ID S4A4_HUMAN Reviewed; 1079 AA. AC Q9Y6R1; C4B714; O15153; Q8NEJ2; Q9H262; Q9NRZ1; Q9UIC0; Q9UIC1; AC Q9UP50; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 01-OCT-2014, entry version 117. DE RecName: Full=Electrogenic sodium bicarbonate cotransporter 1; DE Short=Sodium bicarbonate cotransporter; DE AltName: Full=Na(+)/HCO3(-) cotransporter; DE AltName: Full=Solute carrier family 4 member 4; DE AltName: Full=kNBC1; GN Name=SLC4A4; Synonyms=NBC, NBC1, NBCE1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Kidney; RX PubMed=9235899; DOI=10.1074/jbc.272.31.19111; RA Burnham C.E., Amlal H., Wang Z., Shull G.E., Soleimani M.; RT "Cloning and functional expression of a human kidney Na+:HCO3- RT cotransporter."; RL J. Biol. Chem. 272:19111-19114(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Pancreas; RX PubMed=9651366; DOI=10.1074/jbc.273.28.17689; RA Abuladze N., Lee I., Newman D., Hwang J., Boorer K., Pushkin A., RA Kurtz I.; RT "Molecular cloning, chromosomal localization, tissue distribution, and RT functional expression of the human pancreatic sodium bicarbonate RT cotransporter."; RL J. Biol. Chem. 273:17689-17695(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Heart, Kidney, and Prostate; RX PubMed=10069984; RA Choi I., Romero M.F., Khandoudi N., Bril A., Boron W.F.; RT "Cloning and characterization of a human electrogenic Na+-HCO-3 RT cotransporter isoform (hhNBC)."; RL Am. J. Physiol. 276:C576-C584(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN CORNEAL RP ENDOTHELIAL CELLS, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RC TISSUE=Corneal endothelium; RX PubMed=12907161; DOI=10.1016/S0014-4835(03)00150-7; RA Sun X.C., Bonanno J.A.; RT "Identification and cloning of the Na/HCO3- cotransporter (NBC) in RT human corneal endothelium."; RL Exp. Eye Res. 77:287-295(2003). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Skeletal muscle; RA Pushkin A., Abuladze N., Kurtz I.; RT "Homo sapiens sodium bicarbonate cotransporter NBC1 splice variant."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Yamada H., Nagayoshi A., Kuroda Y., Mizutani A., Ando H., Seki G., RA Mikoshiba K.; RT "cDNA cloning and characterization of human sodium bicarbonate RT cotransporter, bNBC, a brain type splicing variant of SLC4A4 gene."; RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Kidney; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP REGULATION, MUTAGENESIS OF SER-1026, AND PHOSPHORYLATION AT SER-1026. RX PubMed=11744745; DOI=10.1113/jphysiol.2001.012956; RA Gross E., Hawkins K., Pushkin A., Sassani P., Dukkipati R., RA Abuladze N., Hopfer U., Kurtz I.; RT "Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter RT kNBC1 shifts the HCO(3)(-):Na(+) stoichiometry from 3:1 to 2:1 in RT murine proximal tubule cells."; RL J. Physiol. (Lond.) 537:659-665(2001). RN [10] RP ERRATUM. RA Gross E., Hawkins K., Pushkin A., Sassani P., Dukkipati R., RA Abuladze N., Hopfer U., Kurtz I.; RL J. Physiol. (Lond.) 538:1003-1003(2002). RN [11] RP TISSUE SPECIFICITY. RX PubMed=11743927; DOI=10.1016/S0003-9969(01)00098-X; RA Park K., Hurley P.T., Roussa E., Cooper G.J., Smith C.P., Thevenod F., RA Steward M.C., Case R.M.; RT "Expression of a sodium bicarbonate cotransporter in human parotid RT salivary glands."; RL Arch. Oral Biol. 47:1-9(2002). RN [12] RP REGULATION, MUTAGENESIS OF ASP-1030; ASP-1032 AND ASP-1033, AND RP INTERACTION WITH CA2. RX PubMed=12411514; DOI=10.1113/jphysiol.2002.029777; RA Gross E., Pushkin A., Abuladze N., Fedotoff O., Kurtz I.; RT "Regulation of the sodium bicarbonate cotransporter kNBC1 function: RT role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding."; RL J. Physiol. (Lond.) 544:679-685(2002). RN [13] RP GLYCOSYLATION. RX PubMed=12604466; DOI=10.1152/ajprenal.00131.2002; RA Choi I., Hu L., Rojas J.D., Schmitt B.M., Boron W.F.; RT "Role of glycosylation in the renal electrogenic Na+-HCO3- RT cotransporter (NBCe1)."; RL Am. J. Physiol. 