PTGDS_HUMAN
ID PTGDS_HUMAN Reviewed; 190 AA.
AC P41222; B2R727; Q5SQ10; Q7M4P3; Q9UC22; Q9UCC9; Q9UCD9;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Prostaglandin-H2 D-isomerase;
DE EC=5.3.99.2 {ECO:0000269|PubMed:20667974};
DE AltName: Full=Beta-trace protein;
DE AltName: Full=Cerebrin-28;
DE AltName: Full=Glutathione-independent PGD synthase;
DE AltName: Full=Lipocalin-type prostaglandin-D synthase;
DE Short=L-PGDS {ECO:0000303|PubMed:20667974};
DE AltName: Full=Prostaglandin-D2 synthase;
DE Short=PGD2 synthase;
DE Short=PGDS;
DE Short=PGDS2;
DE Flags: Precursor;
GN Name=PTGDS; Synonyms=PDS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=1902577; DOI=10.1073/pnas.88.9.4020;
RA Nagata A., Suzuki Y., Igarashi M., Eguchi N., Toh H., Urade Y.,
RA Hayaishi O.;
RT "Human brain prostaglandin D synthase has been evolutionarily
RT differentiated from lipophilic-ligand carrier proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4020-4024(1991).
RN [2]
RP SEQUENCE REVISION TO 12; 16; 19; 36; 56; 73; 77; 99; 100; 127 AND 176.
RA Nagata A., Suzuki Y., Igarashi M., Eguchi N., Toh H., Urade Y.,
RA Hayaishi O.;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=1385416; DOI=10.1016/s0021-9258(18)50077-6;
RA White D.M., Mikol D.D., Espinosa R., Weimer B., le Beau M.M.,
RA Stefansson K.;
RT "Structure and chromosomal localization of the human gene for a brain form
RT of prostaglandin D2 synthase.";
RL J. Biol. Chem. 267:23202-23208(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RA Lu J.C., Li X.Y., Huang Y.F., Zhang X.R.;
RT "cDNA cloning and sequence analysis of prostaglandin D synthase in human
RT testis.";
RL (In) Robaire B., Chemes H., Morales C.R. (eds.);
RL Andrology in the 21st century, pp.189-193, Medimond Publishing Company
RL Inc., Englewood (2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP PROTEIN SEQUENCE OF 23-190, AND GLYCOSYLATION AT ASN-51 AND ASN-78.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=8336134; DOI=10.1111/j.1471-4159.1993.tb02145.x;
RA Hoffmann A., Conradt H.S., Gross G., Nimtz M., Lottspeich F., Wurster U.;
RT "Purification and chemical characterization of beta-trace protein from
RT human cerebrospinal fluid: its identification as prostaglandin D
RT synthase.";
RL J. Neurochem. 61:451-456(1993).
RN [13]
RP PROTEIN SEQUENCE OF 23-37; 67-77; 117-126 AND 169-178, TISSUE SPECIFICITY,
RP AND GLYCOSYLATION.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=7692978;
RA Harrington M.G., Aebersold R., Martin B.M., Merril C.R., Hood L.;
RT "Identification of a brain-specific human cerebrospinal fluid glycoprotein,
RT beta-trace protein.";
RL Appl. Theor. Electrophor. 3:229-234(1993).
RN [14]
RP PROTEIN SEQUENCE OF 23-50.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=7689714; DOI=10.1016/0304-3940(93)90179-o;
RA Zahn M., Maeder M., Schmidt B., Bollensen E., Felgenhauer K.;
RT "Purification and N-terminal sequence of beta-trace, a protein abundant in
RT human cerebrospinal fluid.";
RL Neurosci. Lett. 154:93-95(1993).
RN [15]
RP PROTEIN SEQUENCE OF 23-41.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=1726844; DOI=10.1016/0006-8993(91)91666-o;
RA Kuruvilla A.P., Hochwald G.M., Ghiso J., Castano E.M., Pizzolato M.,
RA Frangione B.;
RT "Isolation and amino terminal sequence of beta-trace, a novel protein from
RT human cerebrospinal fluid.";
RL Brain Res. 565:337-340(1991).
