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 24-JAN-2024, entry version 160. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. DR RefSeq; XP_016868745.1; XM_017013256.1. DR AlphaFoldDB; O94830; -. DR SMR; O94830; -. DR BioGRID; 116862; 43. 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; 9606-ENSP00000380352; -. DR PeptideAtlas; O94830; -. DR ProteomicsDB; 3807; -. DR ProteomicsDB; 50475; -. [O94830-1] DR Pumba; O94830; -. DR Antibodypedia; 4449; 94 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 AGR; HGNC:29106; -. 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; DGRNCQY; -. DR OrthoDB; 1365902at2759; -. DR PhylomeDB; O94830; -. DR TreeFam; TF314133; -. DR PathwayCommons; O94830; -. DR Reactome; R-HSA-1483166; Synthesis of PA. DR SignaLink; O94830; -. DR SIGNOR; O94830; -. DR BioGRID-ORCS; 23259; 13 hits in 1152 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 202 other cell types or tissues. DR ExpressionAtlas; O94830; baseline and differential. 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: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: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 CDD; cd09585; SAM_DDHD2; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR InterPro; IPR004177; DDHD_dom. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR004170; WWE-dom. DR PANTHER; PTHR23509; PA-PL1 PHOSPHOLIPASE FAMILY; 1. DR PANTHER; PTHR23509:SF7; PHOSPHOLIPASE DDHD2; 1. 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; SAM/Pointed domain; 1. DR PROSITE; PS51043; DDHD; 1. DR PROSITE; PS50918; WWE; 1. DR Genevisible; O94830; HS. 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 FT A-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 FT A-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 FT A-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 //