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Protein

Solute carrier organic anion transporter family member 4C1

Gene

SLCO4C1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ouabain. Involved in the uptake of the dipeptidyl peptidase-4 inhibitor sitagliptin and hence may play a role in its transport into and out of renal proximal tubule cells. May be involved in the first step of the transport pathway of digoxin and various compounds into the urine in the kidney. May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells. This ion-transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation. May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg.By similarity2 Publications

Kineticsi

  1. KM=7.8 µM for digoxin1 Publication
  2. KM=0.38 µM for ouabain1 Publication
  3. KM=5.9 µM for thyroxine1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Biological processi

    Differentiation, Ion transport, Spermatogenesis, Transport

    Enzyme and pathway databases

    ReactomeiR-HSA-879518. Transport of organic anions.

    Protein family/group databases

    TCDBi2.A.60.1.11. the organo anion transporter (oat) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Solute carrier organic anion transporter family member 4C1
    Alternative name(s):
    OATP-H
    Organic anion transporter M1
    Short name:
    OATP-M1
    Solute carrier family 21 member 20
    Gene namesi
    Name:SLCO4C1Imported
    Synonyms:OATP4C11 Publication, OATPX, SLC21A20Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:23612. SLCO4C1.

    Subcellular locationi

    • Basolateral cell membrane By similarity; Multi-pass membrane protein By similarity

    • Note: Detected at the basolateral membrane of the proximal tubule cell in the kidney.By similarity

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 105105CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei106 – 12621Helical; Name=1Sequence analysisAdd
    BLAST
    Topological domaini127 – 14519ExtracellularSequence analysisAdd
    BLAST
    Transmembranei146 – 16621Helical; Name=2Sequence analysisAdd
    BLAST
    Topological domaini167 – 1726CytoplasmicSequence analysis
    Transmembranei173 – 19725Helical; Name=3Sequence analysisAdd
    BLAST
    Topological domaini198 – 22326ExtracellularSequence analysisAdd
    BLAST
    Transmembranei224 – 25431Helical; Name=4Sequence analysisAdd
    BLAST
    Topological domaini255 – 27420CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei275 – 29521Helical; Name=5Sequence analysisAdd
    BLAST
    Topological domaini296 – 31116ExtracellularSequence analysisAdd
    BLAST
    Transmembranei312 – 33625Helical; Name=6Sequence analysisAdd
    BLAST
    Topological domaini337 – 37741CytoplasmicSequence analysisAdd
    BLAST
    Transmembranei378 – 39922Helical; Name=7Sequence analysisAdd
    BLAST
    Topological domaini400 – 41920ExtracellularSequence analysisAdd
    BLAST
    Transmembranei420 – 44324Helical; Name=8Sequence analysisAdd
    BLAST
    Topological domaini444 – 4474CytoplasmicSequence analysis
    Transmembranei448 – 47124Helical; Name=9Sequence analysisAdd
    BLAST
    Topological domaini472 – 580109ExtracellularSequence analysisAdd
    BLAST
    Transmembranei581 – 60323Helical; Name=10Sequence analysisAdd
    BLAST
    Topological domaini604 – 6129CytoplasmicSequence analysis
    Transmembranei613 – 63826Helical; Name=11Sequence analysisAdd
    BLAST
    Topological domaini639 – 67234ExtracellularSequence analysisAdd
    BLAST
    Transmembranei673 – 69018Helical; Name=12Sequence analysisAdd
    BLAST
    Topological domaini691 – 72434CytoplasmicSequence analysisAdd
    BLAST

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134892408.

    Chemistry

    ChEMBLiCHEMBL2073690.
    DrugBankiDB00509. Dextrothyroxine.
    DB01396. Digitoxin.
    DB00390. Digoxin.
    DB00451. Levothyroxine.
    DB00279. Liothyronine.
    DB01583. Liotrix.
    DB00563. Methotrexate.
    DB01092. Ouabain.
    DB06335. Saxagliptin.

    Polymorphism and mutation databases

    BioMutaiSLCO4C1.
    DMDMi74749598.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 724724Solute carrier organic anion transporter family member 4C1PRO_0000337151Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei15 – 151PhosphoserineBy similarity
    Modified residuei16 – 161PhosphoserineBy similarity
    Modified residuei24 – 241PhosphoserineBy similarity
    Modified residuei26 – 261PhosphoserineBy similarity
    Modified residuei28 – 281PhosphoserineBy similarity
    Disulfide bondi501 ↔ 526PROSITE-ProRule annotation
    Disulfide bondi505 ↔ 516PROSITE-ProRule annotation
    Disulfide bondi507 ↔ 530PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Phosphoprotein

    Proteomic databases

    EPDiQ6ZQN7.
    MaxQBiQ6ZQN7.
    PaxDbiQ6ZQN7.
    PRIDEiQ6ZQN7.

