ID SO4A1_RAT Reviewed; 723 AA.
AC Q99N01;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 24-JAN-2024, entry version 129.
DE RecName: Full=Solute carrier organic anion transporter family member 4A1;
DE AltName: Full=Organic anion-transporting polypeptide E;
DE Short=OATP-E {ECO:0000303|PubMed:11316767};
DE AltName: Full=Sodium-independent organic anion transporter E;
DE AltName: Full=Solute carrier family 21 member 12;
GN Name=Slco4a1; Synonyms=Oatp4a1, Oatpe, Slc21a12;
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, AND TRANSPORTER ACTIVITY.
RC TISSUE=Retina;
RX PubMed=11316767; DOI=10.1210/endo.142.5.8115;
RA Fujiwara K., Adachi H., Nishio T., Unno M., Tokui T., Okabe M., Onogawa T.,
RA Suzuki T., Asano N., Tanemoto M., Seki M., Shiiba K., Suzuki M., Kondo Y.,
RA Nunoki K., Shimosegawa T., Iinuma K., Ito S., Matsuno S., Abe T.;
RT "Identification of thyroid hormone transporters in humans: different
RT molecules are involved in a tissue-specific manner.";
RL Endocrinology 142:2005-2012(2001).
CC -!- FUNCTION: Organic anion antiporter with apparent broad substrate
CC specificity. Recognizes various substrates including thyroid hormones
CC 3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4) and 3,3',5'-triiodo-
CC L-thyronine (rT3), conjugated steroids such as estrone 3-sulfate and
CC estradiol 17-beta glucuronide, bile acids such as taurocholate and
CC prostanoids such as prostaglandin E2, likely operating in a tissue-
CC specific manner (PubMed:11316767) (By similarity). May be involved in
CC uptake of metabolites from the circulation into organs such as kidney,
CC liver or placenta. Possibly drives the selective transport of thyroid
CC hormones and estrogens coupled to an outward glutamate gradient across
CC the microvillous membrane of the placenta (By similarity). The
CC transport mechanism, its electrogenicity and potential tissue-specific
CC counterions remain to be elucidated (Probable).
CC {ECO:0000250|UniProtKB:Q96BD0, ECO:0000269|PubMed:11316767,
CC ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,3',5-triiodo-L-thyronine(out) + L-glutamate(in) = 3,3',5-
CC triiodo-L-thyronine(in) + L-glutamate(out); Xref=Rhea:RHEA:72299,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:533015;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72300;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(in) + L-thyroxine(out) = L-glutamate(out) + L-
CC thyroxine(in); Xref=Rhea:RHEA:72303, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:58448; Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72304;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone 3-sulfate(out) + L-glutamate(in) = estrone 3-
CC sulfate(in) + L-glutamate(out); Xref=Rhea:RHEA:72239,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:60050;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72240;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutamate(in) + taurocholate(out) = L-glutamate(out) +
CC taurocholate(in); Xref=Rhea:RHEA:72307, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:36257; Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72308;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,3',5-triiodo-L-thyronine(out) = 3,3',5-triiodo-L-
CC thyronine(in); Xref=Rhea:RHEA:71811, ChEBI:CHEBI:533015;
CC Evidence={ECO:0000269|PubMed:11316767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71812;
CC Evidence={ECO:0000305|PubMed:11316767};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-thyroxine(out) = L-thyroxine(in); Xref=Rhea:RHEA:71819,
CC ChEBI:CHEBI:58448; Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71820;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,3',5'-triiodo-L-thyronine(out) = 3,3',5'-triiodo-L-
CC thyronine(in); Xref=Rhea:RHEA:71815, ChEBI:CHEBI:57261;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71816;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone 3-sulfate(out) = estrone 3-sulfate(in);
CC Xref=Rhea:RHEA:71835, ChEBI:CHEBI:60050;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71836;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(out) = 17beta-
CC estradiol 17-O-(beta-D-glucuronate)(in); Xref=Rhea:RHEA:72691,
CC ChEBI:CHEBI:82961; Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72692;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurocholate(out) = taurocholate(in); Xref=Rhea:RHEA:71703,
CC ChEBI:CHEBI:36257; Evidence={ECO:0000269|PubMed:11316767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71704;
CC Evidence={ECO:0000305|PubMed:11316767};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin E2(out) = prostaglandin E2(in);
CC Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50985;
CC Evidence={ECO:0000250|UniProtKB:Q96BD0};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96BD0};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- DOMAIN: A conserved histidine residue in the third TMD (His-190) may
CC play an essential role in the pH sensitivity of SLCO4A1/OATP4A1-
CC mediated substrate transport. {ECO:0000250|UniProtKB:Q96BD0}.
