DDHD2_HUMAN
ID DDHD2_HUMAN Reviewed; 711 AA.
AC O94830; B3KWV2; B3KXB5; Q9H8X7;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Phospholipase DDHD2 {ECO:0000305};
DE EC=3.1.1.-;
DE AltName: Full=DDHD domain-containing protein 2;
DE AltName: Full=KIAA0725p;
DE AltName: Full=SAM, WWE and DDHD domain-containing protein 1;
GN Name=DDHD2 {ECO:0000312|HGNC:HGNC:29106}; Synonyms=KIAA0725, SAMWD1;
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] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-351, AND CATALYTIC ACTIVITY.
RX PubMed=11788596; DOI=10.1074/jbc.m111092200;
RA Nakajima K., Sonoda H., Mizoguchi T., Aoki J., Arai H., Nagahama M.,
RA Tagaya M., Tani K.;
RT "A novel phospholipase A1 with sequence homology to a mammalian Sec23p-
RT interacting protein, p125.";
RL J. Biol. Chem. 277:11329-11335(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 139-711 (ISOFORM 1), AND VARIANT
RP MET-186.
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 220-711 (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 [7]
RP SUBCELLULAR LOCATION.
RX PubMed=15623529; DOI=10.1074/jbc.m409673200;
RA Shimoi W., Ezawa I., Nakamoto K., Uesaki S., Gabreski G., Aridor M.,
RA Yamamoto A., Nagahama M., Tagaya M., Tani K.;
RT "p125 is localized in endoplasmic reticulum exit sites and involved in
RT their organization.";
RL J. Biol. Chem. 280:10141-10148(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-351.
RX PubMed=20932832; DOI=10.1016/j.febslet.2010.09.047;
RA Sato S., Inoue H., Kogure T., Tagaya M., Tani K.;
RT "Golgi-localized KIAA0725p regulates membrane trafficking from the Golgi
RT apparatus to the plasma membrane in mammalian cells.";
RL FEBS Lett. 584:4389-4395(2010).
RN [9]
RP FUNCTION, PHOSPHOLIPID-BINDING, INTERACTION WITH DDHD1, HOMOOLIGOMER
RP FORMATION, MUTAGENESIS OF SER-351; ARG-434; LYS-435 AND LYS-436, AND
RP CATALYTIC ACTIVITY.
RX PubMed=22922100; DOI=10.1016/j.bbamcr.2012.02.002;
RA Inoue H., Baba T., Sato S., Ohtsuki R., Takemori A., Watanabe T.,
RA Tagaya M., Tani K.;
RT "Roles of SAM and DDHD domains in mammalian intracellular phospholipase A1
RT KIAA0725p.";
RL Biochim. Biophys. Acta 1823:930-939(2012).
RN [10]
RP INVOLVEMENT IN SPG54.
RX PubMed=24482476; DOI=10.1126/science.1247363;
RA Novarino G., Fenstermaker A.G., Zaki M.S., Hofree M., Silhavy J.L.,
RA Heiberg A.D., Abdellateef M., Rosti B., Scott E., Mansour L., Masri A.,
RA Kayserili H., Al-Aama J.Y., Abdel-Salam G.M., Karminejad A., Kara M.,
RA Kara B., Bozorgmehri B., Ben-Omran T., Mojahedi F., Mahmoud I.G.,
RA Bouslam N., Bouhouche A., Benomar A., Hanein S., Raymond L., Forlani S.,
RA Mascaro M., Selim L., Shehata N., Al-Allawi N., Bindu P.S., Azam M.,
RA Gunel M., Caglayan A., Bilguvar K., Tolun A., Issa M.Y., Schroth J.,
RA Spencer E.G., Rosti R.O., Akizu N., Vaux K.K., Johansen A., Koh A.A.,
RA Megahed H., Durr A., Brice A., Stevanin G., Gabriel S.B., Ideker T.,
RA Gleeson J.G.;
RT "Exome sequencing links corticospinal motor neuron disease to common
RT neurodegenerative disorders.";
RL Science 343:506-511(2014).
RN [11]
RP VARIANT SPG54 HIS-660.
