toward choloyl-CoA KM=2.2 mM for 2-fluoro-beta-alanine toward choloyl-CoA KM=5.8 mM for glycine toward choloyl-CoA KM=19.3 µM for arachidoyl-CoA Vmax=0.33 µmol/min/mg enzyme with taurine as substrate for acyltransferase activity Vmax=0.19 µmol/min/mg enzyme with 2-fluoro-beta-alanine as substrate for acyltransferase activity Vmax=0.77 µmol/min/mg enzyme with glycine as substrate for acyltransferase activity Vmax=223 nmol/min/mg enzyme with arachidoyl-CoA as substrate for acyl-CoA thioesterase activity

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Acyltransferase Hydrolase Serine esterase Transferase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	acyl-CoA metabolic process Inferred from electronic annotation. Source: InterPro bile acid metabolic process Ref.1 Traceable author statement. Source: ProtInc digestion Ref.6 Traceable author statement. Source: ProtInc glycine metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Ref.1 Traceable author statement. Source: ProtInc peroxisomal matrix Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	N-acyltransferase activity Ref.7 Inferred from direct assay. Source: MGI carboxylesterase activity Inferred from electronic annotation. Source: UniProtKB-KW glycine N-choloyltransferase activity Inferred from electronic annotation. Source: EC palmitoyl-CoA hydrolase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 418	418	Bile acid-CoA:amino acid N-acyltransferase		PRO_0000202159
Sites
	Active site	235	1	Charge relay system Probable
	Active site	328	1	Charge relay system Probable
	Active site	362	1	Charge relay system Probable
Natural variations
	Natural variant	20	1	R → Q: dbSNP rs1572983. Ref.2 Ref.4 Ref.5		VAR_052303
	Natural variant	76	1	M → V in FHCA. dbSNP rs28937579. Ref.9		VAR_023737
Experimental info
	Mutagenesis	235	1	C → A: Abolishes activity. Ref.8 Ref.7
	Mutagenesis	235	1	C → S: Lowers N-acyltransferase activity; enhanced thioesterase activity presumably dependent on the formation of a bile acid-enzyme covalent intermediate via a thioester bond. Ref.8 Ref.7
	Mutagenesis	328	1	D → A: Abolishes activity. Ref.8 Ref.7
	Mutagenesis	362	1	H → A: Abolishes activity. Ref.8 Ref.7
	Mutagenesis	372	1	C → A: Retains activity.
	Mutagenesis	417	1	Q → K: Translocation to peroxisomes. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q14032-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4B290BAEE97F23B3	FASTA	418	46,299
	10 20 30 40 50 60 MIQLTATPVS ALVDEPVHIR ATGLIPFQMV SFQASLEDEN GDMFYSQAHY RANEFGEVDL 70 80 90 100 110 120 NHASSLGGDY MGVHPMGLFW SLKPEKLLTR LLKRDVMNRP FQVQVKLYDL ELIVNNKVAS 130 140 150 160 170 180 APKASLTLER WYVAPGVTRI KVREGRLRGA LFLPPGEGLF PGVIDLFGGL GGLLEFRASL 190 200 210 220 230 240 LASRGFASLA LAYHNYEDLP RKPEVTDLEY FEEAANFLLR HPKVFGSGVG VVSVCQGVQI 250 260 270 280 290 300 GLSMAIYLKQ VTATVLINGT NFPFGIPQVY HGQIHQPLPH SAQLISTNAL GLLELYRTFE 310 320 330 340 350 360 TTQVGASQYL FPIEEAQGQF LFIVGEGDKT INSKAHAEQA IGQLKRHGKN NWTLLSYPGA 370 380 390 400 410 GHLIEPPYSP LCCASTTHDL RLHWGGEVIP HAAAQEHAWK EIQRFLRKHL IPDVTSQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase." Falany C.N., Johnson M.R., Barnes S., Diasio R.B. J. Biol. Chem. 269:19375-19379(1994) [PubMed: 8034703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-17, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES. Tissue: Liver.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-20.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT GLN-20.
