S4A4_BOVIN
ID S4A4_BOVIN Reviewed; 1079 AA.
AC Q9GL77;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 25-MAY-2022, entry version 113.
DE RecName: Full=Electrogenic sodium bicarbonate cotransporter 1;
DE Short=Sodium bicarbonate cotransporter;
DE AltName: Full=Solute carrier family 4 member 4;
GN Name=SLC4A4; Synonyms=NBC, NBCE1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Cornea;
RX PubMed=11029313; DOI=10.1152/ajpcell.2000.279.5.c1648;
RA Sun X.C., Bonanno J.A., Jelamskii S., Xie Q.;
RT "Expression and localization of Na(+)-HCO(3)(-) cotransporter in bovine
RT corneal endothelium.";
RL Am. J. Physiol. 279:C1648-C1655(2000).
RN [2]
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-cotransporter
RT (NBCe1).";
RL Am. J. Physiol. 284:F1199-F1206(2003).
RN [3]
RP INTERACTION WITH AHCYL2, AND TISSUE SPECIFICITY.
RX PubMed=24472682; DOI=10.1016/j.febslet.2013.12.036;
RA Yamaguchi S., Ishikawa T.;
RT "AHCYL2 (long-IRBIT) as a potential regulator of the electrogenic Na(+)-
RT HCO3(-) cotransporter NBCe1-B.";
RL FEBS Lett. 588:672-677(2014).
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:0000250|UniProtKB:Q9Y6R1,
CC ECO:0000269|PubMed:11029313}.
CC -!- ACTIVITY REGULATION: Inhibited by stilbene derivatives and regulated by
CC cyclic AMP. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with CA2/carbonic
CC anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter
CC activity (By similarity). Interacts with AHCYL1 (via PEST domain when
CC phosphorylated); the interaction increases SLC4A4 activity (By
CC similarity). Interacts with AHCYL2 (PubMed:24472682).
CC {ECO:0000250|UniProtKB:O88343, ECO:0000250|UniProtKB:Q9Y6R1,
CC ECO:0000269|PubMed:24472682}.
CC -!- INTERACTION:
CC Q9GL77; F1MWH2: AHCYL1; NbExp=3; IntAct=EBI-9076174, EBI-9079878;
CC Q9GL77; A6QLP2: AHCYL2; NbExp=5; IntAct=EBI-9076174, EBI-9076161;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:11029313}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11029313}.
CC -!- TISSUE SPECIFICITY: Expressed in acinar cells (at protein level).
CC {ECO:0000269|PubMed:24472682}.
CC -!- PTM: Phosphorylation of Ser-1026 by PKA increases the binding of CA2
CC and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1
CC to 2:1. Phosphorylated in presence of STK39 and dephosphorylated in
CC presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4
CC activity. {ECO:0000250|UniProtKB:O88343, ECO:0000250|UniProtKB:Q9Y6R1}.
CC -!- PTM: N-glycosylated. May not be necessary for the transporter basic
CC functions. {ECO:0000269|PubMed:12604466}.
CC -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC {ECO:0000305}.
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DR EMBL; AF308160; AAG29539.1; -; mRNA.
DR RefSeq; NP_777030.1; NM_174605.1.
DR AlphaFoldDB; Q9GL77; -.
DR SMR; Q9GL77; -.
DR IntAct; Q9GL77; 2.
DR MINT; Q9GL77; -.
DR STRING; 9913.ENSBTAP00000003032; -.
DR PaxDb; Q9GL77; -.
DR PRIDE; Q9GL77; -.
DR GeneID; 282360; -.
DR KEGG; bta:282360; -.
DR CTD; 8671; -.
DR eggNOG; KOG1172; Eukaryota.
DR InParanoid; Q9GL77; -.
DR OrthoDB; 265068at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
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:0005452; F:inorganic anion exchanger activity; IEA:InterPro.
DR GO; GO:0008510; F:sodium:bicarbonate symporter activity; ISS:UniProtKB.
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:0006814; P:sodium ion transport; ISS:UniProtKB.