RX PubMed=23176823; DOI=10.1016/j.ajhg.2012.10.017;
RA Schuurs-Hoeijmakers J.H., Geraghty M.T., Kamsteeg E.J., Ben-Salem S.,
RA de Bot S.T., Nijhof B., van de Vondervoort I.I., van der Graaf M.,
RA Nobau A.C., Otte-Holler I., Vermeer S., Smith A.C., Humphreys P.,
RA Schwartzentruber J., Ali B.R., Al-Yahyaee S.A., Tariq S., Pramathan T.,
RA Bayoumi R., Kremer H.P., van de Warrenburg B.P., van den Akker W.M.,
RA Gilissen C., Veltman J.A., Janssen I.M., Vulto-van Silfhout A.T.,
RA van der Velde-Visser S., Lefeber D.J., Diekstra A., Erasmus C.E.,
RA Willemsen M.A., Vissers L.E., Lammens M., van Bokhoven H., Brunner H.G.,
RA Wevers R.A., Schenck A., Al-Gazali L., de Vries B.B., de Brouwer A.P.;
RT "Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a
RT recessive form of complex hereditary spastic paraplegia.";
RL Am. J. Hum. Genet. 91:1073-1081(2012).
CC -!- FUNCTION: Phospholipase that hydrolyzes preferentially phosphatidic
CC acid, including 1,2-dioleoyl-sn-phosphatidic acid, and
CC phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-
CC phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P),
CC phosphatidylinositol 5-phosphate (PI(5)P) and possibly
CC phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in
CC the maintenance of the endoplasmic reticulum and/or Golgi structures.
CC May regulate the transport between Golgi apparatus and plasma membrane.
CC {ECO:0000269|PubMed:11788596, ECO:0000269|PubMed:20932832,
CC ECO:0000269|PubMed:22922100}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = (9Z)-
CC octadecenoate + 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+);
CC Xref=Rhea:RHEA:45128, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:74546, ChEBI:CHEBI:77593;
CC Evidence={ECO:0000269|PubMed:22922100};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45129;
CC Evidence={ECO:0000305|PubMed:22922100};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:40943, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64839,
CC ChEBI:CHEBI:77593; Evidence={ECO:0000269|PubMed:11788596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40944;
CC Evidence={ECO:0000305|PubMed:11788596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine + H(+) + hexadecanoate; Xref=Rhea:RHEA:45132,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:73007, ChEBI:CHEBI:76088;
CC Evidence={ECO:0000269|PubMed:11788596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45133;
CC Evidence={ECO:0000305|PubMed:11788596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-
CC serine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine +
CC H(+) + hexadecanoate; Xref=Rhea:RHEA:43968, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75029,
CC ChEBI:CHEBI:77342; Evidence={ECO:0000269|PubMed:11788596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43969;
CC Evidence={ECO:0000305|PubMed:11788596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:38783, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:73001,
CC ChEBI:CHEBI:76071; Evidence={ECO:0000269|PubMed:11788596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38784;
CC Evidence={ECO:0000305|PubMed:11788596};
CC -!- SUBUNIT: Forms homooligomers and, to a much smaller extent,
CC heterooligomers with DDHD1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum-Golgi
CC intermediate compartment. Golgi apparatus, cis-Golgi network.
CC Note=Cycles between the Golgi apparatus and the cytosol. DDHD2
CC recruitment to the Golgi/endoplasmic reticulum-Golgi intermediate
CC compartment (ERGIC) is regulated by the levels of phosphoinositides,
CC including PI(4)P.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O94830-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O94830-2; Sequence=VSP_056087;
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level).
CC {ECO:0000269|PubMed:11788596}.
CC -!- DOMAIN: SAM and DDHD domains together are required for phospholipid
CC binding.
CC -!- DISEASE: Spastic paraplegia 54, autosomal recessive (SPG54)
CC [MIM:615033]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. Complicated forms are recognized by
CC additional variable features including spastic quadriparesis, seizures,
CC dementia, amyotrophy, extrapyramidal disturbance, cerebral or
CC cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well
CC as by extra neurological manifestations. SPG54 patients have delayed
CC psychomotor development, intellectual disability, and early-onset
CC spasticity of the lower limbs. Brain MRI shows a thin corpus callosum
CC and periventricular white matter lesions. {ECO:0000269|PubMed:23176823,
CC ECO:0000269|PubMed:24482476}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PA-PLA1 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-31 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH10504.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB14470.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK023218; BAB14470.1; ALT_INIT; mRNA.
DR EMBL; AK125904; BAG54264.1; -; mRNA.
DR EMBL; AK127040; BAG54427.1; -; mRNA.
