GDE1_HUMAN
ID GDE1_HUMAN Reviewed; 331 AA.
AC Q9NZC3; O43334; Q6PKF7; Q7KYR4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Glycerophosphodiester phosphodiesterase 1 {ECO:0000305};
DE AltName: Full=Glycerophosphoinositol glycerophosphodiesterase GDE1 {ECO:0000305};
DE EC=3.1.4.44 {ECO:0000250|UniProtKB:Q9JL55};
DE AltName: Full=Lysophospholipase D GDE1 {ECO:0000305};
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q9JL56};
DE AltName: Full=Membrane-interacting protein of RGS16 {ECO:0000303|PubMed:10760272};
DE AltName: Full=RGS16-interacting membrane protein;
GN Name=GDE1 {ECO:0000312|HGNC:HGNC:29644};
GN Synonyms=MIR16 {ECO:0000303|PubMed:10760272};
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], AND TISSUE SPECIFICITY.
RX PubMed=10760272; DOI=10.1073/pnas.97.8.3999;
RA Zheng B., Chen D., Farquhar M.G.;
RT "MIR16, a putative membrane glycerophosphodiester phosphodiesterase,
RT interacts with RGS16.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3999-4004(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Duennebier F.F., Bachmann A.S.;
RT "The role of GDE1/MIR16 in G protein-coupled receptor signaling.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell, Brain, Colon, and Kidney;
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 [5]
RP 3D-STRUCTURE MODELING, AND INTERACTION WITH PRAF2.
RX PubMed=16472945; DOI=10.1016/j.gene.2005.11.023;
RA Bachmann A.S., Duennebier F.F., Mocz G.;
RT "Genomic organization, characterization, and molecular 3D model of GDE1, a
RT novel mammalian glycerophosphoinositol phosphodiesterase.";
RL Gene 371:144-153(2006).
CC -!- FUNCTION: Hydrolyzes the phosphodiester bond of glycerophosphodiesters
CC such as glycerophosphoinositol (GroPIns) and glycerophosphoethanolamine
CC (GroPEth), to yield a glycerol phosphate and an alcohol (By
CC similarity). Hydrolyzes glycerophospho-N-acylethanolamines to N-
CC acylethanolamines in the brain and participates in bioactive N-
CC acylethanolamine biosynthesis such as anandamide (an endocannabinoid),
CC N-palmitoylethanolamine (an anti-inflammatory), and N-
CC oleoylethanolamine (an anorexic). In addition, has a lysophospholipase
CC D activity by hydrolyzing N-acyl-lysoplasmenylethanolamine (N-acyl-
CC lysoPlsEt) to N-acylethanolamine. However lysophospholipase D activity
CC is lower than glycerophosphodiester phosphodiesterase activity (By
CC similarity). Has little or no activity towards glycerophosphocholine
CC (By similarity). {ECO:0000250|UniProtKB:Q9JL55,
CC ECO:0000250|UniProtKB:Q9JL56}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sn-glycero-3-phospho-1D-myo-inositol = H(+) + myo-
CC inositol + sn-glycerol 3-phosphate; Xref=Rhea:RHEA:16501,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17268,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:58444; EC=3.1.4.44;
CC Evidence={ECO:0000250|UniProtKB:Q9JL55};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16502;
CC Evidence={ECO:0000250|UniProtKB:Q9JL55};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-octadecenyl)-sn-glycero-3-phospho-(N-5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine + H2O = 1-O-(1Z-octadecenyl)-sn-
CC glycero-3-phosphate + H(+) + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine; Xref=Rhea:RHEA:53192, ChEBI:CHEBI:2700,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:137016,
CC ChEBI:CHEBI:137017; Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53193;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-(1Z-octadecenyl)-sn-glycero-3-phospho-(N-9Z-octadecenoyl)-
CC ethanolamine + H2O = 1-O-(1Z-octadecenyl)-sn-glycero-3-phosphate +
CC H(+) + N-(9Z-octadecenoyl) ethanolamine; Xref=Rhea:RHEA:53188,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:71466,
CC ChEBI:CHEBI:137010, ChEBI:CHEBI:137017;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53189;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
