MFSD1_MOUSE
ID MFSD1_MOUSE Reviewed; 464 AA.
AC Q9DC37; Q3UWU0; Q8BVZ3;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Major facilitator superfamily domain-containing protein 1;
GN Name=Mfsd1;
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=Bone marrow, Egg, Lung, Tongue, and Wolffian duct;
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 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27981419; DOI=10.1007/s12031-016-0867-8;
RA Perland E., Hellsten S.V., Lekholm E., Eriksson M.M., Arapi V.,
RA Fredriksson R.;
RT "The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC
RT Transporters Affected by Altered Nutrient Intake.";
RL J. Mol. Neurosci. 61:199-214(2017).
RN [5]
RP FUNCTION, INTERACTION WITH GLMP, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DOMAIN, LACK OF GLYCOSYLATION, DISRUPTION PHENOTYPE, MOTIF, AND MUTAGENESIS
RP OF 11-LEU-LEU-12; ASN-76 AND ASN-449.
RX PubMed=31661432; DOI=10.7554/elife.50025;
RA Massa Lopez D., Thelen M., Stahl F., Thiel C., Linhorst A., Sylvester M.,
RA Hermanns-Borgmeyer I., Luellmann-Rauch R., Eskild W., Saftig P., Damme M.;
RT "The lysosomal transporter MFSD1 is essential for liver homeostasis and
RT critically depends on its accessory subunit GLMP.";
RL Elife 8:e50025-e50025(2019).
RN [6]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH GLMP, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 11-LEU-LEU-12.
RX PubMed=32959924; DOI=10.1096/fj.202000912rr;
RA Lopez D.M., Kaehlau L., Jungnickel K.E.J., Loew C., Damme M.;
RT "Characterization of the complex of the lysosomal membrane transporter
RT MFSD1 and its accessory subunit GLMP.";
RL FASEB J. 34:14695-14709(2020).
CC -!- FUNCTION: Lysosomal transporter which is essential for liver
CC homeostasis (PubMed:31661432). Required to maintain stability and
CC lysosomal localization of GLMP (PubMed:31661432, PubMed:32959924).
CC {ECO:0000269|PubMed:31661432, ECO:0000269|PubMed:32959924}.
CC -!- SUBUNIT: Homodimer (PubMed:32959924). Interacts with lysosomal protein
CC GLMP (via lumenal domain); the interaction starts while both proteins
CC are still in the endoplasmic reticulum and is required for stability
CC and lysosomal localization of MFSD1 (PubMed:31661432, PubMed:32959924).
CC {ECO:0000269|PubMed:31661432, ECO:0000269|PubMed:32959924}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:31661432,
CC ECO:0000269|PubMed:32959924}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: In brain, expressed in the cortex, striatum
CC hippocampus, hypothalamus, thalamus and brainstem (at protein level)
CC (PubMed:27981419). Widely expressed with highest levels in kidney and
CC spleen (at protein level) (PubMed:31661432).
CC {ECO:0000269|PubMed:27981419, ECO:0000269|PubMed:31661432}.
CC -!- INDUCTION: After 24 hours of starvation, up-regulated in the brainstem
CC and down-regulated in the cortex and striatum (PubMed:27981419).
CC Following 8 weeks of high-fat diet, down-regulated in brainstem and
CC hypothalamus (PubMed:27981419). {ECO:0000269|PubMed:27981419}.
CC -!- DOMAIN: The dileucine internalization motif is required for lysosomal
CC localization. {ECO:0000269|PubMed:31661432}.
CC -!- PTM: Not N-glycosylated. {ECO:0000269|PubMed:31661432}.
CC -!- DISRUPTION PHENOTYPE: Splenomegaly and development of severe liver
CC disease characterized by extravasation of erythrocytes, sinusoidal
CC damage, loss of liver sinusoidal endothelial cells (LSECs) and fibrosis
CC (PubMed:31661432). Normal life span but there is a significantly higher
CC occurrence of liver tumors in old animals of more than 1.5 years of age
CC (PubMed:31661432). Significantly reduced levels of Glmp
CC (PubMed:31661432, PubMed:32959924). Conditional knockout in LSECs
CC results in a tuberous liver appearance (PubMed:31661432).
CC {ECO:0000269|PubMed:31661432, ECO:0000269|PubMed:32959924}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {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; AK004586; BAB23391.1; -; mRNA.
DR EMBL; AK075859; BAC36010.1; -; mRNA.