RN [16]
RP PROTEIN SEQUENCE OF 23-38, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Seminal plasma;
RX PubMed=9475419; DOI=10.1095/biolreprod58.2.600;
RA Tokugawa Y., Kunishige I., Kubota Y., Shimoya K., Nobunaga T., Kimura T.,
RA Saji F., Murata Y., Eguchi N., Oda H., Urade Y., Hayaishi O.;
RT "Lipocalin-type prostaglandin D synthase in human male reproductive organs
RT and seminal plasma.";
RL Biol. Reprod. 58:600-607(1998).
RN [17]
RP PROTEIN SEQUENCE OF 23-35, TISSUE SPECIFICITY, AND USE AS A MARKER FOR
RP BRAIN TUMOR.
RX PubMed=9844724; DOI=10.1080/15216549800204172;
RA Saso L., Leone M.G., Sorrentino C., Giacomelli S., Silvestrini B.,
RA Grima J., Li J.C.H., Samy E., Mruk D., Cheng C.Y.;
RT "Quantification of prostaglandin D synthetase in cerebrospinal fluid: a
RT potential marker for brain tumor.";
RL Biochem. Mol. Biol. Int. 46:643-656(1998).
RN [18]
RP PROTEIN SEQUENCE OF 23-34.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=8336140; DOI=10.1111/j.1471-4159.1993.tb02156.x;
RA Leone M.G., Saso L., Del Vecchio A., Mo M., Silvestrini B., Cheng C.Y.;
RT "Micropurification of two human cerebrospinal fluid proteins by high
RT performance electrophoresis chromatography.";
RL J. Neurochem. 61:533-540(1993).
RN [19]
RP PROTEIN SEQUENCE OF 30-44, DEVELOPMENTAL STAGE, AND EXPRESSION IN ABNORMAL
RP PREGNANCIES.
RC TISSUE=Amniotic fluid;
RX PubMed=8674187;
RA Melegos D.N., Yu H., Diamandis E.P.;
RT "Prostaglandin D2 synthase: a component of human amniotic fluid and its
RT association with fetal abnormalities.";
RL Clin. Chem. 42:1042-1050(1996).
RN [20]
RP PROTEIN SEQUENCE OF 58-73 AND 123-140, AND TISSUE SPECIFICITY.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=8599604; DOI=10.1016/0167-4889(95)00182-4;
RA Giacomelli S., Leone M.-G., Grima J., Silvestrini B., Cheng C.Y.;
RT "Astrocytes synthesize and secrete prostaglandin D synthetase in vitro.";
RL Biochim. Biophys. Acta 1310:269-276(1996).
RN [21]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND USE AS A MARKER FOR
RP MENINGIOMA.
RX PubMed=9065498; DOI=10.1523/jneurosci.17-07-02376.1997;
RA Yamashima T., Sakuda K., Tohma Y., Yamashita J., Oda H., Irikura D.,
RA Eguchi N., Beuckmann C.T., Kanaoka Y., Urade Y., Hayaishi O.;
RT "Prostaglandin D synthase (beta-trace) in human arachnoid and meningioma
RT cells: roles as a cell marker or in cerebrospinal fluid absorption,
RT tumorigenesis, and calcification process.";
RL J. Neurosci. 17:2376-2382(1997).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=8761996; DOI=10.1016/0304-3940(96)12614-8;
RA Bloedorn B., Maeder M., Urade Y., Hayaishi O., Felgenhauer K., Brueck W.;
RT "Choroid plexus: the major site of mRNA expression for the beta-trace
RT protein (prostaglandin D synthase) in human brain.";
RL Neurosci. Lett. 209:117-120(1996).
RN [23]
RP TISSUE SPECIFICITY.
RX PubMed=9405674; DOI=10.1073/pnas.94.26.14689;
RA Eguchi Y., Eguchi N., Oda H., Seiki K., Kijima Y., Matsu-ura Y., Urade Y.,
RA Hayaishi O.;
RT "Expression of lipocalin-type prostaglandin D synthase (beta-trace) in
RT human heart and its accumulation in the coronary circulation of angina
RT patients.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14689-14694(1997).
