DDHD2_MOUSE
ID DDHD2_MOUSE Reviewed; 699 AA.
AC Q80Y98; E9QKK2; Q0VF66; Q6A008; Q9CVE9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Phospholipase DDHD2 {ECO:0000305};
DE EC=3.1.1.-;
DE AltName: Full=DDHD domain-containing protein 2;
DE AltName: Full=SAM, WWE and DDHD domain-containing protein 1;
GN Name=Ddhd2 {ECO:0000312|MGI:MGI:1919358}; Synonyms=Kiaa0725, Samwd1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-149 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). {ECO:0000250}.
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:0000250|UniProtKB:O94830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45129;
CC Evidence={ECO:0000250|UniProtKB:O94830};
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:0000250|UniProtKB:O94830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40944;
CC Evidence={ECO:0000250|UniProtKB:O94830};
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:0000250|UniProtKB:O94830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45133;
CC Evidence={ECO:0000250|UniProtKB:O94830};
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:0000250|UniProtKB:O94830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43969;
CC Evidence={ECO:0000250|UniProtKB:O94830};
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:0000250|UniProtKB:O94830};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38784;
CC Evidence={ECO:0000250|UniProtKB:O94830};
CC -!- SUBUNIT: Forms homooligomers and, to a much smaller extent,
CC heterooligomers with DDHD1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Endoplasmic
CC reticulum-Golgi intermediate compartment {ECO:0000250}. Golgi
CC apparatus, cis-Golgi network {ECO:0000250}. Note=Cycles between the
CC Golgi apparatus and the cytosol. DDHD2 recruitment to the
CC Golgi/endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is
CC regulated by the levels of phosphoinositides, including PI(4)P (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q80Y98-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80Y98-2; Sequence=VSP_029141, VSP_029143;
CC Name=3;
CC IsoId=Q80Y98-3; Sequence=VSP_029142, VSP_029144;
CC -!- DOMAIN: SAM and DDHD domains together are required for phospholipid
CC binding. {ECO:0000250}.
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=AAH46229.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI18963.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD32288.1; Type=Erroneous initiation; Note=Extended 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; AK173010; BAD32288.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AC156990; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC046229; AAH46229.1; ALT_INIT; mRNA.
DR EMBL; BC118962; AAI18963.1; ALT_FRAME; mRNA.
DR EMBL; AK008529; BAB25722.1; -; mRNA.
DR CCDS; CCDS52529.1; -. [Q80Y98-1]
DR RefSeq; NP_082378.1; NM_028102.1. [Q80Y98-1]
DR RefSeq; XP_006509260.2; XM_006509197.3. [Q80Y98-1]
DR RefSeq; XP_006509261.1; XM_006509198.3. [Q80Y98-1]
DR AlphaFoldDB; Q80Y98; -.
DR SMR; Q80Y98; -.
DR STRING; 10090.ENSMUSP00000033975; -.
DR ChEMBL; CHEMBL3259495; -.
DR iPTMnet; Q80Y98; -.
DR PhosphoSitePlus; Q80Y98; -.
DR EPD; Q80Y98; -.
DR jPOST; Q80Y98; -.
DR MaxQB; Q80Y98; -.
DR PaxDb; Q80Y98; -.
DR PeptideAtlas; Q80Y98; -.
DR PRIDE; Q80Y98; -.
DR ProteomicsDB; 279509; -. [Q80Y98-1]
DR ProteomicsDB; 279510; -. [Q80Y98-2]
DR ProteomicsDB; 279511; -. [Q80Y98-3]
DR Antibodypedia; 4449; 80 antibodies from 19 providers.
DR Ensembl; ENSMUST00000033975; ENSMUSP00000033975; ENSMUSG00000061313. [Q80Y98-1]
DR GeneID; 72108; -.
DR KEGG; mmu:72108; -.
DR UCSC; uc009lgv.2; mouse. [Q80Y98-1]
DR UCSC; uc009lgw.2; mouse. [Q80Y98-2]
DR CTD; 23259; -.
DR MGI; MGI:1919358; Ddhd2.
DR VEuPathDB; HostDB:ENSMUSG00000061313; -.
DR eggNOG; KOG2308; Eukaryota.
DR GeneTree; ENSGT00940000156808; -.