284:F1199-F1206(2003). RN [14] RP TISSUE SPECIFICITY. RX PubMed=14559244; DOI=10.1016/j.bbrc.2003.09.147; RA Yamada H., Yamazaki S., Moriyama N., Hara C., Horita S., Enomoto Y., RA Kudo A., Kawakami H., Tanaka Y., Fujita T., Seki G.; RT "Localization of NBC-1 variants in human kidney and renal cell RT carcinoma."; RL Biochem. Biophys. Res. Commun. 310:1213-1218(2003). RN [15] RP TOPOLOGY. RX PubMed=12534288; DOI=10.1021/bi026826q; RA Tatishchev S., Abuladze N., Pushkin A., Newman D., Liu W., Weeks D., RA Sachs G., Kurtz I.; RT "Identification of membrane topography of the electrogenic sodium RT bicarbonate cotransporter pNBC1 by in vitro RT transcription/translation."; RL Biochemistry 42:755-765(2003). RN [16] RP REGULATION, INTERACTION WITH CA2 AND CA4, AND MUTAGENESIS OF GLY-767. RX PubMed=14567693; DOI=10.1021/bi0353124; RA Alvarez B.V., Loiselle F.B., Supuran C.T., Schwartz G.J., Casey J.R.; RT "Direct extracellular interaction between carbonic anhydrase IV and RT the human NBC1 sodium/bicarbonate co-transporter."; RL Biochemistry 42:12321-12329(2003). RN [17] RP REGULATION, MUTAGENESIS OF THR-49 AND SER-1026, AND PHOSPHORYLATION AT RP THR-49. RX PubMed=12730338; DOI=10.1113/jphysiol.2003.042226; RA Gross E., Fedotoff O., Pushkin A., Abuladze N., Newman D., Kurtz I.; RT "Phosphorylation-induced modulation of pNBC1 function: distinct roles RT for the amino- and carboxy-termini."; RL J. Physiol. (Lond.) 549:673-682(2003). RN [18] RP TISSUE SPECIFICITY. RX PubMed=15329059; DOI=10.1111/j.1365-201X.2004.01297.x; RA Kristensen J.M., Kristensen M., Juel C.; RT "Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and RT human skeletal muscle."; RL Acta Physiol. Scand. 182:69-76(2004). RN [19] RP MUTAGENESIS OF PHE-1057, AND SUBCELLULAR LOCATION. RX PubMed=15273250; DOI=10.1074/jbc.M405780200; RA Li H.C., Worrell R.T., Matthews J.B., Husseinzadeh H., Neumeier L., RA Petrovic S., Conforti L., Soleimani M.; RT "Identification of a carboxyl-terminal motif essential for the RT targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral RT membrane."; RL J. Biol. Chem. 279:43190-43197(2004). RN [20] RP INTERACTION WITH CA2, AND MUTAGENESIS OF 1002-LEU--ASN-1004 AND RP 1030-ASP--ASP-1033. RX PubMed=15218065; DOI=10.1113/jphysiol.2004.065110; RA Pushkin A., Abuladze N., Gross E., Newman D., Tatishchev S., Lee I., RA Fedotoff O., Bondar G., Azimov R., Ngyuen M., Kurtz I.; RT "Molecular mechanism of kNBC1-carbonic anhydrase II interaction in RT proximal tubule cells."; RL J. Physiol. (Lond.) 559:55-65(2004). RN [21] RP INTERACTION WITH CA4. RX PubMed=15563508; DOI=10.1093/hmg/ddi023; RA Yang Z., Alvarez B.V., Chakarova C., Jiang L., Karan G., RA Frederick J.M., Zhao Y., Sauve Y., Li X., Zrenner E., Wissinger B., RA Den Hollander A.I., Katz B., Baehr W., Cremers F.P., Casey J.R., RA Bhattacharya S.S., Zhang K.; RT "Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal RT photoreceptor degeneration."; RL Hum. Mol. Genet. 