ID S4A5_HUMAN Reviewed; 1137 AA. AC Q9BY07; Q32MA7; Q59EQ9; Q8WXD3; Q8WXD7; Q96DS7; Q96DS8; Q9HBU5; DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 08-APR-2008, sequence version 2. DT 03-MAY-2023, entry version 159. DE RecName: Full=Electrogenic sodium bicarbonate cotransporter 4; DE AltName: Full=NBCe2; DE AltName: Full=Solute carrier family 4 member 5; GN Name=SLC4A5 {ECO:0000312|HGNC:HGNC:18168}; GN Synonyms=NBC4 {ECO:0000312|EMBL:AAK26741.1}; 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] {ECO:0000305, ECO:0000312|EMBL:AAG18492.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY. RC TISSUE=Heart {ECO:0000312|EMBL:AAG18492.1}; RX PubMed=10978526; DOI=10.1016/s0167-4781(00)00149-4; RA Pushkin A., Abuladze N., Newman D., Lee I., Xu G., Kurtz I.; RT "Cloning, characterization and chromosomal assignment of NBC4, a new member RT of the sodium bicarbonate cotransporter family."; RL Biochim. Biophys. Acta 1493:215-218(2000). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAK26741.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RC TISSUE=Heart {ECO:0000269|PubMed:11087115}, and RC Testis {ECO:0000312|EMBL:AAK26741.1}; RX PubMed=11087115; DOI=10.1080/15216540050176539; RA Pushkin A., Abuladze N., Newman D., Lee I., Xu G., Kurtz I.; RT "Two C-terminal variants of NBC4, a new member of the sodium bicarbonate RT cotransporter family: cloning, characterization, and localization."; RL IUBMB Life 50:13-19(2000). RN [3] {ECO:0000305, ECO:0000312|EMBL:AAK97073.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Testis {ECO:0000312|EMBL:AAK97073.1}; RX PubMed=12063394; DOI=10.1159/000059340; RA Pushkin A., Abuladze N., Newman D., Tatishchev S., Kurtz I.; RT "Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and RT p150(Glued)."; RL Cytogenet. Cell Genet. 95:163-168(2001). RN [4] {ECO:0000305, ECO:0000312|EMBL:AAK97072.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, TRANSPORTER RP ACTIVITY (ISOFORM 3), AND ACTIVITY REGULATION. RC TISSUE=Testis {ECO:0000312|EMBL:AAK97072.1}; RX PubMed=11788353; DOI=10.1152/ajpcell.00409.2001; RA Sassani P., Pushkin A., Gross E., Gomer A., Abuladze N., Dukkipati R., RA Carpenito G., Kurtz I.; RT "Functional characterization of NBC4: a new electrogenic sodium-bicarbonate RT cotransporter."; RL Am. J. Physiol. 282:C408-C416(2002). RN [5] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TRANSPORTER ACTIVITY (ISOFORM 3), RP AND ACTIVITY REGULATION. RX PubMed=11997242; DOI=10.1152/ajpcell.00589.2001; RA Virkki L.V., Wilson D.A., Vaughan-Jones R.D., Boron W.F.; RT "Functional characterization of human NBC4 as an electrogenic Na+-HCO RT cotransporter (NBCe2)."; RL Am. J. Physiol. 282:C1278-C1289(2002). RN [6] {ECO:0000305, ECO:0000312|EMBL:AAL48291.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RP 8), TRANSPORTER ACTIVITY (ISOFORM 8), AND ACTIVITY REGULATION. RC TISSUE=Liver {ECO:0000269|PubMed:12388414}; RX PubMed=12388414; DOI=10.1152/ajprenal.00055.2002; RA Xu J., Wang Z., Barone S., Petrovic M., Amlal H., Conforti L., Petrovic S., RA Soleimani M.; RT "Expression of the Na+-HCO-3 cotransporter NBC4 in rat kidney and RT characterization of a novel NBC4 variant."; RL Am. J. Physiol. 284:F41-F50(2003). RN [7] {ECO:0000305, ECO:0000312|EMBL:EAW99690.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] {ECO:0000305, ECO:0000312|EMBL:AAI09222.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). 