DR EMBL; AC084024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB018268; BAA34445.1; -; mRNA.
DR EMBL; CH471080; EAW63324.1; -; Genomic_DNA.
DR EMBL; BC010504; AAH10504.1; ALT_INIT; mRNA.
DR CCDS; CCDS34883.1; -. [O94830-1]
DR RefSeq; NP_001157704.1; NM_001164232.1. [O94830-1]
DR RefSeq; NP_056029.2; NM_015214.2. [O94830-1]
DR RefSeq; XP_005273511.1; XM_005273454.2.
DR RefSeq; XP_005273512.1; XM_005273455.3.
DR RefSeq; XP_011542758.1; XM_011544456.1. [O94830-1]
DR RefSeq; XP_016868741.1; XM_017013252.1.
DR RefSeq; XP_016868742.1; XM_017013253.1.
DR RefSeq; XP_016868743.1; XM_017013254.1.
DR RefSeq; XP_016868744.1; XM_017013255.1. [O94830-2]
DR RefSeq; XP_016868745.1; XM_017013256.1.
DR AlphaFoldDB; O94830; -.
DR SMR; O94830; -.
DR BioGRID; 116862; 40.
DR IntAct; O94830; 17.
DR MINT; O94830; -.
DR STRING; 9606.ENSP00000380352; -.
DR SwissLipids; SLP:000001070; -.
DR iPTMnet; O94830; -.
DR PhosphoSitePlus; O94830; -.
DR BioMuta; DDHD2; -.
DR EPD; O94830; -.
DR jPOST; O94830; -.
DR MassIVE; O94830; -.
DR MaxQB; O94830; -.
DR PaxDb; O94830; -.
DR PeptideAtlas; O94830; -.
DR PRIDE; O94830; -.
DR ProteomicsDB; 3807; -.
DR ProteomicsDB; 50475; -. [O94830-1]
DR Antibodypedia; 4449; 80 antibodies from 19 providers.
DR DNASU; 23259; -.
DR Ensembl; ENST00000397166.7; ENSP00000380352.2; ENSG00000085788.14. [O94830-1]
DR Ensembl; ENST00000517385.5; ENSP00000429017.1; ENSG00000085788.14. [O94830-2]
DR Ensembl; ENST00000520272.6; ENSP00000429932.2; ENSG00000085788.14. [O94830-1]
DR GeneID; 23259; -.
DR KEGG; hsa:23259; -.
DR MANE-Select; ENST00000397166.7; ENSP00000380352.2; NM_015214.3; NP_056029.2.
DR UCSC; uc003xlb.4; human. [O94830-1]
DR CTD; 23259; -.
DR DisGeNET; 23259; -.
DR GeneCards; DDHD2; -.
DR HGNC; HGNC:29106; DDHD2.
DR HPA; ENSG00000085788; Low tissue specificity.
DR MalaCards; DDHD2; -.
DR MIM; 615003; gene.
DR MIM; 615033; phenotype.
DR neXtProt; NX_O94830; -.
DR OpenTargets; ENSG00000085788; -.
DR Orphanet; 320380; Autosomal recessive spastic paraplegia type 54.
DR PharmGKB; PA128394618; -.
DR VEuPathDB; HostDB:ENSG00000085788; -.
DR eggNOG; KOG2308; Eukaryota.
DR GeneTree; ENSGT00940000156808; -.
DR HOGENOM; CLU_006932_0_0_1; -.
DR InParanoid; O94830; -.
DR OMA; DEWGATP; -.
DR OrthoDB; 777968at2759; -.
DR PhylomeDB; O94830; -.
DR TreeFam; TF314133; -.
DR PathwayCommons; O94830; -.
DR Reactome; R-HSA-1483166; Synthesis of PA.
DR SignaLink; O94830; -.
DR BioGRID-ORCS; 23259; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; DDHD2; human.
DR GenomeRNAi; 23259; -.
DR Pharos; O94830; Tbio.
DR PRO; PR:O94830; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O94830; protein.
DR Bgee; ENSG00000085788; Expressed in endothelial cell and 200 other tissues.
DR ExpressionAtlas; O94830; baseline and differential.
DR Genevisible; O94830; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0030134; C:COPII-coated ER to Golgi transport vesicle; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0004620; F:phospholipase activity; IBA:GO_Central.
DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central.
DR GO; GO:0034389; P:lipid droplet organization; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0000266; P:mitochondrial fission; IEA:Ensembl.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IEA:Ensembl.