CC -!- SIMILARITY: Belongs to the organo anion transporter (TC 2.A.60) family.
CC {ECO:0000305}.
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DR EMBL; AF239262; AAK30042.1; -; mRNA.
DR AlphaFoldDB; Q99N01; -.
DR SMR; Q99N01; -.
DR STRING; 10116.ENSRNOP00000074703; -.
DR ChEMBL; CHEMBL2073701; -.
DR GlyCosmos; Q99N01; 2 sites, No reported glycans.
DR GlyGen; Q99N01; 2 sites.
DR PhosphoSitePlus; Q99N01; -.
DR PaxDb; 10116-ENSRNOP00000030414; -.
DR Ensembl; ENSRNOT00055001799; ENSRNOP00055001400; ENSRNOG00055001090.
DR Ensembl; ENSRNOT00060001905; ENSRNOP00060001112; ENSRNOG00060001323.
DR UCSC; RGD:620228; rat.
DR AGR; RGD:620228; -.
DR RGD; 620228; Slco4a1.
DR eggNOG; KOG3626; Eukaryota.
DR InParanoid; Q99N01; -.
DR PhylomeDB; Q99N01; -.
DR Reactome; R-RNO-879518; Transport of organic anions.
DR PRO; PR:Q99N01; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015132; F:prostaglandin transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; IDA:RGD.
DR GO; GO:0006811; P:monoatomic ion transport; IEA:UniProtKB-KW.
DR GO; GO:0043252; P:sodium-independent organic anion transport; IBA:GO_Central.
DR GO; GO:0042403; P:thyroid hormone metabolic process; IDA:RGD.
DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR004156; OATP.
DR NCBIfam; TIGR00805; oat; 1.
DR PANTHER; PTHR11388; ORGANIC ANION TRANSPORTER; 1.
DR PANTHER; PTHR11388:SF100; SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY MEMBER 4A1; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR Pfam; PF03137; OATP; 1.
DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1.
DR SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..723
FT /note="Solute carrier organic anion transporter family
FT member 4A1"
FT /id="PRO_0000191069"
FT TOPO_DOM 1..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..194
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..258
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..312
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..337
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 338..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..402
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 403..422
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..446
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..473
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..582
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 583..605
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 606..614
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 615..640
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 641..673
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 674..691
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 692..723
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 500..557
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT REGION 23..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 700..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96BD0"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96BD0"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96BD0"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 506..536
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 521..555
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
SQ SEQUENCE 723 AA; 77634 MW; DB857B514654497B CRC64;
MPQHAMGDKH FLSLPKHLFT STSSTTDSGC DTPPSSRASP ASLRSAHGAL GSSSQPLFEP
QVEKRSSQAA CEVQYLSSGP QSTLCGWQSF TPKCLQVFNT PKGFLFFLCA ASFLQGMTVN
GFINTVITSI ERRFDLHSYQ SGLIASSYDI AACLCLTFVS YFGGNGHKPR WLGWGALVLG
IGSLVFALPH FTAGRYEVEI DDEGLGTETG TCLTNQSQVE CKDRASGLSS YRLIFMLGQL
LHGVGATPLY TLGVTYLDEN VKSSYSPIYI AIFYTAAILG PAAGYLIGGA MLNVYTEVGQ
RTELTTDSPL WVGAWWIGFL GAGIAAFLIA IPILGYPRQL PGSQRYVVMR AAETQQLKDH
SRDNPAFGKT VRDLPLSVWI LLRNPTFILL CLAGATEATL IAGMSTFGPK FFEAQFSLSA
SEAATLFGYL VVPAGGGGTL LGGFLVNKFK LRGSGIIRFC LFCTLTSLLA FFVFLMHCPN
VHMAGVTTGY VGSLLPKGQL DLKAACNALY CCQPRHYSPL CGSDGTMYYS PCYAGCPEGA
VTGPGGQKVY RGCSCILEKA SSGWGNATAG KCASTCQSKP LLLVLVFVVI IFTFLSSIPA
LTATLRCVCD RQRSFALGIQ WIVVRTLGSI PGPIAFGWVI DKACLLWQDQ CGHQGSCFVY
KNEAMSRYLL IAGLTFKVLG FLFFVAAYFL YKSPSVSSDG LEASLPSQSS ASDSPTEQLQ
SNV
//