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; 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 Cell membrane; Disulfide bond; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium transport; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1079
FT /note="Electrogenic sodium bicarbonate cotransporter 1"
FT /id="PRO_0000079226"
FT TOPO_DOM 1..466
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 467..491
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 492..501
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 502..520
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 522..542
FT /note="Discontinuously helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 543..550
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 551..571
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 572..585
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 586..609
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 610..692
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 693..710
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 711..725
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 726..745
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 746..779
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 780..807
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 808..819
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 820..836
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 837
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 838..855
FT /note="Discontinuously helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 856..877
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 878..894
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 895..901
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TRANSMEM 902..918
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 919..960
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT INTRAMEM 961..986
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT TOPO_DOM 987..1079
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT REGION 1..62
FT /note="Required for interaction with AHCYL1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT REGION 40..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 748..779
FT /note="Interaction with CA4"
FT /evidence="ECO:0000250"
FT REGION 1002..1004
FT /note="CA2-binding"
FT /evidence="ECO:0000250"
FT REGION 1012..1079
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1030..1033
FT /note="CA2-binding"
FT /evidence="ECO:0000250"
FT REGION 1057..1059
FT /note="Required for basolateral targeting"
FT /evidence="ECO:0000250"
FT COMPBIAS 54..73
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 238..260
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1012..1039
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1060..1079
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 49
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JI66"
FT MOD_RES 254
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 1026
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT MOD_RES 1029
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT MOD_RES 1044
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88343"
FT MOD_RES 1069
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JI66"
FT CARBOHYD 641
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 661
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 627..629
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT DISULFID 674..686
FT /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
SQ SEQUENCE 1079 AA; 121331 MW; 114367FC093C7B67 CRC64;
MEDEAVLDRG ASFLKHVCDE EEVEGHHTIY IGVHVPKSYR RRRRHKRKTG HREKKEKERI
SENYSDKSDV ENADESSSSI LKPLISPAAE RIRFILGEED DSPAPPQLFT ELDELLAVDG
QEMEWKETAR WIKFEEKVEQ GGERWSKPHV ATLSLHSLFE LRTCMEKGSI MLDREASSLP
QLVEMIVDHQ IETGLLKPDL KDKVTYTLLR KHRHQTKKSN LRSLADIGKT VSSASRMFTN
PDNGSPAMTH RNLTSSSLND ISDKPEKDQL KNKFMKKLPR DAEASNVLVG EVDFLDSPFI
AFVRLQQAVM LGALTEVPVP TRFLFILLGP KGKAKSYHEI GRAIATLMSD EVFHDIAYKA
KDRQDLIAGI DEFLDEVIVL PPGEWDPAIR IEPPKSLPSS DKRKNMYSGG ENVQMNGDTP
PDGGHGGGGH ADCEELQRTG RFCGGLIKDI KRKAPFFASD FYDALNIQAL SAILFIYLAT
VTNAITFGGL LGDATDNMQG VLESFLGTAV SGAIFCLFAG QPLTILSSTG PVLVFERLLF
NFSKDHNFDY LEFRLWIGLW SAFLCLILVA TDASFLVQYF TRFTEEGFSS LISFIFIYDA
FKKMIKLADY YPINSNFKVG YNTQFSCVCM PPDPVNISVS NDTTLAPEDL PTISSSNMYH
NATFDWAFLT TKECLKYGGK LVGNNCGFVP DITLMSFILF LGTYTSSMAL KKFKTSPYFP
TTARKLISDF AIILPILIFC VIDALVGVDT PKLIVPSEFK PTSPNRGWFV APFGGNPWWV
YLAAAIPALL VTILIFMDQQ ITAVIVNRKE HKLKKGAGYH LDLFWVAILM VVCSFMALPW
YVAATVISIA HIDSLKMETE TSAPGEQPKF LGVREQRVTG TLVFILTGLS VFMAPILKFI
PMPVLYGVFL YMGVASLNGV QFMDRLKLLL MPLKHQPDFI YLRHVPLRRV HLFTFLQVLC
LALLWILKST VAAIIFPVMI LALVAVRKGM DYLFSQHDLS FLDDVIPEKD KKKKEDEKKK
KKKKGSVDSD NDDSDCPYSE KVPSIKIPMD IMEQQPFLSD SKPSDRERSP TFLERHTSC
