P24557 (THAS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thromboxane-A synthase
Short name=TXA synthase
Short name=TXS
EC=5.3.99.5

Alternative name(s):
Cytochrome P450 5A1

Gene names

Name:	TBXAS1
Synonyms:	CYP5, CYP5A1

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

General annotation (Comments)

Catalytic activity	(5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-9-alpha,11-alpha-epoxy-15-hydroxythromboxa-5,13-dienoate.
Cofactor	Heme group.
Subunit structure	Monomer.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.10.
Tissue specificity	Platelets, lung, kidney, spleen, macrophages and lung fibroblasts.
Involvement in disease	Ghosal hematodiaphyseal dysplasia (GHDD) [MIM:231095]: Rare autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Aregenerative anemia is characterized by bone marrow failure, so that functional marrow cells are regenerated slowly or not at all. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.17 Thromboxane synthetase deficiency (TBXAS1 deficiency) [MIM:274180]: Characterized by hemorrhagic diathesis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11
Sequence similarities	Belongs to the cytochrome P450 family.
Caution	It is uncertain whether Met-1 is the initiator. An alternative upstream Met is found in primates, but not in other mammals.
Sequence caution	The sequence AAC01761.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAC01761.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99269.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99270.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99271.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99272.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99273.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99274.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99275.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99276.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99277.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99278.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF99279.1 differs from that shown. Reason: Erroneous initiation. The sequence AAH41157.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Prostaglandin biosynthesis Prostaglandin metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Molecular function	Isomerase Monooxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	icosanoid metabolic process Traceable author statement. Source: Reactome prostaglandin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro monooxygenase activity Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Inferred from electronic annotation. Source: InterPro thromboxane-A synthase 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 – 533	533	Thromboxane-A synthase		PRO_0000052256
Regions
	Topological domain	1 – 10	10	Cytoplasmic Potential
	Transmembrane	11 – 31	21	Helical; Potential
	Topological domain	32 – 75	44	Lumenal Potential
	Transmembrane	76 – 96	21	Helical; Potential
	Topological domain	97 – 223	127	Cytoplasmic Potential
	Transmembrane	224 – 244	21	Helical; Potential
	Topological domain	245 – 335	91	Lumenal Potential
	Transmembrane	336 – 356	21	Helical; Potential
	Topological domain	357 – 533	177	Cytoplasmic Potential
Sites
	Metal binding	479	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	60	1	R → H in allele CYP5A1*2. Ref.5 Ref.12 Corresponds to variant rs6138 [ dbSNP | Ensembl ].		VAR_014157
	Natural variant	70	1	L → P. Corresponds to variant rs13306050 [ dbSNP | Ensembl ].		VAR_058465
	Natural variant	70	1	L → V. Corresponds to variant rs4529 [ dbSNP | Ensembl ].		VAR_058466
	Natural variant	82	1	L → P in GHDD. Ref.17		VAR_044386
	Natural variant	85	1	R → W in a breast cancer sample; somatic mutation. Ref.16		VAR_036294
