ID   MFS12_HORSE             Reviewed;         478 AA.
AC   A0A3Q2HW92;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 2.
DT   03-AUG-2022, entry version 14.
DE   RecName: Full=Major facilitator superfamily domain-containing protein 12 {ECO:0000305};
GN   Name=MFSD12 {ECO:0000250|UniProtKB:Q6NUT3};
OS   Equus caballus (Horse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX   NCBI_TaxID=9796;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Thoroughbred;
RX   PubMed=19892987; DOI=10.1126/science.1178158;
RA   Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA   Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA   Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA   Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA   Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA   Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA   Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA   Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA   Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA   Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT   "Genome sequence, comparative analysis, and population genetics of the
RT   domestic horse.";
RL   Science 326:865-867(2009).
RN   [2]
RP   POLYMORPHISM.
RX   PubMed=31635058; DOI=10.3390/genes10100826;
RA   Tanaka J., Leeb T., Rushton J., Famula T.R., Mack M., Jagannathan V.,
RA   Flury C., Bachmann I., Eberth J., McDonnell S.M., Penedo M.C.T.,
RA   Bellone R.R.;
RT   "Frameshift variant in MFSD12 explains the mushroom coat color dilution in
RT   shetland ponies.";
RL   Genes (Basel) 10:0-0(2019).
CC   -!- FUNCTION: Transporter that mediates the import of cysteine into
CC       melanosomes, thereby regulating skin/hair pigmentation. In melanosomes,
CC       cysteine import is required both for normal levels of cystine, the
CC       oxidized dimer of cysteine, and provide cysteine for the production of
CC       the cysteinyldopas used in pheomelanin synthesis, thereby regulating
CC       skin/hair pigmentation. Also catalyzes import of cysteine into
CC       lysosomes in non-pigmented cells. {ECO:0000250|UniProtKB:Q6NUT3}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-cysteine(in) = L-cysteine(out); Xref=Rhea:RHEA:29655,
CC         ChEBI:CHEBI:35235; Evidence={ECO:0000250|UniProtKB:Q6NUT3};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29656;
CC         Evidence={ECO:0000250|UniProtKB:Q6NUT3};
CC   -!- SUBCELLULAR LOCATION: Melanosome membrane
CC       {ECO:0000250|UniProtKB:Q6NUT3}; Multi-pass membrane protein
CC       {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q6NUT3}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- POLYMORPHISM: Genetic variants in MFSD12 cause skin/hair pigmentation
CC       variations and are the cause of mushroom coat color in shetland ponies.
CC       {ECO:0000269|PubMed:31635058}.
CC   -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; A0A3Q2HW92; -.
DR   SMR; A0A3Q2HW92; -.
DR   Ensembl; ENSECAT00000034043; ENSECAP00000039637; ENSECAG00000039454.
DR   GeneTree; ENSGT00950000183102; -.
DR   Proteomes; UP000002281; Chromosome 7.
DR   Bgee; ENSECAG00000039454; Expressed in trophoblast and 23 other tissues.
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; ISS:UniProtKB.
DR   GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0033229; F:cysteine transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015293; F:symporter activity; IEA:InterPro.
DR   GO; GO:0008643; P:carbohydrate transport; IEA:InterPro.
DR   GO; GO:1903712; P:cysteine transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0043474; P:pigment metabolic process involved in pigmentation; IMP:UniProtKB.
DR   Gene3D; 1.20.1250.20; -; 2.
DR   InterPro; IPR039672; MFS_2.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   PANTHER; PTHR11328; PTHR11328; 1.
DR   SUPFAM; SSF103473; SSF103473; 1.
PE   3: Inferred from homology;
KW   Acetylation; Amino-acid transport; Lysosome; Melanin biosynthesis;
KW   Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..478
FT                   /note="Major facilitator superfamily domain-containing
FT                   protein 12"
FT                   /id="PRO_0000452203"
FT   TRANSMEM        27..47
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        57..77
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        98..118
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        125..145
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        169..189
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        217..237
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        278..300
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        309..329
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        339..359
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        362..382
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        401..421
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        437..457
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6NUT3"
SQ   SEQUENCE   478 AA;  51577 MW;  CAEE3FFFDE865A5D CRC64;
     MVPGSPAAGA GPAPRALSLA ARLSYAVGHF LNDLCASMWF TYLLLYLHSV RAYSSRGAGL
     LLLLGQVADG LCTPLVGYEA DRAAGRCARC GPRKAWHLVG TVCVLLSFPF IFSPCLGCGA
     ATPEWAALLY YGPFIVVFQF GWAATQIAHL SLIPELVTSD HEKVELTALR YAFTVVANIT
     VFGAAWLLLR LQGSAREGPP DEAGDHLGVQ DVPVFRTLSL CVVGVGAVFS LLFHLGTRER
     RRPPAQEPDE RSPLLAPATA RPLLLWKHWL REPSFYQVGL LYMSTRLIVN LSQTYIAMYL
     TYSLNLPKKF IATIPLVMYV SGFCSSFLMK PVNKCIGRNM TYFVGLLVIL AFAAWVVLVD
     ELGMAVYVAA VLLGGGCATI LVTSLAMTAD LIGPHTHSGA FVYGAMSFSD KVANGLAVMV
     IQSLHPCSLE LCCRACVGFY HWVMVAVTGG VGVAATLSLC SLLVWPIRLR SWDPGAQP