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 [9] {ECO:0000305, ECO:0000312|EMBL:EAW99690.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-993 (ISOFORM 5), AND VARIANT RP TYR-253. RC TISSUE=Brain {ECO:0000312|EMBL:BAD92989.1}; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [10] {ECO:0000305} RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17715183; DOI=10.1152/ajpregu.00356.2007; RA Damkier H.H., Nielsen S., Praetorius J.; RT "Molecular expression of SLC4-derived Na+-dependent anion transporters in RT selected human tissues."; RL Am. J. Physiol. 293:R2136-R2146(2007). RN [11] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=26447209; DOI=10.1152/ajpregu.00150.2015; RA Gildea J.J., Xu P., Carlson J.M., Gaglione R.T., Bigler Wang D., Kemp B.A., RA Reyes C.M., McGrath H.E., Carey R.M., Jose P.A., Felder R.A.; RT "The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human RT renal proximal tubules shows increased apical expression under high-salt RT conditions."; RL Am. J. Physiol. 309:R1447-R1459(2015). CC -!- FUNCTION: Mediates sodium- and bicarbonate-dependent electrogenic CC sodium bicarbonate cotransport, with a Na(+):HCO3(-) stoichiometry CC varying from 1:2 to 1:3. {ECO:0000269|PubMed:26447209}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 hydrogencarbonate(out) + Na(+)(out) = 2 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72215, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:26447209}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3 hydrogencarbonate(out) + Na(+)(out) = 3 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72219, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:26447209}; CC -!- CATALYTIC ACTIVITY: [Isoform 3]: CC Reaction=2 hydrogencarbonate(out) + Na(+)(out) = 2 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72215, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:11997242}; CC -!- CATALYTIC ACTIVITY: [Isoform 3]: CC Reaction=3 hydrogencarbonate(out) + Na(+)(out) = 3 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72219, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:11788353}; CC -!- CATALYTIC ACTIVITY: [Isoform 8]: CC Reaction=2 hydrogencarbonate(out) + Na(+)(out) = 2 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72215, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:12388414}; CC -!- CATALYTIC ACTIVITY: [Isoform 8]: CC Reaction=3 hydrogencarbonate(out) + Na(+)(out) = 3 CC hydrogencarbonate(in) + Na(+)(in); Xref=Rhea:RHEA:72219, CC ChEBI:CHEBI:17544, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:12388414}; CC -!- ACTIVITY REGULATION: Activity is inhibited by 4,4'-di- CC isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of CC several anion channels and transporters). CC {ECO:0000269|PubMed:26447209}. CC -!- ACTIVITY REGULATION: [Isoform 3]: Activity is inhibited by 4,4'-di- CC isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of CC several anion channels and transporters). {ECO:0000269|PubMed:11788353, CC ECO:0000269|PubMed:11997242}. CC -!