	Natural variant	124	1	V → I. Ref.15		VAR_018378
	Natural variant	160	1	D → E in allele CYP5A1*3. Ref.5 Ref.14 Corresponds to variant rs5768 [ dbSNP | Ensembl ].		VAR_010919
	Natural variant	162	1	L → I. Ref.12 Corresponds to variant rs6137 [ dbSNP | Ensembl ].		VAR_014158
	Natural variant	245	1	N → S in allele CYP5A1*4. Ref.5		VAR_010920
	Natural variant	257	1	K → E. Corresponds to variant rs5769 [ dbSNP | Ensembl ].		VAR_014647
	Natural variant	260	1	R → G. Corresponds to variant rs5770 [ dbSNP | Ensembl ].		VAR_014648
	Natural variant	316	1	Q → K. Corresponds to variant rs5771 [ dbSNP | Ensembl ].		VAR_014649
	Natural variant	331	1	I → T. Ref.12 Corresponds to variant rs6140 [ dbSNP | Ensembl ].		VAR_014159
	Natural variant	356	1	L → V in allele CYP5A1*5. Ref.5 Ref.12 Ref.14 Corresponds to variant rs4529 [ dbSNP | Ensembl ].		VAR_010921
	Natural variant	357	1	L → V. Corresponds to variant rs4529 [ dbSNP | Ensembl ].		VAR_044387
	Natural variant	387	1	E → K. Corresponds to variant rs3735354 [ dbSNP | Ensembl ].		VAR_055565
	Natural variant	388	1	E → K. Ref.15 Corresponds to variant rs3735354 [ dbSNP | Ensembl ].		VAR_018379
	Natural variant	389	1	G → V. Corresponds to variant rs5760 [ dbSNP | Ensembl ].		VAR_016158
	Natural variant	412	1	R → Q in GHDD. Ref.17		VAR_044388
	Natural variant	416	1	Q → E in allele CYP5A1*6. Ref.5 Ref.12 Ref.14 Corresponds to variant rs4528 [ dbSNP | Ensembl ].		VAR_010922
	Natural variant	424	1	R → C. Ref.14 Corresponds to variant rs5762 [ dbSNP | Ensembl ].		VAR_014160
	Natural variant	429	1	A → T. Ref.12 Ref.14 Corresponds to variant rs4526 [ dbSNP | Ensembl ].		VAR_014161
	Natural variant	449	1	E → K in allele CYP5A1*7. Ref.5 Ref.15		VAR_010923
	Natural variant	450	1	T → N in allele CYP5A1*8. Ref.5 Corresponds to variant rs5763 [ dbSNP | Ensembl ].		VAR_010924
	Natural variant	465	1	R → Q in allele CYP5A1*9. Ref.5		VAR_010925
	Natural variant	481	1	G → W in GHDD. Ref.17		VAR_044389
	Natural variant	487	1	L → P in GHDD. Ref.17		VAR_044390
	Natural variant	501	1	R → Q. Ref.15		VAR_018380
	Natural variant	511	1	P → L. Corresponds to variant rs13306050 [ dbSNP | Ensembl ].		VAR_055566
	Natural variant	512	1	L → P. Corresponds to variant rs13306050 [ dbSNP | Ensembl ].		VAR_044391
Experimental info
	Sequence conflict	102	1	E → Q in AAA36742. Ref.7
	Sequence conflict	148	1	L → V in AAC01761. Ref.4
	Sequence conflict	194	1	A → P in AAA60618. Ref.2
	Sequence conflict	194	1	A → P in AAC01761. Ref.4
	Sequence conflict	194	1	A → P in AAF99269. Ref.5
	Sequence conflict	194	1	A → P in AAF99270. Ref.5
	Sequence conflict	194	1	A → P in AAF99271. Ref.5
	Sequence conflict	194	1	A → P in AAF99272. Ref.5
	Sequence conflict	194	1	A → P in AAF99273. Ref.5
	Sequence conflict	194	1	A → P in AAF99274. Ref.5
	Sequence conflict	194	1	A → P in AAF99275. Ref.5
	Sequence conflict	194	1	A → P in AAF99276. Ref.5
	Sequence conflict	194	1	A → P in AAF99277. Ref.5
	Sequence conflict	194	1	A → P in AAF99278. Ref.5
	Sequence conflict	194	1	A → P in AAF99279. Ref.5
	Sequence conflict	194	1	A → P in AAA36742. Ref.7
	Sequence conflict	385	1	S → G no nucleotide entry Ref.1
	Sequence conflict	483	1	R → H in BAA07011. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P24557 [UniParc]. Last modified July 28, 2009. Version 3. Checksum: E95E7B7EA77E6DDC	FASTA	533	60,518
