MRP5_HUMAN
ID MRP5_HUMAN Reviewed; 1437 AA.
AC O15440; B9EIQ2; O14517; Q29ZA9; Q29ZB1; Q86UX3; Q86W30; Q9UN85; Q9UNP5;
AC Q9UQC3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=ATP-binding cassette sub-family C member 5;
DE EC=7.6.2.- {ECO:0000269|PubMed:12637526, ECO:0000269|PubMed:12695538, ECO:0000269|PubMed:15899835, ECO:0000269|PubMed:17229149, ECO:0000269|PubMed:25964343, ECO:0000269|PubMed:26515061};
DE EC=7.6.2.2 {ECO:0000269|PubMed:10840050, ECO:0000269|PubMed:12435799, ECO:0000269|PubMed:12695538, ECO:0000269|PubMed:15899835};
DE AltName: Full=Multi-specific organic anion transporter C {ECO:0000303|PubMed:9827529};
DE Short=MOAT-C {ECO:0000303|PubMed:9827529};
DE AltName: Full=Multidrug resistance-associated protein 5;
DE AltName: Full=SMRP;
DE AltName: Full=pABC11 {ECO:0000303|PubMed:10438534};
GN Name=ABCC5; Synonyms=MRP5;
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9827529; DOI=10.1093/jnci/90.22.1735;
RA Belinsky M.G., Bain L.J., Balsara B.B., Testa J.R., Kruh G.D.;
RT "Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT
RT subfamily of transporter proteins.";
RL J. Natl. Cancer Inst. 90:1735-1741(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10438534; DOI=10.1074/jbc.274.33.23541;
RA McAleer M.A., Breen M.A., White N.L., Matthews N.;
RT "pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of
RT proteins, has anion transporter activity but does not confer multidrug
RT resistance when overexpressed in human embryonic kidney 293 cells.";
RL J. Biol. Chem. 274:23541-23548(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10721709; DOI=10.1016/s0378-1119(99)00529-6;
RA Suzuki T., Sasaki H., Kuh H.J., Agui M., Tatsumi Y., Tanabe S., Terada M.,
RA Saijo N., Nishio K.;
RT "Detailed structural analysis on both human MRP5 and mouse mrp5
RT transcripts.";
RL Gene 242:167-173(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain, and Ovarian carcinoma;
RX PubMed=10840050; DOI=10.1073/pnas.120159197;
RA Wijnholds J., Mol C.A.A.M., van Deemter L., de Haas M., Scheffer G.L.,
RA Baas F., Beijnen J.H., Scheper R.J., Hatse S., De Clercq E., Balzarini J.,
RA Borst P.;
RT "Multidrug-resistance protein 5 is a multispecific organic anion
RT transporter able to transport nucleotide analogs.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7476-7481(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Retina;
RX PubMed=17521428; DOI=10.1186/1471-2199-8-42;
RA Stojic J., Stohr H., Weber B.H.;
RT "Three novel ABCC5 splice variants in human retina and their role as
RT regulators of ABCC5 gene expression.";
RL BMC Mol. Biol. 8:42-42(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Skeletal muscle;
RA Ito T., Kato R., Ishikawa T.;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Pancreas;
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 492-1437 (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9325169; DOI=10.1006/bbrc.1997.7346;
RA Suzuki T., Nishio K., Sasaki H., Kurokawa H., Saito-Ohara F., Ikeuch T.,
RA Tanabe S., Terada M., Saijo N.;
RT "cDNA cloning of a short type of multidrug resistance protein homologue,
RT SMRP, from a human lung cancer cell line.";
RL Biochem. Biophys. Res. Commun. 238:790-794(1997).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1216-1437 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9270026;
RA Kool M., de Haas M., Scheffer G.L., Scheper R.J., van Eijk M.J.,
RA Juijn J.A., Baas F., Borst P.;
RT "Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues
RT of the multidrug resistance-associated protein gene (MRP1), in human cancer
RT cell lines.";
RL Cancer Res. 57:3537-3547(1997).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RX PubMed=10893247; DOI=10.1074/jbc.m005463200;
RA Jedlitschky G., Burchell B., Keppler D.;
RT "The multidrug resistance protein 5 functions as an ATP-dependent export
RT pump for cyclic nucleotides.";
RL J. Biol. Chem. 275:30069-30074(2000).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12435799; DOI=10.1124/mol.62.6.1321;
RA Wielinga P.R., Reid G., Challa E.E., van der Heijden I., van Deemter L.,
RA de Haas M., Mol C., Kuil A.J., Groeneveld E., Schuetz J.D., Brouwer C.,
RA De Abreu R.A., Wijnholds J., Beijnen J.H., Borst P.;
RT "Thiopurine metabolism and identification of the thiopurine metabolites
RT transported by MRP4 and MRP5 overexpressed in human embryonic kidney
RT cells.";
RL Mol. Pharmacol. 62:1321-1331(2002).
