VP13D_DROME
ID VP13D_DROME Reviewed; 3919 AA.
AC Q9VU08;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Intermembrane lipid transfer protein Vps13D {ECO:0000305};
DE AltName: Full=Vacuolar protein sorting-associated protein 13D {ECO:0000303|PubMed:29307555};
GN Name=Vps13D {ECO:0000312|FlyBase:FBgn0052113};
GN ORFNames=CG32113 {ECO:0000312|FlyBase:FBgn0052113};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=29604224; DOI=10.1002/ana.25220;
RA Seong E., Insolera R., Dulovic M., Kamsteeg E.J., Trinh J., Brueggemann N.,
RA Sandford E., Li S., Ozel A.B., Li J.Z., Jewett T., Kievit A.J.A.,
RA Muenchau A., Shakkottai V., Klein C., Collins C.A., Lohmann K.,
RA van de Warrenburg B.P., Burmeister M.;
RT "Mutations in VPS13D lead to a new recessive ataxia with spasticity and
RT mitochondrial defects.";
RL Ann. Neurol. 83:1075-1088(2018).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF PHE-2308.
RX PubMed=29307555; DOI=10.1016/j.cub.2017.11.064;
RA Anding A.L., Wang C., Chang T.K., Sliter D.A., Powers C.M., Hofmann K.,
RA Youle R.J., Baehrecke E.H.;
RT "Vps13D Encodes a Ubiquitin-Binding Protein that Is Required for the
RT Regulation of Mitochondrial Size and Clearance.";
RL Curr. Biol. 28:287-295(2018).
CC -!- FUNCTION: Mediates the transfer of lipids between membranes at
CC organelle contact sites (By similarity). Functions in promoting
CC mitochondrial clearance by mitochondrial autophagy (mitophagy), also
CC possibly by positively regulating mitochondrial fission
CC (PubMed:29307555). Mitophagy plays an important role in regulating cell
CC health and mitochondrial size and homeostasis (PubMed:29307555).
CC {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:29307555}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29307555}. Lysosome
CC {ECO:0000269|PubMed:29307555}.
CC -!- TISSUE SPECIFICITY: Expressed in intestinal cells (at protein level).
CC {ECO:0000269|PubMed:29307555}.
CC -!- DOMAIN: The UBA domain binds to 'Lys-63'-linked polyubiquitin chains,
CC but neither to linear nor 'Lys-48'-linked polyubiquitin chains.
CC Required for mitochondrial size regulation and for mitochondrial
CC clearance in the intestine. {ECO:0000269|PubMed:29307555}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown leads to 100% lethality
CC at the larval or pupal stage. {ECO:0000269|PubMed:29307555,
CC ECO:0000269|PubMed:29604224}.
CC -!- SIMILARITY: Belongs to the VPS13 family. {ECO:0000305}.
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DR EMBL; AE014296; AAF49887.3; -; Genomic_DNA.
DR RefSeq; NP_729825.2; NM_168512.4.
DR IntAct; Q9VU08; 7.
DR STRING; 7227.FBpp0271898; -.
DR PaxDb; Q9VU08; -.
DR PRIDE; Q9VU08; -.
DR EnsemblMetazoa; FBtr0273390; FBpp0271898; FBgn0052113.
DR GeneID; 39448; -.
DR KEGG; dme:Dmel_CG32113; -.
DR UCSC; CG32113-RB; d. melanogaster.
DR CTD; 55187; -.
DR FlyBase; FBgn0052113; Vps13D.
DR VEuPathDB; VectorBase:FBgn0052113; -.
DR eggNOG; KOG1796; Eukaryota.
DR GeneTree; ENSGT00950000183083; -.
DR HOGENOM; CLU_000131_0_0_1; -.
DR InParanoid; Q9VU08; -.
DR OMA; LFGTCPT; -.
DR OrthoDB; 4159at2759; -.
DR PhylomeDB; Q9VU08; -.
DR SignaLink; Q9VU08; -.