14:255-265(2005). RN [22] RP MUTAGENESIS OF TYR-477; ASP-493; ALA-494; GLU-503; SER-504; GLU-536; RP GLU-552; ARG-554; ARG-582; GLU-586; ASP-599; ALA-600; LYS-602; RP LYS-603; ASP-691; PHE-700; LYS-711; LYS-712; LYS-714; THR-715; RP THR-721; ARG-724; LYS-725; SER-728; ASP-729; ASP-743; ASP-749; RP LYS-752; ARG-766; GLU-775; ASP-798; 808-ARG--LYS-809; RP 814-LYS--LYS-815; HIS-820; ASP-822; HIS-851; ASP-853; RP 858-GLU--GLU-860; 875-GLU--ARG-877; LYS-898; 925-ARG--LYS-927; RP ARG-948; ARG-949; HIS-951; LYS-968 AND ARG-987. RX PubMed=15817634; DOI=10.1113/jphysiol.2005.084988; RA Abuladze N., Azimov R., Newman D., Sassani P., Liu W., Tatishchev S., RA Pushkin A., Kurtz I.; RT "Critical amino acid residues involved in the electrogenic sodium- RT bicarbonate cotransporter kNBC1-mediated transport."; RL J. Physiol. (Lond.) 565:717-730(2005). RN [23] RP VARIANTS PRTA-OA SER-342 AND HIS-554. RX PubMed=10545938; DOI=10.1038/15440; RA Igarashi T., Inatomi J., Sekine T., Cha S.H., Kanai Y., Kunimi M., RA Tsukamoto K., Satoh H., Shimadzu M., Tozawa F., Mori T., Shiobara M., RA Seki G., Endou H.; RT "Mutations in SLC4A4 cause permanent isolated proximal renal tubular RT acidosis with ocular abnormalities."; RL Nat. Genet. 23:264-266(1999). RN [24] RP VARIANT PRTA-OA LEU-471. RX PubMed=15471865; DOI=10.1074/jbc.M406591200; RA Dinour D., Chang M.-H., Satoh J., Smith B.L., Angle N., Knecht A., RA Serban I., Holtzman E.J., Romero M.F.; RT "A novel missense mutation in the sodium bicarbonate cotransporter RT (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through RT ion transport defects."; RL J. Biol. Chem. 279:52238-52246(2004). RN [25] RP VARIANTS PRTA-OA SER-342; LEU-471 AND HIS-554, AND MUTAGENESIS OF RP GLU-135. RX PubMed=15713912; DOI=10.1152/ajprenal.00032.2005; RA Li H.C., Szigligeti P., Worrell R.T., Matthews J.B., Conforti L., RA Soleimani M.; RT "Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal RT trafficking in polarized kidney cells: a basis of proximal renal RT tubular acidosis."; RL Am. J. Physiol. 289:F61-F71(2005). RN [26] RP VARIANTS PRTA-OA SER-342; SER-529; HIS-554; VAL-843 AND CYS-925. RX PubMed=15930088; DOI=10.1681/ASN.2004080667; RA Horita S., Yamada H., Inatomi J., Moriyama N., Sekine T., Igarashi T., RA Endo Y., Dasouki M., Ekim M., Al-Gazali L., Shimadzu M., Seki G., RA Fujita T.; RT "Functional analysis of NBC1 mutants associated with proximal renal RT tubular acidosis and ocular abnormalities."; RL J. Am. Soc. Nephrol. 16:2270-2278(2005). CC -!- FUNCTION: Electrogenic sodium/bicarbonate cotransporter with a CC Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate CC bicarbonate influx/efflux at the basolateral membrane of cells and CC regulate intracellular pH. {ECO:0000269|PubMed:10069984, CC ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:9235899, CC ECO:0000269|PubMed:9651366}. CC -!- ENZYME REGULATION: Inhibited by stilbene derivatives and regulated CC by cyclic AMP. CC -!- SUBUNIT: Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic CC anhydrase 4 which may regulate transporter activity. CC {ECO:0000269|PubMed:12411514, ECO:0000269|PubMed:14567693, CC ECO:0000269|PubMed:15218065, ECO:0000269|PubMed:15563508}. CC -!