S22AE_HUMAN
ID S22AE_HUMAN Reviewed; 594 AA.
AC Q9Y267; A0AVS9; A1L4H6; B2RCX3; Q6DJT3;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 4.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Solute carrier family 22 member 14 {ECO:0000303|PubMed:33882315};
DE AltName: Full=Organic cation transporter-like 4 {ECO:0000303|PubMed:10072596};
DE Short=ORCTL-4 {ECO:0000303|PubMed:10072596};
GN Name=SLC22A14 {ECO:0000303|PubMed:33882315, ECO:0000312|HGNC:HGNC:8495};
GN Synonyms=OCTL2 {ECO:0000303|PubMed:10231028},
GN ORCTL4 {ECO:0000303|PubMed:10072596};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS THR-144;
RP MET-284 AND GLY-292.
RX PubMed=10072596; DOI=10.1159/000015197;
RA Nishiwaki T., Daigo Y., Tamari M., Fujii Y., Nakamura Y.;
RT "Molecular cloning, mapping, and characterization of two novel human genes,
RT ORCTL3 and ORCTL4, bearing homology to organic-cation transporters.";
RL Cytogenet. Cell Genet. 83:251-255(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-144; MET-284 AND
RP GLY-292.
RX PubMed=10231028; DOI=10.1093/dnares/6.1.37;
RA Daigo Y., Isomura M., Nishiwaki T., Tamari M., Ishikawa S., Kai M.,
RA Takeuchi K., Yamane Y., Hayashi R., Minami M., Fujino M.A., Hojo Y.,
RA Uchiyama I., Takagi T., Nakamura Y.;
RT "Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3.";
RL DNA Res. 6:37-44(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS MET-284; GLY-292 AND
RP ARG-560.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS MET-284 AND
RP GLY-292.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS MET-284; GLY-292 AND
RP ARG-560.
RC TISSUE=Brain;
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 [7]
RP TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-388;
RP TYR-395 AND ARG-487.
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 (By similarity). 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 (By similarity).
CC Required for sperm motility and normal sperm flagellar structure (By
CC similarity). {ECO:0000250|UniProtKB:Q497L9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=riboflavin(in) = riboflavin(out); Xref=Rhea:RHEA:35015,
CC ChEBI:CHEBI:57986; Evidence={ECO:0000269|PubMed:33882315};
CC -!- INTERACTION:
CC Q9Y267; Q96HJ5: MS4A3; NbExp=4; IntAct=EBI-12824155, EBI-12806656;
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:0000250|UniProtKB:Q497L9}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to the principle piece of the sperm tail.
CC {ECO:0000250|UniProtKB:Q497L9}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10072596}.
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; AB011082; BAA76351.1; -; mRNA.
DR EMBL; AB026898; BAA77626.1; -; Genomic_DNA.
DR EMBL; AK315317; BAG37720.1; -; mRNA.
DR EMBL; AP006193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64529.1; -; Genomic_DNA.
DR EMBL; BC075070; AAH75070.1; -; mRNA.
DR EMBL; BC075071; AAH75071.1; -; mRNA.
DR EMBL; BC126482; AAI26483.1; -; mRNA.
DR EMBL; BC130543; AAI30544.1; -; mRNA.
DR CCDS; CCDS2677.1; -.
DR RefSeq; NP_001306962.1; NM_001320033.1.
DR RefSeq; NP_004794.2; NM_004803.4.
DR RefSeq; XP_005265642.1; XM_005265585.4.
DR RefSeq; XP_011532547.1; XM_011534245.2.
DR AlphaFoldDB; Q9Y267; -.
DR SMR; Q9Y267; -.
DR BioGRID; 114789; 7.
DR IntAct; Q9Y267; 2.
DR STRING; 9606.ENSP00000273173; -.
DR TCDB; 2.A.1.19.22; the major facilitator superfamily (mfs).
DR GlyGen; Q9Y267; 4 sites.
DR iPTMnet; Q9Y267; -.
DR PhosphoSitePlus; Q9Y267; -.
DR BioMuta; SLC22A14; -.
DR DMDM; 313104317; -.
DR MassIVE; Q9Y267; -.
DR PaxDb; Q9Y267; -.
DR PeptideAtlas; Q9Y267; -.
DR PRIDE; Q9Y267; -.
DR ProteomicsDB; 85672; -.
DR Antibodypedia; 28576; 49 antibodies from 13 providers.
DR DNASU; 9389; -.
DR Ensembl; ENST00000273173.4; ENSP00000273173.4; ENSG00000144671.11.
DR Ensembl; ENST00000448498.6; ENSP00000396283.1; ENSG00000144671.11.
DR GeneID; 9389; -.
DR KEGG; hsa:9389; -.
DR MANE-Select; ENST00000448498.6; ENSP00000396283.1; NM_001320033.2; NP_001306962.1.
DR UCSC; uc003cib.3; human.
DR CTD; 9389; -.
DR GeneCards; SLC22A14; -.
DR HGNC; HGNC:8495; SLC22A14.