RN [24]
RP TISSUE SPECIFICITY.
RX PubMed=10462696;
RX DOI=10.1002/(sici)1097-4547(19990901)57:5<730::aid-jnr14>3.0.co;2-7;
RA Bloedorn B., Brueck W., Tumani H., Michel U., Rieckmann P., Althans N.,
RA Maeder M.;
RT "Expression of the beta-trace protein in human pachymeninx as revealed by
RT in situ hybridization and immunocytochemistry.";
RL J. Neurosci. Res. 57:730-734(1999).
RN [25]
RP TISSUE SPECIFICITY, AND USE AS A MARKER FOR RENAL INJURY IN HYPERTENSION.
RX PubMed=11882588; DOI=10.1161/hy0202.102835;
RA Hirawa N., Uehara Y., Yamakado M., Toya Y., Gomi T., Ikeda T., Eguchi Y.,
RA Takagi M., Oda H., Seiki K., Urade Y., Umemura S.;
RT "Lipocalin-type prostaglandin D synthase in essential hypertension.";
RL Hypertension 39:449-454(2002).
RN [26]
RP INDUCTION BY THYROID HORMONE.
RX PubMed=9162076; DOI=10.1074/jbc.272.22.14387;
RA White D.M., Takeda T., DeGroot L.J., Stefansson K., Arnason B.G.W.;
RT "Beta-trace gene expression is regulated by a core promoter and a distal
RT thyroid hormone response element.";
RL J. Biol. Chem. 272:14387-14393(1997).
RN [27]
RP USE AS A MARKER FOR NEUROLOGICAL DISORDERS.
RX PubMed=11669522;
RX DOI=10.1002/1522-2683(200109)22:16<3433::aid-elps3433>3.0.co;2-y;
RA Hiraoka A., Seiki K., Oda H., Eguchi N., Urade Y., Tominaga I., Baba K.;
RT "Charge microheterogeneity of the beta-trace proteins (lipocalin-type
RT prostaglandin D synthase) in the cerebrospinal fluid of patients with
RT neurological disorders analyzed by capillary isoelectrofocusing.";
RL Electrophoresis 22:3433-3437(2001).
RN [28]
RP USE AS A MARKER FOR RENAL INJURY IN DIABETES MELLITUS.
RX PubMed=11287775; DOI=10.1159/000045937;
RA Hirawa N., Uehara Y., Ikeda T., Gomi T., Hamano K., Totsuka Y.,
RA Yamakado M., Takagi M., Eguchi N., Oda H., Seiki K., Nakajima H., Urade Y.;
RT "Urinary prostaglandin D synthase (beta-trace) excretion increases in the
RT early stage of diabetes mellitus.";
RL Nephron 87:321-327(2001).
RN [29]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [30]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [31]
RP GLYCOSYLATION AT ASN-78.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [32]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-51 AND ASN-78, AND STRUCTURE OF
RP CARBOHYDRATES.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [33]
RP GLYCOSYLATION AT ASN-78, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [34]
RP GLYCOSYLATION AT SER-29, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 29-190 OF MUTANT ALA-65 IN
RP COMPLEXES WITH FATTY ACIDS, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP MUTAGENESIS OF LYS-59; MET-64; CYS-65; LEU-79; PHE-83; LEU-131 AND TYR-149,
RP AND DOMAIN.
