GDPD3_HUMAN
ID GDPD3_HUMAN Reviewed; 318 AA.
AC Q7L5L3; Q9H652;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Lysophospholipase D GDPD3 {ECO:0000305};
DE EC=3.1.4.- {ECO:0000269|PubMed:27637550};
DE AltName: Full=Glycerophosphodiester phosphodiesterase 7 {ECO:0000250|UniProtKB:Q99LY2};
DE AltName: Full=Glycerophosphodiester phosphodiesterase domain-containing protein 3;
GN Name=GDPD3 {ECO:0000312|HGNC:HGNC:28638};
GN Synonyms=GDE7 {ECO:0000303|PubMed:27637550};
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [4]
RP CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=27637550; DOI=10.1016/j.bbalip.2016.09.008;
RA Rahman I.A., Tsuboi K., Hussain Z., Yamashita R., Okamoto Y., Uyama T.,
RA Yamazaki N., Tanaka T., Tokumura A., Ueda N.;
RT "Calcium-dependent generation of N-acylethanolamines and lysophosphatidic
RT acids by glycerophosphodiesterase GDE7.";
RL Biochim. Biophys. Acta 1861:1881-1892(2016).
CC -!- FUNCTION: Hydrolyzes lysoglycerophospholipids to produce
CC lysophosphatidic acid (LPA) and the corresponding amines
CC (PubMed:27637550). Shows a preference for 1-O-alkyl-sn-glycero-3-
CC phosphocholine (lyso-PAF), lysophosphatidylcholine (lyso-PC) and N-
CC acylethanolamine lysophospholipids (PubMed:27637550). Does not display
CC glycerophosphodiester phosphodiesterase activity, since it cannot
CC hydrolyze either glycerophosphoinositol or glycerophosphocholine.
CC {ECO:0000250|UniProtKB:Q99LY2, ECO:0000269|PubMed:27637550}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:38975, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57518, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000250|UniProtKB:Q99LY2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000269|PubMed:27637550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:27637550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-octadecenyl)-sn-glycero-3-phospho-N-hexadecanoyl-
CC ethanolamine + H2O = 1-O-(1Z-octadecenyl)-sn-glycero-3-phosphate +
CC H(+) + N-hexadecanoylethanolamine; Xref=Rhea:RHEA:53184,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71464,
CC ChEBI:CHEBI:137009, ChEBI:CHEBI:137017;
CC Evidence={ECO:0000269|PubMed:27637550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53185;
CC Evidence={ECO:0000305|PubMed:27637550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1-(9Z-octadecenoyl)-
CC sn-glycero-3-phosphoethanolamine = 1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphate + H(+) + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine;
CC Xref=Rhea:RHEA:45544, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:74544, ChEBI:CHEBI:85223;
CC Evidence={ECO:0000269|PubMed:27637550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45545;
CC Evidence={ECO:0000305|PubMed:27637550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N,1-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H(+) + N-(9Z-octadecenoyl) ethanolamine; Xref=Rhea:RHEA:56460,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71466,
CC ChEBI:CHEBI:74544, ChEBI:CHEBI:85222;
CC Evidence={ECO:0000269|PubMed:27637550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56461;
CC Evidence={ECO:0000305|PubMed:27637550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H(+) + N-hexadecanoylethanolamine; Xref=Rhea:RHEA:53168,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71464,
CC ChEBI:CHEBI:74544, ChEBI:CHEBI:85217;
CC Evidence={ECO:0000269|PubMed:27637550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53169;
CC Evidence={ECO:0000305|PubMed:27637550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC hexadecyl-sn-glycero-3-phosphate + choline + H(+);
CC Xref=Rhea:RHEA:41143, ChEBI:CHEBI:15354, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:64496, ChEBI:CHEBI:77580;
CC Evidence={ECO:0000250|UniProtKB:Q99LY2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41144;
CC Evidence={ECO:0000250|UniProtKB:Q99LY2};
CC -!- ACTIVITY REGULATION: Lysophospholipase D activity is stimulated by
CC calcium. Loss of lysophospholipase D activity in presence of EDTA.
CC {ECO:0000269|PubMed:27637550}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q99LY2}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q99LY2}. Cytoplasm,
CC perinuclear region {ECO:0000250|UniProtKB:Q99LY2}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:27637550}. Note=Partially co-localized
CC with CANX. {ECO:0000250|UniProtKB:Q99LY2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7L5L3-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7L5L3-1; Sequence=VSP_036888;
CC -!- TISSUE SPECIFICITY: Widely expressed, with high level in kidney and
CC ovary. {ECO:0000269|PubMed:27637550}.
CC -!- SIMILARITY: Belongs to the glycerophosphoryl diester phosphodiesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02714.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK026256; BAB15414.1; -; mRNA.
DR EMBL; AC012645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002714; AAH02714.2; ALT_INIT; mRNA.
