ID B3A4_RAT Reviewed; 953 AA.
AC Q8K4V2;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 124.
DE RecName: Full=Anion exchange protein 4 {ECO:0000305};
DE Short=AE 4;
DE Short=Anion exchanger 4;
DE AltName: Full=Solute carrier family 4 member 9;
GN Name=Slc4a9 {ECO:0000312|RGD:628811};
GN Synonyms=Ae4 {ECO:0000303|PubMed:12225984};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=12225984; DOI=10.1152/ajpcell.00512.2001;
RA Ko S.B.H., Luo X., Hager H., Rojek A., Choi J.Y., Licht C., Suzuki M.,
RA Muallem S., Nielsen S., Ishibashi K.;
RT "AE4 is a DIDS-sensitive Cl(-)/HCO(-)(3) exchanger in the basolateral
RT membrane of the renal CCD and the SMG duct.";
RL Am. J. Physiol. 283:C1206-C1218(2002).
CC -!- FUNCTION: Electroneutral Cl(-)/HCO3(-) antiporter that favors chloride
CC ion entry and efflux of hydrogencarbonate and sodium ion across the
CC basolateral membrane and may participate in salivary secretion
CC (PubMed:12225984). Also mediates Cl(-)/HCO3(-) exchange activity in the
CC presence of K(+) as well as Cs(+), Li(+), and Rb(+). Does not
CC contribute to Cl(-)/HCO3(-) exchanger in the apical membrane of the
CC upper villous epithelium (By similarity).
CC {ECO:0000250|UniProtKB:A0A494BA31, ECO:0000269|PubMed:12225984}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) + 2 hydrogencarbonate(out) + Na(+)(out) =
CC chloride(out) + 2 hydrogencarbonate(in) + Na(+)(in);
CC Xref=Rhea:RHEA:72739, ChEBI:CHEBI:17544, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:A0A494BA31};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + 2 hydrogencarbonate(in) + K(+)(in) =
CC chloride(in) + 2 hydrogencarbonate(out) + K(+)(out);
CC Xref=Rhea:RHEA:75059, ChEBI:CHEBI:17544, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:29103; Evidence={ECO:0000250|UniProtKB:A0A494BA31};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + 2 hydrogencarbonate(in) + Li(+)(in) =
CC chloride(in) + 2 hydrogencarbonate(out) + Li(+)(out);
CC Xref=Rhea:RHEA:75063, ChEBI:CHEBI:17544, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:49713; Evidence={ECO:0000250|UniProtKB:A0A494BA31};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + 2 hydrogencarbonate(in) + Rb(+)(in) =
CC chloride(in) + 2 hydrogencarbonate(out) + Rb(+)(out);
CC Xref=Rhea:RHEA:75067, ChEBI:CHEBI:17544, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:49847; Evidence={ECO:0000250|UniProtKB:A0A494BA31};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(out) + Cs(+)(in) + 2 hydrogencarbonate(in) =
CC chloride(in) + Cs(+)(out) + 2 hydrogencarbonate(out);
CC Xref=Rhea:RHEA:75071, ChEBI:CHEBI:17544, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:49547; Evidence={ECO:0000250|UniProtKB:A0A494BA31};
CC -!- ACTIVITY REGULATION: 4,4'-diisothiocyanatodihydrostilbene-
CC 2,2'- disulfonic acid (H2DIDS) potently inhibits
CC chloride/hydrogencarbonate antiporter activity with 50% inhibition at
CC about 5 uM (PubMed:12225984). Completely inhibits
CC chloride/hydrogencarbonate antiporter activity at 200 uM of 4,4'-
CC diisothiocyano-trans-stilbene-2,2'-disulfonic acid (DIDS)
CC (PubMed:12225984). {ECO:0000269|PubMed:12225984}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:12225984}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localized in the basolateral membrane of both
CC alpha-intercalated cells and beta-intercalated cells in the cortical
CC collecting duct (CCD) kidney cells (PubMed:12225984). Localized in the
CC basolateral membrane of the submandibular gland (SMG) duct (By
CC similarity). {ECO:0000250|UniProtKB:A0A494BA31,
CC ECO:0000269|PubMed:12225984}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and gastrointestinal tract
CC (PubMed:12225984). In kidney, it is highly expressed in the cortex,
CC expressed at intermediate level in the outer medulla and not expressed
CC in the inner medulla (PubMed:12225984). It is expressed in the cecum,
CC while it is absent in other segments of gastrointestinal tract
CC (PubMed:12225984). Highly expressed in the cortical collecting duct
CC (CCD) (PubMed:12225984). Expressed in both alpha-intercalated cells and
CC beta-intercalated cells in the CCD (at protein level)
CC (PubMed:12225984). {ECO:0000269|PubMed:12225984}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000305}.
