ID U4UMW9_DENPD Unreviewed; 497 AA. AC U4UMW9; DT 11-DEC-2013, integrated into UniProtKB/TrEMBL. DT 11-DEC-2013, sequence version 1. DT 27-NOV-2024, entry version 30. DE RecName: Full=Lysosomal dipeptide transporter MFSD1 {ECO:0000256|ARBA:ARBA00044985}; DE AltName: Full=Major facilitator superfamily domain-containing protein 1 {ECO:0000256|ARBA:ARBA00045018}; GN ORFNames=D910_08841 {ECO:0000313|EMBL:ERL91511.1}; OS Dendroctonus ponderosae (Mountain pine beetle). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Coleoptera; Polyphaga; Cucujiformia; OC Curculionidae; Scolytinae; Dendroctonus. OX NCBI_TaxID=77166 {ECO:0000313|EMBL:ERL91511.1, ECO:0000313|Proteomes:UP000030742}; RN [1] {ECO:0000313|EMBL:ERL91511.1, ECO:0000313|Proteomes:UP000030742} RP NUCLEOTIDE SEQUENCE. RX PubMed=23537049; DOI=10.1186/gb-2013-14-3-r27; RA Keeling C.I., Yuen M.M., Liao N.Y., Docking T.R., Chan S.K., Taylor G.A., RA Palmquist D.L., Jackman S.D., Nguyen A., Li M., Henderson H., Janes J.K., RA Zhao Y., Pandoh P., Moore R., Sperling F.A., Huber D.P., Birol I., RA Jones S.J., Bohlmann J.; RT "Draft genome of the mountain pine beetle, Dendroctonus ponderosae Hopkins, RT a major forest pest."; RL Genome Biol. 14:R27-R27(2013). CC -!- FUNCTION: Lysosomal dipeptide uniporter that selectively exports CC lysine, arginine or histidine-containing dipeptides with a net positive CC charge from the lysosome lumen into the cytosol. Could play a role in a CC specific type of protein O-glycosylation indirectly regulating CC macrophages migration and tissue invasion. Also essential for liver CC homeostasis. {ECO:0000256|ARBA:ARBA00045709}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alanyl-L-lysine(out) = L-alanyl-L-lysine(in); CC Xref=Rhea:RHEA:79415, ChEBI:CHEBI:192470; CC Evidence={ECO:0000256|ARBA:ARBA00044919}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alpha-aminoacyl-L-arginine(out) = L-alpha-aminoacyl-L- CC arginine(in); Xref=Rhea:RHEA:79367, ChEBI:CHEBI:229968; CC Evidence={ECO:0000256|ARBA:ARBA00044881}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alpha-aminoacyl-L-histidine(out) = L-alpha-aminoacyl-L- CC histidine(in); Xref=Rhea:RHEA:79375, ChEBI:CHEBI:229967; CC Evidence={ECO:0000256|ARBA:ARBA00044884}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alpha-aminoacyl-L-lysine(out) = L-alpha-aminoacyl-L- CC lysine(in); Xref=Rhea:RHEA:79383, ChEBI:CHEBI:229966; CC Evidence={ECO:0000256|ARBA:ARBA00044893}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-arginyl-L-alpha-amino acid(out) = L-arginyl-L-alpha-amino CC acid(in); Xref=Rhea:RHEA:79371, ChEBI:CHEBI:84315; CC Evidence={ECO:0000256|ARBA:ARBA00044899}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-arginyl-glycine(out) = L-arginyl-glycine(in); CC Xref=Rhea:RHEA:79391, ChEBI:CHEBI:229955; CC Evidence={ECO:0000256|ARBA:ARBA00044903}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-aspartyl-L-lysine(out) = L-aspartyl-L-lysine(in); CC Xref=Rhea:RHEA:79411, ChEBI:CHEBI:229953; CC Evidence={ECO:0000256|ARBA:ARBA00044898}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidyl-L-alpha-amino acid(out) = L-histidyl-L-alpha-amino CC acid(in); Xref=Rhea:RHEA:79379, ChEBI:CHEBI:229964; CC Evidence={ECO:0000256|ARBA:ARBA00044912}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidyl-glycine(out) = L-histidyl-glycine(in); CC Xref=Rhea:RHEA:79395, ChEBI:CHEBI:229957; CC Evidence={ECO:0000256|ARBA:ARBA00044878}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-L-alanine(out) = L-lysyl-L-alanine(in); CC Xref=Rhea:RHEA:79399, ChEBI:CHEBI:229954; CC