DR HOGENOM; CLU_006932_0_0_1; -.
DR InParanoid; Q80Y98; -.
DR OMA; DEWGATP; -.
DR OrthoDB; 777968at2759; -.
DR PhylomeDB; Q80Y98; -.
DR TreeFam; TF314133; -.
DR Reactome; R-MMU-1483166; Synthesis of PA.
DR BioGRID-ORCS; 72108; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Ddhd2; mouse.
DR PRO; PR:Q80Y98; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q80Y98; protein.
DR Bgee; ENSMUSG00000061313; Expressed in brown adipose tissue and 262 other tissues.
DR ExpressionAtlas; Q80Y98; baseline and differential.
DR Genevisible; Q80Y98; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
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; ISO:MGI.
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; IDA:MGI.
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; IDA:MGI.
DR GO; GO:0034389; P:lipid droplet organization; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0000266; P:mitochondrial fission; IMP:MGI.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IMP:MGI.
DR GO; GO:0019433; P:triglyceride catabolic process; IMP:MGI.
DR GO; GO:0008542; P:visual learning; IMP:MGI.
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; Golgi apparatus; Hydrolase;
KW Lipid degradation; Lipid metabolism; Phosphoprotein; Reference proteome.
FT CHAIN 1..699
FT /note="Phospholipase DDHD2"
FT /id="PRO_0000309331"
FT DOMAIN 30..112
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 383..445
FT /note="SAM"
FT DOMAIN 484..688
FT /note="DDHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00378"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 599..635
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 610..631
FT /note="Basic and acidic residues"
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:0007744|PubMed:21183079"
FT VAR_SEQ 1
FT /note="M -> MRGQKVRFSSFKASAQARPPVRVPHAPSACPARARRPTSARRRSQVS
FT RESPSPHRTSRDTSEDLSAPPALTGSAASAGALLSTAGALRSPRCGDWGAAAGSARPPR
FT PAWESEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029141"
FT VAR_SEQ 283..382
FT /note="IDLQRITLPSINRLRHFTNDTILDVFFYNSPTYCQTIVDTVASEMNRIYTLF
FT LQRNPDFKGGVSIAGHSLGSLILFDILTNQKNSIGDIDSEKGSLSSAE -> M (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_029142"
FT VAR_SEQ 448..528
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029143"
FT VAR_SEQ 529..562
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_029144"
FT CONFLICT 637
FT /note="S -> N (in Ref. 1; BAD32288 and 3; AAI18963)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 699 AA; 79577 MW; BB12F07F9200ACC7 CRC64;
MSSGESHQEQ LSQSDPSPSP NSCSSFELID MDASSSYEPV SPHWFYCKVL DSKELWIPFN
SEDSQQLEDA YGSGKDCNER IVPTDGGRYD VHLGERMRYA VYWDELPSEV RRCTWFYKGD
KDNKYVPYSE SFSQVLEDTY MLAVTLDEWK KKIESPNREI IVLHNPKLMV HYQPIAGSDE
WGSTSTEQGR PRSVKRGVEN IPVDIHCGEP LQIDHLVFVV HGIGPACDLR FRSIVQCVND
FRSVSLNLLQ THFKKAQENE QIGRVEFLPV NWHSPLHSTG VDIDLQRITL PSINRLRHFT
NDTILDVFFY NSPTYCQTIV DTVASEMNRI YTLFLQRNPD FKGGVSIAGH SLGSLILFDI
LTNQKNSIGD IDSEKGSLSS AEDRGDASTL EEDLKKLQLS EFVTVFEKEK VDREALALCT
DRDLQEMGIP LGPRKKILNH FSARKNSVSI NRPAMSASEV NISKENGDYL DVGIGQVSVK
YPRLNYKPEI FFAFGSPIGM FLTVRGLRRI DPNYKFPTCK GFFNIYHPFD PVAYRIEPMV
APGIEFEPML IPHHKGRKRM HLELREGLTR MSMDLKNNLL GSLRMAWKSF TRGPYPALQA
SETAEETEAE PESSSEKSNE ANTEEPPVEV KEEAPISVGM LNGGQRIDYV LQEKPIESFN
EYLFALQSHL CYWESEDTVL LVLKEIYQTQ GVFLDQPLQ