DR HPA; ENSG00000144671; Tissue enriched (testis).
DR MIM; 604048; gene.
DR neXtProt; NX_Q9Y267; -.
DR OpenTargets; ENSG00000144671; -.
DR PharmGKB; PA32815; -.
DR VEuPathDB; HostDB:ENSG00000144671; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162395; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q9Y267; -.
DR OMA; PGIMEVP; -.
DR OrthoDB; 704438at2759; -.
DR PhylomeDB; Q9Y267; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; Q9Y267; -.
DR SignaLink; Q9Y267; -.
DR BioGRID-ORCS; 9389; 9 hits in 1057 CRISPR screens.
DR GenomeRNAi; 9389; -.
DR Pharos; Q9Y267; Tdark.
DR PRO; PR:Q9Y267; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y267; protein.
DR Bgee; ENSG00000144671; Expressed in pancreatic ductal cell and 112 other tissues.
DR ExpressionAtlas; Q9Y267; baseline and differential.
DR Genevisible; Q9Y267; HS.
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; IEA:Ensembl.
DR GO; GO:0032217; F:riboflavin transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl.
DR GO; GO:0048240; P:sperm capacitation; IEA:Ensembl.
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..594
FT /note="Solute carrier family 22 member 14"
FT /id="PRO_0000230784"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..184
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..235
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..297
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..379
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 401..408
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..488
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 489..509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 510..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 534..538
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 539..559
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 560..594
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 566..594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..594
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 108
FT /note="P -> H (in dbSNP:rs9847584)"
FT /id="VAR_055108"
FT VARIANT 112
FT /note="K -> E (in dbSNP:rs2073714)"
FT /id="VAR_055109"
FT VARIANT 144
FT /note="I -> T (in dbSNP:rs194685)"
FT /evidence="ECO:0000269|PubMed:10072596,
FT ECO:0000269|PubMed:10231028"
FT /id="VAR_055110"
FT VARIANT 245
FT /note="S -> L (in dbSNP:rs1078846)"
FT /id="VAR_055111"
FT VARIANT 284
FT /note="V -> M (in dbSNP:rs818818)"
FT /evidence="ECO:0000269|PubMed:10072596,
FT ECO:0000269|PubMed:10231028, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_055112"
FT VARIANT 292
FT /note="S -> G (in dbSNP:rs818817)"
FT /evidence="ECO:0000269|PubMed:10072596,
FT ECO:0000269|PubMed:10231028, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_055113"
FT VARIANT 466
FT /note="L -> P (in dbSNP:rs34256819)"
FT /id="VAR_055114"
FT VARIANT 512
FT /note="A -> V (in dbSNP:rs2070492)"
FT /id="VAR_055115"
FT VARIANT 560
FT /note="P -> R (in dbSNP:rs240033)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_055116"
FT MUTAGEN 388
FT /note="W->A: Strongly reduced riboflavin transport; when
FT associated with A-395 and A-487."
FT /evidence="ECO:0000269|PubMed:33882315"
FT MUTAGEN 395
FT /note="Y->A: Strongly reduced riboflavin transport; when
FT associated with A-388 and A-487."
FT /evidence="ECO:0000269|PubMed:33882315"
FT MUTAGEN 487
FT /note="R->A: Strongly reduced riboflavin transport; when
FT associated with A-388 and A-395."
FT /evidence="ECO:0000269|PubMed:33882315"
FT CONFLICT 282
FT /note="G -> W (in Ref. 1; BAA76351 and 2; BAA77626)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="R -> H (in Ref. 3; BAG37720)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 594 AA; 66684 MW; 7EA290B06222B681 CRC64;
MAGEENFKEE LRSQDASRNL NQHEVAGHPH SWSLEMLLRR LRAVHTKQDD KFANLLDAVG
EFGTFQQRLV ALTFIPSIMS AFFMFADHFV FTAQKPYCNT SWILAVGPHL SKAEQLNLTI
PQAPNGSFLT CFMYLPVPWN LDSIIQFGLN DTDTCQDGWI YPDAKKRSLI NEFDLVCGME
TKKDTAQIMF MAGLPIGSLI FRLITDKMGR YPAILLSLLG LIIFGFGTAF MNSFHLYLFF
RFGISQSVVG YAISSISLAT EWLVGEHRAH AIILGHCFFA VGAVLLTGIA YSLPHWQLLF
LVGGILVIPF ISYIWILPES PRWLMMKGKV KEAKQVLCYA ASVNKKTIPS NLLDELQLPR
KKVTRASVLD FCKNRQLCKV TLVMSCVWFT VSYTYFTLSL RMRELGVSVH FRHVVPSIME
VPARLCCIFL LQQIGRKWSL AVTLLQAIIW CLLLLFLPEG EDGLRLKWPR CPATELKSMT
ILVLMLREFS LAATVTVFFL YTAELLPTVL RATGLGLVSL ASVAGAILSL TIISQTPSLL
PIFLCCVLAI VAFSLSSLLP ETRDQPLSES LNHSSQIRNK VKDMKTKETS SDDV