DR BioGRID-ORCS; 39448; 0 hits in 1 CRISPR screen.
DR ChiTaRS; CG32113; fly.
DR GenomeRNAi; 39448; -.
DR PRO; PR:Q9VU08; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0052113; Expressed in oviduct (Drosophila) and 25 other tissues.
DR Genevisible; Q9VU08; DM.
DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IDA:FlyBase.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0000423; P:mitophagy; IMP:UniProtKB.
DR GO; GO:0045053; P:protein retention in Golgi apparatus; IBA:GO_Central.
DR GO; GO:0006623; P:protein targeting to vacuole; IBA:GO_Central.
DR CDD; cd14306; UBA_VP13D; 1.
DR InterPro; IPR000772; Ricin_B_lectin.
DR InterPro; IPR041969; VP13D_UBA.
DR InterPro; IPR026847; VPS13.
DR InterPro; IPR026854; VPS13-like_N.
DR InterPro; IPR031645; VPS13_C.
DR InterPro; IPR031642; VPS13_mid_rpt.
DR InterPro; IPR031646; VPS13_N2.
DR InterPro; IPR009543; VPS13_VAB.
DR PANTHER; PTHR16166; PTHR16166; 2.
DR Pfam; PF12624; Chorein_N; 1.
DR Pfam; PF06650; SHR-BD; 1.
DR Pfam; PF16908; VPS13; 1.
DR Pfam; PF16909; VPS13_C; 1.
DR Pfam; PF16910; VPS13_mid_rpt; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Lectin; Lipid transport; Lysosome; Reference proteome;
KW Transport.
FT CHAIN 1..3919
FT /note="Intermembrane lipid transfer protein Vps13D"
FT /id="PRO_0000445548"
FT DOMAIN 4..114
FT /note="Chorein N-terminal"
FT /evidence="ECO:0000255"
FT DOMAIN 2292..2334
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212,
FT ECO:0000269|PubMed:29307555"
FT DOMAIN 2837..3113
FT /note="SHR-BD"
FT /evidence="ECO:0000255"
FT REGION 706..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3749..3768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3750..3765
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 2308
FT /note="F->A: Loss of 'Lys-63'-linked polyubiquitin chain
FT binding."
FT /evidence="ECO:0000269|PubMed:29307555"
SQ SEQUENCE 3919 AA; 445040 MW; B2F6CD3B6373005F CRC64;
MLRDLITWVL NTYLGKYLEN LNSAQLSVAL LSGEVELENI PIRKDALRSF NLPVEVTAGS
IRKIKLQIPV RQFRTSPWCI SIEGLFCIIC PKNLDNWDYE KEKLQDLEYK LAVLDTAEAG
