MFS12_MOUSE
ID MFS12_MOUSE Reviewed; 476 AA.
AC Q3U481; Q3U376;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Major facilitator superfamily domain-containing protein 12 {ECO:0000305};
DE AltName: Full=Protein grizzled {ECO:0000303|PubMed:29025994};
GN Name=Mfsd12 {ECO:0000312|MGI:MGI:3604804};
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, and NOD; TISSUE=Bone marrow;
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].
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 IDENTIFICATION BY 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 DISRUPTION PHENOTYPE, AND VARIANT 163-LEU--ALA-165 DEL.
RX PubMed=29025994; DOI=10.1126/science.aan8433;
RG NISC Comparative Sequencing Program;
RA Crawford N.G., Kelly D.E., Hansen M.E.B., Beltrame M.H., Fan S.,
RA Bowman S.L., Jewett E., Ranciaro A., Thompson S., Lo Y., Pfeifer S.P.,
RA Jensen J.D., Campbell M.C., Beggs W., Hormozdiari F., Mpoloka S.W.,
RA Mokone G.G., Nyambo T., Meskel D.W., Belay G., Haut J., Rothschild H.,
RA Zon L., Zhou Y., Kovacs M.A., Xu M., Zhang T., Bishop K., Sinclair J.,
RA Rivas C., Elliot E., Choi J., Li S.A., Hicks B., Burgess S., Abnet C.,
RA Watkins-Chow D.E., Oceana E., Song Y.S., Eskin E., Brown K.M., Marks M.S.,
RA Loftus S.K., Pavan W.J., Yeager M., Chanock S., Tishkoff S.A.;
RT "Loci associated with skin pigmentation identified in African
RT populations.";
RL Science 358:0-0(2017).
RN [5]
RP FUNCTION.
RX PubMed=33208952; DOI=10.1038/s41586-020-2937-x;
RA Adelmann C.H., Traunbauer A.K., Chen B., Condon K.J., Chan S.H.,
RA Kunchok T., Lewis C.A., Sabatini D.M.;
RT "MFSD12 mediates the import of cysteine into melanosomes and lysosomes.";
RL Nature 588:699-704(2020).
CC -!- FUNCTION: Transporter that mediates the import of cysteine into
CC melanosomes, thereby regulating skin/hair pigmentation
CC (PubMed:33208952). In melanosomes, cysteine import is required both for
CC normal levels of cystine, the oxidized dimer of cysteine, and provide
CC cysteine for the production of the cysteinyldopas used in pheomelanin
CC synthesis, thereby regulating skin/hair pigmentation (PubMed:33208952).
CC Also catalyzes import of cysteine into lysosomes in non-pigmented cells
CC (By similarity). {ECO:0000250|UniProtKB:Q6NUT3,
CC ECO:0000269|PubMed:33208952}.
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 -!- DISRUPTION PHENOTYPE: Mice are darker and display a uniformly gray coat
CC color, rather than the expected agouti coat color (PubMed:29025994).
CC Coat color change is caused by a lack of pheomelanin, resulting in
CC white, rather than yellow, banding of hairs (PubMed:29025994).
CC {ECO:0000269|PubMed:29025994}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
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DR EMBL; AK149678; BAE29021.1; -; mRNA.
DR EMBL; AK154386; BAE32552.1; -; mRNA.
DR EMBL; AK154902; BAE32913.1; -; mRNA.
DR EMBL; AK171084; BAE42237.1; -; mRNA.
DR EMBL; BC118620; AAI18621.1; -; mRNA.
DR EMBL; BC119790; AAI19791.1; -; mRNA.
DR CCDS; CCDS35996.1; -.
DR RefSeq; NP_082933.2; NM_028657.3.
DR AlphaFoldDB; Q3U481; -.
DR SMR; Q3U481; -.
DR STRING; 10090.ENSMUSP00000036116; -.
DR iPTMnet; Q3U481; -.
DR PhosphoSitePlus; Q3U481; -.
DR PaxDb; Q3U481; -.
DR PRIDE; Q3U481; -.
DR ProteomicsDB; 292313; -.
DR Antibodypedia; 23242; 68 antibodies from 17 providers.
DR DNASU; 73822; -.
DR Ensembl; ENSMUST00000044844; ENSMUSP00000036116; ENSMUSG00000034854.
DR GeneID; 73822; -.
DR KEGG; mmu:73822; -.
DR UCSC; uc007gho.1; mouse.
DR CTD; 126321; -.
DR MGI; MGI:3604804; Mfsd12.
DR VEuPathDB; HostDB:ENSMUSG00000034854; -.
DR eggNOG; KOG4830; Eukaryota.
DR GeneTree; ENSGT00390000005318; -.
DR HOGENOM; CLU_030068_1_0_1; -.
DR InParanoid; Q3U481; -.
DR OMA; MAMVPEL; -.
DR OrthoDB; 605453at2759; -.
DR PhylomeDB; Q3U481; -.
DR TreeFam; TF314080; -.
DR BioGRID-ORCS; 73822; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Mfsd12; mouse.
DR PRO; PR:Q3U481; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3U481; protein.
DR Bgee; ENSMUSG00000034854; Expressed in epithelium of small intestine and 208 other tissues.
DR ExpressionAtlas; Q3U481; baseline and differential.
DR Genevisible; Q3U481; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; ISO:MGI.
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:0048022; P:negative regulation of melanin biosynthetic process; IMP:CACAO.
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..476
FT /note="Major facilitator superfamily domain-containing
FT protein 12"
FT /id="PRO_0000274523"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 307..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 344..364
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
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 163..165
FT /note="Missing (in grizzled (gr), mice show a uniformly
FT gray coat color, rather than the expected agouti coat
FT color)"
FT /evidence="ECO:0000269|PubMed:29025994"
FT CONFLICT 400
FT /note="V -> A (in Ref. 1; BAE32913)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 51504 MW; 0599DDA9672F5DDB CRC64;
MSPPSDDAGP GPPRTLSLAA RLSFAVGHFL NDLCAGMWFT YLLLFLHSVR GYSSRGAGLL
LLLGQVADGL CTPLVGYEAD RASCVRCGPR KAWHLAGTVC VLLSFPFIFS PCLGCGEATP
EWAALLYYGP FIVVFQFGWA ATQIAHLSLI PELVTSDHEK VELTALRYAF TVVANITVYG
AAWLLLHLQG SAHGEQDISV GDQLGVQDVP VFRNLALLVV GVGAIFSLLF HLGTKEGHRS
QHWGNEPNEH TPLVAPAAQP LLLWKHWLRE PAFYQVGMLY MTTRLIVNLS QTYIAMYLTY
SLSLPKKFIA TIPLVMYLSG FFSSFLMKPV NRRIGRNMTY FTGLLVILAF AAWVALADNL
GVAVYGAAVL LGAGCATILV TSLAMTADLI GPHTHSGAFV YGAMSFSDKV ANGLAVMAVQ
SLHPCPSELC CGACISFYHW VMTAVTGGVG VAAALALCSL LIWPIRIRNR DPRDRP