- INTERACTION: CC P48283:CA4 (xeno); NbExp=2; IntAct=EBI-6859278, EBI-6859264; CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane CC {ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:15273250}; Multi- CC pass membrane protein {ECO:0000269|PubMed:12907161, CC ECO:0000269|PubMed:15273250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=hcNBC, hhNBC, hNBC1, pNBC, pNCB1, pNBC-1, NBC1b; CC IsoId=Q9Y6R1-1; Sequence=Displayed; CC Name=2; Synonyms=hkNBC, hkNBCe1, kNBC, kNBC1, kNBC-1, NBC1a; CC IsoId=Q9Y6R1-2; Sequence=VSP_016704, VSP_016705; CC Name=3; CC IsoId=Q9Y6R1-3; Sequence=VSP_016704, VSP_016705, VSP_016706, CC VSP_016707; CC Name=4; CC IsoId=Q9Y6R1-4; Sequence=VSP_016708; CC Name=5; CC IsoId=Q9Y6R1-5; Sequence=VSP_041003; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in pancreas and to a CC lower extent in heart, skeletal muscle, liver, parotid salivary CC glands, prostate, colon, stomach, thyroid, brain and spinal chord. CC Corneal endothelium cells express only isoform 1 (at protein CC level). Isoform 2 is specifically expressed in kidney at the level CC of proximal tubules. {ECO:0000269|PubMed:10069984, CC ECO:0000269|PubMed:11743927, ECO:0000269|PubMed:12907161, CC ECO:0000269|PubMed:14559244, ECO:0000269|PubMed:15329059, CC ECO:0000269|PubMed:9235899, ECO:0000269|PubMed:9651366}. CC -!- PTM: Phosphorylation of Ser-1026 by PKA increases the binding of CC CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter CC from 3:1 to 2:1. Phosphorylation of Thr-49 regulates isoform 1 CC conductance. {ECO:0000269|PubMed:11744745, CC ECO:0000269|PubMed:12730338}. CC -!- PTM: N-glycosylation is not necessary for the transporter basic CC functions. {ECO:0000269|PubMed:12604466}. CC -!- DISEASE: Renal tubular acidosis, proximal, with ocular CC abnormalities and mental retardation (pRTA-OA) [MIM:604278]: An CC extremely rare autosomal recessive syndrome characterized by short CC stature, profound proximal renal tubular acidosis, mental CC retardation, bilateral glaucoma, cataracts and bandkeratopathy. CC pRTA is due to a failure of the proximal tubular cells to reabsorb CC filtered bicarbonate from the urine, leading to urinary CC bicarbonate wasting and subsequent acidemia. CC {ECO:0000269|PubMed:10545938, ECO:0000269|PubMed:15471865, CC ECO:0000269|PubMed:15713912, ECO:0000269|PubMed:15930088}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Note=Loss of interaction with and stimulation by CA4 is CC the cause of retinitis pigmentosa type 17 (RP17). CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family. CC {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; AF007216; AAC51645.1; -; mRNA. DR EMBL; AF011390; AAC39840.1; -; mRNA. DR EMBL; AF053753; AAF21718.1; -; mRNA. DR EMBL; AF053754; AAF21719.1; -; mRNA. DR EMBL; AF069510; AAD42020.1; -; mRNA. DR EMBL; AF310248; AAG47773.1; -; mRNA. DR EMBL; AF157492; AAF80343.1; -; mRNA. DR EMBL; AB470072; BAH58226.1; -; mRNA. DR EMBL; AC019089; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079230; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096713; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC110783; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC112226; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC030977; AAH30977.1; -; mRNA. DR CCDS; CCDS3549.1; -. [Q9Y6R1-2] DR CCDS; CCDS43236.1; -. [Q9Y6R1-1] DR CCDS; CCDS47071.1; -. [Q9Y6R1-5] DR RefSeq; NP_001091954.1; NM_001098484.2. [Q9Y6R1-1] DR RefSeq; NP_003750.1; NM_003759.3. [Q9Y6R1-2] DR UniGene; Hs.5462; -. DR ProteinModelPortal; Q9Y6R1; -. DR SMR; Q9Y6R1; 107-382, 453-493. DR BioGrid; 114219; 1. DR DIP; DIP-59373N; -. DR IntAct; Q9Y6R1; 4. DR STRING; 9606.ENSP00000393557; -. DR DrugBank; DB01390; Sodium bicarbonate. DR TCDB; 2.A.31.2.12; the anion exchanger (ae) family. DR PhosphoSite; Q9Y6R1; -. DR DMDM; 74721543; -. DR MaxQB; Q9Y6R1; -. DR PaxDb; Q9Y6R1; -. DR PRIDE; Q9Y6R1; -. DR DNASU; 8671; -. DR Ensembl; ENST00000264485; ENSP00000264485; ENSG00000080493. [Q9Y6R1-1] DR Ensembl; ENST00000340595; ENSP00000344272; ENSG00000080493. [Q9Y6R1-2] DR