- ACTIVITY REGULATION: [Isoform 8]: Activity is inhibited by 4,4'-di- CC isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of CC several anion channels and transporters). CC {ECO:0000269|PubMed:12388414}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:17715183, ECO:0000269|PubMed:26447209}; Multi-pass CC membrane protein {ECO:0000255}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q6RI88}; Multi-pass membrane protein CC {ECO:0000255}. Note=Expressed in the apical plasma membrane domain of a CC subset of collecting ducts in the renal medulla. CC {ECO:0000269|PubMed:17715183}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1 {ECO:0000269|PubMed:11087115}; Synonyms=NBC4a CC {ECO:0000269|PubMed:11087115}; CC IsoId=Q9BY07-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:10978526, ECO:0000269|PubMed:11087115}; CC Synonyms=NBC4b {ECO:0000269|PubMed:11087115}; CC IsoId=Q9BY07-2; Sequence=VSP_052778; CC Name=3 {ECO:0000269|PubMed:11788353}; Synonyms=NBC4c CC {ECO:0000269|PubMed:11788353}; CC IsoId=Q9BY07-3; Sequence=VSP_052776; CC Name=4 {ECO:0000269|PubMed:12063394}; Synonyms=NBC4d CC {ECO:0000269|PubMed:12063394}; CC IsoId=Q9BY07-4; Sequence=VSP_052775; CC Name=5; Synonyms=isoform d variant; CC IsoId=Q9BY07-5; Sequence=VSP_052771, VSP_052773, VSP_052777; CC Name=6 {ECO:0000269|PubMed:12388414}; Synonyms=NBC4f CC {ECO:0000269|PubMed:12388414}; CC IsoId=Q9BY07-6; Sequence=VSP_052772, VSP_052774, VSP_052776, CC VSP_052778, VSP_052780, VSP_052781; CC Name=7 {ECO:0000269|PubMed:15489334}; CC IsoId=Q9BY07-7; Sequence=VSP_052770, VSP_052772, VSP_052776; CC Name=8 {ECO:0000269|PubMed:12388414}; Synonyms=NBC4e CC {ECO:0000269|PubMed:12388414}; CC IsoId=Q9BY07-8; Sequence=VSP_052779; CC -!- TISSUE SPECIFICITY: Highest expression observed in liver, spleen and CC testis; moderate expression in the choroid plexus, hippocampus, CC cerebrum and cerebellum of brain, and in kidney cortex and kidney CC medulla. Also observed in heart, pancreas, muscle, lung, placenta, CC stomach and small intestine. Weakest expression seen in peripheral CC blood lymphocytes, colon, duodenum, jejunum, ileum and skeletal muscle. CC {ECO:0000269|PubMed:10978526, ECO:0000269|PubMed:11087115, CC ECO:0000269|PubMed:17715183, ECO:0000269|PubMed:26447209}. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in the brain, heart, kidney, CC testis, pancreas, muscle and peripheral blood leukocytes. CC {ECO:0000269|PubMed:11788353}. CC -!- MISCELLANEOUS: [Isoform 5]: Incomplete sequence. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family. CC {ECO:0000255}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG18492.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAL50802.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=EAW99691.1; Type=Frameshift; 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; AF207661; AAG18492.1; ALT_FRAME; mRNA. DR EMBL; AF243499; AAK26741.1; -; mRNA. DR EMBL; AF293338; AAK97073.1; -; mRNA. DR EMBL; AF293337; AAK97072.1; -; mRNA. DR EMBL; AF452248; AAL48291.1; -; mRNA. DR EMBL; AF453528; AAL50802.1; ALT_FRAME; mRNA. DR EMBL; CH471053; EAW99690.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99691.1; ALT_FRAME; Genomic_DNA. DR EMBL; CH471053; EAW99693.1; -; Genomic_DNA. DR EMBL; BC109221; AAI09222.1; -; mRNA. DR EMBL; AB209752; BAD92989.1; -; mRNA. DR CCDS; CCDS1936.1; -. [Q9BY07-1] DR CCDS; CCDS1937.1; -. [Q9BY07-3] DR RefSeq; NP_067019.3; NM_021196.3. [Q9BY07-1] DR RefSeq; NP_597812.1; NM_133478.2. [Q9BY07-3] DR AlphaFoldDB; Q9BY07; -. DR SMR; Q9BY07; -. DR BioGRID; 121791; 4. DR IntAct; Q9BY07; 2. DR MINT; Q9BY07; -. DR STRING; 9606.ENSP00000251768; -. DR DrugBank; DB01390; Sodium bicarbonate. DR TCDB; 2.A.31.2.17; the anion exchanger (ae) family. DR