VMP1_MOUSE
ID VMP1_MOUSE Reviewed; 406 AA.
AC Q99KU0; A2V655; Q3TX07; Q8BHD3;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Vacuole membrane protein 1 {ECO:0000305};
DE AltName: Full=NF-E2-inducible protein 2 {ECO:0000303|Ref.2};
DE Short=Protein ni-2 {ECO:0000303|Ref.2};
GN Name=Vmp1 {ECO:0000303|PubMed:28890335, ECO:0000312|MGI:MGI:1923159};
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 [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Spleen;
RA Yamazaki S., Muta T., Takeshige K.;
RT "A novel lipopolysaccharide-inducible gene (#25).";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Nagata Y., Oda M., Haruta H., Todokoro K.;
RT "NF-E2 induceble novel gene.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [6]
RP FUNCTION.
RX PubMed=17940279; DOI=10.1074/jbc.m706956200;
RA Ropolo A., Grasso D., Pardo R., Sacchetti M.L., Archange C., Lo Re A.,
RA Seux M., Nowak J., Gonzalez C.D., Iovanna J.L., Vaccaro M.I.;
RT "The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in
RT mammalian cells.";
RL J. Biol. Chem. 282:37124-37133(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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).
RN [8]
RP FUNCTION.
RX PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005;
RA Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L.,
RA Chen S., Liu P., Feng D., Zhang H.;
RT "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity
RT to Control ER-Isolation Membrane Contacts for Autophagosome Formation.";
RL Mol. Cell 67:974.e6-989.e6(2017).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31526472; DOI=10.7554/elife.48834;
RA Morishita H., Zhao Y.G., Tamura N., Nishimura T., Kanda Y., Sakamaki Y.,
RA Okazaki M., Li D., Mizushima N.;
RT "A critical role of VMP1 in lipoprotein secretion.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Phospholipid scramblase involved in lipid homeostasis and
CC membrane dynamics processes (By similarity). Has phospholipid
CC scramblase activity toward cholesterol and phosphatidylserine, as well
CC as phosphatidylethanolamine and phosphatidylcholine (By similarity).
CC Required for autophagosome formation: participates in early stages of
CC autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by
CC reequilibrating the leaflets of the ER as lipids are extracted by ATG2
CC (ATG2A or ATG2B) to mediate autophagosome assembly (PubMed:17940279,
CC PubMed:28890335). Regulates ATP2A2 activity to control ER-isolation
CC membrane contacts for autophagosome formation (By similarity). In
CC addition to autophagy, involved in other processes in which
CC phospholipid scramblase activity is required (By similarity). Modulates
CC ER contacts with lipid droplets, mitochondria and endosomes (By
CC similarity). Plays an essential role in formation of cell junctions
CC (PubMed:31526472). Upon stress such as bacterial and viral infection,
CC promotes formation of cytoplasmic vacuoles followed by cell death (By
CC similarity). Involved in the cytoplasmic vacuolization of acinar cells
CC during the early stage of acute pancreatitis (By similarity).
CC {ECO:0000250|UniProtKB:Q91ZQ0, ECO:0000250|UniProtKB:Q96GC9,
CC ECO:0000269|PubMed:17940279, ECO:0000269|PubMed:28890335,
CC ECO:0000269|PubMed:31526472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-
CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663,
CC ChEBI:CHEBI:57262; Evidence={ECO:0000250|UniProtKB:Q96GC9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:Q96GC9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000250|UniProtKB:Q96GC9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-
CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895,
CC ChEBI:CHEBI:64612; Evidence={ECO:0000250|UniProtKB:Q96GC9};
CC -!- SUBUNIT: Interacts with BECN1 (By similarity). Interacts with TJP1.
CC Interacts with TP53INP2. Interacts with TMEM41B. Interacts with ATP2A2,
CC PLN and SLN; competes with PLN and SLN to prevent them from forming an
CC inhibitory complex with ATP2A2. Interacts with ATG2A (By similarity).
CC {ECO:0000250|UniProtKB:Q91ZQ0, ECO:0000250|UniProtKB:Q96GC9}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate
CC compartment membrane {ECO:0000250|UniProtKB:Q91ZQ0}; Multi-pass
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000250|UniProtKB:Q96GC9}; Multi-pass membrane protein
CC {ECO:0000255}. Vacuole membrane {ECO:0000250|UniProtKB:Q91ZQ0}; Multi-
CC pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q96GC9}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: The VTT domain was previously called the SNARE-assoc domain. As
CC there is no evidence that this domain associates with SNARE proteins,
CC it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.
CC {ECO:0000250|UniProtKB:Q96GC9}.
CC -!- DISRUPTION PHENOTYPE: Mutants show early embryonic lethality with lipid
CC accumulation in the visceral endoderm (PubMed:31526472). Intestinal
CC epithelial cell-specific knockout show accumulation of lipids in
CC intestinal epithelial cells (PubMed:31526472).
CC {ECO:0000269|PubMed:31526472}.
