FITM2_DROME
ID FITM2_DROME Reviewed; 423 AA.
AC Q9VRJ2; Q8I933; Q95TQ4;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Acyl-coenzyme A diphosphatase FITM2 {ECO:0000255|HAMAP-Rule:MF_03230};
DE EC=3.6.1.- {ECO:0000255|HAMAP-Rule:MF_03230};
DE AltName: Full=Fat storage-inducing transmembrane protein {ECO:0000303|PubMed:28067622, ECO:0000312|FlyBase:FBgn0035586};
DE AltName: Full=Fat storage-inducing transmembrane protein 2 {ECO:0000255|HAMAP-Rule:MF_03230};
DE AltName: Full=Fat-inducing protein 2 {ECO:0000255|HAMAP-Rule:MF_03230};
GN Name=Fitm2 {ECO:0000255|HAMAP-Rule:MF_03230};
GN Synonyms=Fit2 {ECO:0000255|HAMAP-Rule:MF_03230},
GN Fitm {ECO:0000303|PubMed:28067622, ECO:0000312|FlyBase:FBgn0035586};
GN ORFNames=CG10671 {ECO:0000312|FlyBase:FBgn0035586};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28067622; DOI=10.1242/dmm.026476;
RA Zazo Seco C., Castells-Nobau A., Joo S.H., Schraders M., Foo J.N.,
RA van der Voet M., Velan S.S., Nijhof B., Oostrik J., de Vrieze E.,
RA Katana R., Mansoor A., Huynen M., Szklarczyk R., Oti M., Tranebjaerg L.,
RA van Wijk E., Scheffer-de Gooyert J.M., Siddique S., Baets J., de Jonghe P.,
RA Kazmi S.A., Sadananthan S.A., van de Warrenburg B.P., Khor C.C.,
RA Goepfert M.C., Qamar R., Schenck A., Kremer H., Siddiqi S.;
RT "A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor
RT regression and signs of ichthyosis and sensory neuropathy.";
RL Dis. Model. Mech. 10:105-118(2017).
CC -!- FUNCTION: Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes
CC fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-
CC bisphosphate (By similarity). Preferentially hydrolyzes unsaturated
CC long-chain acyl-CoA substrates in the endoplasmic reticulum (ER) lumen
CC (By similarity). This catalytic activity is required for maintaining ER
CC structure and for lipid droplets (LDs) biogenesis, which are lipid
CC storage organelles involved in maintaining lipid and energy homeostasis
CC (PubMed:28067622) (By similarity). May directly bind to diacylglycerol
CC (DAGs) and triacylglycerol, which is also important for LD biogenesis
CC (By similarity). May support directional budding of nacent LDs from the
CC ER into the cytosol by reducing DAG levels at sites of LD formation (By
CC similarity). Plays a role in the regulation of cell morphology and
CC cytoskeletal organization (PubMed:28067622) (By similarity). Required
CC for correct morphology of nociceptive multi-dendritic sensory neurons
CC (PubMed:28067622). Required for normal mechanical amplification in
CC hearing (PubMed:28067622). {ECO:0000255|HAMAP-Rule:MF_03230,
CC ECO:0000269|PubMed:28067622}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acyl-CoA + H2O = adenosine 3',5'-bisphosphate + an acyl-4'-
CC phosphopantetheine + 2 H(+); Xref=Rhea:RHEA:50044, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58342, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:132023; Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50045;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC -!- INTERACTION:
CC Q9VRJ2; O96757: stumps; NbExp=4; IntAct=EBI-75319, EBI-74922;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03230}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_03230}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q9VRJ2-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VRJ2-2; Sequence=VSP_031494;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in loss of
CC auditory sensitivity (PubMed:28067622). In the whole body or
CC specifically in muscle cells or fat body, results in locomotor
CC impairment, uncontrolled and uncoordinated wing movements leading to
CC flightless phenotype (PubMed:28067622). In nociceptive dorsal class IV
CC dendritic arborization C (ddaC) neurons results in altered branching
CC and dendritic field coverage in third instar larvae (PubMed:28067622).
CC In fat body reduces lipid droplet size with aging (PubMed:28067622). In
CC all neurons does not show any of the phenotypes above
CC (PubMed:28067622). {ECO:0000269|PubMed:28067622}.
CC -!- SIMILARITY: Belongs to the FIT family. FIT2 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03230}.
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; AE014296; AAF50803.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN12239.2; -; Genomic_DNA.