TCDB; 2.A.31.2.8; the anion exchanger (ae) family. DR GlyConnect; 2038; 1 N-Linked glycan (1 site). DR GlyCosmos; Q9BY07; 1 site, 2 glycans. DR GlyGen; Q9BY07; 1 site, 2 N-linked glycans (1 site). DR iPTMnet; Q9BY07; -. DR PhosphoSitePlus; Q9BY07; -. DR BioMuta; SLC4A5; -. DR DMDM; 182691595; -. DR MassIVE; Q9BY07; -. DR MaxQB; Q9BY07; -. DR PaxDb; Q9BY07; -. DR PeptideAtlas; Q9BY07; -. DR ProteomicsDB; 79546; -. [Q9BY07-1] DR ProteomicsDB; 79547; -. [Q9BY07-2] DR ProteomicsDB; 79548; -. [Q9BY07-3] DR ProteomicsDB; 79549; -. [Q9BY07-4] DR ProteomicsDB; 79550; -. [Q9BY07-5] DR ProteomicsDB; 79551; -. [Q9BY07-6] DR ProteomicsDB; 79552; -. [Q9BY07-7] DR ProteomicsDB; 79553; -. [Q9BY07-8] DR Antibodypedia; 47475; 74 antibodies from 17 providers. DR DNASU; 57835; -. DR Ensembl; ENST00000346834.8; ENSP00000251768.7; ENSG00000188687.18. [Q9BY07-1] DR Ensembl; ENST00000358683.8; ENSP00000351513.4; ENSG00000188687.18. [Q9BY07-7] DR Ensembl; ENST00000377632.5; ENSP00000366859.1; ENSG00000188687.18. [Q9BY07-4] DR Ensembl; ENST00000377634.8; ENSP00000366861.4; ENSG00000188687.18. [Q9BY07-1] DR Ensembl; ENST00000394019.7; ENSP00000377587.2; ENSG00000188687.18. [Q9BY07-3] DR Ensembl; ENST00000423644.5; ENSP00000395804.2; ENSG00000188687.18. [Q9BY07-3] DR GeneID; 57835; -. DR KEGG; hsa:57835; -. DR MANE-Select; ENST00000394019.7; ENSP00000377587.2; NM_133478.3; NP_597812.1. [Q9BY07-3] DR UCSC; uc002skn.3; human. [Q9BY07-1] DR AGR; HGNC:18168; -. DR CTD; 57835; -. DR DisGeNET; 57835; -. DR GeneCards; SLC4A5; -. DR HGNC; HGNC:18168; SLC4A5. DR HPA; ENSG00000188687; Tissue enhanced (choroid plexus, retina, thyroid gland). DR MIM; 606757; gene. DR neXtProt; NX_Q9BY07; -. DR OpenTargets; ENSG00000188687; -. DR VEuPathDB; HostDB:ENSG00000188687; -. DR eggNOG; KOG1172; Eukaryota. DR GeneTree; ENSGT00940000157488; -. DR HOGENOM; CLU_002289_5_0_1; -. DR InParanoid; Q9BY07; -. DR OMA; DLYEGFH; -. DR OrthoDB; 1013180at2759; -. DR PhylomeDB; Q9BY07; -. DR TreeFam; TF313630; -. DR PathwayCommons; Q9BY07; -. DR Reactome; R-HSA-425381; Bicarbonate transporters. DR SignaLink; Q9BY07; -. DR BioGRID-ORCS; 57835; 107 hits in 1154 CRISPR screens. DR ChiTaRS; SLC4A5; human. DR GeneWiki; SLC4A5; -. DR GenomeRNAi; 57835; -. DR Pharos; Q9BY07; Tbio. DR PRO; PR:Q9BY07; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9BY07; protein. DR Bgee; ENSG00000188687; Expressed in sural nerve and 98 other tissues. DR ExpressionAtlas; Q9BY07; baseline and differential. DR Genevisible; Q9BY07; HS. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0008509; F:monoatomic anion transmembrane transporter activity; IEA:InterPro. DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; IDA:UniProtKB. DR GO; GO:0005452; F:solute:inorganic anion antiporter activity; IEA:InterPro. DR GO; GO:0015701; P:bicarbonate transport; IBA:GO_Central. DR GO; GO:0033326; P:cerebrospinal fluid secretion; IEA:Ensembl. DR GO; GO:0002064; P:epithelial cell development; IEA:Ensembl. DR GO; GO:0048311; P:mitochondrion distribution; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl. DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central. DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IEA:Ensembl. DR GO; GO:0003014; P:renal system process; IBA:GO_Central. