ID   B3A2_RAT                Reviewed;        1234 AA.
AC   P23347;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1991, sequence version 1.
DT   24-JAN-2024, entry version 163.
DE   RecName: Full=Anion exchange protein 2;
DE            Short=AE 2;
DE            Short=Anion exchanger 2;
DE   AltName: Full=Band 3-related protein 2;
DE            Short=B3RP-2;
DE   AltName: Full=Non-erythroid band 3-like protein;
DE   AltName: Full=Solute carrier family 4 member 2;
GN   Name=Slc4a2; Synonyms=Ae2, B3rp2;
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].
RC   TISSUE=Stomach;
RX   PubMed=2294114; DOI=10.1016/s0021-9258(19)40253-6;
RA   Kudrycki K.E., Newman P.R., Shull G.E.;
RT   "cDNA cloning and tissue distribution of mRNAs for two proteins that are
RT   related to the band 3 Cl-/HCO3-exchanger.";
RL   J. Biol. Chem. 265:462-471(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP   REGULATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=2371270; DOI=10.1073/pnas.87.14.5278;
RA   Lindsey A.E., Schneider K., Simmons D.M., Baron R., Lee B.S., Kopito R.R.;
RT   "Functional expression and subcellular localization of an anion exchanger
RT   cloned from choroid plexus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:5278-5282(1990).
RN   [3]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=10600827; DOI=10.1152/ajpgi.1999.277.6.g1288;
RA   Roussa E., Romero M.F., Schmitt B.M., Boron W.F., Alper S.L., Thevenod F.;
RT   "Immunolocalization of anion exchanger AE2 and Na(+)-HCO(-)(3)
RT   cotransporter in rat parotid and submandibular glands.";
RL   Am. J. Physiol. 277:G1288-G1296(1999).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145 AND THR-254, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=8141271; DOI=10.1152/ajpcell.1994.266.2.c559;
RA   Stuart-Tilley A., Sardet C., Pouyssegur J., Schwartz M.A., Brown D.,
RA   Alper S.L.;
RT   "Immunolocalization of anion exchanger AE2 and cation exchanger NHE-1 in
RT   distinct adjacent cells of gastric mucosa.";
RL   Am. J. Physiol. 266:C559-C568(1994).
RN   [6]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=22310983; DOI=10.1007/s00418-012-0927-2;
RA   Schwabe K., Cetin Y.;
RT   "Guanylin and functional coupling proteins in the hepatobiliary system of
RT   rat and guinea pig.";
RL   Histochem. Cell Biol. 137:589-597(2012).
CC   -!- FUNCTION: Sodium-independent anion exchanger which mediates the
CC       electroneutral exchange of chloride for bicarbonate ions across the
CC       cell membrane (PubMed:2371270). Plays an important role in osteoclast
CC       differentiation and function (By similarity). Regulates bone resorption
CC       and calpain-dependent actin cytoskeleton organization in osteoclasts
CC       via anion exchange-dependent control of pH (By similarity). Essential
CC       for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation,
CC       modulating CD8(+) T-cell responses (By similarity).
CC       {ECO:0000250|UniProtKB:P13808, ECO:0000269|PubMed:2371270}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(out) + hydrogencarbonate(in) = chloride(in) +
CC         hydrogencarbonate(out); Xref=Rhea:RHEA:72363, ChEBI:CHEBI:17544,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:2371270};
CC   -!- ACTIVITY REGULATION: Inhibited by 4,4'-diisothiocyanatostilbene-2,2'-
CC       disulfonic acid (DIDS). {ECO:0000269|PubMed:2371270}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:22310983}; Multi-pass membrane protein
CC       {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:10600827,
CC       ECO:0000269|PubMed:8141271}; Multi-pass membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in the parotid and submandibular glands
CC       (at protein level) (PubMed:10600827). Expressed in the gastric mucosa
CC       (at protein level) (PubMed:8141271). Expressed in the choroid plexus
CC       epithelium (at protein level) (PubMed:2371270). Expressed in the liver
CC       and gallbladder (PubMed:22310983). {ECO:0000269|PubMed:10600827,
CC       ECO:0000269|PubMed:22310983, ECO:0000269|PubMed:2371270,
CC       ECO:0000269|PubMed:8141271}.
CC   -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC       {ECO:0000305}.
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DR   EMBL; J05166; AAA40799.1; -; mRNA.