DR EMBL; AY058613; AAL13842.1; -; mRNA.
DR RefSeq; NP_647944.2; NM_139687.3. [Q9VRJ2-1]
DR RefSeq; NP_729053.2; NM_168110.3. [Q9VRJ2-2]
DR AlphaFoldDB; Q9VRJ2; -.
DR BioGRID; 64064; 3.
DR IntAct; Q9VRJ2; 1.
DR STRING; 7227.FBpp0076880; -.
DR PaxDb; Q9VRJ2; -.
DR PRIDE; Q9VRJ2; -.
DR EnsemblMetazoa; FBtr0077177; FBpp0076880; FBgn0035586. [Q9VRJ2-2]
DR EnsemblMetazoa; FBtr0077178; FBpp0076881; FBgn0035586. [Q9VRJ2-1]
DR GeneID; 38596; -.
DR KEGG; dme:Dmel_CG10671; -.
DR UCSC; CG10671-RA; d. melanogaster. [Q9VRJ2-1]
DR CTD; 38596; -.
DR FlyBase; FBgn0035586; Fitm.
DR VEuPathDB; VectorBase:FBgn0035586; -.
DR eggNOG; KOG3750; Eukaryota.
DR GeneTree; ENSGT00530000063693; -.
DR HOGENOM; CLU_049499_0_0_1; -.
DR InParanoid; Q9VRJ2; -.
DR OMA; YYHIMIE; -.
DR PhylomeDB; Q9VRJ2; -.
DR Reactome; R-DME-8964572; Lipid particle organization.
DR BioGRID-ORCS; 38596; 0 hits in 3 CRISPR screens.
DR ChiTaRS; CG10671; fly.
DR GenomeRNAi; 38596; -.
DR PRO; PR:Q9VRJ2; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035586; Expressed in crop (Drosophila) and 25 other tissues.
DR Genevisible; Q9VRJ2; DM.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:FlyBase.
DR GO; GO:0010945; F:CoA pyrophosphatase activity; ISS:UniProtKB.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0036115; P:fatty-acyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0140042; P:lipid droplet formation; ISS:UniProtKB.
DR GO; GO:0034389; P:lipid droplet organization; IMP:FlyBase.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0050773; P:regulation of dendrite development; IMP:FlyBase.
DR GO; GO:0007605; P:sensory perception of sound; IMP:FlyBase.
DR GO; GO:0030730; P:sequestering of triglyceride; ISS:FlyBase.
DR HAMAP; MF_03230; FITM2; 1.
DR InterPro; IPR019388; FIT.
DR InterPro; IPR046401; FITM1/2.
DR PANTHER; PTHR23129; PTHR23129; 1.
DR Pfam; PF10261; Scs3p; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Hydrolase; Lipid metabolism;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..423
FT /note="Acyl-coenzyme A diphosphatase FITM2"
FT /id="PRO_0000319577"
FT TOPO_DOM 1..75
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 97..113
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..191
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..299
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 408..423
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 200
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03230"
FT ACT_SITE 294
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03230"
FT VAR_SEQ 1
FT /note="M -> MRWHCLVTGKCVWQPLNFDTHDSFAFTFAFHSQHYQKRQQTTQFSSD
FT TLWTRATAPAM (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_031494"
FT CONFLICT 200
FT /note="H -> D (in Ref. 3; AAL13842)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 423 AA; 47884 MW; 50EA0F971D0809F7 CRC64;
MATKRRPLRP NLGGTAGSPS SSGSNMNFRP GGPDITRSEA RGTRPTAAPT SIREILVMGV
IHLCKKTIFF NTDLKVALYL GSLFVISVIG DFVPFPKTYF ARSDNLFNQY FVKIGWGWTL
LFVVPFLVLS AYTITCGDHK RMLRHHFPRI VIATFFWFFW TKLFNVVENS YGRCTTKGYA
TKSSCLKAGH LWKGFDISGH AFILIHSSLV LIEEARPIIR WETIKEHIRN ERHNRSTAEN
SGTNPLRTLN EEQMRSLQFL YKRLTPIIRT LFIGMAALQL LWDIMLVGTM LYYHRMIEKV
ISGIIAILTW YFTYRFWYPT PGLLPEAPGN GSFSYQREIP TFPFKRPSHL STGAATTSSG
SNSSRTNLNG KAATTGVPRD QQIPTFMGMP LFTSPKAASA AANLLMSDQQ KRERDREQQT
LES