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central. DR Gene3D; 1.10.287.570; Helical hairpin bin; 1. DR InterPro; IPR013769; Band3_cytoplasmic_dom. DR InterPro; IPR011531; HCO3_transpt-like_TM_dom. DR InterPro; IPR003020; HCO3_transpt_euk. DR InterPro; IPR003024; Na/HCO3_transpt. DR InterPro; IPR016152; PTrfase/Anion_transptr. DR PANTHER; PTHR11453; ANION EXCHANGE PROTEIN; 1. DR PANTHER; PTHR11453:SF20; ELECTROGENIC SODIUM BICARBONATE COTRANSPORTER 4; 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; Phoshotransferase/anion transport protein; 1. DR TIGRFAMs; TIGR00834; ae; 1. PE 2: Evidence at transcript level; KW Alternative splicing; Anion exchange; Cell membrane; Ion transport; KW Membrane; Reference proteome; Sodium; Sodium transport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1137 FT /note="Electrogenic sodium bicarbonate cotransporter 4" FT /id="PRO_0000328920" FT TOPO_DOM 1..521 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 522..544 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 545..555 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 556..587 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 588..606 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 607..628 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 629..742 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 743..762 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 763..773 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 774..795 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 796..828 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 829..847 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 848..866 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 867..883 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 884..888 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 889..908 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 909..928 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 929..948 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 949..953 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 954..971 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 972..1016 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1017..1034 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1035..1039 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1040..1057 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1058..1137 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 64..94 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 221..255 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 438..478 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1079..1137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..27 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 68..94 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 231..245 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1079..1099 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1112..1137 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 27..91 FT /note="ECPPIHIGLPVPTYPQRKTDQKGHLSGLQKVHWGLRPDQPQQELTGPGSGAS FT SQDSSMDLISRTR -> G (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_052770" FT VAR_SEQ 88..91 FT /note="SRTR -> EHKG (in isoform 5)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_052771" FT VAR_SEQ 774..811 FT /note="Missing (in isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:12388414, FT ECO:0000303|PubMed:15489334" FT /id="VSP_052772" FT VAR_SEQ 866..993 FT /note="KAAGYHLDLFWVGILMALCSFMGLPWYVAATVISIAHIDSLKMETETSAPGE FT QPQFLGVREQRVTGIIVFILTGISVFLAPILKCIPLPVLYGVFLYMGVASLNGIQMGTG FT GSEFKIQKKLTPFWERC -> GTESNRHHRLHPDGNLCLPGSHPKVYPPAGAVRSLPLH FT GRGLPEWHPVLGTLQALPDASQAPAGPCLPAARAAAPDPPLHPGADPLPGGALDPQIHG FT GCHHLPGHDPGPHHRSKASGFHLFPARPGLD (in isoform 5)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_052773" FT VAR_SEQ 866..924 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:12388414" FT /id="VSP_052774" FT VAR_SEQ 950..1046 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12063394" FT /id="VSP_052775" FT VAR_SEQ 973..988 FT /note="Missing (in isoform 3, isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:11788353, FT ECO:0000303|PubMed:11997242, ECO:0000303|PubMed:12388414, FT ECO:0000303|PubMed:15489334" FT /id="VSP_052776" FT VAR_SEQ 994..1137 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_052777" FT VAR_SEQ 1046 FT /note="M -> MSLSTTD (in isoform 2 and isoform 6)" FT /evidence="ECO:0000303|PubMed:10978526, FT ECO:0000303|PubMed:11087115, ECO:0000303|PubMed:12388414" FT /id="VSP_052778" FT VAR_SEQ 1068..1137 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:12388414" FT /id="VSP_052779" FT VAR_SEQ 1071..1075 FT /note="NILPE -> KIEFP (in isoform 6)" FT /evidence="ECO:0000303|PubMed:12388414" FT /id="VSP_052780" FT VAR_SEQ 1076..1137 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:12388414" FT /id="VSP_052781" FT VARIANT 251 FT /note="S -> N (in dbSNP:rs17009792)" FT /id="VAR_048350" FT VARIANT 253 FT /note="H -> Y (in dbSNP:rs55651232)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_061032" FT CONFLICT 612 FT /note="H -> Y (in Ref. 6; AAL48291/AAL50802)" FT /evidence="ECO:0000305" FT CONFLICT 699 FT /note="A -> T (in Ref. 6; AAL48291)" FT /evidence="ECO:0000305" FT CONFLICT 759 FT /note="L -> R (in Ref. 6; AAL50802)" FT /evidence="ECO:0000305" FT CONFLICT 813 FT /note="T -> P (in Ref. 2; AAK26741)" FT /evidence="ECO:0000305" FT CONFLICT 896 FT /note="T -> M (in Ref. 6; AAL48291)" FT /evidence="ECO:0000305" FT CONFLICT 923 FT /note="G -> R (in Ref. 6; AAL48291)" FT /evidence="ECO:0000305" SQ SEQUENCE 1137 AA; 126255 MW; ED4E4A4DC2CA17F1 CRC64; MKVKEEKAGV GKLDHTNHRR RFPDQKECPP IHIGLPVPTY PQRKTDQKGH LSGLQKVHWG LRPDQPQQEL TGPGSGASSQ DSSMDLISRT RSPAAEQLQD ILGEEDEAPN PTLFTEMDTL QHDGDQMEWK ESARWIKFEE KVEEGGERWS KPHVSTLSLH SLFELRTCLQ TGTVLLDLDS GSLPQIIDDV IEKQIEDGLL RPELRERVSY VLLRRHRHQT KKPIHRSLAD IGKSVSTTNR SPARSPGAGP SLHHSTEDLR MRQSANYGRL CHAQSRSMND ISLTPNTDQR KNKFMKKIPK DSEASNVLVG EVDFLDQPFI AFVRLIQSAM LGGVTEVPVP TRFLFILLGP SGRAKSYNEI GRAIATLMVD DLFSDVAYKA RNREDLIAGI DEFLDEVIVL PPGEWDPNIR IEPPKKVPSA DKRKSVFSLA ELGQMNGSVG GGGGAPGGGN GGGGGGGSGG GAGSGGAGGT SSGDDGEMPA MHEIGEELIW TGRFFGGLCL DIKRKLPWFP SDFYDGFHIQ SISAILFIYL GCITNAITFG GLLGDATDNY QGVMESFLGT AMAGSLFCLF SGQPLIILSS TGPILIFEKL LFDFSKGNGL DYMEFRLWIG LHSAVQCLIL VATDASFIIK YITRFTEEGF STLISFIFIY DAIKKMIGAF KYYPINMDFK PNFITTYKCE CVAPDTVNTT VFNASAPLAP DTNASLYNLL NLTALDWSLL SKKECLSYGG RLLGNSCKFI PDLALMSFIL FFGTYSMTLT LKKFKFSRYF PTKVRALVAD FSIVFSILMF CGIDACFGLE TPKLHVPSVI KPTRPDRGWF VAPFGKNPWW VYPASILPAL LVTILIFMDQ QITAVIVNRK ENKLKKAAGY HLDLFWVGIL MALCSFMGLP WYVAATVISI AHIDSLKMET ETSAPGEQPQ FLGVREQRVT GIIVFILTGI SVFLAPILKC IPLPVLYGVF LYMGVASLNG IQMGTGGSEF KIQKKLTPFW ERCKLFLMPA KHQPDHAFLR HVPLRRIHLF TLVQILCLAV LWILKSTVAA IIFPVMILGL IIVRRLLDFI FSQHDLAWID NILPEKEKKE TDKKRKRKKG AHEDCDEEPQ FPPPSVIKIP MESVQSDPQN GIHCIARKRS SSWSYSL //