ID SL9C1_HUMAN Reviewed; 1177 AA. AC Q4G0N8; Q6ZRP4; Q7RTP2; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 2. DT 24-JUL-2024, entry version 143. DE RecName: Full=Solute carrier family 9 member C1; DE AltName: Full=Na(+)/H(+) exchanger 10; DE Short=NHE-10; DE AltName: Full=Sodium/hydrogen exchanger 10; DE AltName: Full=Solute carrier family 9 member 10; DE AltName: Full=Sperm-specific Na(+)/H(+) exchanger; DE Short=sNHE; GN Name=SLC9C1; Synonyms=SLC9A10; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-158; RP VAL-286; MET-348; VAL-364; ALA-424; ILE-705; LYS-732; ILE-768 AND SER-826. 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 IDENTIFICATION. RX PubMed=12783626; DOI=10.1186/1471-2164-4-22; RA Oduru S., Campbell J.L., Karri S., Hendry W.J., Khan S.A., Williams S.C.; RT "Gene discovery in the hamster: a comparative genomics approach for gene RT annotation by sequencing of hamster testis cDNAs."; RL BMC Genomics 4:22-22(2003). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY, AND CAUTION. RX PubMed=37669933; DOI=10.1038/s41467-023-40855-0; RA Grahn E., Kaufmann S.V., Askarova M., Ninov M., Welp L.M., Berger T.K., RA Urlaub H., Kaupp U.B.; RT "Control of intracellular pH and bicarbonate by CO2 diffusion into human RT sperm."; RL Nat. Commun. 14:5395-5395(2023). CC -!- FUNCTION: Sperm-specific solute carrier involved in intracellular pH CC regulation of spermatozoa. Required for sperm motility and fertility. CC Involved in sperm cell hyperactivation, a step needed for sperm CC motility which is essential late in the preparation of sperm for CC fertilization. Required for the expression and bicarbonate regulation CC of the soluble adenylyl cyclase (sAC) (By similarity). CC {ECO:0000250|UniProtKB:Q6UJY2}. CC -!- SUBUNIT: Interacts with soluble adenylyl cyclase (sAC). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane CC {ECO:0000250|UniProtKB:Q6UJY2}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q4G0N8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q4G0N8-2; Sequence=VSP_027010; CC -!- TISSUE SPECIFICITY: Sperm. {ECO:0000269|PubMed:37669933}. CC -!- DOMAIN: The ion transport-like region is related to the membrane CC segments of voltage-gated ion channels. Its function is unknown (By CC similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1) CC transporter (TC 2.A.36) family. {ECO:0000305}. CC -!- CAUTION: The transport mechanisms that drive proton efflux in sperm CC appear to be species-specific. While sea urchin SLC9C1 ortholog CC functions as a voltage-gated and cAMP-sensitive sodium:proton exchanger CC that dominantly regulates proton efflux in sperm, no such transporter CC activity is observed for human SLC9C1. Consistently, functionally CC conserved residues in the transport, voltage sensor and cyclic CC nucleotide-binding domains present in sea urchin SLC9C1 are missing in CC mammalian SLC9C1, suggesting alternative transport mechanisms between CC species. The transport activity of SLC9C1 remains to be elucidated. CC {ECO:0000269|PubMed:37669933}. CC -!- SEQUENCE CAUTION: CC Sequence=DAA01462.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK128084; BAC87265.1; -; mRNA. DR EMBL; BC044801; AAH44801.1; -; mRNA. DR EMBL; BK001328; DAA01462.1; ALT_SEQ; mRNA. DR CCDS; CCDS33817.1; -. [Q4G0N8-1] DR CCDS; CCDS82818.1; -. [Q4G0N8-2] DR RefSeq; NP_001307460.1; NM_001320531.1. [Q4G0N8-2] DR RefSeq; NP_898884.1; NM_183061.2. [Q4G0N8-1] DR AlphaFoldDB; Q4G0N8; -. DR SMR; Q4G0N8; -. DR BioGRID; 130083; 2. DR IntAct; Q4G0N8; 1. DR STRING; 9606.ENSP00000306627; -. DR TCDB; 2.A.36.7.5; the monovalent cation:proton antiporter-1 (cpa1) family. DR GlyCosmos; Q4G0N8; 1 site, No reported glycans. DR GlyGen; Q4G0N8; 1 site. DR iPTMnet; Q4G0N8; -. DR PhosphoSitePlus; Q4G0N8; -. DR BioMuta; SLC9C1; -. DR DMDM; 158563886; -. DR MassIVE; Q4G0N8; -. DR PaxDb; 9606-ENSP00000306627; -. DR PeptideAtlas; Q4G0N8; -. DR ProteomicsDB; 62117; -. [Q4G0N8-1] DR ProteomicsDB; 62118; -. [Q4G0N8-2] DR Antibodypedia; 52176; 21 antibodies from 15 providers. DR DNASU; 285335; -. DR Ensembl; ENST00000305815.10; ENSP00000306627.5; ENSG00000172139.15. [Q4G0N8-1] DR Ensembl; ENST00000487372.5; ENSP00000420688.1; ENSG00000172139.15. [Q4G0N8-2] DR Ensembl; ENST00000642317.2; ENSP00000495147.1; ENSG00000285044.2. [Q4G0N8-1] DR