RN [14]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=12695538; DOI=10.1124/mol.63.5.1094;
RA Reid G., Wielinga P., Zelcer N., De Haas M., Van Deemter L., Wijnholds J.,
RA Balzarini J., Borst P.;
RT "Characterization of the transport of nucleoside analog drugs by the human
RT multidrug resistance proteins MRP4 and MRP5.";
RL Mol. Pharmacol. 63:1094-1103(2003).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12637526; DOI=10.1074/jbc.m212723200;
RA Wielinga P.R., van der Heijden I., Reid G., Beijnen J.H., Wijnholds J.,
RA Borst P.;
RT "Characterization of the MRP4- and MRP5-mediated transport of cyclic
RT nucleotides from intact cells.";
RL J. Biol. Chem. 278:17664-17671(2003).
RN [16]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15501592; DOI=10.1016/j.neuroscience.2004.07.051;
RA Nies A.T., Jedlitschky G., Koenig J., Herold-Mende C., Steiner H.H.,
RA Schmitt H.P., Keppler D.;
RT "Expression and immunolocalization of the multidrug resistance proteins,
RT MRP1-MRP6 (ABCC1-ABCC6), in human brain.";
RL Neuroscience 129:349-360(2004).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15899835; DOI=10.1158/0008-5472.can-04-2810;
RA Wielinga P., Hooijberg J.H., Gunnarsdottir S., Kathmann I., Reid G.,
RA Zelcer N., van der Born K., de Haas M., van der Heijden I., Kaspers G.,
RA Wijnholds J., Jansen G., Peters G., Borst P.;
RT "The human multidrug resistance protein MRP5 transports folates and can
RT mediate cellular resistance against antifolates.";
RL Cancer Res. 65:4425-4430(2005).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17229149; DOI=10.1111/j.1742-4658.2006.05591.x;
RA de Wolf C.J., Yamaguchi H., van der Heijden I., Wielinga P.R.,
RA Hundscheid S.L., Ono N., Scheffer G.L., de Haas M., Schuetz J.D.,
RA Wijnholds J., Borst P.;
RT "cGMP transport by vesicles from human and mouse erythrocytes.";
RL FEBS J. 274:439-450(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509 AND THR-513, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-509, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-19; SER-60; SER-505
RP AND SER-509, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24836561; DOI=10.1016/j.cmet.2014.03.030;
RA Korolnek T., Zhang J., Beardsley S., Scheffer G.L., Hamza I.;
RT "Control of metazoan heme homeostasis by a conserved multidrug resistance
RT protein.";
RL Cell Metab. 19:1008-1019(2014).
