SO4C1_HUMAN
ID SO4C1_HUMAN Reviewed; 724 AA.
AC Q6ZQN7; Q86UG5;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Solute carrier organic anion transporter family member 4C1;
DE AltName: Full=OATP-H;
DE AltName: Full=Organic anion transporter M1;
DE Short=OATP-M1;
DE AltName: Full=Solute carrier family 21 member 20;
GN Name=SLCO4C1 {ECO:0000312|EMBL:EAW49099.1, ECO:0000312|HGNC:HGNC:23612};
GN Synonyms=OATP4C1 {ECO:0000303|PubMed:14993604}, OATPX,
GN SLC21A20 {ECO:0000312|HGNC:HGNC:23612};
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] {ECO:0000305, ECO:0000312|EMBL:AAQ03086.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND INHIBITION.
RC TISSUE=Kidney {ECO:0000269|PubMed:14993604};
RX PubMed=14993604; DOI=10.1073/pnas.0304987101;
RA Mikkaichi T., Suzuki T., Onogawa T., Tanemoto M., Mizutamari H., Okada M.,
RA Chaki T., Masuda S., Tokui T., Eto N., Abe M., Satoh F., Unno M.,
RA Hishinuma T., Inui K., Ito S., Goto J., Abe T.;
RT "Isolation and characterization of a digoxin transporter and its rat
RT homologue expressed in the kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:3569-3574(2004).
RN [2] {ECO:0000312|EMBL:AAP33047.2}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Fu-Zhang W.;
RT "Cloning and characterization of two novel OATP genes on human 5q21.1.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:BAC87647.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea {ECO:0000312|EMBL:BAC87647.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4] {ECO:0000312|EMBL:AAP33047.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=17314201; DOI=10.1124/jpet.106.116517;
RA Chu X.-Y., Bleasby K., Yabut J., Cai X., Chan G.H., Hafey M.J., Xu S.,
RA Bergman A.J., Braun M.P., Dean D.C., Evers R.;
RT "Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human
RT organic anion transporter 3, organic anion transporting polypeptide 4C1,
RT and multidrug resistance P-glycoprotein.";
RL J. Pharmacol. Exp. Ther. 321:673-683(2007).
CC -!- FUNCTION: Organic anion transporter, capable of transporting
CC pharmacological substances such as digoxin, ouabain, thyroxine,
CC methotrexate and cAMP. May participate in the regulation of membrane
CC transport of ouabain. Involved in the uptake of the dipeptidyl
CC peptidase-4 inhibitor sitagliptin and hence may play a role in its
CC transport into and out of renal proximal tubule cells. May be involved
CC in the first step of the transport pathway of digoxin and various
CC compounds into the urine in the kidney. May be involved in sperm
CC maturation by enabling directed movement of organic anions and
CC compounds within or between cells. This ion-transporting process is
CC important to maintain the strict epididymal homeostasis necessary for
CC sperm maturation. May have a role in secretory functions since seminal
CC vesicle epithelial cells are assumed to secrete proteins involved in
CC decapacitation by modifying surface proteins to facilitate the
CC acquisition of the ability to fertilize the egg.
CC {ECO:0000250|UniProtKB:Q8BGD4, ECO:0000269|PubMed:14993604,
CC ECO:0000269|PubMed:17314201}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.8 uM for digoxin {ECO:0000269|PubMed:14993604};
CC KM=0.38 uM for ouabain {ECO:0000269|PubMed:14993604};
CC KM=5.9 uM for thyroxine {ECO:0000269|PubMed:14993604};
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q71MB6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q71MB6}. Note=Detected at the basolateral
CC membrane of the proximal tubule cell in the kidney.
CC {ECO:0000250|UniProtKB:Q71MB6}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in kidney but also weakly
CC expressed in both fetal liver and kidney.
CC {ECO:0000269|PubMed:14993604}.
CC -!- MISCELLANEOUS: SLCO4C1-mediated digoxin uptake is inhibited by digoxin
CC itself and related compounds such as ouabain, digitoxin and
CC digoxigenin. {ECO:0000269|PubMed:14993604}.
CC -!- SIMILARITY: Belongs to the organo anion transporter (TC 2.A.60) family.
CC {ECO:0000255}.
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DR EMBL; AF401643; AAQ03086.1; -; mRNA.
DR EMBL; AY273896; AAP33047.2; -; mRNA.
DR EMBL; AK128854; BAC87647.1; -; mRNA.
DR EMBL; CH471086; EAW49099.1; -; Genomic_DNA.
DR CCDS; CCDS34205.1; -.
DR RefSeq; NP_851322.3; NM_180991.4.
DR AlphaFoldDB; Q6ZQN7; -.
DR SMR; Q6ZQN7; -.
DR BioGRID; 131662; 42.
DR IntAct; Q6ZQN7; 2.
DR STRING; 9606.ENSP00000309741; -.
DR BindingDB; Q6ZQN7; -.
DR ChEMBL; CHEMBL2073690; -.
DR DrugBank; DB00509; Dextrothyroxine.
DR DrugBank; DB01396; Digitoxin.
DR DrugBank; DB00390; Digoxin.
DR DrugBank; DB01137; Levofloxacin.
DR DrugBank; DB00279; Liothyronine.
DR DrugBank; DB01583; Liotrix.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB01092; Ouabain.
DR DrugBank; DB06335; Saxagliptin.