Ensembl; ENST00000647463.1; ENSP00000495048.1; ENSG00000285044.2. [Q4G0N8-2] DR GeneID; 285335; -. DR KEGG; hsa:285335; -. DR MANE-Select; ENST00000305815.10; ENSP00000306627.5; NM_183061.3; NP_898884.1. DR UCSC; uc003dyu.4; human. [Q4G0N8-1] DR AGR; HGNC:31401; -. DR CTD; 285335; -. DR DisGeNET; 285335; -. DR GeneCards; SLC9C1; -. DR HGNC; HGNC:31401; SLC9C1. DR HPA; ENSG00000172139; Group enriched (skin, testis). DR MIM; 612738; gene. DR neXtProt; NX_Q4G0N8; -. DR OpenTargets; ENSG00000172139; -. DR PharmGKB; PA134914619; -. DR VEuPathDB; HostDB:ENSG00000172139; -. DR eggNOG; KOG1965; Eukaryota. DR GeneTree; ENSGT00940000162055; -. DR HOGENOM; CLU_003400_1_0_1; -. DR InParanoid; Q4G0N8; -. DR OMA; RVVTFDC; -. DR OrthoDB; 1220385at2759; -. DR PhylomeDB; Q4G0N8; -. DR TreeFam; TF328865; -. DR PathwayCommons; Q4G0N8; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR SignaLink; Q4G0N8; -. DR BioGRID-ORCS; 285335; 9 hits in 1142 CRISPR screens. DR ChiTaRS; SLC9C1; human. DR GeneWiki; SLC9A10; -. DR GenomeRNAi; 285335; -. DR Pharos; Q4G0N8; Tdark. DR PRO; PR:Q4G0N8; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q4G0N8; Protein. DR Bgee; ENSG00000172139; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 63 other cell types or tissues. DR ExpressionAtlas; Q4G0N8; baseline and differential. DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005216; F:monoatomic ion channel activity; IEA:InterPro. DR GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central. DR GO; GO:0015385; F:sodium:proton antiporter activity; IBA:GO_Central. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0030317; P:flagellated sperm motility; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central. DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central. DR GO; GO:0098719; P:sodium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW. DR CDD; cd00038; CAP_ED; 1. DR Gene3D; 6.10.140.1330; -; 1. DR Gene3D; 2.60.120.10; Jelly Rolls; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1. DR InterPro; IPR006153; Cation/H_exchanger. DR InterPro; IPR018422; Cation/H_exchanger_CPA1. DR InterPro; IPR000595; cNMP-bd_dom. DR InterPro; IPR018490; cNMP-bd_dom_sf. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10110; SODIUM/HYDROGEN EXCHANGER; 1. DR PANTHER; PTHR10110:SF87; SODIUM_HYDROGEN EXCHANGER 10; 1. DR Pfam; PF00027; cNMP_binding; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF00999; Na_H_Exchanger; 1. DR SUPFAM; SSF51206; cAMP-binding domain-like; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR PROSITE; PS50042; CNMP_BINDING_3; 1. PE 1: Evidence at protein level; KW Alternative splicing; Antiport; Cell membrane; Cell projection; Cilium; KW Developmental protein; Differentiation; Flagellum; Ion transport; Membrane; KW Reference proteome; Sodium; Sodium transport; Spermatogenesis; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..1177 FT /note="Solute carrier family 9 member C1" FT /id="PRO_0000295704" FT TOPO_DOM 1..17 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 18..37 FT /note="Helical; Name=TM1" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 38..42 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 43..60 FT /note="Helical; Name=TM2" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 61..76 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 77..93 FT /note="Helical; Name=TM3" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 94..103 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 104..129 FT /note="Helical; Name=TM4" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 130..135 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 136..161 FT /note="Helical; Name=TM5" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 162..164 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 165..190 FT /note="Helical; Name=TM6" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 191..204 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 205..236 FT /note="Helical; Name=TM7, linker" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 237..240 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 241..262 FT /note="Helical; Name=TM8" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 263..265 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 266..279 FT /note="Helical; Name=TM9" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 280..286 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 287..319 FT /note="Helical; Name=TM10" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 320..324 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 325..354 FT /note="Helical; Name=TM11" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 355..360 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 361..391 FT /note="Helical; Name=TM12" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 392..395 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 396..426 FT /note="Helical; Name=TM13" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 427..612 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 613..633 FT /note="Helical; Name=S1" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 634..637 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 638..664 FT /note="Helical; Name=S2" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 665..671 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 672..696 FT /note="Helical; Name=S3" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 697..704 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 705..731 FT /note="Helical; Name=S4" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT TOPO_DOM 732..1177 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 104..191 FT /note="Transport core domain" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT REGION 325..426 FT /note="Transport core domain" FT /evidence="ECO:0000250|UniProtKB:A3RL54" FT REGION 598..678 FT /note="Ion transport-like" FT VAR_SEQ 294..341 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027010" FT VARIANT 158 FT /note="I -> V (in dbSNP:rs9828502)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033324" FT VARIANT 286 FT /note="I -> V (in dbSNP:rs9872691)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033325" FT VARIANT 348 FT /note="I -> M (in dbSNP:rs9809404)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033326" FT VARIANT 364 FT /note="I -> V (in dbSNP:rs9809384)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_050233" FT VARIANT 424 FT /note="T -> A (in dbSNP:rs6768523)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033327" FT VARIANT 705 FT /note="T -> I (in dbSNP:rs4434123)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033328" FT VARIANT 732 FT /note="Q -> K (in dbSNP:rs6781844)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033329" FT VARIANT 768 FT /note="S -> I (in dbSNP:rs9288938)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_033330" FT VARIANT 826 FT /note="G -> S (in dbSNP:rs28516377)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_061369" FT CONFLICT 74 FT /note="M -> I (in Ref. 1; BAC87265)" FT /evidence="ECO:0000305" FT CONFLICT 785 FT /note="E -> D (in Ref. 1; BAC87265)" FT /evidence="ECO:0000305" FT CONFLICT 788 FT /note="I -> T (in Ref. 1; BAC87265)" FT /evidence="ECO:0000305" SQ SEQUENCE 1177 AA; 135206 MW; FD04B5B41D0EA2DC CRC64; MAGIFKEFFF STEDLPEVIL TLSLISSIGA FLNRHLEDFP IPVPVILFLL GCSFEVLSFT SSQVQRYANA IQWMSPDLFF RIFTPVVFFT TAFDMDTYML QKLFWQILLI SIPGFLVNYI LVLWHLASVN QLLLKPTQWL LFSAILVSSD PMLTAAAIRD LGLSRSLISL INGESLMTSV ISLITFTSIM DFDQRLQSKR NHTLAEEIVG GICSYIIASF LFGILSSKLI QFWMSTVFGD DVNHISLIFS ILYLIFYICE LVGMSGIFTL AIVGLLLNST SFKAAIEETL LLEFWTFLSR IAFLMVFTFF GLLIPAHTYL YIEFVDIYYS LNIYLTLIVL RFLTLLLISP VLSRVGHEFS WRWIFIMVCS EMKGMPNINM ALLLAYSDLY FGSDKEKSQI LFHGVLVCLI TLVVNRFILP VAVTILGLRD ATSTKYKSVC CTFQHFQELT KSAASALKFD KDLANADWNM IEKAITLENP YMLNEEETTE HQKVKCPHCN KEIDEIFNTE AMELANRRLL SAQIASYQRQ YRNEILSQSA VQVLVGAAES FGEKKGKCMS LDTIKNYSES QKTVTFARKL LLNWVYNTRK EKEGPSKYFF FRICHTIVFT EEFEHVGYLV ILMNIFPFII SWISQLNVIY HSELKHTNYC FLTLYILEAL LKIAAMRKDF FSHAWNIFEL AITLIGILHV ILIEIDTIKY IFNETEVIVF IKVVQFFRIL RIFKLIAPKL LQIIDKRMSH QKTFWYGILK GYVQGEADIM TIIDQITSSK QIKQMLLKQV IRNMEHAIKE LGYLEYDHPE IAVTVKTKEE INVMLNMATE ILKAFGLKGI ISKTEGAGIN KLIMAKKKEV LDSQSIIRPL TVEEVLYHIP WLDKNKDYIN FIQEKAKVVT FDCGNDIFEE GDEPKGIYII ISGMVKLEKS KPGLGIDQMV ESKEKDFPII DTDYMLSGEI IGEINCLTNE PMKYSATCKT VVETCFIPKT HLYDAFEQCS PLIKQKMWLK LGLAITARKI REHLSYEDWN YNMQLKLSNI YVVDIPMSTK TDIYDENLIY VILIHGAVED CLLRKTYRAP FLIPITCHQI QSIEDFTKVV IIQTPINMKT FRRNIRKFVP KHKSYLTPGL IGSVGTLEEG IQEERNVKED GAHSAATARS PQPCSLLGTK FNCKESPRIN LRKVRKE //