RX PubMed=20667974; DOI=10.1096/fj.10-164863;
RA Zhou Y., Shaw N., Li Y., Zhao Y., Zhang R., Liu Z.J.;
RT "Structure-function analysis of human l-prostaglandin D synthase bound with
RT fatty acid molecules.";
RL FASEB J. 24:4668-4677(2010).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 23-190 IN COMPLEX WITH SUBSTRATE
RP ANALOG.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the human lipocalin-type prostaglandin D synthase
RT crystallised with the substrate analog 9,11-dideoxy-
RT 9alpha,11alpha- epoxymethanoprostaglandin f2alpha.";
RL Submitted (JAN-2010) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the conversion of PGH2 to PGD2, a prostaglandin
CC involved in smooth muscle contraction/relaxation and a potent inhibitor
CC of platelet aggregation (PubMed:20667974). Involved in a variety of CNS
CC functions, such as sedation, NREM sleep and PGE2-induced allodynia, and
CC may have an anti-apoptotic role in oligodendrocytes. Binds small non-
CC substrate lipophilic molecules, including biliverdin, bilirubin,
CC retinal, retinoic acid and thyroid hormone, and may act as a scavenger
CC for harmful hydrophobic molecules and as a secretory retinoid and
CC thyroid hormone transporter. Possibly involved in development and
CC maintenance of the blood-brain, blood-retina, blood-aqueous humor and
CC blood-testis barrier. It is likely to play important roles in both
CC maturation and maintenance of the central nervous system and male
CC reproductive system (PubMed:20667974, PubMed:9475419). Involved in
CC PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by
CC immature mast cells and acts on nearby fibroblasts upstream to PTDGS to
CC synthesize PGD2, which in turn promotes mast cell maturation and
CC degranulation via PTGDR (By similarity). {ECO:0000250|UniProtKB:O09114,
CC ECO:0000269|PubMed:20667974, ECO:0000269|PubMed:9475419}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = prostaglandin D2; Xref=Rhea:RHEA:10600,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57406; EC=5.3.99.2;
CC Evidence={ECO:0000269|PubMed:20667974};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20667974, ECO:0000269|Ref.36}.
CC -!- INTERACTION:
CC P41222; P54253: ATXN1; NbExp=5; IntAct=EBI-948821, EBI-930964;
CC P41222; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-948821, EBI-3866279;
CC P41222; P55212: CASP6; NbExp=3; IntAct=EBI-948821, EBI-718729;
CC P41222; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-948821, EBI-3867333;
CC P41222; P42858: HTT; NbExp=3; IntAct=EBI-948821, EBI-466029;
CC P41222; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-948821, EBI-10172290;
CC P41222; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-948821, EBI-11953334;
CC P41222; P13473-2: LAMP2; NbExp=3; IntAct=EBI-948821, EBI-21591415;
CC P41222; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-948821, EBI-2623095;
CC P41222; Q9UHD9: UBQLN2; NbExp=6; IntAct=EBI-948821, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum
CC {ECO:0000269|PubMed:9065498}. Nucleus membrane
CC {ECO:0000269|PubMed:9065498}. Golgi apparatus
CC {ECO:0000269|PubMed:9065498}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:9065498}. Secreted {ECO:0000269|PubMed:9065498}.
CC Note=Detected on rough endoplasmic reticulum of arachnoid and menigioma
CC cells. Localized to the nuclear envelope, Golgi apparatus, secretory
CC vesicles and spherical cytoplasmic structures in arachnoid trabecular
CC cells, and to circular cytoplasmic structures in meningeal macrophages
CC and perivascular microglial cells. In oligodendrocytes, localized to
CC the rough endoplasmic reticulum and nuclear envelope. In retinal
CC pigment epithelial cells, localized to distinct cytoplasmic domains
CC including the perinuclear region. Also secreted.
CC -!- TISSUE SPECIFICITY: Abundant in the brain and CNS, where it is
CC expressed in tissues of the blood-brain barrier and secreted into the
CC cerebro-spinal fluid. Abundantly expressed in the heart. In the male
CC reproductive system, it is expressed in the testis, epididymis and
CC prostate, and is secreted into the seminal fluid. Expressed in the eye
CC and secreted into the aqueous humor. Lower levels detected in various
CC tissue fluids such as serum, normal urine, ascitic fluid and tear
CC fluid. Also found in a number of other organs including ovary, fimbriae
CC of the fallopian tubes, kidney, leukocytes.
CC {ECO:0000269|PubMed:10462696, ECO:0000269|PubMed:11882588,
CC ECO:0000269|PubMed:7692978, ECO:0000269|PubMed:8599604,
CC ECO:0000269|PubMed:8761996, ECO:0000269|PubMed:9065498,
CC ECO:0000269|PubMed:9405674, ECO:0000269|PubMed:9475419,
CC ECO:0000269|PubMed:9844724}.