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DR EMBL; AB024339; BAC10662.1; -; mRNA.
DR RefSeq; NP_690921.1; NM_152938.1.
DR AlphaFoldDB; Q8K4V2; -.
DR SMR; Q8K4V2; -.
DR STRING; 10116.ENSRNOP00000025137; -.
DR GlyCosmos; Q8K4V2; 2 sites, No reported glycans.
DR GlyGen; Q8K4V2; 4 sites.
DR iPTMnet; Q8K4V2; -.
DR PhosphoSitePlus; Q8K4V2; -.
DR PaxDb; 10116-ENSRNOP00000025137; -.
DR GeneID; 266612; -.
DR KEGG; rno:266612; -.
DR UCSC; RGD:628811; rat.
DR AGR; RGD:628811; -.
DR CTD; 83697; -.
DR RGD; 628811; Slc4a9.
DR eggNOG; KOG1172; Eukaryota.
DR InParanoid; Q8K4V2; -.
DR OrthoDB; 1013180at2759; -.
DR PhylomeDB; Q8K4V2; -.
DR Reactome; R-RNO-425381; Bicarbonate transporters.
DR PRO; PR:Q8K4V2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0140900; F:chloride:bicarbonate antiporter activity; IDA:UniProtKB.
DR GO; GO:0140892; F:sodium,bicarbonate:chloride antiporter activity; ISO:RGD.
DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; ISS:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; IBA:GO_Central.
DR GO; GO:0006820; P:monoatomic anion transport; IDA:RGD.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0046541; P:saliva secretion; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
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 NCBIfam; TIGR00834; ae; 1.
DR PANTHER; PTHR11453; ANION EXCHANGE PROTEIN; 1.
DR PANTHER; PTHR11453:SF52; ANION EXCHANGE PROTEIN 4; 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; Phoshotransferase/anion transport protein; 1.
PE 1: Evidence at protein level;
KW Anion exchange; Antiport; Cell membrane; Glycoprotein; Ion transport;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..953
FT /note="Anion exchange protein 4"
FT /id="PRO_0000079225"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 501..521
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 594..614
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 635..655
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 682..702
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 728..748
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 785..805
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 807..827
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 869..889
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 20..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..953
FT /note="Membrane (anion exchange)"
FT REGION 916..938
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..931
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 932
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 949
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 953 AA; 105320 MW; 625A98A969821F85 CRC64;
MKLPGQEDFE GSDAHENVCS EQLDGDLGPG SGLDGPSDID NGKAQGCKDP LLFIQLNELL
GWPQALEWRE TGRWLLFEEK LDIGAGRWSA PHVPTLALPS LQKLRGLLAE GIVLLDCPAR
SLLELVEQVV RVESLSPELR GQLQALLLQR PQHHIQTTGI RPCRRSNAFR KASRDEDTLL
KHQNPLRQKL PPGAEAAAVL AGELGFLEQP LAAFVRLQNP VVLEPLTEVV LPSRFFCLLL
GPSTLGRSYH ETGRAAAVLL SDPQFQWSVR RASNLHDLLA ALDAFLQEVT ALPPGRWDRT
ARIPPPKCLP SQHKRFPSKL QEVTSLSRQS AALAENKHHH GPHTPIPELQ RTGRLFGGLV
QDVRRKACWY PSDFLDALHP QCFSAVLYIY LATVTNAITF GGLLGDATEG AQGVLESFLG
TAVAGATFCL MAGQPLTILS STGPVLVFER LLFSFSRDYS LDYLPFRLWV GIWVATFCLA
LVATEASLLV RYFTRFTEEG FCALISLIFI YDAVGKMLNL IRAYPIQRPG SPAYSCFCQY
PGTGGNASEF DSTMFKDTED VLNVHPGLVN ASFLPPSECI RQGGYPRGPS CHTVPDIAFF
SLLLFFTSFL CAIALKHVKN SRLFPSVVRK VFSDFSSVLA ILLGCGLDAF LGLATPKLLV
PTEFKPTLPG RGWLVSPFGA NPWWLSVAAA LPALLLSILI FMDQQITAVI LNRAEYRLQK
GAGFHLDLFC VAVLMLFTSA LGLPWYVSAT VISLAHMDSL RRESKACVPG EDPNFLGIRE
QRLTGLVVFI LTGVSIFLAP VLKFIPMPVL YGIFLYMGVA ALSSMQFMKR VQLLLMPRKH
QPDVLLLRHV PLIRVHLFTA IQLACLGLLW VIKSTPAAIV FPLMLLGLVA VRKALEWIFS
PQELLWLDEL MPEEEKTIPE NRPEPEHLFS GNDSENSELM YQPKAPEINI SVN
//
