FITM2_MOUSE
ID FITM2_MOUSE Reviewed; 262 AA.
AC P59266; B9EHX3; Q5BKP7;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 2 {ECO:0000255|HAMAP-Rule:MF_03230, ECO:0000303|PubMed:30923760};
DE AltName: Full=Fat-inducing protein 2 {ECO:0000255|HAMAP-Rule:MF_03230};
GN Name=Fitm2 {ECO:0000255|HAMAP-Rule:MF_03230, ECO:0000312|MGI:MGI:2444508};
GN Synonyms=Fit2 {ECO:0000255|HAMAP-Rule:MF_03230};
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].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Cerebellum;
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 [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].
RC 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 FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18160536; DOI=10.1073/pnas.0708579105;
RA Kadereit B., Kumar P., Wang W.-J., Miranda D., Snapp E.L., Severina N.,
RA Torregroza I., Evans T., Silver D.L.;
RT "Evolutionarily conserved gene family important for fat storage.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:94-99(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, and Liver;
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).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASN-80.
RX PubMed=22106267; DOI=10.1073/pnas.1110817108;
RA Gross D.A., Zhan C., Silver D.L.;
RT "Direct binding of triglyceride to fat storage-inducing transmembrane
RT proteins 1 and 2 is important for lipid droplet formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19581-19586(2011).
RN [7]
RP FUNCTION.
RX PubMed=26504167; DOI=10.1083/jcb.201505067;
RA Choudhary V., Ojha N., Golden A., Prinz W.A.;
RT "A conserved family of proteins facilitates nascent lipid droplet budding
RT from the ER.";
RL J. Cell Biol. 211:261-271(2015).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=30923760; DOI=10.1016/j.heliyon.2019.e01292;
RA Nishihama N., Nagayama T., Makino S., Koishi R.;
RT "Mice lacking fat storage-inducing transmembrane protein 2 show improved
RT profiles upon pressure overload-induced heart failure.";
RL Heliyon 5:e01292-e01292(2019).
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 such as oleoyl-CoA/(9Z)-octadecenoyl-CoA
CC and arachidonoyl-CoA/(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA in the
CC endoplasmic reticulum (ER) lumen (By similarity). This catalytic
CC activity is required for maintaining ER structure and for lipid
CC droplets (LDs) biogenesis, which are lipid storage organelles involved
CC in maintaining lipid and energy homeostasis (PubMed:18160536,
CC PubMed:26504167) (By similarity). Directly binds to diacylglycerol
CC (DAGs) and triacylglycerol, which is also important for LD biogenesis
CC (PubMed:22106267) (By similarity). May support directional budding of
CC nacent LDs from the ER into the cytosol by reducing DAG levels at sites
CC of LD formation (By similarity). Plays a role in the regulation of cell
CC morphology and cytoskeletal organization (By similarity).
CC {ECO:0000255|HAMAP-Rule:MF_03230, ECO:0000269|PubMed:18160536,
CC ECO:0000269|PubMed:22106267, ECO:0000269|PubMed:26504167}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + H2O = adenosine 3',5'-bisphosphate + 2
CC H(+) + S-(9Z-octadecenoyl)-4'-phosphopantetheine;
CC Xref=Rhea:RHEA:65564, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57387, ChEBI:CHEBI:58343, ChEBI:CHEBI:156553;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65565;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = adenosine 3',5'-
CC bisphosphate + 2 H(+) + S-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-4'-
CC phosphopantetheine; Xref=Rhea:RHEA:65568, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57368, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:156554; Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65569;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+)
CC + S-hexadecanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:50032,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:132018; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03230};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03230};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18160536, ECO:0000269|PubMed:22106267}; Multi-pass
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_03230}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in white and
CC brown adipose tissues (at protein level). In the heart, mRNA expression
CC levels do not correlate well with protein levels, suggesting post-
CC transcriptional regulation in this organ.
CC {ECO:0000269|PubMed:18160536}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice display embryonic
CC lethality (PubMed:30923760). Heterozygous knockout mice exhibit
CC shortened left ventricular end-diastolic dimension and shortened left
CC ventricular end-systolic dimension (PubMed:30923760). They also exhibit
CC improved profiles upon pressure overload-induced heart failure
CC (PubMed:30923760). {ECO:0000269|PubMed:30923760}.
CC -!- SIMILARITY: Belongs to the FIT family. {ECO:0000255|HAMAP-
CC 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; AK040900; BAC30737.1; -; mRNA.