DR   PIR; A34911; A34911.
DR   RefSeq; NP_058744.1; NM_017048.2.
DR   RefSeq; XP_006235936.1; XM_006235874.3.
DR   RefSeq; XP_006235937.1; XM_006235875.3.
DR   AlphaFoldDB; P23347; -.
DR   SMR; P23347; -.
DR   BioGRID; 246904; 1.
DR   IntAct; P23347; 1.
DR   STRING; 10116.ENSRNOP00000019666; -.
DR   GlyCosmos; P23347; 3 sites, No reported glycans.
DR   GlyGen; P23347; 3 sites.
DR   iPTMnet; P23347; -.
DR   PhosphoSitePlus; P23347; -.
DR   PaxDb; 10116-ENSRNOP00000019666; -.
DR   Ensembl; ENSRNOT00000019666.3; ENSRNOP00000019666.2; ENSRNOG00000014347.6.
DR   Ensembl; ENSRNOT00055038994; ENSRNOP00055031664; ENSRNOG00055022682.
DR   Ensembl; ENSRNOT00060038512; ENSRNOP00060031771; ENSRNOG00060021745.
DR   Ensembl; ENSRNOT00065029119; ENSRNOP00065023080; ENSRNOG00065017378.
DR   GeneID; 24780; -.
DR   KEGG; rno:24780; -.
DR   AGR; RGD:3711; -.
DR   CTD; 6522; -.
DR   RGD; 3711; Slc4a2.
DR   eggNOG; KOG1172; Eukaryota.
DR   GeneTree; ENSGT00940000158259; -.
DR   HOGENOM; CLU_002289_1_0_1; -.
DR   InParanoid; P23347; -.
DR   OMA; RYQRMPT; -.
DR   OrthoDB; 1013180at2759; -.
DR   PhylomeDB; P23347; -.
DR   TreeFam; TF313630; -.
DR   Reactome; R-RNO-425381; Bicarbonate transporters.
DR   PRO; PR:P23347; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000014347; Expressed in stomach and 19 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0015108; F:chloride transmembrane transporter activity; ISO:RGD.
DR   GO; GO:0140900; F:chloride:bicarbonate antiporter activity; IDA:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR   GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0097186; P:amelogenesis; ISO:RGD.
DR   GO; GO:0015701; P:bicarbonate transport; IBA:GO_Central.
DR   GO; GO:0006821; P:chloride transport; ISO:RGD.
DR   GO; GO:0048565; P:digestive tract development; IEP:RGD.
DR   GO; GO:0043377; P:negative regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR   GO; GO:2000565; P:negative regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR   GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB.
DR   GO; GO:0070175; P:positive regulation of enamel mineralization; ISO:RGD.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:0045124; P:regulation of bone resorption; ISS:UniProtKB.
DR   GO; GO:0051453; P:regulation of intracellular pH; IMP:RGD.
DR   GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR   GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR   Gene3D; 1.10.287.570; Helical hairpin bin; 1.
DR   InterPro; IPR001717; Anion_exchange.
DR   InterPro; IPR002978; Anion_exchange_2.
DR   InterPro; IPR018241; Anion_exchange_CS.
DR   InterPro; IPR013769; Band3_cytoplasmic_dom.
DR   InterPro; IPR011531; HCO3_transpt-like_TM_dom.
DR   InterPro; IPR003020; HCO3_transpt_euk.
DR   InterPro; IPR016152; PTrfase/Anion_transptr.
DR   NCBIfam; TIGR00834; ae; 1.
DR   PANTHER; PTHR11453; ANION EXCHANGE PROTEIN; 1.
DR   PANTHER; PTHR11453:SF14; ANION EXCHANGE PROTEIN 2; 1.
DR   Pfam; PF07565; Band_3_cyto; 1.
DR   Pfam; PF00955; HCO3_cotransp; 1.
DR   PRINTS; PR00165; ANIONEXCHNGR.
DR   PRINTS; PR01188; ANIONEXHNGR2.
DR   PRINTS; PR01231; HCO3TRNSPORT.
DR   SUPFAM; SSF55804; Phoshotransferase/anion transport protein; 1.
DR   PROSITE; PS00219; ANION_EXCHANGER_1; 1.
DR   PROSITE; PS00220; ANION_EXCHANGER_2; 1.
DR   Genevisible; P23347; RN.