Ensembl; ENST00000351898; ENSP00000307349; ENSG00000080493. [Q9Y6R1-4] DR Ensembl; ENST00000425175; ENSP00000393557; ENSG00000080493. [Q9Y6R1-5] DR Ensembl; ENST00000512686; ENSP00000422400; ENSG00000080493. [Q9Y6R1-3] DR GeneID; 8671; -. DR KEGG; hsa:8671; -. DR UCSC; uc003hfy.3; human. [Q9Y6R1-1] DR UCSC; uc003hga.2; human. [Q9Y6R1-3] DR UCSC; uc003hgc.4; human. [Q9Y6R1-2] DR UCSC; uc010iib.3; human. [Q9Y6R1-4] DR CTD; 8671; -. DR GeneCards; GC04P072017; -. DR HGNC; HGNC:11030; SLC4A4. DR HPA; CAB022493; -. DR HPA; HPA035628; -. DR HPA; HPA035629; -. DR MIM; 603345; gene. DR MIM; 604278; phenotype. DR neXtProt; NX_Q9Y6R1; -. DR Orphanet; 93607; Autosomal recessive proximal renal tubular acidosis. DR PharmGKB; PA35898; -. DR eggNOG; NOG251607; -. DR HOVERGEN; HBG004326; -. DR InParanoid; Q9Y6R1; -. DR KO; K13575; -. DR OMA; VCSFMAL; -. DR OrthoDB; EOG7TMZR0; -. DR PhylomeDB; Q9Y6R1; -. DR TreeFam; TF313630; -. DR Reactome; REACT_19298; Bicarbonate transporters. DR ChiTaRS; SLC4A4; human. DR GeneWiki; SLC4A4; -. DR GenomeRNAi; 8671; -. DR NextBio; 32523; -. DR PRO; PR:Q9Y6R1; -. DR ArrayExpress; Q9Y6R1; -. DR Bgee; Q9Y6R1; -. DR CleanEx; HS_SLC4A4; -. DR Genevestigator; Q9Y6R1; -. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro. DR GO; GO:0005515; F:protein binding; IPI:DFLAT. DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; TAS:ProtInc. DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome. DR GO; GO:0006811; P:ion transport; TAS:Reactome. DR GO; GO:0035725; P:sodium ion transmembrane transport; TAS:GOC. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. DR GO; GO:0006810; P:transport; TAS:ProtInc. DR Gene3D; 3.40.1100.10; -; 1. DR InterPro; IPR013769; Band3_cytoplasmic_dom. DR InterPro; IPR011531; HCO3_transpt_C. DR InterPro; IPR003020; HCO3_transpt_euk. DR InterPro; IPR003024; Na/HCO3_transpt. DR InterPro; IPR016152; PTrfase/Anion_transptr. DR PANTHER; PTHR11453; PTHR11453; 1. DR Pfam; PF07565; Band_3_cyto; 1. DR Pfam; PF00955; HCO3_cotransp; 1. DR PRINTS; PR01231; HCO3TRNSPORT. DR PRINTS; PR01232; NAHCO3TRSPRT. DR SUPFAM; SSF55804; SSF55804; 1. DR TIGRFAMs; TIGR00834; ae; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Complete proteome; KW Disease mutation; Glycoprotein; Ion transport; Membrane; KW Phosphoprotein; Reference proteome; Retinitis pigmentosa; Sodium; KW Sodium transport; Symport; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1 1079 Electrogenic sodium bicarbonate FT cotransporter 1. FT /FTId=PRO_0000079227. FT TOPO_DOM 1 468 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 469 488 Helical. {ECO:0000255}. FT TOPO_DOM 489 504 Extracellular. {ECO:0000255}. FT TRANSMEM 505 526 Helical. {ECO:0000255}. FT TOPO_DOM 527 554 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 555 580 Helical. {ECO:0000255}. FT TOPO_DOM 581 691 Extracellular. {ECO:0000255}. FT TRANSMEM 692 710 Helical. {ECO:0000255}. FT TOPO_DOM 711 725 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 726 748 Helical. {ECO:0000255}. FT TOPO_DOM 749 777 Extracellular. {ECO:0000255}. FT TRANSMEM 778 797 Helical. {ECO:0000255}. FT TOPO_DOM 798 822 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 823 847 Helical. {ECO:0000255}. FT TOPO_DOM 848 881 Extracellular. {ECO:0000255}. FT TRANSMEM 882 901 Helical. {ECO:0000255}. FT TOPO_DOM 902 949 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 950 967 Helical. {ECO:0000255}. FT TOPO_DOM 968 970 Extracellular. {ECO:0000255}. FT TRANSMEM 971 986 Helical. {ECO:0000255}. FT TOPO_DOM 987 1079 