B3A4_HUMAN
ID B3A4_HUMAN Reviewed; 983 AA.
AC Q96Q91; B7ZL63; D3DQD4; D3DQD5; D3DQD6; E9PDK1; Q96RM5; Q9BXF2; Q9BXN3;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2003, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Anion exchange protein 4;
DE Short=AE 4;
DE Short=Anion exchanger 4;
DE AltName: Full=Sodium bicarbonate cotransporter 5;
DE AltName: Full=Solute carrier family 4 member 9;
GN Name=SLC4A9; Synonyms=AE4, SBC5;
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] (ISOFORM 2).
RC TISSUE=Kidney, and Testis;
RX PubMed=11302728; DOI=10.1006/bbrc.2001.4692;
RA Parker M.D., Ourmozdi E.P., Tanner M.J.A.;
RT "Human BTR1, a new bicarbonate transporter superfamily member and human AE4
RT from kidney.";
RL Biochem. Biophys. Res. Commun. 282:1103-1109(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=11305939; DOI=10.1186/gb-2001-2-4-research0011;
RA Lipovich L., Lynch E.D., Lee M.K., King M.-C.;
RT "A novel sodium bicarbonate cotransporter-like gene in an ancient
RT duplicated region: SLC4A9 at 5q31.";
RL Genome Biol. 2:RESEARCH0011.1-RESEARCH0011.13(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Karet F.E.;
RT "Cloning and characterization of human AE4.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Lung, Placenta, and 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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-983 (ISOFORM 3), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RA Ishibashi K.;
RT "Molecular cloning of human sodium bicarbonate cotransporter 5.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Probable apical anion exchanger of the kidney cortex.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96Q91-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96Q91-2; Sequence=VSP_007085, VSP_007086, VSP_007087;
CC Name=3;
CC IsoId=Q96Q91-3; Sequence=VSP_007085;
CC Name=4;
CC IsoId=Q96Q91-4; Sequence=VSP_007085, VSP_044785;
CC -!- TISSUE SPECIFICITY: Kidney specific. {ECO:0000269|PubMed:11305939,
CC ECO:0000269|Ref.7}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK28832.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF336237; AAK16733.1; -; mRNA.
DR EMBL; AF313465; AAK28832.1; ALT_INIT; mRNA.
DR EMBL; AF332961; AAK69625.1; -; mRNA.
DR EMBL; AC008438; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62062.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62063.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62064.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62066.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62067.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62068.1; -; Genomic_DNA.
DR EMBL; BC136262; AAI36263.1; -; mRNA.
DR EMBL; BC143602; AAI43603.1; -; mRNA.
DR EMBL; AB032762; BAA93010.1; -; mRNA.
DR CCDS; CCDS47278.1; -. [Q96Q91-3]
DR CCDS; CCDS58973.1; -. [Q96Q91-1]
DR CCDS; CCDS58974.1; -. [Q96Q91-4]
DR CCDS; CCDS58975.1; -. [Q96Q91-2]
DR RefSeq; NP_001245355.1; NM_001258426.1. [Q96Q91-2]
DR RefSeq; NP_001245356.1; NM_001258427.1. [Q96Q91-4]
DR RefSeq; NP_001245357.1; NM_001258428.1. [Q96Q91-1]
DR RefSeq; NP_113655.2; NM_031467.2. [Q96Q91-3]
DR AlphaFoldDB; Q96Q91; -.
DR SMR; Q96Q91; -.
DR STRING; 9606.ENSP00000427661; -.
DR TCDB; 2.A.31.2.13; the anion exchanger (ae) family.
DR GlyGen; Q96Q91; 2 sites.
DR iPTMnet; Q96Q91; -.
DR PhosphoSitePlus; Q96Q91; -.
DR BioMuta; SLC4A9; -.
DR DMDM; 29427950; -.
DR EPD; Q96Q91; -.
DR MassIVE; Q96Q91; -.
DR PaxDb; Q96Q91; -.
DR PeptideAtlas; Q96Q91; -.
DR PRIDE; Q96Q91; -.
DR Antibodypedia; 62629; 117 antibodies from 21 providers.
DR DNASU; 83697; -.
DR Ensembl; ENST00000432095.6; ENSP00000410056.2; ENSG00000113073.15. [Q96Q91-2]
DR Ensembl; ENST00000506545.5; ENSP00000422855.1; ENSG00000113073.15. [Q96Q91-4]
DR Ensembl; ENST00000506757.7; ENSP00000424424.1; ENSG00000113073.15. [Q96Q91-3]
DR Ensembl; ENST00000507527.1; ENSP00000427661.1; ENSG00000113073.15. [Q96Q91-1]
DR GeneID; 83697; -.
DR KEGG; hsa:83697; -.
DR MANE-Select; ENST00000506757.7; ENSP00000424424.1; NM_031467.3; NP_113655.2. [Q96Q91-3]
DR UCSC; uc003lfk.3; human. [Q96Q91-1]
DR CTD; 83697; -.
DR DisGeNET; 83697; -.
DR GeneCards; SLC4A9; -.
DR HGNC; HGNC:11035; SLC4A9.
DR HPA; ENSG00000113073; Tissue enriched (kidney).