WRSEKGKQME SYYFSSYNNW LKYGTNMATN IIDNIELKIS DVHFRFEDIV DTGKSKICTG
IKIGSLTAQS CDCDWTNGSY KMNNNEMNYK LVELKELSVY WDLLHEDIKC QSYSNQEILE
KMHSTCELRS HNFIIKPICA TARWKRDKCQ QVIRTKDKPR VSCELLVPEV VIDISKVQRL
QMLDKLSEIR QVKEVRQYRL KRPTCTVESN PIAWWKYATI CHGFDFKKNE EKWLMLKENL
RYMLLYKSII LNPNENLSAA DKEFKAYIES DRKISDLTIM RRICFEKVFT KGFAFESQNE
QGKNMLFHWF PNWMGWYANS PSTPNNEQDE SLKHLEDDIL VALENSLQNS SDLKSDAVFG
HFSIKLLKGL VILQTEDKLN DGRNKSMEMQ FNNFSAYLQL SPQLTSYTVG ISLQEVYLID
KTSSDTMHNY LIKPQTGNTA TPNQLVKNAA LQEDILFQLQ YENCNHLRFQ LNIKSKGLDL
IYNEDAIQWL LDFLADSNSF KYSPRNRVAK KTDFMKNWNE MFSGNEVNRK IWMFEIEIFA
PRIIFLENYK VSNSLMVLLD FGKLEMRKME VKRVIPVIES AVTENTSDDD ETYLTPCSTP
PASEKSGSES PTLLENPKTE SFLNKNVQLE YVLHNKIYDK YLINFTNLQV LVCKYEERWQ
ACLKTSSNFH LIDKFNINLT LEQRNIFTVD PEYPSFMLFG TCPTILIHGN EELINNCCNI
MKPIIKASKE MENIYRGGNT IYASERIKNL AEDDRSRVVI EFVMDQLVIE MQSTERSIAE
LQIIGARAGL TKEPHETNIS MSVHGLLLVD AIQSFGPDFE LLVASHRHVG MDSLSGSLKH
SAIVSPTSPG SPNFFDRATS PHMITKAVQN IKMGDRSTEF CDDEDSTALI SVDIKIVPPN
ESNSMQLHTT SITFNSLDII ANQDTIIEIL NFAKRTLLAQ NIFPSESPES PKEATEAPVD
VVDQVDHKSH NEIFFDFFRL NILLLYTIKR DKFNVGRKVG TVTLTEAKIN ASFQSDLSII
GSLGGIQVID ITSEAFCHPR ILSVGRDQIL RASDTNKQTV LSQLSNEIYS NNYNEETKSD
ESDAISFQSH WSDKTTCTFQ MRMASASYTH CPRFLRDVNA CITYFKRSLR EFATSIGNKA
TDMAKEFVQQ VRAVEQIGPV YPQRNRQDNW LDIIISSPII ILPISNTSTN VLIANLGKIS
CSNAVKCDSD EFNESYTIEI KNTYVYSLNI DEGEYSFNVH PAKNKDAIPI LHDTAITLQL
YAGYSDDNDE DKQLNRFSIK GSMVEALKVS LNRKQYELLL ESIRYATNFS NEVLNESDEL
DQNGDIEPTA NIDAESIIST TIQFSVPVFQ INLQNEYHND LINLTFKNFN VKHISKGFDK
DVEVVLKSVL MEDLKSDLTS PFRNMVTSVD LEQKIKKNEM TSSSCPDLPS YCNSLKNRSS
SVPSCFYNHM QVKVFGGDQK YTSSNKNELG KKKESQTLVI YKSHTGRSAQ NGKLEQTSSI
QFNCLNLAIC VERWYTIFDF FGLVSVDNVN EKYPEEMKLV EKHIDKVCSK LKVSIRSFNF
TLIRNESLLS RVNVSNAVFM ILQDPYSKIV EGCLGSVSVN DLTKYGNIYK QKFLTSGTEA
LNFVYKKKLV DLEALNTLDT DSTLRINMSA VHYIHTKRFS TELHVFVKDL LQLQTPVIRK
LKKHGSEQNM RPSKMKLVIQ ADSPVIVLPS SYNRNEVIIA YLGQFSLKNS FHFASDNNII
SKMSATPSKD EILDVMRIDL VNINLFSGER SSMKAKADQE KDRIIIADMN FLRLGQPFFN
ESCFLHLQLE RNLSADAHRV CPDISVQGTF SKLSGIINIQ QYKLIRSFLN NNIGEQTDDI
YMNYHNNSCT SIERLSTINL MPKNEVSKIV SILISIRILL EDVSLLLALN TSQSAAIEPL