Cytoplasmic. {ECO:0000255}. FT REGION 748 779 Interaction with CA4. FT REGION 1002 1004 CA2-binding. FT REGION 1030 1033 CA2-binding. FT REGION 1057 1059 Required for basolateral targeting. FT COMPBIAS 1009 1024 Lys-rich. FT MOD_RES 30 30 Phosphotyrosine. {ECO:0000250}. FT MOD_RES 49 49 Phosphothreonine; by PKA. FT {ECO:0000269|PubMed:12730338}. FT MOD_RES 254 254 Phosphothreonine. {ECO:0000250}. FT MOD_RES 257 257 Phosphoserine. {ECO:0000250}. FT MOD_RES 262 262 Phosphoserine. {ECO:0000250}. FT MOD_RES 1026 1026 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:11744745}. FT MOD_RES 1029 1029 Phosphoserine. {ECO:0000250}. FT MOD_RES 1034 1034 Phosphoserine. {ECO:0000250}. FT CARBOHYD 641 641 N-linked (GlcNAc...). {ECO:0000250}. FT CARBOHYD 661 661 N-linked (GlcNAc...). {ECO:0000250}. FT VAR_SEQ 1 44 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9235899}. FT /FTId=VSP_016704. FT VAR_SEQ 45 85 HKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLI FT -> MSTENVEGKPSNLGERGRARSSTFLRVVQPMFNHSIFT FT SAV (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9235899}. FT /FTId=VSP_016705. FT VAR_SEQ 635 690 ANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECS FT KYGGNLVGNNCNFVP -> GEGITLCVYARFVFGGRCRLHA FT CKFSTCCHGPQELVLFFSLKNSATEFDVSLPEVF (in FT isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_016706. FT VAR_SEQ 691 1079 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_016707. FT VAR_SEQ 813 896 Missing (in isoform 4). FT {ECO:0000303|Ref.5}. FT /FTId=VSP_016708. FT VAR_SEQ 1034 1079 SDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLE FT RHTSC -> EKDHQHSLNATHHADKIPFLQSLGMPSPPRTP FT VKVVPQIRIELEPEDNDYFWRSKGTETTL (in isoform FT 5). {ECO:0000303|Ref.6}. FT /FTId=VSP_041003. FT VARIANT 342 342 R -> S (in pRTA-OA; mistargeting and FT altered function). FT {ECO:0000269|PubMed:10545938, FT ECO:0000269|PubMed:15713912, FT ECO:0000269|PubMed:15930088}. FT /FTId=VAR_024751. FT VARIANT 471 471 S -> L (in pRTA-OA; mistargeting to the FT apical membrane and altered function). FT {ECO:0000269|PubMed:15471865, FT ECO:0000269|PubMed:15713912}. FT /FTId=VAR_024752. FT VARIANT 529 529 T -> S (in pRTA-OA; mistargeting and FT altered function). FT {ECO:0000269|PubMed:15930088}. FT /FTId=VAR_024753. FT VARIANT 554 554 R -> H (in pRTA-OA; mistargeting and FT altered function). FT {ECO:0000269|PubMed:10545938, FT ECO:0000269|PubMed:15713912, FT ECO:0000269|PubMed:15930088}. FT /FTId=VAR_024754. FT VARIANT 843 843 A -> V (in pRTA-OA; altered function). FT {ECO:0000269|PubMed:15930088}. FT /FTId=VAR_024755. FT VARIANT 925 925 R -> C (in pRTA-OA; altered function). FT {ECO:0000269|PubMed:15930088}. FT /FTId=VAR_024756. FT MUTAGEN 49 49 T->A: Loss of conductance regulation by FT cAMP; isoform 1. FT {ECO:0000269|PubMed:12730338, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 49 49 T->D: Loss of conductance regulation by FT cAMP; isoform 1. FT {ECO:0000269|PubMed:12730338, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 135 135 E->R: Mistargeting and altered function. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15713912}. FT MUTAGEN 477 477 Y->F: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 493 493 D->N: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 494 494 A->K: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 503 503 E->Q: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 504 504 S->L: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 536 536 E->Q: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 552 552 E->N: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 554 554 R->D: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 582 582 R->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 582 582 R->Q: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 586 586 E->Q: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 599 599 D->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 600 600 A->T: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 602 602 K->Q: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 603 603 K->Q: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 691 691 D->R: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 700 700 F->M: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 711 711 K->E,N,Q: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 711 711 K->R: No effect on the sodium-dependent FT ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 712 712 K->N: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 714 714 K->Q: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 715 715 T->N: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 721 721 T->G: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 724 724 R->E: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 725 725 K->N: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 728 728 S->G: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 729 729 D->N,R: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 743 743 D->K,N: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 749 749 D->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 752 752 K->Q: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 766 766 R->Q: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 767 767 G->T: Alters interaction with CA4. FT {ECO:0000269|PubMed:14567693, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 775 775 E->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 798 798 D->E,N,R: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 808 809 RK->NN: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 814 815 KK->NN: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 820 820 H->D,N,S,R: Moderate reduction of the FT sodium-dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 822 822 D->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 851 851 H->N: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 853 853 D->N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 858 860 ETE->MSK: Moderate reduction of the FT sodium-dependent ion transport activity. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 875 877 EQR->QQQ: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 875 875 E->Q: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 898 898 K->E: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 925 927 RLK->NLN: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 948 948 R->E: Strong reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 949 949 R->E: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 951 951 H->D: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 951 951 H->N,R: Prevents membrane targeting. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 968 968 K->Q: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 987 987 R->E,N: Moderate reduction of the sodium- FT dependent ion transport activity. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15817634}. FT MUTAGEN 1002 1002 L->N: Partial loss of interaction with FT CA2. {ECO:0000269|PubMed:15218065}. FT MUTAGEN 1003 1003 D->N: Abolishes interaction with CA2. FT {ECO:0000269|PubMed:15218065}. FT MUTAGEN 1004 1004 D->N: Partial loss of interaction with FT CA2. {ECO:0000269|PubMed:15218065}. FT MUTAGEN 1026 1026 S->A: Prevents phosphorylation by PKA. FT Loss of regulation by cAMP of the FT transporter stoichiometry. FT {ECO:0000269|PubMed:11744745, FT ECO:0000269|PubMed:12730338, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1026 1026 S->D: Loss of regulation by cAMP of the FT transporter stoichiometry. Shifts FT transporter stoichiometry from 3:1 to FT 2:1. {ECO:0000269|PubMed:11744745, FT ECO:0000269|PubMed:12730338, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1030 1033 DNDD->NNNN: Abolishes interaction with FT CA2. {ECO:0000269|PubMed:12411514, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1030 1030 D->N: Loss of regulation by cAMP of the FT transporter stoichiometry. Abolishes FT interaction with CA2. FT {ECO:0000269|PubMed:12411514, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1032 1032 D->N: Loss of regulation by cAMP of the FT transporter stoichiometry. Partial loss FT of interaction with CA2. FT {ECO:0000269|PubMed:12411514, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1033 1033 D->N: No effect on regulation by cAMP of FT the transporter stoichiometry. Partial FT loss of interaction with CA2. FT {ECO:0000269|PubMed:12411514, FT ECO:0000269|PubMed:15218065}. FT MUTAGEN 1057 1057 F->A: Targeting to apical membrane. FT {ECO:0000269|PubMed:15218065, FT ECO:0000269|PubMed:15273250}. FT CONFLICT 6 6 V -> A (in Ref. 4; AAG47773). FT {ECO:0000305}. FT CONFLICT 49 49 T -> A (in Ref. 6; BAH58226). FT {ECO:0000305}. FT CONFLICT 78 78 S -> G (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 256 256 S -> F (in Ref. 3; AAD42020). FT {ECO:0000305}. FT CONFLICT 263 263 D -> E (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 298 298 P -> H (in Ref. 6; BAH58226). FT {ECO:0000305}. FT CONFLICT 364 364 H -> R (in Ref. 3; AAF21719). FT {ECO:0000305}. FT CONFLICT 605 605 I -> V (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 654 654 S -> P (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 749 749 D -> G (in Ref. 3; AAF21719). FT {ECO:0000305}. FT CONFLICT 799 799 Q -> R (in Ref. 4; AAG47773). FT {ECO:0000305}. FT CONFLICT 856 856 K -> R (in Ref. 4; AAG47773). FT {ECO:0000305}. FT CONFLICT 912 912 M -> R (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 913 913 G -> R (in Ref. 3; AAF21719). FT {ECO:0000305}. FT CONFLICT 940 940 I -> V (in Ref. 3; AAF21718). FT {ECO:0000305}. FT CONFLICT 1007 1007 P -> S (in Ref. 3; AAF21719). FT {ECO:0000305}. FT CONFLICT 1069 1069 S -> P (in Ref. 3; AAF21719). FT {ECO:0000305}. SQ SEQUENCE 1079 AA; 121461 MW; 14B981A94DD64293 CRC64; MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG HKEKKEKERI SENYSDKSDI ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP QLVEMIVDHQ IETGLLKPEL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDTPFI AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA KDRHDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP HDGGHGGGGH GDCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF NFSKDNNFDY LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA FKKMIKLADY YPINSNFKVG YNTLFSCTCV PPDPANISIS NDTTLAPEYL PTMSSTDMYH NTTFDWAFLS KKECSKYGGN LVGNNCNFVP DITLMSFILF LGTYTSSMAL KKFKTSPYFP TTARKLISDF AIILSILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV PPFGENPWWV CLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VICSLMALPW YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK KKKKGSLDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD SKPSDRERSP TFLERHTSC //