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:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53185;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-sn-glycero-3-
CC phosphoethanolamine = H(+) + N-(4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoyl ethanolamine + sn-glycerol 3-phosphate;
CC Xref=Rhea:RHEA:45444, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:85250, ChEBI:CHEBI:85252;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45445;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-eicosanoyl-sn-glycero-3-phosphoethanolamine = H(+) +
CC N-eicosanoyl ethanolamine + sn-glycerol 3-phosphate;
CC Xref=Rhea:RHEA:45440, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:85228, ChEBI:CHEBI:85253;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45441;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-sn-glycero-3-phosphoethanolamine = H(+) +
CC N-hexadecanoylethanolamine + sn-glycerol 3-phosphate;
CC Xref=Rhea:RHEA:45436, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:71464, ChEBI:CHEBI:85226;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45437;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine =
CC H(+) + N-(9Z-octadecenoyl) ethanolamine + sn-glycerol 3-phosphate;
CC Xref=Rhea:RHEA:45432, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:71466, ChEBI:CHEBI:85229;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45433;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC phosphoethanolamine = H(+) + N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC ethanolamine + sn-glycerol 3-phosphate; Xref=Rhea:RHEA:45428,
CC ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57597, ChEBI:CHEBI:85230;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45429;
CC Evidence={ECO:0000250|UniProtKB:Q9JL56};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9JL55};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA, calcium chloride, and zinc
CC chloride. Enhanced by magnesium chloride (By similarity).
CC Glycerophosphodiester phosphodiesterase activity can be modulated by G-
CC protein signaling pathways (By similarity).
CC {ECO:0000250|UniProtKB:Q9JL55, ECO:0000250|UniProtKB:Q9JL56}.
CC -!- SUBUNIT: Interacts with PRAF2 (PubMed:16472945). Interacts with RGS16
CC (By similarity). {ECO:0000250|UniProtKB:Q9JL55,
CC ECO:0000269|PubMed:16472945}.
CC -!- INTERACTION:
CC Q9NZC3; Q14973: SLC10A1; NbExp=3; IntAct=EBI-2833330, EBI-3923031;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9JL55};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q9JL55}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Perinuclear vesicles and cell membrane.
CC {ECO:0000250|UniProtKB:Q9JL55}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10760272}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9JL55}.
CC -!- SIMILARITY: Belongs to the glycerophosphoryl diester phosphodiesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC05440.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAC05803.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF212862; AAF65234.1; -; mRNA.
DR EMBL; AY463154; AAR25624.1; -; mRNA.
DR EMBL; U91321; AAC05440.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC003108; AAC05803.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC014981; AAH14981.1; -; mRNA.
DR EMBL; BC025273; AAH25273.1; -; mRNA.
DR CCDS; CCDS10578.1; -.
DR PIR; T01371; T01371.
DR RefSeq; NP_057725.1; NM_016641.3.
DR AlphaFoldDB; Q9NZC3; -.
DR SMR; Q9NZC3; -.
DR BioGRID; 119618; 33.
DR IntAct; Q9NZC3; 14.
DR MINT; Q9NZC3; -.
DR STRING; 9606.ENSP00000261386; -.
DR GlyGen; Q9NZC3; 3 sites.
DR iPTMnet; Q9NZC3; -.
DR PhosphoSitePlus; Q9NZC3; -.
DR SwissPalm; Q9NZC3; -.
DR BioMuta; GDE1; -.
DR DMDM; 74734724; -.
DR EPD; Q9NZC3; -.
DR jPOST; Q9NZC3; -.
DR MassIVE; Q9NZC3; -.
DR MaxQB; Q9NZC3; -.
DR PaxDb; Q9NZC3; -.
DR PeptideAtlas; Q9NZC3; -.
DR PRIDE; Q9NZC3; -.
DR ProteomicsDB; 83361; -.