ACIHFLKSTL EIDLFSDGSQ DIDLISSNIL IVDERNESDK SNENVFKNIL EPSKKEVRIE
NSVQVEVHCR KKATFSKYTI MLNNMRVFAL LSFLDQLKSY LQEDSPAPVV NNAANQIAQK
PQIDTSISTE YVVNITDSEI IFAEECSRLD SNAIILKSTT VICYKPNSNI VPLSLDINHL
EIFSCTLDAE EESALSIIDP FTLIIELRSN CLNILIQKHL NIRLSYVDVK LFSRMARLLP
TQTSRPKNVI SKADSDLEKA APLVAMGFEI SDCLYAMQIN NWRINDAAIW LSQQKQNTYR
NPALEMKTAV VDASLISVFI IDDCMDADVP LLEVSLSKFL LNFTFQTQDP NPKETNIRHY
SLGNIDTEVS VNYYNRRLSG WEPVAETWES NLNWKYTKGH LDNKKRFEIG ISSKQMLKLN
VTSTFIELFH MVLKNWTNDF NDNGAKNFRQ RSPFIPFALQ NLSGTPLLFK PIYAPLGDLT
RSDLQQVELI KNWYSVQPNE TKTFDFSQKS KLRHVHSHQL NLHQIFVQIH GWTLIGPISV
DKVGMFFRTT KLDSQFLTKS RIVFDISLIG SAQKLIKVKS SLGVINKLDR NVFLKMTLKG
THSDGLSSIS VIKPNDELSV PLKFIDASLY VAHNTSESDA YEDTGFSNEE ILWKACGKDD
TRQLLAGYDT NKSILYTFVN ISREIYHCKE QNLPGHKITL LPPLKINNML CCDLMFKIHE
HATGRINSSE SVNIYNVNIC QPLNLSITLD NFQLSGQLKI PVSHRGVIEP KLKLIDIQKR
ELHVRVSIQS VPGKGMELYI SAPVWIINKT GLPLIYKQEG TSHTAAGQFE EHETARQVAP
LMFSFSDQEG SPALVLRLGK AYGSNNMWCK SFSTHKDLAD RDLRAENTKG SYAIGISVRR
GRGLYACTTF VTLSPRFHLH NRSGYKLEFM QLCDIVNYDR PDPRKIISAP VDCNFAFHWP
NWDQEQIICV RIPEIECCCW SKGIPIKDVQ SLYINVRNEW GEMFFLRLEI ISKDATFILL
FTDARTLPPP IRIDNCSEVV INFSQLRSKP VWITPVRPQS SLSYVMDDPL GQQILLMEAP
GGNMIEFPIN NKNNIKKTLT YTNFIYIAFQ GTFERSNEEE NTHRQLVLGV RGKKVVIVEK
NSGDRSQLWL MNSNGQLEHE GSTPPIQTND ANAVRLVLDL EKAPNPMEFT NLVVRTPNKQ
RVTTQTWRFE NGRLMCHANM CVQSRFGESG LKPNYEAVVG RTENRASSSK QIPIGQHIVA
QKLRPGSGQL ELSTKMDGPI STIEICDIKI KQNSVFLTPD LLWMHASLNN RQITDKGKVS
FVHEYLINVE LVKGIGISII ARKPCEEIMF ISLDHINCDI VQSALENSLD LNIAYIQIDN
QLLDAVSPIA LHTQTSNDLE ETQNAVVLKL KMLPSPNKNA IIFKYLTLDL KPSTASLEEK
LILKVASFLG YGKINRQNLS VQYQFENTDD KPFLQDMKRY YFENLSIGAT QVRLSAFTSS
KLPVELHETK KALGLTLIKF EDALIELDRY SDKLHFETMD VYRKELKKHY INQVKWHAAA
ILGSVDFLGN PLGFANDLSE GVSGLIFEGS VKSLVKNVTH GISNSTAKLT ETLSDSLGKV
VLDDHDNETR QRILELQSNT SGGHLAAGLK GLGFGLLGGV TSIVRHTYDG ATSDGVPGFL
SGLGKGLVGT VTKPIIGVLD LASETASAVR ETSRDSHRNA PERKRLPRCV TGAPGGLLPL
YSNRQSKGQQ YLYLINQKNF SEKIISYEPN LWSDKEARLR LLVSTEYVRI FSLSDANPTI
MFECHVSEIL SCHPVVTNAG TTPTTSSRAS ASHYIEISTN LPKITRPRIR CRSEECAEAA
SRCINYAKSV FDEREHAVL