	10 20 30 40 50 60 MEALGFLKLE VNGPMVTVAL SVALLALLKW YSTSAFSRLE KLGLRHPKPS PFIGNLTFFR 70 80 90 100 110 120 QGFWESQMEL RKLYGPLCGY YLGRRMFIVI SEPDMIKQVL VENFSNFTNR MASGLEFKSV 130 140 150 160 170 180 ADSVLFLRDK RWEEVRGALM SAFSPEKLNE MVPLISQACD LLLAHLKRYA ESGDAFDIQR 190 200 210 220 230 240 CYCNYTTDVV ASVAFGTPVD SWQAPEDPFV KHCKRFFEFC IPRPILVLLL SFPSIMVPLA 250 260 270 280 290 300 RILPNKNRDE LNGFFNKLIR NVIALRDQQA AEERRRDFLQ MVLDARHSAS PMGVQDFDIV 310 320 330 340 350 360 RDVFSSTGCK PNPSRQHQPS PMARPLTVDE IVGQAFIFLI AGYEIITNTL SFATYLLATN 370 380 390 400 410 420 PDCQEKLLRE VDVFKEKHMA PEFCSLEEGL PYLDMVIAET LRMYPPAFRF TREAAQDCEV 430 440 450 460 470 480 LGQRIPAGAV LEMAVGALHH DPEHWPSPET FNPERFTAEA RQQHRPFTYL PFGAGPRSCL 490 500 510 520 530 GVRLGLLEVK LTLLHVLHKF RFQACPETQV PLQLESKSAL GPKNGVYIKI VSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human platelet thromboxane A synthase." Yokoyama C., Miyata A., Ihara H., Ullrich V., Tanabe T. Biochem. Biophys. Res. Commun. 178:1479-1484(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Platelet.
[2]	"Primary structure of human thromboxane synthase determined from the cDNA sequence." Ohashi K., Ruan K.H., Kulmacz R.J., Wu K.K., Wang L.-H. J. Biol. Chem. 267:789-793(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Characterization of the human gene (TBXAS1) encoding thromboxane synthase." Miyata A., Yokoyama C., Ihara H., Bandoh S., Takeda O., Takahashi E., Tanabe T. Eur. J. Biochem. 224:273-279(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Peripheral blood.
[4]	"Human thromboxane A2 synthase." Shen R.-F. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Identification of genetic variants in the human thromboxane synthase gene (CYP5A1)." Chevalier D., Lo-Guidice J.-M., Sergent E., Allorge D., Debuysere H., Ferrari N., Libersa C., Lhermitte M., Broly F. Mutat. Res. 432:61-67(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-60; GLU-160; SER-245; VAL-356; GLU-416; LYS-449; ASN-450 AND GLN-465.
[6]	"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]. Tissue: Brain.
[7]	"Isolation of partial complementary DNA encoding human thromboxane synthase." Wang L.-H., Oshashi K., Wu K.K. Biochem. Biophys. Res. Commun. 177:286-291(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-244. Tissue: Lung.
[8]	"Immunoaffinity purification of human thromboxane synthase." Nuesing R., Schneider-Voss S., Ullrich V. Arch. Biochem. Biophys. 280:325-330(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 1-26; 96-110 AND 237-280.
[9]	Nuesing R. Thesis (1990), University of Konstanz, Germany Cited for: PARTIAL PROTEIN SEQUENCE.
[10]	"Amino-terminal topology of thromboxane synthase in the endoplasmic reticulum." Ruan K.H., Wang L.-H., Wu K.K., Kulmacz R.J. J. Biol. Chem. 268:19483-19490(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.
[11]	"Severe bleeding associated with defective thromboxane synthetase." Mestel F., Oetliker O., Beck E., Felix R., Imbach P., Wagner H.P. Lancet 1:157-157(1980) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE.
[12]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-60; ILE-162; THR-331; VAL-356; GLU-416 AND THR-429.
[13]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[14]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLU-160; VAL-356; GLU-416; CYS-424 AND THR-429.
[15]	"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population." Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y. J. Hum. Genet. 48:249-270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-124; LYS-388; LYS-449 AND GLN-501.
[16]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] TRP-85.
[17]	"Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome)." Genevieve D., Proulle V., Isidor B., Bellais S., Serre V., Djouadi F., Picard C., Vignon-Savoye C., Bader-Meunier B., Blanche S., de Vernejoul M.-C., Legeai-Mallet L., Fischer A.-M., Le Merrer M., Dreyfus M., Gaussem P., Munnich A., Cormier-Daire V. Nat. Genet. 40:284-286(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GHDD PRO-82; GLN-412; TRP-481 AND PRO-487.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP5A1 alleles

