S22AO_HUMAN
ID S22AO_HUMAN Reviewed; 552 AA.
AC Q8N4F4; A0A087WWM3; C9JC66;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2020, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Steroid transmembrane transporter SLC22A24 {ECO:0000303|PubMed:31553721};
DE AltName: Full=Solute carrier family 22 member 24 {ECO:0000312|HGNC:HGNC:28542};
GN Name=SLC22A24 {ECO:0000312|HGNC:HGNC:28542};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP FUNCTION.
RX PubMed=17714910; DOI=10.1016/j.ygeno.2007.03.017;
RA Jacobsson J.A., Haitina T., Lindblom J., Fredriksson R.;
RT "Identification of six putative human transporters with structural
RT similarity to the drug transporter SLC22 family.";
RL Genomics 90:595-609(2007).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, POLYMORPHISM, VARIANT 501-TYR--PHE-552 DEL, CHARACTERIZATION OF
RP VARIANT 501-TYR--PHE-552 DEL, AND ISOFORM 1; ISOFORM 2 AND ISOFORM 3.
RX PubMed=31553721; DOI=10.1371/journal.pgen.1008208;
RA Yee S.W., Stecula A., Chien H.C., Zou L., Feofanova E.V., van Borselen M.,
RA Cheung K.W.K., Yousri N.A., Suhre K., Kinchen J.M., Boerwinkle E.,
RA Irannejad R., Yu B., Giacomini K.M.;
RT "Unraveling the functional role of the orphan solute carrier, SLC22A24 in
RT the transport of steroid conjugates through metabolomic and genome-wide
RT association studies.";
RL PLoS Genet. 15:E1008208-E1008208(2019).
CC -!- FUNCTION: Steroid transmembrane transporter that functions in the
CC reabsorption of conjugated steroids in the kidney and is involved in
CC steroid homeostasis. {ECO:0000269|PubMed:31553721,
CC ECO:0000305|PubMed:17714910}.
CC -!- FUNCTION: [Isoform 2]: Similar uptake function as Isoform 1.
CC {ECO:0000269|PubMed:31553721}.
CC -!- FUNCTION: [Isoform 3]: Lack of transporter activity.
CC {ECO:0000269|PubMed:31553721}.
CC -!- ACTIVITY REGULATION: Transport is chloride sensitive and transtimulated
CC by glutaric acid (PubMed:31553721). Transport is inhibited by anionic
CC compounds from different chemical classes (PubMed:31553721).
CC {ECO:0000269|PubMed:31553721}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.6 uM for estrone sulfate {ECO:0000269|PubMed:31553721};
CC KM=17.5 uM for estradiol-17beta-D-glucuronide
CC {ECO:0000269|PubMed:31553721};
CC KM=10.5 uM for taurocholic acid {ECO:0000269|PubMed:31553721};
CC KM=33.4 uM for glycocholic acid {ECO:0000269|PubMed:31553721};
CC KM=741 uM for androstanediol glucuronide
CC {ECO:0000303|PubMed:31553721};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane; Multi-pass membrane
CC protein {ECO:0000269|PubMed:31553721}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Membrane; Multi-pass membrane
CC protein {ECO:0000269|PubMed:31553721}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N4F4-2; Sequence=Displayed;
CC Name=3;
CC IsoId=Q8N4F4-1; Sequence=VSP_060488, VSP_060489;
CC Name=2;
CC IsoId=Q8N4F4-3; Sequence=VSP_060490;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Localized to the kidney
CC (PubMed:31553721). Highly specific expression pattern in the nephron,
CC localized to segment 3 of the proximal tubule (PubMed:31553721).
CC {ECO:0000269|PubMed:31553721}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Localized to the kidney
CC (PubMed:31553721). Highly specific expression pattern in the nephron,
CC localized to segment 3 of the proximal tubule (PubMed:31553721).
CC {ECO:0000269|PubMed:31553721}.
CC -!- POLYMORPHISM: [Isoform 2]: Presence of two potential AG acceptor sites
CC at the splice junction between exons 9 and 10, thus resulting in two
CC different splice variants. {ECO:0000303|PubMed:31553721}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
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DR EMBL; KF459672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034394; AAH34394.1; -; mRNA.
DR CCDS; CCDS73308.1; -. [Q8N4F4-2]
DR CCDS; CCDS76422.1; -. [Q8N4F4-1]
DR RefSeq; NP_001129978.2; NM_001136506.2. [Q8N4F4-2]
DR RefSeq; NP_775857.2; NM_173586.2. [Q8N4F4-1]
DR AlphaFoldDB; Q8N4F4; -.
DR SMR; Q8N4F4; -.
DR BioGRID; 129508; 1.
DR IntAct; Q8N4F4; 2.
DR MINT; Q8N4F4; -.
DR STRING; 9606.ENSP00000480336; -.
DR TCDB; 2.A.1.19.21; the major facilitator superfamily (mfs).
DR PhosphoSitePlus; Q8N4F4; -.
DR BioMuta; SLC22A24; -.
DR DMDM; 74728846; -.