    PTM databases

    iPTMnetiQ6ZQN7.
    PhosphoSiteiQ6ZQN7.

    Expressioni

    Tissue specificityi

    Predominantly expressed in kidney but also weakly expressed in both fetal liver and kidney.1 Publication

    Gene expression databases

    BgeeiQ6ZQN7.
    CleanExiHS_SLCO4C1.
    GenevisibleiQ6ZQN7. HS.

    Organism-specific databases

    HPAiHPA036516.

    Interactioni

    Protein-protein interaction databases

    BioGridi131662. 2 interactions.
    IntActiQ6ZQN7. 1 interaction.
    STRINGi9606.ENSP00000309741.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6ZQN7.
    SMRiQ6ZQN7. Positions 143-169, 599-641.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini495 – 54955Kazal-likePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 Kazal-like domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3626. Eukaryota.
    ENOG410XRSF. LUCA.
    GeneTreeiENSGT00760000119014.
    HOGENOMiHOG000231270.
    HOVERGENiHBG100565.
    InParanoidiQ6ZQN7.
    KOiK14355.
    OMAiVFTFMAG.
    OrthoDBiEOG75TMBK.
    PhylomeDBiQ6ZQN7.
    TreeFamiTF317540.

    Family and domain databases

    InterProiIPR002350. Kazal_dom.
    IPR020846. MFS_dom.
    IPR004156. OA_transporter.
    [Graphical view]
    PANTHERiPTHR11388. PTHR11388. 1 hit.
    PfamiPF07648. Kazal_2. 1 hit.
    PF03137. OATP. 1 hit.
    [Graphical view]
    SUPFAMiSSF103473. SSF103473. 3 hits.
    TIGRFAMsiTIGR00805. oat. 1 hit.
    PROSITEiPS51465. KAZAL_2. 1 hit.
    PS50850. MFS. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q6ZQN7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKSAKGIENL AFVPSSPDIL RRLSASPSQI EVSALSSDPQ RENSQPQELQ
    60 70 80 90 100
    KPQEPQKSPE PSLPSAPPNV SEEKLRSLSL SEFEEGSYGW RNFHPQCLQR
    110 120 130 140 150
    CNTPGGFLLH YCLLAVTQGI VVNGLVNISI STVEKRYEMK SSLTGLISSS
    160 170 180 190 200
    YDISFCLLSL FVSFFGERGH KPRWLAFAAF MIGLGALVFS LPQFFSGEYK
    210 220 230 240 250
    LGSLFEDTCV TTRNSTSCTS STSSLSNYLY VFILGQLLLG AGGTPLYTLG
    260 270 280 290 300
    TAFLDDSVPT HKSSLYIGTG YAMSILGPAI GYVLGGQLLT IYIDVAMGES
    310 320 330 340 350
    TDVTEDDPRW LGAWWIGFLL SWIFAWSLII PFSCFPKHLP GTAEIQAGKT
    360 370 380 390 400
    SQAHQSNSNA DVKFGKSIKD FPAALKNLMK NAVFMCLVLS TSSEALITTG
    410 420 430 440 450
    FATFLPKFIE NQFGLTSSFA ATLGGAVLIP GAALGQILGG FLVSKFRMTC
    460 470 480 490 500
    KNTMKFALFT SGVALTLSFV FMYAKCENEP FAGVSESYNG TGELGNLIAP
    510 520 530 540 550
    CNANCNCSRS YYYPVCGDGV QYFSPCFAGC SNPVAHRKPK VYYNCSCIER
    560 570 580 590 600
    KTEITSTAET FGFEAKAGKC ETHCAKLPIF LCIFFIVIIF TFMAGTPITV
    610 620 630 640 650
    SILRCVNHRQ RSLALGIQFM VLRLLGTIPG PIIFGFTIDS TCILWDINDC
    660 670 680 690 700
    GIKGACWIYD NIKMAHMLVA ISVTCKVITM FFNGFAIFLY KPPPSATDVS
    710 720
    FHKENAVVTN VLAEQDLNKI VKEG
    Length:724
    Mass (Da):78,948
    Last modified:July 5, 2004 - v1
    Checksum:i7AC275B99E20A8EC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti672 – 6721S → C in AAP33047 (Ref. 2) Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF401643 mRNA. Translation: AAQ03086.1.
    AY273896 mRNA. Translation: AAP33047.2.
    AK128854 mRNA. Translation: BAC87647.1.
    CH471086 Genomic DNA. Translation: EAW49099.1.
    CCDSiCCDS34205.1.
    RefSeqiNP_851322.3. NM_180991.4.
    UniGeneiHs.127648.