Cross-references

Sequence databases
EMBL GenBank DDBJ	M80647 mRNA. Translation: AAA60618.1. D34625 Genomic DNA. Translation: BAA07011.1. L36085 , L36075, L36076, L36077, L36078, L36079, L36080, L36081, L36082, L36083, L36084 Genomic DNA. Translation: AAC01761.1. Different initiation. AF233615 Genomic DNA. Translation: AAF99269.1. Different initiation. AF233616 Genomic DNA. Translation: AAF99270.1. Different initiation. AF233617 Genomic DNA. Translation: AAF99271.1. Different initiation. AF233618 Genomic DNA. Translation: AAF99272.1. Different initiation. AF233619 Genomic DNA. Translation: AAF99273.1. Different initiation. AF233620 Genomic DNA. Translation: AAF99274.1. Different initiation. AF233621 Genomic DNA. Translation: AAF99275.1. Different initiation. AF233622 Genomic DNA. Translation: AAF99276.1. Different initiation. AF233623 Genomic DNA. Translation: AAF99277.1. Different initiation. AF233624 Genomic DNA. Translation: AAF99278.1. Different initiation. AF233625 Genomic DNA. Translation: AAF99279.1. Different initiation. BC041157 mRNA. Translation: AAH41157.1. Different initiation. M74055 mRNA. Translation: AAA36742.1.
IPI	IPI00788599.
PIR	A41766. S48161.
RefSeq	NP_001052.2. NM_001061.4. NP_001124438.1. NM_001130966.2.
UniGene	Hs.520757.
3D structure databases
ProteinModelPortal	P24557.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4823512.
PTM databases
PhosphoSite	P24557.
Polymorphism databases
DMDM	254763392.
Proteomic databases
PaxDb	P24557.
PRIDE	P24557.
Protocols and materials databases
DNASU	6916.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000263552; ENSP00000263552; ENSG00000059377. ENST00000336425; ENSP00000338087; ENSG00000059377. ENST00000436047; ENSP00000392361; ENSG00000059377. ENST00000448866; ENSP00000402536; ENSG00000059377.
GeneID	6916.
KEGG	hsa:6916.
UCSC	uc010lne.3. human.
Organism-specific databases
CTD	6916.
GeneCards	GC07P139476.
HGNC	HGNC:11609. TBXAS1.
MIM	231095. phenotype. 274180. gene+phenotype.
neXtProt	NX_P24557.
Orphanet	220443. Bleeding diathesis due to thromboxane synthesis deficiency. 1802. Ghosal hematodiaphyseal dysplasia.
PharmGKB	PA349.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOVERGEN	HBG108567.
InParanoid	P24557.
KO	K01832.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P24557.
Bgee	P24557.
Genevestigator	P24557.
GermOnline	ENSG00000059377. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 2 hits.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Pfam	PF00067. p450. 2 hits. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P24557.
ChEMBL	CHEMBL1835.
GenomeRNAi	6916.
NextBio	27051.
SOURCE	Search...

Entry information

Entry name

THAS_HUMAN

Accession

Primary (citable) accession number: P24557
Secondary accession number(s): O14987 , Q16844, Q8IUN1, Q9GZW4, Q9HD77, Q9HD78, Q9HD79, Q9HD80, Q9HD81, Q9HD82, Q9HD83, Q9HD84

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	July 28, 2009
Last modified:	May 1, 2013
This is version 150 of the entry and version 3 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.