DR PaxDb; Q8N4F4; -.
DR PeptideAtlas; Q8N4F4; -.
DR PRIDE; Q8N4F4; -.
DR Antibodypedia; 28899; 67 antibodies from 18 providers.
DR DNASU; 283238; -.
DR Ensembl; ENST00000326192.5; ENSP00000321549.5; ENSG00000197658.9. [Q8N4F4-1]
DR Ensembl; ENST00000417740.5; ENSP00000396586.1; ENSG00000197658.9. [Q8N4F4-3]
DR Ensembl; ENST00000612278.4; ENSP00000480336.1; ENSG00000197658.9. [Q8N4F4-2]
DR GeneID; 283238; -.
DR KEGG; hsa:283238; -.
DR MANE-Select; ENST00000612278.4; ENSP00000480336.1; NM_001136506.2; NP_001129978.2.
DR UCSC; uc010rmn.3; human. [Q8N4F4-2]
DR CTD; 283238; -.
DR DisGeNET; 283238; -.
DR GeneCards; SLC22A24; -.
DR HGNC; HGNC:28542; SLC22A24.
DR HPA; ENSG00000197658; Group enriched (brain, kidney).
DR MIM; 611698; gene.
DR neXtProt; NX_Q8N4F4; -.
DR OpenTargets; ENSG00000197658; -.
DR PharmGKB; PA162403543; -.
DR VEuPathDB; HostDB:ENSG00000197658; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000164763; -.
DR HOGENOM; CLU_001265_33_3_1; -.
DR InParanoid; Q8N4F4; -.
DR OMA; CSHDDLH; -.
DR OrthoDB; 464838at2759; -.
DR PhylomeDB; Q8N4F4; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; Q8N4F4; -.
DR SignaLink; Q8N4F4; -.
DR BioGRID-ORCS; 283238; 8 hits in 310 CRISPR screens.
DR ChiTaRS; SLC22A24; human.
DR GenomeRNAi; 283238; -.
DR Pharos; Q8N4F4; Tdark.
DR PRO; PR:Q8N4F4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q8N4F4; protein.
DR Bgee; ENSG00000197658; Expressed in buccal mucosa cell and 4 other tissues.
DR Genevisible; Q8N4F4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015711; P:organic anion transport; IBA:GO_Central.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR GO; GO:0035382; P:sterol transmembrane transport; IDA:UniProtKB.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Ion transport; Lipid metabolism; Membrane;
KW Reference proteome; Steroid metabolism; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..552
FT /note="Steroid transmembrane transporter SLC22A24"
FT /id="PRO_0000317526"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 278..322
FT /note="KMVESARWLIINNQLDEGLKELRRVAHINGKKNTEETLTTELVRS -> YEQ
FT SPHSLPVSEAMVDIERKILTPGICSVSGLVLSHDVHSTYCVT (in isoform 3)"
FT /id="VSP_060488"
FT VAR_SEQ 323..552
FT /note="Missing (in isoform 3)"
FT /id="VSP_060489"
FT VAR_SEQ 533..534
FT /note="DR -> E (in isoform 2)"
FT /id="VSP_060490"
FT VARIANT 501..552
FT /note="Missing (decreased sterol transport; probable
FT decreased expression due to nonsense-mediated decay;
FT dbSNP:rs1123134)"
FT /evidence="ECO:0000269|PubMed:31553721"
FT /id="VAR_083069"
FT CONFLICT Q8N4F4-1:58
FT /note="T -> S (in Ref. 2; AAH34394.1)"
FT /evidence="ECO:0000305"
FT CONFLICT Q8N4F4-1:299
FT /note="L -> V (in Ref. 2; AAH34394.1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 552 AA; 61701 MW; D4F58177CD6CDCE9 CRC64;
MGFDVLLDQV GGMGRFQICL IAFFCITNIL LFPNIVLENF TAFTPSHRCW VPLLDNDTVS
DNDTGTLSKD DLLRISIPLD SNLRPQKCQR FIHPQWQLLH LNGTFPNTNE PDTEPCVDGW
VYDRSSFLST IVTEWDLVCE SQSLKSMVQS LFMAGSLLGG LIYGHLSDRV GRKIICKLCF
LQLAISNTCA AFAPTFLVYC ILRFLAGFST MTILGNTFIL SLEWTLPRSR SMTIMVLLCS
YSVGQMLLGG LAFAIQDWHI LQLTVSTPII VLFLSSWKMV ESARWLIINN QLDEGLKELR
RVAHINGKKN TEETLTTELV RSTMKKELDA VRIKTSIFSL FRAPKLRMRV FGLCFVRFAI
TVPFYGLILN LQHLGSNVSL FQILCGAVTF TARCVSLLTL NHMGRRISQI LFTFPVGLFI
LVNTFLPQEM QILRVVLATL GIGSVSAASN SASVHHNELV PTILRSTVAG INAVSGRTGA
ALAPLLMTLM AYSPHLPWIS YGVFPILAVP VILLLPETRD LPLPNTIQDV ENDRKDSRNI
KQEDTCMKVT QF