DR GO; GO:0019433; P:triglyceride catabolic process; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR004177; DDHD_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR004170; WWE-dom.
DR Pfam; PF02862; DDHD; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF02825; WWE; 1.
DR SMART; SM01127; DDHD; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS51043; DDHD; 1.
DR PROSITE; PS50918; WWE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Disease variant; Golgi apparatus;
KW Hereditary spastic paraplegia; Hydrolase; Lipid degradation;
KW Lipid metabolism; Neurodegeneration; Phosphoprotein; Reference proteome.
FT CHAIN 1..711
FT /note="Phospholipase DDHD2"
FT /id="PRO_0000309330"
FT DOMAIN 30..112
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 385..448
FT /note="SAM"
FT DOMAIN 495..700
FT /note="DDHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00378"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 351
FT /evidence="ECO:0000305"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Y98"
FT VAR_SEQ 1..381
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056087"
FT VARIANT 186
FT /note="T -> M (in dbSNP:rs2306899)"
FT /evidence="ECO:0000269|PubMed:9872452"
FT /id="VAR_036930"
FT VARIANT 660
FT /note="D -> H (in SPG54; dbSNP:rs375168720)"
FT /evidence="ECO:0000269|PubMed:23176823"
FT /id="VAR_069574"
FT MUTAGEN 351
FT /note="S->A: Abolishes phospholipase activity. Loss of
FT efficient targeting to the Golgi apparatus. No effect on
FT PI(3)P-, PI(4)P-, PI(5)P-binding."
FT /evidence="ECO:0000269|PubMed:11788596,
FT ECO:0000269|PubMed:20932832, ECO:0000269|PubMed:22922100"
FT MUTAGEN 434
FT /note="R->A: Loss of phospholipid binding and of
FT Golgi/ERGIC localization; when associated with A-435 and A-
FT 436."
FT /evidence="ECO:0000269|PubMed:22922100"
FT MUTAGEN 435
FT /note="K->A: Loss of phospholipid binding and of
FT Golgi/ERGIC localization; when associated with A-434 and A-
FT 436."
FT /evidence="ECO:0000269|PubMed:22922100"
FT MUTAGEN 436
FT /note="K->A: Loss of phospholipid binding and of
FT Golgi/ERGIC localization; when associated with A-434 and A-
FT 435."
FT /evidence="ECO:0000269|PubMed:22922100"
FT CONFLICT 292
FT /note="S -> G (in Ref. 2; BAB14470)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="D -> G (in Ref. 5; BAA34445)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 711 AA; 81032 MW; 8C03CD9254B1DBFB CRC64;
MSSVQSQQEQ LSQSDPSPSP NSCSSFELID MDAGSLYEPV SPHWFYCKII DSKETWIPFN
SEDSQQLEEA YSSGKGCNGR VVPTDGGRYD VHLGERMRYA VYWDELASEV RRCTWFYKGD
KDNKYVPYSE SFSQVLEETY MLAVTLDEWK KKLESPNREI IILHNPKLMV HYQPVAGSDD
WGSTPTEQGR PRTVKRGVEN ISVDIHCGEP LQIDHLVFVV HGIGPACDLR FRSIVQCVND
FRSVSLNLLQ THFKKAQENQ QIGRVEFLPV NWHSPLHSTG VDVDLQRITL PSINRLRHFT
NDTILDVFFY NSPTYCQTIV DTVASEMNRI YTLFLQRNPD FKGGVSIAGH SLGSLILFDI
LTNQKDSLGD IDSEKDSLNI VMDQGDTPTL EEDLKKLQLS EFFDIFEKEK VDKEALALCT
DRDLQEIGIP LGPRKKILNY FSTRKNSMGI KRPAPQPASG ANIPKESEFC SSSNTRNGDY
LDVGIGQVSV KYPRLIYKPE IFFAFGSPIG MFLTVRGLKR IDPNYRFPTC KGFFNIYHPF
DPVAYRIEPM VVPGVEFEPM LIPHHKGRKR MHLELREGLT RMSMDLKNNL LGSLRMAWKS
FTRAPYPALQ ASETPEETEA EPESTSEKPS DVNTEETSVA VKEEVLPINV GMLNGGQRID
YVLQEKPIES FNEYLFALQS HLCYWESEDT VLLVLKEIYQ TQGIFLDQPL Q