DR TCDB; 2.A.60.1.11; the organo anion transporter (oat) family.
DR GlyGen; Q6ZQN7; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6ZQN7; -.
DR PhosphoSitePlus; Q6ZQN7; -.
DR BioMuta; SLCO4C1; -.
DR DMDM; 74749598; -.
DR EPD; Q6ZQN7; -.
DR jPOST; Q6ZQN7; -.
DR MassIVE; Q6ZQN7; -.
DR MaxQB; Q6ZQN7; -.
DR PaxDb; Q6ZQN7; -.
DR PeptideAtlas; Q6ZQN7; -.
DR PRIDE; Q6ZQN7; -.
DR ProteomicsDB; 68081; -.
DR Antibodypedia; 48357; 66 antibodies from 16 providers.
DR DNASU; 353189; -.
DR Ensembl; ENST00000310954.7; ENSP00000309741.6; ENSG00000173930.9.
DR GeneID; 353189; -.
DR KEGG; hsa:353189; -.
DR MANE-Select; ENST00000310954.7; ENSP00000309741.6; NM_180991.5; NP_851322.3.
DR UCSC; uc003knm.4; human.
DR CTD; 353189; -.
DR DisGeNET; 353189; -.
DR GeneCards; SLCO4C1; -.
DR HGNC; HGNC:23612; SLCO4C1.
DR HPA; ENSG00000173930; Tissue enriched (kidney).
DR MIM; 609013; gene.
DR neXtProt; NX_Q6ZQN7; -.
DR OpenTargets; ENSG00000173930; -.
DR PharmGKB; PA134892408; -.
DR VEuPathDB; HostDB:ENSG00000173930; -.
DR eggNOG; KOG3626; Eukaryota.
DR GeneTree; ENSGT01050000244906; -.
DR HOGENOM; CLU_008954_2_1_1; -.
DR InParanoid; Q6ZQN7; -.
DR OMA; VTCKVIT; -.
DR OrthoDB; 228564at2759; -.
DR PhylomeDB; Q6ZQN7; -.
DR TreeFam; TF317540; -.
DR PathwayCommons; Q6ZQN7; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-879518; Transport of organic anions.
DR SABIO-RK; Q6ZQN7; -.
DR SignaLink; Q6ZQN7; -.
DR BioGRID-ORCS; 353189; 14 hits in 1069 CRISPR screens.
DR GenomeRNAi; 353189; -.
DR Pharos; Q6ZQN7; Tchem.
DR PRO; PR:Q6ZQN7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q6ZQN7; protein.
DR Bgee; ENSG00000173930; Expressed in nephron tubule and 111 other tissues.
DR Genevisible; Q6ZQN7; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043252; P:sodium-independent organic anion transport; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 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 PANTHER; PTHR11388; PTHR11388; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR Pfam; PF03137; OATP; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00805; oat; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Differentiation; Disulfide bond;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Spermatogenesis; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..724
FT /note="Solute carrier organic anion transporter family
FT member 4C1"
FT /id="PRO_0000337151"
FT TOPO_DOM 1..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..145
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 167..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..197
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..223
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..254
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..274
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..311
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..336
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..399
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..419
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..443
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 444..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..471
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..580
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 581..603
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 604..612
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 613..638
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 639..672
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 673..690
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 691..724
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 495..549
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT REGION 30..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71MB6"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGD4"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGD4"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGD4"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGD4"
FT DISULFID 501..530
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 507..526
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 516..547
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CONFLICT 672
FT /note="S -> C (in Ref. 2; AAP33047)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 724 AA; 78948 MW; 7AC275B99E20A8EC CRC64;
MKSAKGIENL AFVPSSPDIL RRLSASPSQI EVSALSSDPQ RENSQPQELQ KPQEPQKSPE
PSLPSAPPNV SEEKLRSLSL SEFEEGSYGW RNFHPQCLQR CNTPGGFLLH YCLLAVTQGI
VVNGLVNISI STVEKRYEMK SSLTGLISSS YDISFCLLSL FVSFFGERGH KPRWLAFAAF
MIGLGALVFS LPQFFSGEYK LGSLFEDTCV TTRNSTSCTS STSSLSNYLY VFILGQLLLG
AGGTPLYTLG TAFLDDSVPT HKSSLYIGTG YAMSILGPAI GYVLGGQLLT IYIDVAMGES
TDVTEDDPRW LGAWWIGFLL SWIFAWSLII PFSCFPKHLP GTAEIQAGKT SQAHQSNSNA
DVKFGKSIKD FPAALKNLMK NAVFMCLVLS TSSEALITTG FATFLPKFIE NQFGLTSSFA
ATLGGAVLIP GAALGQILGG FLVSKFRMTC KNTMKFALFT SGVALTLSFV FMYAKCENEP
FAGVSESYNG TGELGNLIAP CNANCNCSRS YYYPVCGDGV QYFSPCFAGC SNPVAHRKPK
VYYNCSCIER KTEITSTAET FGFEAKAGKC ETHCAKLPIF LCIFFIVIIF TFMAGTPITV
SILRCVNHRQ RSLALGIQFM VLRLLGTIPG PIIFGFTIDS TCILWDINDC GIKGACWIYD
NIKMAHMLVA ISVTCKVITM FFNGFAIFLY KPPPSATDVS FHKENAVVTN VLAEQDLNKI
VKEG