CC -!- DEVELOPMENTAL STAGE: Expression in the amniotic fluid increases
CC dramatically during weeks 12 to 25 of pregnancy. Levels decrease slowly
CC after 25 weeks. {ECO:0000269|PubMed:8674187}.
CC -!- INDUCTION: By IL1B/interleukin-1 beta and thyroid hormone. Probably
CC induced by dexamethasone, dihydrotestosterone (DHT), progesterone,
CC retinoic acid and retinal. Repressed by the Notch-Hes signaling
CC pathway. {ECO:0000269|PubMed:9162076}.
CC -!- DOMAIN: Forms a beta-barrel structure that accommodates hydrophobic
CC ligands in its interior. {ECO:0000269|PubMed:20667974}.
CC -!- PTM: N- and O-glycosylated. Both N-glycosylation recognition sites are
CC almost quantitatively occupied by N-glycans of the biantennary complex
CC type, with a considerable proportion of structures bearing a bisecting
CC GlcNAc. N-glycan at Asn-78: dHex1Hex5HexNAc4. Agalacto structure as
CC well as sialylated and nonsialylated oligosaccharides bearing alpha2-
CC 3- and/or alpha2-6-linked NeuNAc are present.
CC {ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19838169,
CC ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:23234360,
CC ECO:0000269|PubMed:7692978, ECO:0000269|PubMed:8336134}.
CC -!- MISCELLANEOUS: It has been proposed that the urinary and serum levels
CC may provide a sensitive indicator of renal damage in diabetes mellitus
CC and hypertension. Elevated levels in the coronary circulation may also
CC be associated with angina. Changes in charge and molecular weight
CC microheterogeneity, due to modification of the N-linked
CC oligosaccharides, may be associated with neurodegenerative disease and
CC multiple sclerosis. Detected in meningioma but not in other brain
CC tumors and may be considered a specific cell marker for meningioma.
CC Expression levels in amniotic fluid are altered in abnormal
CC pregnancies. Levels are lower in pregnancies with trisomic fetuses and
CC fetuses with renal abnormalities.
CC -!- SIMILARITY: Belongs to the calycin superfamily. Lipocalin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ptgds/";
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DR EMBL; M61900; AAA36494.2; -; mRNA.
DR EMBL; M98538; AAB51074.1; -; Genomic_DNA.
DR EMBL; M98537; AAB51074.1; JOINED; Genomic_DNA.
DR EMBL; AY026356; AAK07679.1; -; mRNA.
DR EMBL; DQ297141; ABB84464.1; -; Genomic_DNA.
DR EMBL; AK312817; BAG35674.1; -; mRNA.
DR EMBL; AK075333; BAG52113.1; -; mRNA.
DR EMBL; AL807752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88321.1; -; Genomic_DNA.
DR EMBL; BC005939; AAH05939.1; -; mRNA.
DR EMBL; BT019921; AAV38724.1; -; mRNA.
DR EMBL; BT019922; AAV38725.1; -; mRNA.
DR CCDS; CCDS7019.1; -.
DR PIR; A44455; A44455.
DR PIR; PH1567; PH1567.
DR RefSeq; NP_000945.3; NM_000954.5.
DR PDB; 2WWP; X-ray; 2.00 A; A/B=23-190.
DR PDB; 3O19; X-ray; 1.66 A; A=29-190.
DR PDB; 3O22; X-ray; 1.40 A; A=29-190.
DR PDB; 3O2Y; X-ray; 1.70 A; A/B=29-190.
DR PDB; 4IMN; X-ray; 2.09 A; A=23-190.
DR PDB; 4IMO; X-ray; 1.88 A; A=23-190.
DR PDB; 4ORR; X-ray; 1.40 A; A=1-190.
DR PDB; 4ORS; X-ray; 1.40 A; A/B=1-190.
DR PDB; 4ORU; X-ray; 1.55 A; A/B=1-190.
DR PDB; 4ORW; X-ray; 1.66 A; A/B=1-190.
DR PDB; 4ORX; X-ray; 1.60 A; A/B=1-190.
DR PDB; 4ORY; X-ray; 1.80 A; A/B/C/D/E/F/G/H=1-190.
DR PDB; 4OS0; X-ray; 1.75 A; A/B=1-190.