DR EMBL; AK135235; BAE22467.1; -; mRNA.
DR EMBL; AK136108; BAE22824.1; -; mRNA.
DR EMBL; AK152444; BAE31224.1; -; mRNA.
DR EMBL; AK159554; BAE35179.1; -; mRNA.
DR EMBL; BC024891; AAH24891.1; -; mRNA.
DR CCDS; CCDS38450.1; -.
DR RefSeq; NP_080089.1; NM_025813.3.
DR AlphaFoldDB; Q9DC37; -.
DR SMR; Q9DC37; -.
DR STRING; 10090.ENSMUSP00000029344; -.
DR iPTMnet; Q9DC37; -.
DR PhosphoSitePlus; Q9DC37; -.
DR SwissPalm; Q9DC37; -.
DR EPD; Q9DC37; -.
DR jPOST; Q9DC37; -.
DR MaxQB; Q9DC37; -.
DR PaxDb; Q9DC37; -.
DR PeptideAtlas; Q9DC37; -.
DR PRIDE; Q9DC37; -.
DR ProteomicsDB; 293464; -.
DR Antibodypedia; 54152; 96 antibodies from 25 providers.
DR DNASU; 66868; -.
DR Ensembl; ENSMUST00000029344; ENSMUSP00000029344; ENSMUSG00000027775.
DR GeneID; 66868; -.
DR KEGG; mmu:66868; -.
DR UCSC; uc008plp.1; mouse.
DR CTD; 64747; -.
DR MGI; MGI:1914118; Mfsd1.
DR VEuPathDB; HostDB:ENSMUSG00000027775; -.
DR eggNOG; KOG4686; Eukaryota.
DR GeneTree; ENSGT00390000011700; -.
DR HOGENOM; CLU_024694_3_1_1; -.
DR InParanoid; Q9DC37; -.
DR OMA; YYSAIFP; -.
DR OrthoDB; 941048at2759; -.
DR PhylomeDB; Q9DC37; -.
DR TreeFam; TF323603; -.
DR BioGRID-ORCS; 66868; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Mfsd1; mouse.
DR PRO; PR:Q9DC37; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9DC37; protein.
DR Bgee; ENSMUSG00000027775; Expressed in stroma of bone marrow and 262 other tissues.
DR Genevisible; Q9DC37; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0061462; P:protein localization to lysosome; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Lysosome; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..464
FT /note="Major facilitator superfamily domain-containing
FT protein 1"
FT /id="PRO_0000273383"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 330..350
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 360..380
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 11..12
FT /note="Dileucine internalization motif"
FT /evidence="ECO:0000269|PubMed:31661432"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MUTAGEN 11..12
FT /note="LL->AA: Mislocalization to the plasma membrane.
FT Localizes to lysosomes when expressed with wild-type Glmp."
FT /evidence="ECO:0000269|PubMed:31661432,
FT ECO:0000269|PubMed:32959924"
FT MUTAGEN 76
FT /note="N->A: No change in molecular weight, indicating lack
FT of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:31661432"
FT MUTAGEN 449
FT /note="N->A: No change in molecular weight, indicating lack
FT of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:31661432"
FT CONFLICT 2
FT /note="E -> Q (in Ref. 1; BAC36010)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="A -> T (in Ref. 1; BAE22824)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 51396 MW; 16FAD48DB8DDFE1F CRC64;
MEDEDGEDRA LLGGRREADS AVHGAPRALS ALCDPSRLAH RLVVLSLMCF LGFGSYFCYD
NPAALQTQVK RDMQVNTTKF MLLYAWYSWP NVVLCFLGGF LIDRIFGIRW GTVIFSCFVC
IGQVIFALGG IFNAFWLMEL GRFVFGIGGE SLAVAQNTYA VSWFKGKELN LVFGLQLSMA
RIGSTVNMNL MGWLYGKIEA LLGSAGHMTL GVTLMIGCIT CIFSLICALA LAYLDRRAEK
ILHKEQGKTG EVIKLRDIKD FSLPLILVFV ICVCYYVAVF PFIGLGKVFF MEKFRFSSQS
ASAINSIVYI ISAPMSPLFG LLVDKTGKNI IWVLYAVAAT LVSHMMLAFT FWNPWIAMCL
LGFSYSLLAC ALWPMVAFIV PEHQLGTAYG FMQSIQNLGL AVIAILAGMI LDSKGYLLLE
VFFIACVSLS LLAVVCLYLV NRAQGGNLNY SAKQRERMKL SHPE
