S22AE_MOUSE
ID S22AE_MOUSE Reviewed; 629 AA.
AC Q497L9;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Solute carrier family 22 member 14 {ECO:0000303|PubMed:27811987, ECO:0000303|PubMed:33882315};
GN Name=Slc22a14 {ECO:0000303|PubMed:33882315, ECO:0000312|MGI:MGI:2685974};
GN Synonyms=Gm1128 {ECO:0000312|MGI:MGI:2685974};
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=27811987; DOI=10.1038/srep36468;
RA Maruyama S.Y., Ito M., Ikami Y., Okitsu Y., Ito C., Toshimori K., Fujii W.,
RA Yogo K.;
RT "A critical role of solute carrier 22a14 in sperm motility and male
RT fertility in mice.";
RL Sci. Rep. 6:36468-36468(2016).
RN [4]
RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-275 AND 391-SER--SER-394.
RX PubMed=33882315; DOI=10.1016/j.celrep.2021.109025;
RA Kuang W., Zhang J., Lan Z., Deepak R.N.V.K., Liu C., Ma Z., Cheng L.,
RA Zhao X., Meng X., Wang W., Wang X., Xu L., Jiao Y., Luo Q., Meng Z.,
RA Kee K., Liu X., Deng H., Li W., Fan H., Chen L.;
RT "SLC22A14 is a mitochondrial riboflavin transporter required for sperm
RT oxidative phosphorylation and male fertility.";
RL Cell Rep. 35:109025-109025(2021).
CC -!- FUNCTION: Riboflavin transporter localized at the inner mitochondrial
CC membrane of the spermatozoa midpiece, which is required for male
CC fertility (PubMed:33882315). SLC22A14-mediated riboflavin transport is
CC essential for spermatozoa energy generation and motility: riboflavin is
CC the precursor of FMN and FAD, which are coenzymes of many enzymes in
CC the TCA cycle (the citric acid cycle) in mitochondria
CC (PubMed:33882315). Required for sperm motility and normal sperm
CC flagellar structure (PubMed:27811987, PubMed:33882315).
CC {ECO:0000269|PubMed:27811987, ECO:0000269|PubMed:33882315}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=riboflavin(in) = riboflavin(out); Xref=Rhea:RHEA:35015,
CC ChEBI:CHEBI:57986; Evidence={ECO:0000269|PubMed:33882315};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:33882315}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, cilium, flagellum membrane
CC {ECO:0000269|PubMed:27811987}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to the principle piece of the sperm tail.
CC {ECO:0000269|PubMed:27811987}.
CC -!- TISSUE SPECIFICITY: Testis-specific (at protein level)
CC (PubMed:27811987). Specifically expressed in male germ cells (at
CC protein level) (PubMed:27811987). {ECO:0000269|PubMed:27811987}.
CC -!- DISRUPTION PHENOTYPE: Male mice show severe infertility
CC (PubMed:27811987, PubMed:33882315). Defects are caused by impaired
CC riboflavin transport that suppresses the oxidative phosphorylation and
CC reprograms spermatozoa energy metabolism by disrupting flavoenzyme
CC functions (PubMed:33882315). In mutant spermatozoa, fatty acid beta-
CC oxidation is defective with significantly reduced levels of acyl-
CC carnitines and metabolites from the TCA cycle (the citric acid cycle)
CC and accumulation of triglycerides and free fatty acids
CC (PubMed:33882315). Sperms display abnormal flagellar bending and
CC impaired motility and capacitation (PubMed:27811987).
CC {ECO:0000269|PubMed:27811987, ECO:0000269|PubMed:33882315}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
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DR EMBL; AC055818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC128702; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC100471; AAI00472.1; -; mRNA.
DR CCDS; CCDS23609.1; -.
DR RefSeq; NP_001032838.1; NM_001037749.2.
DR RefSeq; XP_011241282.1; XM_011242980.1.
DR RefSeq; XP_011241283.1; XM_011242981.1.
DR RefSeq; XP_011241284.1; XM_011242982.1.