[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], VARIANT GLN-20. Tissue: Liver.
[6]	"Purification and characterization of bile acid-CoA:amino acid N-acyltransferase from human liver." Johnson M.R., Barnes S., Kwakye J.B., Diasio R.B. J. Biol. Chem. 266:10227-10233(1991) [PubMed: 2037576] [Abstract] Cited for: TISSUE SPECIFICITY, CATALYTIC ACTIVITY, SUBUNIT. Tissue: Liver.
[7]	"Conserved residues in the putative catalytic triad of human bile acid Coenzyme A:amino acid N-acyltransferase." Sfakianos M.K., Wilson L., Sakalian M., Falany C.N., Barnes S. J. Biol. Chem. 277:47270-47275(2002) [PubMed: 12239217] [Abstract] Cited for: MUTAGENESIS OF CYS-235; ASP-328 AND HIS-362.
[8]	"The human bile acid-CoA:amino acid N-acyltransferase functions in the conjugation of fatty acids to glycine." O'Byrne J., Hunt M.C., Rai D.K., Saeki M., Alexson S.E. J. Biol. Chem. 278:34237-34244(2003) [PubMed: 12810727] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-235; ASP-328; HIS-362 AND GLN-417.
[9]	"Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT." Carlton V.E.H., Harris B.Z., Puffenberger E.G., Batta A.K., Knisely A.S., Robinson D.L., Strauss K.A., Shneider B.L., Lim W.A., Salen G., Morton D.H., Bull L.N. Nat. Genet. 34:91-96(2003) [PubMed: 12704386] [Abstract] Cited for: VARIANT FHCA VAL-76.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	L34081 mRNA. Translation: AAC37550.1. CR541918 mRNA. Translation: CAG46716.1. AL359893 Genomic DNA. Translation: CAH72995.1. CH471105 Genomic DNA. Translation: EAW58943.1. BC009567 mRNA. Translation: AAH09567.1. BC107424 mRNA. Translation: AAI07425.1.
IPI	IPI00017819.
PIR	A53965.
RefSeq	NP_001121082.1. NP_001692.1.
UniGene	Hs.284712 Hs.715720
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q14032.
Proteomic databases
PRIDE	Q14032.
Genome annotation databases
Ensembl	ENST00000259407; ENSP00000259407; ENSG00000136881; Homo sapiens. [Genome view] ENST00000395051; ENSP00000378491; ENSG00000136881; Homo sapiens. [Genome view]
GeneID	570.
KEGG	hsa:570.
UCSC	uc004bbd.2. human.
Organism-specific databases
CTD	570.
GeneCards	GC09M103162.
H-InvDB	HIX0008242.
HGNC	HGNC:932. BAAT.
HPA	HPA021251.
MIM	602938. gene. 607748. phenotype.
PharmGKB	PA25231.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07453.
HOGENOM	HBG713807.
HOVERGEN	Q14032.
InParanoid	Q14032.
OMA	NGPNFVF.
OrthoDB	EOG9F4VX5.
PhylomeDB	Q14032.
Enzyme and pathway databases
BRENDA	2.3.1.65. 247. 3.1.2.2. 247.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q14032.
Bgee	Q14032.
CleanEx	HS_BAAT.
Genevestigator	Q14032.
GermOnline	ENSG00000136881. Homo sapiens.
Family and domain databases
InterPro	IPR016662. Acyl-CoA_thioEstase_long-chain. IPR006862. Thio_Ohase/aa_AcTrfase. [Graphical view]
Pfam	PF04775. Bile_Hydr_Trans. 1 hit. [Graphical view]
PIRSF	PIRSF016521. Acyl-CoA_hydro. 1 hit.
ProtoNet	Search...
Other Resources
DrugBank	DB00145. Glycine.
NextBio	2319.
SOURCE	Search...

Entry information

Entry name

BAAT_HUMAN

Accession

Primary (citable) accession number: Q14032
Secondary accession number(s): Q3B7W9, Q96L31

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	November 1, 1996
Last modified:	February 9, 2010
This is version 75 of the entry and version 1 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.