DR PDB; 4OS3; X-ray; 1.40 A; A/B=1-190.
DR PDB; 4OS8; X-ray; 1.69 A; A/B=1-190.
DR PDB; 5WY9; X-ray; 1.45 A; A=23-190.
DR PDBsum; 2WWP; -.
DR PDBsum; 3O19; -.
DR PDBsum; 3O22; -.
DR PDBsum; 3O2Y; -.
DR PDBsum; 4IMN; -.
DR PDBsum; 4IMO; -.
DR PDBsum; 4ORR; -.
DR PDBsum; 4ORS; -.
DR PDBsum; 4ORU; -.
DR PDBsum; 4ORW; -.
DR PDBsum; 4ORX; -.
DR PDBsum; 4ORY; -.
DR PDBsum; 4OS0; -.
DR PDBsum; 4OS3; -.
DR PDBsum; 4OS8; -.
DR PDBsum; 5WY9; -.
DR AlphaFoldDB; P41222; -.
DR SMR; P41222; -.
DR BioGRID; 111702; 31.
DR IntAct; P41222; 23.
DR MINT; P41222; -.
DR STRING; 9606.ENSP00000360687; -.
DR BindingDB; P41222; -.
DR ChEMBL; CHEMBL3430865; -.
DR DrugBank; DB00162; Vitamin A.
DR DrugCentral; P41222; -.
DR GuidetoPHARMACOLOGY; 1380; -.
DR SwissLipids; SLP:000000141; -.
DR GlyConnect; 685; 149 N-Linked glycans (3 sites), 19 O-Linked glycans (5 sites).
DR GlyGen; P41222; 8 sites, 155 N-linked glycans (3 sites), 12 O-linked glycans (5 sites).
DR iPTMnet; P41222; -.
DR PhosphoSitePlus; P41222; -.
DR BioMuta; PTGDS; -.
DR DMDM; 730305; -.
DR UCD-2DPAGE; P41222; -.
DR CPTAC; CPTAC-686; -.
DR jPOST; P41222; -.
DR MassIVE; P41222; -.
DR PaxDb; P41222; -.
DR PeptideAtlas; P41222; -.
DR PRIDE; P41222; -.
DR ProteomicsDB; 55431; -.
DR ABCD; P41222; 1 sequenced antibody.
DR Antibodypedia; 1507; 365 antibodies from 32 providers.
DR DNASU; 5730; -.
DR Ensembl; ENST00000371625.8; ENSP00000360687.3; ENSG00000107317.13.
DR GeneID; 5730; -.
DR KEGG; hsa:5730; -.
DR MANE-Select; ENST00000371625.8; ENSP00000360687.3; NM_000954.6; NP_000945.3.
DR UCSC; uc004cke.4; human.
DR CTD; 5730; -.
DR DisGeNET; 5730; -.
DR GeneCards; PTGDS; -.
DR HGNC; HGNC:9592; PTGDS.
DR HPA; ENSG00000107317; Tissue enhanced (brain, heart muscle, testis).
DR MIM; 176803; gene.
DR neXtProt; NX_P41222; -.
DR OpenTargets; ENSG00000107317; -.
DR PharmGKB; PA33945; -.
DR VEuPathDB; HostDB:ENSG00000107317; -.
DR eggNOG; ENOG502S6GK; Eukaryota.
DR GeneTree; ENSGT01050000244979; -.
DR HOGENOM; CLU_094061_1_1_1; -.
DR InParanoid; P41222; -.
DR OMA; WFREKKS; -.
DR OrthoDB; 1341030at2759; -.
DR PhylomeDB; P41222; -.
DR TreeFam; TF336103; -.
DR BioCyc; MetaCyc:HS02989-MON; -.
DR BRENDA; 5.3.99.2; 2681.
DR PathwayCommons; P41222; -.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR Reactome; R-HSA-9690406; Transcriptional regulation of testis differentiation.
DR SABIO-RK; P41222; -.
DR SignaLink; P41222; -.
DR SIGNOR; P41222; -.
DR BioGRID-ORCS; 5730; 2 hits in 1073 CRISPR screens.
DR ChiTaRS; PTGDS; human.