Evidence={ECO:0000256|ARBA:ARBA00044876}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-L-alpha-amino acid(out) = L-lysyl-L-alpha-amino CC acid(in); Xref=Rhea:RHEA:79387, ChEBI:CHEBI:229965; CC Evidence={ECO:0000256|ARBA:ARBA00044891}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-L-lysine(out) = L-lysyl-L-lysine(in); CC Xref=Rhea:RHEA:79403, ChEBI:CHEBI:229956; CC Evidence={ECO:0000256|ARBA:ARBA00044900}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-glycine(out) = L-lysyl-glycine(in); CC Xref=Rhea:RHEA:79407, ChEBI:CHEBI:191202; CC Evidence={ECO:0000256|ARBA:ARBA00044924}; CC -!- SUBUNIT: Homodimer. Interacts with lysosomal protein GLMP (via lumenal CC domain); the interaction starts while both proteins are still in the CC endoplasmic reticulum and is required for stabilization of MFSD1 in CC lysosomes but has no direct effect on its targeting to lysosomes or CC transporter activity. {ECO:0000256|ARBA:ARBA00046376}. CC -!- SUBCELLULAR LOCATION: Lysosome membrane CC {ECO:0000256|ARBA:ARBA00004155}; Multi-pass membrane protein CC {ECO:0000256|ARBA:ARBA00004155}. CC -!- SIMILARITY: Belongs to the major facilitator superfamily. CC {ECO:0000256|ARBA:ARBA00008335}. 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; KB632288; ERL91511.1; -; Genomic_DNA. DR AlphaFoldDB; U4UMW9; -. DR STRING; 77166.U4UMW9; -. DR Proteomes; UP000030742; Unassembled WGS sequence. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro. DR CDD; cd17340; MFS_MFSD1; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 2. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR052187; MFSD1. DR PANTHER; PTHR23512; MAJOR FACILITATOR SUPERFAMILY DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR23512:SF3; MAJOR FACILITATOR SUPERFAMILY DOMAIN-CONTAINING PROTEIN 1; 1. DR Pfam; PF07690; MFS_1; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. PE 3: Inferred from homology; KW Lysosome {ECO:0000256|ARBA:ARBA00023228}; KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius}; KW Reference proteome {ECO:0000313|Proteomes:UP000030742}; KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989, KW ECO:0000256|SAM:Phobius}; Transport {ECO:0000256|ARBA:ARBA00022448}. FT TRANSMEM 32..52 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 73..95 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 107..125 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 203..225 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 255..274 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 286..306 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 313..332 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 338..363 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 370..389 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TRANSMEM 401..423 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 33..426 FT /note="Major facilitator superfamily (MFS) profile" FT /evidence="ECO:0000259|PROSITE:PS50850" SQ SEQUENCE 497 AA; 55180 MW; 7A39A8E8B95E5317 CRC64; MEGGPNIQVA VEDEETCCDR AYHLCCHPSG KAHRFLALIF MCILGFGSYF CYDNPSALQK QFKQDLNLTE TQFTALYSVY SWPNVVMCFV GGFLIDQVFG IRAGANIFMG LTLIGQLLFT AAVYVNQYWL MILGRFVFGV GSESLAVAQN NYAVLWFKGK ELNMVFGLQM SIARMGSTVN FWLMEPIYQW VSTSSTGTKI LGLSLLIASA TCLFSTICSL ILGYMDKRAE RMTRRSEART TEAVRITDAK HFKGTFWLVT CICVTYYNAI FPFISLAQMN VKDADHISSL IYLISGIISP FTGFLIDKIG LNILWILIST VGTIIAHLLL GFTACDPYIG VIILGVAYSV LASGLWPLVA VIIPEYQLGT AYGVCQAVQN LGLAIVSIIT GSIVDKWGFR VLSMFFLGNL FMAFMFTSIL LIIDQRERGV LNLTPGGRKK HQEVILEEIV QRQRLLSAEQ LPVDVEAPAQ ESADNNSGSD DTRLRNRYIS AVDRLSS //