DR CCDS; CCDS10671.2; -. [Q7L5L3-2]
DR RefSeq; NP_077283.2; NM_024307.2. [Q7L5L3-2]
DR AlphaFoldDB; Q7L5L3; -.
DR SMR; Q7L5L3; -.
DR BioGRID; 122571; 50.
DR IntAct; Q7L5L3; 11.
DR STRING; 9606.ENSP00000384363; -.
DR SwissLipids; SLP:000001905; -.
DR iPTMnet; Q7L5L3; -.
DR PhosphoSitePlus; Q7L5L3; -.
DR BioMuta; GDPD3; -.
DR DMDM; 226694188; -.
DR EPD; Q7L5L3; -.
DR jPOST; Q7L5L3; -.
DR MassIVE; Q7L5L3; -.
DR MaxQB; Q7L5L3; -.
DR PaxDb; Q7L5L3; -.
DR PeptideAtlas; Q7L5L3; -.
DR PRIDE; Q7L5L3; -.
DR ProteomicsDB; 68809; -. [Q7L5L3-2]
DR ProteomicsDB; 68810; -. [Q7L5L3-1]
DR Antibodypedia; 51979; 128 antibodies from 17 providers.
DR DNASU; 79153; -.
DR Ensembl; ENST00000406256.8; ENSP00000384363.3; ENSG00000102886.15. [Q7L5L3-2]
DR GeneID; 79153; -.
DR KEGG; hsa:79153; -.
DR MANE-Select; ENST00000406256.8; ENSP00000384363.3; NM_024307.3; NP_077283.2.
DR UCSC; uc002dwp.4; human. [Q7L5L3-2]
DR CTD; 79153; -.
DR DisGeNET; 79153; -.
DR GeneCards; GDPD3; -.
DR HGNC; HGNC:28638; GDPD3.
DR HPA; ENSG00000102886; Tissue enhanced (esophagus).
DR MIM; 616318; gene.
DR neXtProt; NX_Q7L5L3; -.
DR OpenTargets; ENSG00000102886; -.
DR PharmGKB; PA142671741; -.
DR VEuPathDB; HostDB:ENSG00000102886; -.
DR eggNOG; KOG2258; Eukaryota.
DR GeneTree; ENSGT00940000160759; -.
DR HOGENOM; CLU_030006_5_1_1; -.
DR InParanoid; Q7L5L3; -.
DR OMA; KWAIMRK; -.
DR OrthoDB; 1218115at2759; -.
DR PhylomeDB; Q7L5L3; -.
DR TreeFam; TF328545; -.
DR BRENDA; 3.1.4.39; 2681.
DR PathwayCommons; Q7L5L3; -.
DR Reactome; R-HSA-6814848; Glycerophospholipid catabolism.
DR SignaLink; Q7L5L3; -.
DR BioGRID-ORCS; 79153; 9 hits in 1075 CRISPR screens.
DR GenomeRNAi; 79153; -.
DR Pharos; Q7L5L3; Tbio.
DR PRO; PR:Q7L5L3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q7L5L3; protein.
DR Bgee; ENSG00000102886; Expressed in mucosa of transverse colon and 147 other tissues.
DR ExpressionAtlas; Q7L5L3; baseline and differential.
DR Genevisible; Q7L5L3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IMP:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IMP:UniProtKB.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; IMP:UniProtKB.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; IEA:Ensembl.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR030395; GP_PDE_dom.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR Pfam; PF03009; GDPD; 1.
DR SUPFAM; SSF51695; SSF51695; 1.
DR PROSITE; PS51704; GP_PDE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Endoplasmic reticulum; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..318
FT /note="Lysophospholipase D GDPD3"
FT /id="PRO_0000251936"
FT TOPO_DOM 1..2
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 24..198
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..318
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 39..308
FT /note="GP-PDE"
FT BINDING 71
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 73
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 86
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..62
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036888"
SQ SEQUENCE 318 AA; 36596 MW; 4BD2FF25CF0CA22E CRC64;
MSLLLYYALP ALGSYAMLSI FFLRRPHLLH TPRAPTFRIR LGAHRGGSGE LLENTMEAME
NSMAQRSDLL ELDCQLTRDR VVVVSHDENL CRQSGLNRDV GSLDFEDLPL YKEKLEVYFS
PGHFAHGSDR RMVRLEDLFQ RFPRTPMSVE IKGKNEELIR EIAGLVRRYD RNEITIWASE
KSSVMKKCKA ANPEMPLSFT ISRGFWVLLS YYLGLLPFIP IPEKFFFCFL PNIINRTYFP
FSCSCLNQLL AVVSKWLIMR KSLIRHLEER GVQVVFWCLN EESDFEAAFS VGATGVITDY
PTALRHYLDN HGPAARTS