PE   1: Evidence at protein level;
KW   Anion exchange; Antiport; Cell membrane; Glycoprotein; Ion transport;
KW   Lipoprotein; Membrane; Methylation; Palmitate; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1234
FT                   /note="Anion exchange protein 2"
FT                   /id="PRO_0000079218"
FT   TOPO_DOM        1..704
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        705..728
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        734..771
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        791..813
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        823..843
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        844..893
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        894..911
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        912..926
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        927..947
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        981..1003
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1029..1050
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1084..1129
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1156..1192
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..239
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          287..315
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          446..467
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          705..1234
FT                   /note="Membrane (anion exchange)"
FT   COMPBIAS        33..55
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        62..99
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        169..183
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         113
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P04920"
FT   MOD_RES         145
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         171
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13808"
FT   MOD_RES         173
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P13808"
FT   MOD_RES         240
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P04920"
FT   MOD_RES         254
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         271
FT                   /note="N6-methyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P04920"
FT   MOD_RES         440
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P04920"
FT   LIPID           1166
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        856
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        866
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        878
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        206
FT                   /note="G -> A (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        925..926
FT                   /note="RR -> PG (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1018..1019
FT                   /note="ML -> IV (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1156..1157
FT                   /note="MH -> ID (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1234 AA;  136636 MW;  FAB4ED12BB916216 CRC64;
     MSSAPRRPAS GADSLHTPEP ESLSPGTPGF PEQEEEDELR TLGVERFEEI LQEAGSRGGE
     EPGRSYGEED FEYHRQSSHH IHHPLSTHLP PDARRRKTPQ GPGRKPRRRP GASPTGETPT
     IEEGEEDEDE VGEAEGFRAP PQQPSPASSP SAVQFFLQED EGTDRKAERT SPSPPTQTPH
     QEAAPRASKG AQTGTLVEEM VAVASGTAGG DDGGAAGRPL TKAQPGHRSY NLQERRRIGS
     MTGVEQALLP RVPTDESEAQ TLATADLDLM KSHRFEDVPG VRRHLVRKNA KGSTQAAREG
     REPGPTPRAR PRAPHKPHEV FVELNELQLD KNQEPQWRET ARWIKFEEDV EEETERWGKP
     HVASLSFRSL LELRRTLAHG AVLLDLDQQT LPGVAHQVVE QMVISDQIKA EDRANVLRAL
     LLKHSHPSDE KEFSFPRNIS AGSLGSLLGH HHAQGTESDP HVTEPLIGGV PETRLEVDRE
     RELPPPAPPA GITRSKSKHE LKLLEKIPEN AEATVVLVGC VEFLSRPTMA FVRLREAVEL
     DAVLEVPVPV RFLFLLLGPS SANMDYHEIG RSISTLMSDK QFHEAAYLAD ERDDLLTAIN
     AFLDCSVVLP PSEVQGEELL RSVAHFQRQM LKKREEQGRL LPPGAGLEPK SAQDKALLQM
     VEVAGAAEDD PLRRTGRPFG GLIRDVRRRY PHYLSDFRDA LDPQCLAAVI FIYFAALSPA
     ITFGGLLGEK TQDLIGVSEL IMSTALQGVI FCLLGAQPLL VIGFSGPLLV FEEAFFSFCK
     SNQLEYLVGR VWIGFWLVLL ALLMVALEGS FLVRFVSRFT QEIFAFLISL IFIYETFYKL
     IKIFQEHPLH GCSVSNDSEA DSSSNNMTWA ATTLAPDNSS ASGQERPRGQ PNTALLSLVL
     MAGTFFIAFF LRKFKNSRFF PGRIRRVIGD FGVPIAILIM VLVDYSIEDT YTQKLSVPSG
     FSVTAPDKRG WVINPLGEKT PFPVWMMVAS LLPAVLVFIL IFMETQITTL IISKKERMLQ
     KGSGFHLDLL LIVAMGGICA LFGLPWLAAA TVRSVTHANA LTVMSKAVAP GDKPKIQEVK
     EQRVTGLLVA LLVGLSMVIG DLLRQIPLAV LFGIFLYMGV TSLNGIQFYE RLHLLLMPPK
     HHPDVTYVKK VRTMRMHLFT ALQLLCLALL WAVMSTAASL AFPFILILTV PLRMVVLTRI
     FTEREMKCLD ANEAEPVFDE CEGVDEYNEM PMPV
//