CC -!- SIMILARITY: Belongs to the VMP1 family. {ECO:0000305}.
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DR EMBL; AB047550; BAF47367.1; -; mRNA.
DR EMBL; AB076609; BAD06453.1; -; mRNA.
DR EMBL; AK043091; BAC31456.1; -; mRNA.
DR EMBL; AK077443; BAC36803.1; -; mRNA.
DR EMBL; AK159468; BAE35109.1; -; mRNA.
DR EMBL; AL592222; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL604063; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004013; AAH04013.1; -; mRNA.
DR CCDS; CCDS25203.1; -.
DR RefSeq; NP_083754.2; NM_029478.3.
DR RefSeq; XP_006534466.1; XM_006534403.3.
DR AlphaFoldDB; Q99KU0; -.
DR STRING; 10090.ENSMUSP00000018315; -.
DR iPTMnet; Q99KU0; -.
DR PhosphoSitePlus; Q99KU0; -.
DR EPD; Q99KU0; -.
DR MaxQB; Q99KU0; -.
DR PaxDb; Q99KU0; -.
DR PeptideAtlas; Q99KU0; -.
DR PRIDE; Q99KU0; -.
DR ProteomicsDB; 275180; -.
DR TopDownProteomics; Q99KU0; -.
DR Antibodypedia; 31116; 282 antibodies from 27 providers.
DR DNASU; 75909; -.
DR Ensembl; ENSMUST00000018315; ENSMUSP00000018315; ENSMUSG00000018171.
DR GeneID; 75909; -.
DR KEGG; mmu:75909; -.
DR UCSC; uc007ksv.1; mouse.
DR CTD; 81671; -.
DR MGI; MGI:1923159; Vmp1.
DR VEuPathDB; HostDB:ENSMUSG00000018171; -.
DR eggNOG; KOG1109; Eukaryota.
DR GeneTree; ENSGT00390000007230; -.
DR HOGENOM; CLU_033298_0_1_1; -.
DR InParanoid; Q99KU0; -.
DR OMA; EEPYDKR; -.
DR PhylomeDB; Q99KU0; -.
DR TreeFam; TF313699; -.
DR BioGRID-ORCS; 75909; 26 hits in 75 CRISPR screens.
DR ChiTaRS; Vmp1; mouse.
DR PRO; PR:Q99KU0; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99KU0; protein.
DR Bgee; ENSMUSG00000018171; Expressed in placenta labyrinth and 259 other tissues.
DR ExpressionAtlas; Q99KU0; baseline and differential.
DR Genevisible; Q99KU0; MM.
DR GO; GO:0000421; C:autophagosome membrane; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0000407; C:phagophore assembly site; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017128; F:phospholipid scramblase activity; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0016240; P:autophagosome membrane docking; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IDA:GO_Central.
DR GO; GO:0034329; P:cell junction assembly; ISS:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0007566; P:embryo implantation; IDA:MGI.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0042953; P:lipoprotein transport; IMP:UniProtKB.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; ISS:UniProtKB.
DR GO; GO:0140056; P:organelle localization by membrane tethering; ISS:UniProtKB.
DR GO; GO:1901896; P:positive regulation of ATPase-coupled calcium transmembrane transporter activity; ISS:UniProtKB.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Cell adhesion; Cell membrane;
KW Endoplasmic reticulum; Lipid transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Vacuole.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96GC9"
FT CHAIN 2..406
FT /note="Vacuole membrane protein 1"
FT /id="PRO_0000284547"
FT TOPO_DOM 2..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..98
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 327..363
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 385..406
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..316
FT /note="VTT domain"
FT /evidence="ECO:0000250|UniProtKB:Q96GC9"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96GC9"
FT CONFLICT 13
FT /note="I -> V (in Ref. 2; BAD06453 and 5; AAH04013)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="E -> K (in Ref. 3; BAE35109)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="Q -> H (in Ref. 1; BAF47367)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 45960 MW; 2EFE789F29E2CF5D CRC64;
MAENGKNCDQ RRIAMSKDQH NGSLTDPSSV HEKKRRDREE RQNIVLWRQP LITLQYFSLE
TLVVLKEWTS KLWHRQSIVV SFLLLLAALV ATYYVEGAHQ QYVQRIEKQF LLYAYWIGLG
ILSSVGLGTG LHTFLLYLGP HIASVTLAAY ECNSVNFPEP PYPDQIICPE EEGAEGAISL
WSIISKVRIE ACMWGIGTAI GELPPYFMAR AARLSGAEPD DEEYQEFEEM LEHAEAAQDF
ASRAKLAVQK LVQKVGFFGI LACASIPNPL FDLAGITCGH FLVPFWTFFG ATLIGKAIIK
MHIQKIFVIV TFSKHIVEQM VTFIGAVPGI GPSLQKPFQE YLEAQRQKLH HRSEAGTPQG
ENWLSWMFEK LVVAMVCYFV LSIINSMAQN YAKRIQQRLN SEEKTK
