MFS12_CANLF
ID MFS12_CANLF Reviewed; 478 AA.
AC F1PZV2;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-APR-2021, sequence version 3.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Major facilitator superfamily domain-containing protein 12 {ECO:0000305};
GN Name=MFSD12 {ECO:0000250|UniProtKB:Q6NUT3};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [2]
RP POLYMORPHISM, VARIANT CYS-51, AND CHARACTERIZATION OF VARIANT CYS-51.
RX PubMed=31117290; DOI=10.3390/genes10050386;
RA Hedan B., Cadieu E., Botherel N., Dufaure de Citres C., Letko A.,
RA Rimbault M., Droegemueller C., Jagannathan V., Derrien T., Schmutz S.,
RA Leeb T., Andre C.;
RT "Identification of a missense variant in MFSD12 involved in dilution of
RT phaeomelanin leading to white or cream coat color in dogs.";
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 white or cream coat color in dogs of
CC various breeds lacking eumelanin (PubMed:31117290). Pigmentation
CC variations are caused by dilution of pheomelanin (PubMed:31117290).
CC {ECO:0000269|PubMed:31117290}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; AAEX03012579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F1PZV2; -.
DR SMR; F1PZV2; -.
DR STRING; 9612.ENSCAFP00000028343; -.
DR PaxDb; F1PZV2; -.
DR eggNOG; KOG4830; Eukaryota.
DR HOGENOM; CLU_030068_2_0_1; -.
DR InParanoid; F1PZV2; -.
DR OrthoDB; 605453at2759; -.
DR TreeFam; TF314080; -.
DR Proteomes; UP000002254; Chromosome 20.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0071702; P:organic substance transport; IBA:GO_Central.
DR GO; GO:0043474; P:pigment metabolic process involved in pigmentation; IMP:UniProtKB.
DR GO; GO:0048021; P:regulation of melanin biosynthetic process; 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 1: Evidence at protein level;
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_0000452202"
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 171..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..307
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 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q6NUT3"
FT VARIANT 51
FT /note="R -> C (induces white cream or cream coat color,
FT caused by dilution of pheomelanin)"
FT /evidence="ECO:0000269|PubMed:31117290"
SQ SEQUENCE 478 AA; 51883 MW; BE425E0941272C58 CRC64;
MGPGPPAAGA AAPPRPLSLS ARLSYAVGHF LNDLCASMWF TYLLLYLHSV RAYSSRGAGL
LLLLGHVADG LCTPLVGYEA DRAAGRCVRC GPRKAWHLVG TVCVLLSFPF IFSPCLGCGP
ATPEWAALLY YGPFIVIFQF GWAATQIAHL SLIPELATND HEKVELTALR YAFTVVANIT
VYAAAWFLLH LQGSPNVEMA RDASDQLGIQ DVQVFQNLSL LVIGVGAVFS LLFHLGTREG
RRPQVEEPDE NRPLLAPTTA RPLLLWRHWL REPAFYQVGL LYMSTRLIVN LSQTYIAMYL
TYSLSLPKKF IATIPLVMYL SGFCSSFLMK PVNKCIGRNL TYFTGLLVIL AFAAWVALAD
RLGMAVYAAA VLLGSGCATI LVTSLAMTAD LIGPHTHSGA FVYGAMSFSD KVANGLAVMA
IQSLYPCSLE ICCRACMGFY RWVMVAATGG VGVAATLCLC SLLIWPIRLR SWDPGAQP