    Genome annotation databases

    EnsembliENST00000310954; ENSP00000309741; ENSG00000173930.
    GeneIDi353189.
    KEGGihsa:353189.
    UCSCiuc003knm.4. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF401643 mRNA. Translation: AAQ03086.1.
    AY273896 mRNA. Translation: AAP33047.2.
    AK128854 mRNA. Translation: BAC87647.1.
    CH471086 Genomic DNA. Translation: EAW49099.1.
    CCDSiCCDS34205.1.
    RefSeqiNP_851322.3. NM_180991.4.
    UniGeneiHs.127648.

    3D structure databases

    ProteinModelPortaliQ6ZQN7.
    SMRiQ6ZQN7. Positions 143-169, 599-641.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi131662. 2 interactions.
    IntActiQ6ZQN7. 1 interaction.
    STRINGi9606.ENSP00000309741.

    Chemistry

    ChEMBLiCHEMBL2073690.
    DrugBankiDB00509. Dextrothyroxine.
    DB01396. Digitoxin.
    DB00390. Digoxin.
    DB00451. Levothyroxine.
    DB00279. Liothyronine.
    DB01583. Liotrix.
    DB00563. Methotrexate.
    DB01092. Ouabain.
    DB06335. Saxagliptin.

    Protein family/group databases

    TCDBi2.A.60.1.11. the organo anion transporter (oat) family.

    PTM databases

    iPTMnetiQ6ZQN7.
    PhosphoSiteiQ6ZQN7.

    Polymorphism and mutation databases

    BioMutaiSLCO4C1.
    DMDMi74749598.

    Proteomic databases

    EPDiQ6ZQN7.
    MaxQBiQ6ZQN7.
    PaxDbiQ6ZQN7.
    PRIDEiQ6ZQN7.

    Protocols and materials databases

    DNASUi353189.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000310954; ENSP00000309741; ENSG00000173930.
    GeneIDi353189.
    KEGGihsa:353189.
    UCSCiuc003knm.4. human.

    Organism-specific databases

    CTDi353189.
    GeneCardsiSLCO4C1.
    H-InvDBHIX0024798.
    HGNCiHGNC:23612. SLCO4C1.
    HPAiHPA036516.
    MIMi609013. gene.
    neXtProtiNX_Q6ZQN7.
    PharmGKBiPA134892408.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3626. Eukaryota.
    ENOG410XRSF. LUCA.
    GeneTreeiENSGT00760000119014.
    HOGENOMiHOG000231270.
    HOVERGENiHBG100565.
    InParanoidiQ6ZQN7.
    KOiK14355.
    OMAiVFTFMAG.
    OrthoDBiEOG75TMBK.
    PhylomeDBiQ6ZQN7.
    TreeFamiTF317540.

    Enzyme and pathway databases

    ReactomeiR-HSA-879518. Transport of organic anions.

    Miscellaneous databases

    GenomeRNAii353189.
    PROiQ6ZQN7.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ6ZQN7.
    CleanExiHS_SLCO4C1.
    GenevisibleiQ6ZQN7. HS.

    Family and domain databases

    InterProiIPR002350. Kazal_dom.
    IPR020846. MFS_dom.
    IPR004156. OA_transporter.
    [Graphical view]
    PANTHERiPTHR11388. PTHR11388. 1 hit.
    PfamiPF07648. Kazal_2. 1 hit.
    PF03137. OATP. 1 hit.
    [Graphical view]
    SUPFAMiSSF103473. SSF103473. 3 hits.
    TIGRFAMsiTIGR00805. oat. 1 hit.
    PROSITEiPS51465. KAZAL_2. 1 hit.
    PS50850. MFS. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, INHIBITION.
      Tissue: Kidney1 Publication.
    2. "Cloning and characterization of two novel OATP genes on human 5q21.1."
      Fu-Zhang W.
      Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: TracheaImported.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein."
      Chu X.-Y., Bleasby K., Yabut J., Cai X., Chan G.H., Hafey M.J., Xu S., Bergman A.J., Braun M.P., Dean D.C., Evers R.
      J. Pharmacol. Exp. Ther. 321:673-683(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiSO4C1_HUMAN
    AccessioniPrimary (citable) accession number: Q6ZQN7
    Secondary accession number(s): Q86UG5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: July 5, 2004
    Last modified: June 8, 2016
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    SLCO4C1-mediated digoxin uptake is inhibited by digoxin itself and related compounds such as ouabain, digitoxin and digoxigenin.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.