DR EvolutionaryTrace; P41222; -.
DR GeneWiki; Prostaglandin_D2_synthase; -.
DR GenomeRNAi; 5730; -.
DR Pharos; P41222; Tchem.
DR PRO; PR:P41222; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P41222; protein.
DR Bgee; ENSG00000107317; Expressed in left testis and 93 other tissues.
DR ExpressionAtlas; P41222; baseline and differential.
DR Genevisible; P41222; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005504; F:fatty acid binding; IDA:UniProtKB.
DR GO; GO:0004667; F:prostaglandin-D synthase activity; IDA:UniProtKB.
DR GO; GO:0005501; F:retinoid binding; ISS:UniProtKB.
DR GO; GO:0036094; F:small molecule binding; IEA:InterPro.
DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW.
DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; ISS:UniProtKB.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR Gene3D; 2.40.128.20; -; 1.
DR InterPro; IPR012674; Calycin.
DR InterPro; IPR002345; Lipocalin.
DR InterPro; IPR022272; Lipocalin_CS.
DR InterPro; IPR000566; Lipocln_cytosolic_FA-bd_dom.
DR InterPro; IPR002972; PstgldnD_synth.
DR PANTHER; PTHR11430; PTHR11430; 1.
DR PANTHER; PTHR11430:SF86; PTHR11430:SF86; 1.
DR Pfam; PF00061; Lipocalin; 1.
DR SUPFAM; SSF50814; SSF50814; 1.
DR PROSITE; PS00213; LIPOCALIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Golgi apparatus; Isomerase; Lipid biosynthesis;
KW Lipid metabolism; Mast cell degranulation; Membrane; Nucleus;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Secreted; Signal; Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:1726844,
FT ECO:0000269|PubMed:7689714, ECO:0000269|PubMed:7692978,
FT ECO:0000269|PubMed:8336134, ECO:0000269|PubMed:8336140,
FT ECO:0000269|PubMed:9475419, ECO:0000269|PubMed:9844724"
FT CHAIN 23..190
FT /note="Prostaglandin-H2 D-isomerase"
FT /id="PRO_0000017945"
FT ACT_SITE 65
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:20667974"
FT CARBOHYD 29
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:8336134"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:22171320, ECO:0000269|PubMed:8336134"
FT DISULFID 89..186
FT /evidence="ECO:0000250|UniProtKB:O09114"
FT VARIANT 56
FT /note="R -> Q (in dbSNP:rs11552179)"
FT /id="VAR_004273"
FT MUTAGEN 59
FT /note="K->A: Increases enzyme activity about two-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 64
FT /note="M->A: Reduces enzyme activity almost ten-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 65
FT /note="C->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 79
FT /note="L->A: Reduces enzyme activity over ten-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 83
FT /note="F->A: Reduces enzyme activity about five-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 131
FT /note="L->A: Reduces enzyme activity almost ten-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT MUTAGEN 149
FT /note="Y->A: Increases enzyme activity about two-fold."
FT /evidence="ECO:0000269|PubMed:20667974"
FT CONFLICT 25
FT /note="E -> P (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 33
FT /note="N -> L (in Ref. 17; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 41..51
FT /evidence="ECO:0007829|PDB:3O22"
FT HELIX 53..60
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 75..85
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 88..98
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:3O22"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:4ORR"
FT STRAND 115..123
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 125..138
FT /evidence="ECO:0007829|PDB:3O22"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:3O22"
FT HELIX 157..169
FT /evidence="ECO:0007829|PDB:3O22"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3O22"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:3O22"
SQ SEQUENCE 190 AA; 21029 MW; DF35FE48AD0D5EF3 CRC64;
MATHHTLWMG LALLGVLGDL QAAPEAQVSV QPNFQQDKFL GRWFSAGLAS NSSWLREKKA
ALSMCKSVVA PATDGGLNLT STFLRKNQCE TRTMLLQPAG SLGSYSYRSP HWGSTYSVSV
VETDYDQYAL LYSQGSKGPG EDFRMATLYS RTQTPRAELK EKFTAFCKAQ GFTEDTIVFL
PQTDKCMTEQ