DR EMBL; AK043244; BAC31503.1; -; mRNA.
DR EMBL; AK163611; BAE37420.1; -; mRNA.
DR EMBL; AL591488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090994; AAH90994.1; -; mRNA.
DR EMBL; BC138522; AAI38523.1; -; mRNA.
DR EMBL; BC138532; AAI38533.1; -; mRNA.
DR CCDS; CCDS38315.1; -.
DR RefSeq; NP_775573.1; NM_173397.4.
DR AlphaFoldDB; P59266; -.
DR BioGRID; 230786; 258.
DR STRING; 10090.ENSMUSP00000105045; -.
DR iPTMnet; P59266; -.
DR PhosphoSitePlus; P59266; -.
DR EPD; P59266; -.
DR jPOST; P59266; -.
DR MaxQB; P59266; -.
DR PaxDb; P59266; -.
DR PeptideAtlas; P59266; -.
DR PRIDE; P59266; -.
DR ProteomicsDB; 267590; -.
DR Antibodypedia; 51829; 10 antibodies from 1 providers.
DR DNASU; 228859; -.
DR Ensembl; ENSMUST00000109418; ENSMUSP00000105045; ENSMUSG00000048486.
DR GeneID; 228859; -.
DR KEGG; mmu:228859; -.
DR UCSC; uc008nsv.1; mouse.
DR CTD; 128486; -.
DR MGI; MGI:2444508; Fitm2.
DR VEuPathDB; HostDB:ENSMUSG00000048486; -.
DR eggNOG; KOG3750; Eukaryota.
DR GeneTree; ENSGT00530000063693; -.
DR HOGENOM; CLU_049499_1_1_1; -.
DR InParanoid; P59266; -.
DR OMA; ERCAWFL; -.
DR OrthoDB; 1621925at2759; -.
DR PhylomeDB; P59266; -.
DR Reactome; R-MMU-8964572; Lipid particle organization.
DR BioGRID-ORCS; 228859; 17 hits in 74 CRISPR screens.
DR ChiTaRS; Fitm2; mouse.
DR PRO; PR:P59266; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P59266; protein.
DR Bgee; ENSMUSG00000048486; Expressed in interventricular septum and 196 other tissues.
DR Genevisible; P59266; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0010945; F:CoA pyrophosphatase activity; ISS:UniProtKB.
DR GO; GO:0019992; F:diacylglycerol binding; IDA:UniProtKB.
DR GO; GO:0017129; F:triglyceride binding; IDA:UniProtKB.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; IMP:BHF-UCL.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0036115; P:fatty-acyl-CoA catabolic process; ISS:UniProtKB.
DR GO; GO:0140042; P:lipid droplet formation; IDA:UniProtKB.
DR GO; GO:0034389; P:lipid droplet organization; IDA:BHF-UCL.
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:0010890; P:positive regulation of sequestering of triglyceride; IDA:BHF-UCL.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0010866; P:regulation of triglyceride biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0030730; P:sequestering of triglyceride; IMP:MGI.
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 Endoplasmic reticulum; Hydrolase; Lipid metabolism; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..262
FT /note="Acyl-coenzyme A diphosphatase FITM2"
FT /id="PRO_0000021036"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 24..44
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..57
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 79..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 115..145
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 167..190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..218
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 155
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03230"
FT ACT_SITE 214
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03230"
FT MUTAGEN 80
FT /note="N->A: Decreased specific binding to triglyceride.
FT Decreased lipid droplet size. No change in protein
FT expression levels and subcellular localization to the ER."
FT /evidence="ECO:0000269|PubMed:22106267"
SQ SEQUENCE 262 AA; 30016 MW; D28B971C521953BC CRC64;
MEHLERCAWF LRGTLVRATV RRHLPWALVA AMLAGSVVKE LSPLPESYLS NKRNVLNVYF
VKLAWAWTVC LLLPFIALTN YHLTGKTSLV LRRLSTLLVG TAIWYICTAL FSNIEHYTGS
CYQSPALEGI RQEHRSKQQC HREGGFWHGF DISGHSFLLT FCALMIVEEM AVLHEVKTDR
GHHLHAAITT LVVALGFLTF IWVWMFLCTA VYFHDLTQKV FGTMFGLLGW YGTYGYWYLK
SFSPGLPPQS CSLTLKRDTY KK