DR Antibodypedia; 25375; 170 antibodies from 24 providers.
DR DNASU; 51573; -.
DR Ensembl; ENST00000353258.8; ENSP00000261386.3; ENSG00000006007.12.
DR GeneID; 51573; -.
DR KEGG; hsa:51573; -.
DR MANE-Select; ENST00000353258.8; ENSP00000261386.3; NM_016641.4; NP_057725.1.
DR UCSC; uc002dgh.4; human.
DR CTD; 51573; -.
DR DisGeNET; 51573; -.
DR GeneCards; GDE1; -.
DR HGNC; HGNC:29644; GDE1.
DR HPA; ENSG00000006007; Low tissue specificity.
DR MIM; 605943; gene.
DR neXtProt; NX_Q9NZC3; -.
DR OpenTargets; ENSG00000006007; -.
DR PharmGKB; PA162389327; -.
DR VEuPathDB; HostDB:ENSG00000006007; -.
DR eggNOG; KOG2258; Eukaryota.
DR GeneTree; ENSGT00510000047820; -.
DR HOGENOM; CLU_030006_2_1_1; -.
DR InParanoid; Q9NZC3; -.
DR OMA; KHHWMTL; -.
DR OrthoDB; 1218115at2759; -.
DR PhylomeDB; Q9NZC3; -.
DR TreeFam; TF313692; -.
DR BioCyc; MetaCyc:HS00157-MON; -.
DR BRENDA; 3.1.4.44; 2681.
DR PathwayCommons; Q9NZC3; -.
DR Reactome; R-HSA-6814848; Glycerophospholipid catabolism.
DR SignaLink; Q9NZC3; -.
DR BioGRID-ORCS; 51573; 20 hits in 1091 CRISPR screens.
DR ChiTaRS; GDE1; human.
DR GenomeRNAi; 51573; -.
DR Pharos; Q9NZC3; Tbio.
DR PRO; PR:Q9NZC3; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9NZC3; protein.
DR Bgee; ENSG00000006007; Expressed in left ventricle myocardium and 202 other tissues.
DR ExpressionAtlas; Q9NZC3; baseline and differential.
DR Genevisible; Q9NZC3; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008889; F:glycerophosphodiester phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0047395; F:glycerophosphoinositol glycerophosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0004622; F:lysophospholipase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006580; P:ethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; TAS:UniProtKB.
DR GO; GO:0070291; P:N-acylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; ISS:UniProtKB.
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 Cell membrane; Cytoplasmic vesicle; Glycoprotein; Hydrolase;
KW Lipid metabolism; Magnesium; Membrane; Metal-binding; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..331
FT /note="Glycerophosphodiester phosphodiesterase 1"
FT /id="PRO_0000251944"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..247
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 65..331
FT /note="GP-PDE"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT BINDING 99
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT BINDING 174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255"
FT CARBOHYD 168
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 218
FT /note="R -> Q (in dbSNP:rs2072086)"
FT /id="VAR_044018"
FT VARIANT 328
FT /note="E -> K (in dbSNP:rs34137361)"
FT /id="VAR_044019"
SQ SEQUENCE 331 AA; 37718 MW; EFE567E71DBD4AC5 CRC64;
MWLWEDQGGL LGPFSFLLLV LLLVTRSPVN ACLLTGSLFV LLRVFSFEPV PSCRALQVLK
PRDRISAIAH RGGSHDAPEN TLAAIRQAAK NGATGVELDI EFTSDGIPVL MHDNTVDRTT
DGTGRLCDLT FEQIRKLNPA ANHRLRNDFP DEKIPTLREA VAECLNHNLT IFFDVKGHAH
KATEALKKMY MEFPQLYNNS VVCSFLPEVI YKMRQTDRDV ITALTHRPWS LSHTGDGKPR
YDTFWKHFIF VMMDILLDWS MHNILWYLCG ISAFLMQKDF VSPAYLKKWS AKGIQVVGWT
VNTFDEKSYY ESHLGSSYIT DSMVEDCEPH F