DR MIM; 610207; gene.
DR neXtProt; NX_Q96Q91; -.
DR OpenTargets; ENSG00000113073; -.
DR PharmGKB; PA35901; -.
DR VEuPathDB; HostDB:ENSG00000113073; -.
DR eggNOG; KOG1172; Eukaryota.
DR GeneTree; ENSGT00940000160970; -.
DR HOGENOM; CLU_002289_5_1_1; -.
DR InParanoid; Q96Q91; -.
DR OMA; GEMPPIT; -.
DR OrthoDB; 265068at2759; -.
DR PhylomeDB; Q96Q91; -.
DR TreeFam; TF313630; -.
DR PathwayCommons; Q96Q91; -.
DR Reactome; R-HSA-425381; Bicarbonate transporters.
DR BioGRID-ORCS; 83697; 10 hits in 1058 CRISPR screens.
DR GenomeRNAi; 83697; -.
DR Pharos; Q96Q91; Tbio.
DR PRO; PR:Q96Q91; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q96Q91; protein.
DR Bgee; ENSG00000113073; Expressed in adult mammalian kidney and 126 other tissues.
DR Genevisible; Q96Q91; HS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015301; F:anion:anion antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015701; P:bicarbonate transport; IBA:GO_Central.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 3.40.930.10; -; 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; PTHR11453; 1.
DR Pfam; PF07565; Band_3_cyto; 2.
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 2: Evidence at transcript level;
KW Alternative splicing; Anion exchange; Antiport; Disulfide bond;
KW Glycoprotein; Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..983
FT /note="Anion exchange protein 4"
FT /id="PRO_0000079223"
FT TOPO_DOM 1..414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 500..520
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..623
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 624..644
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 686..711
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 712..732
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 758..778
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 815..835
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 837..857
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 899..919
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 186..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 332..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..983
FT /note="Membrane (anion exchange)"
FT REGION 946..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 946..963
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 576
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 566..568
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT DISULFID 609..621
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT VAR_SEQ 77..100
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11302728,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4,
FT ECO:0000303|Ref.7"
FT /id="VSP_007085"
FT VAR_SEQ 384..394
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11302728"
FT /id="VSP_007086"
FT VAR_SEQ 592..594
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11302728"
FT /id="VSP_007087"
FT VAR_SEQ 595..657
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044785"
FT CONFLICT 23
FT /note="G -> W (in Ref. 5; AAI36263/AAI43603)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="R -> T (in Ref. 4; AAK69625)"
FT /evidence="ECO:0000305"
FT CONFLICT 453
FT /note="V -> M (in Ref. 1; AAK16733)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="R -> K (in Ref. 1; AAK16733)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 983 AA; 108248 MW; E2AEB04C9D27E6BC CRC64;
MEMKLPGQEG FEASSAPRNI PSGELDSNPD PGTGPSPDGP SDTESKELGV PKDPLLFIQL
NELLGWPQAL EWRETGSSSA SLLLDMGEMP SITLSTHLHH RWVLFEEKLE VAAGRWSAPH
VPTLALPSLQ KLRSLLAEGL VLLDCPAQSL LELVEQVTRV ESLSPELRGQ LQALLLQRPQ
HYNQTTGTRP CWGSTHPRKA SDNEEAPLRE QCQNPLRQKL PPGAEAGTVL AGELGFLAQP
LGAFVRLRNP VVLGSLTEVS LPSRFFCLLL GPCMLGKGYH EMGRAAAVLL SDPQFQWSVR
RASNLHDLLA ALDAFLEEVT VLPPGRWDPT ARIPPPKCLP SQHKRLPSQQ REIRGPAVPR
LTSAEDRHRH GPHAHSPELQ RTGRLFGGLI QDVRRKVPWY PSDFLDALHL QCFSAVLYIY
LATVTNAITF GGLLGDATDG AQGVLESFLG TAVAGAAFCL MAGQPLTILS STGPVLVFER
LLFSFSRDYS LDYLPFRLWV GIWVATFCLV LVATEASVLV RYFTRFTEEG FCALISLIFI
YDAVGKMLNL THTYPIQKPG SSAYGCLCQY PGPGGNESQW IRTRPKDRDD IVSMDLGLIN
ASLLPPPECT RQGGHPRGPG CHTVPDIAFF SLLLFLTSFF FAMALKCVKT SRFFPSVVRK
GLSDFSSVLA ILLGCGLDAF LGLATPKLMV PREFKPTLPG RGWLVSPFGA NPWWWSVAAA
LPALLLSILI FMDQQITAVI LNRMEYRLQK GAGFHLDLFC VAVLMLLTSA LGLPWYVSAT
VISLAHMDSL RRESRACAPG ERPNFLGIRE QRLTGLVVFI LTGASIFLAP VLKFIPMPVL
YGIFLYMGVA ALSSIQFTNR VKLLLMPAKH QPDLLLLRHV PLTRVHLFTA IQLACLGLLW
IIKSTPAAII FPLMLLGLVG VRKALERVFS PQELLWLDEL MPEEERSIPE KGLEPEHSFS
GSDSEDSELM YQPKAPEINI SVN