DR RefSeq; XP_011241285.1; XM_011242983.1.
DR AlphaFoldDB; Q497L9; -.
DR SMR; Q497L9; -.
DR STRING; 10090.ENSMUSP00000091289; -.
DR GlyGen; Q497L9; 4 sites.
DR PhosphoSitePlus; Q497L9; -.
DR PaxDb; Q497L9; -.
DR PRIDE; Q497L9; -.
DR ProteomicsDB; 337333; -.
DR Antibodypedia; 28576; 49 antibodies from 13 providers.
DR Ensembl; ENSMUST00000093775; ENSMUSP00000091289; ENSMUSG00000070280.
DR Ensembl; ENSMUST00000170400; ENSMUSP00000131982; ENSMUSG00000070280.
DR GeneID; 382113; -.
DR KEGG; mmu:382113; -.
DR UCSC; uc009sak.1; mouse.
DR CTD; 9389; -.
DR MGI; MGI:2685974; Slc22a14.
DR VEuPathDB; HostDB:ENSMUSG00000070280; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162395; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q497L9; -.
DR OMA; PGIMEVP; -.
DR OrthoDB; 704438at2759; -.
DR PhylomeDB; Q497L9; -.
DR TreeFam; TF315847; -.
DR BioGRID-ORCS; 382113; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Slc22a14; mouse.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q497L9; protein.
DR Bgee; ENSMUSG00000070280; Expressed in spermatid and 17 other tissues.
DR ExpressionAtlas; Q497L9; baseline and differential.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR GO; GO:0097228; C:sperm principal piece; IDA:MGI.
DR GO; GO:0032217; F:riboflavin transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0048240; P:sperm capacitation; IMP:MGI.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cilium; Flagellum; Glycoprotein; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..629
FT /note="Solute carrier family 22 member 14"
FT /id="PRO_0000452752"
FT TOPO_DOM 1..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..183
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..240
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..295
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..409
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..436
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 437..457
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 458..463
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..496
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..523
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 524..544
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 545..629
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 149
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 275
FT /note="H->A: Strongly reduced riboflavin transport; when
FT associated with 391-A--A-394."
FT /evidence="ECO:0000269|PubMed:33882315"
FT MUTAGEN 391..394
FT /note="SYIS->AYIA: Strongly reduced riboflavin transport;
FT when associated with A-275."
FT /evidence="ECO:0000269|PubMed:33882315"
SQ SEQUENCE 629 AA; 71009 MW; 72012C036A4D86A5 CRC64;
MKEDQNYKTA FGSQNSRDTH RHEISFPSQN WSLEMLLRRL KAIDARRDDK FASVMDAIGE
FGTFQWRLVV LTFIPSILST FFIFSHHFLL TAQRPYCNTS WILEVGPNLT EDEQLNLTLP
RAPNGSFLTC LMYIPVPWDL DSIIHFGLNY TETCKFGWIY PFAHTRSLIN EFDLVCGNEP
NKENGLTVFL SGVLTGSLLF GFLSDKLGRY PIILLSLLGF LIFGFGTAFV SSFYQYLFFR
FFVAQASVGY AICSVSLVME WLVGEHRAQA VILQHSFLTI GVILLTGLAY KVVHWRLLCL
LGGMPMFPLI CNIWVLRESP RWLMVRGKVE EAKKVLCYAA EVNKKTIPLN LLNELQISGK
KVAKASILDF CTNQHLFKVV LAIGCVWFTV SYISFTLNLK MNDFGLDVYF VQMVRSIVAV
PARLCCIILL EYFGRKWALN LTLFLVTSMC LFLLFLPQEP KSTIILTLML AEFSMAGTLS
IFFIYTAELL PTVLRSTGLG MVSLAWVAGA ISSVAIFKQT KTQLPIFFCC LCCVLALCFS
SLVPETGSQS LRDSIEYNIR DSIEPKDRNK DVPMVIAEES MSDIVADSEV TNTTLNAVTF
KPEENSLLNM TLEVPKMDLP VQSLKAQPP