RN [23]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26515061; DOI=10.1074/jbc.m115.692103;
RA Jansen R.S., Mahakena S., de Haas M., Borst P., van de Wetering K.;
RT "ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux
RT Transporter of Glutamate Conjugates and Analogs.";
RL J. Biol. Chem. 290:30429-30440(2015).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25964343; DOI=10.1073/pnas.1424638112;
RA Jansen R.S., Addie R., Merkx R., Fish A., Mahakena S., Bleijerveld O.B.,
RA Altelaar M., Ijlst L., Wanders R.J., Borst P., van de Wetering K.;
RT "N-lactoyl-amino acids are ubiquitous metabolites that originate from
RT CNDP2-mediated reverse proteolysis of lactate and amino acids.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:6601-6606(2015).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family that actively extrudes physiological compounds, and xenobiotics
CC from cells. Mediates ATP-dependent transport of endogenous metabolites
CC such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro)
CC (PubMed:10893247, PubMed:15899835, PubMed:25964343, PubMed:17229149,
CC PubMed:12695538, PubMed:12637526). Acts also as a general glutamate
CC conjugate and analog transporter that can limit the brain levels of
CC endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers
CC resistance to the antiviral agent PMEA (PubMed:12695538). Able to
CC transport several anticancer drugs including methotrexate, and
CC nucleotide analogs in vitro, however it does with low affinity, thus
CC the exact role of ABCC5 in mediating resistance still needs to be
CC elucidated (PubMed:10840050, PubMed:15899835, PubMed:12435799,
CC PubMed:12695538). Acts as a heme transporter required for the
CC translocation of cytosolic heme to the secretory pathway
CC (PubMed:24836561). May play a role in energy metabolism by regulating
CC the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine
CC cells (By similarity). {ECO:0000250|UniProtKB:Q9R1X5,
CC ECO:0000269|PubMed:10840050, ECO:0000269|PubMed:10893247,
CC ECO:0000269|PubMed:12435799, ECO:0000269|PubMed:12637526,
CC ECO:0000269|PubMed:12695538, ECO:0000269|PubMed:15899835,
CC ECO:0000269|PubMed:17229149, ECO:0000269|PubMed:24836561,
CC ECO:0000269|PubMed:25964343, ECO:0000269|PubMed:26515061}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:10840050,
CC ECO:0000269|PubMed:12435799, ECO:0000269|PubMed:12695538,
CC ECO:0000269|PubMed:15899835};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic GMP(in) + ATP + H2O = 3',5'-cyclic GMP(out) + ADP
CC + H(+) + phosphate; Xref=Rhea:RHEA:66188, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57746, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:10893247, ECO:0000269|PubMed:12637526,
CC ECO:0000269|PubMed:12695538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66189;
CC Evidence={ECO:0000305|PubMed:10893247};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP(in) + ATP + H2O = 3',5'-cyclic AMP(out) + ADP
CC + H(+) + phosphate; Xref=Rhea:RHEA:66184, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58165, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:10893247, ECO:0000269|PubMed:12637526,
CC ECO:0000269|PubMed:12695538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66185;
CC Evidence={ECO:0000305|PubMed:10893247};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + N-acetyl-L-aspartyl-L-glutamate(in) = ADP + H(+) +
CC N-acetyl-L-aspartyl-L-glutamate(out) + phosphate;
CC Xref=Rhea:RHEA:66728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:76931,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66729;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate(in) =
CC ADP + H(+) + N-acetyl-L-aspartyl-L-glutamyl-L-glutamate(out) +
CC phosphate; Xref=Rhea:RHEA:66732, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:76935, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66733;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + N-acetyl-L-glutamate(in) = ADP + H(+) + N-acetyl-
CC L-glutamate(out) + phosphate; Xref=Rhea:RHEA:66740,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:44337, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66741;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + N-acetyl-L-aspartate(in) = ADP + H(+) + N-acetyl-
CC L-aspartate(out) + phosphate; Xref=Rhea:RHEA:66744,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16953,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66745;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-2-[5-amino-1-(beta-D-ribosyl)imidazole-4-
CC carboxamido]succinate(in) + ATP + H2O = (2S)-2-[5-amino-1-(beta-D-
CC ribosyl)imidazole-4-carboxamido]succinate(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:66752, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167466, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66753;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + domoate(in) + H2O = ADP + domoate(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:66756, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:167470, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66757;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-citrylglutamate(in) + H2O = ADP + beta-
CC citrylglutamate(out) + H(+) + phosphate; Xref=Rhea:RHEA:66736,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:76942, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66737;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + kainate(in) = ADP + H(+) + kainate(out) +
CC phosphate; Xref=Rhea:RHEA:66760, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:156548, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:26515061};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66761;
CC Evidence={ECO:0000305|PubMed:26515061};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + N-[(S)-lactoyl]-L-phenylalanine(in) = ADP + H(+) +
CC N-[(S)-lactoyl]-L-phenylalanine(out) + phosphate;
CC Xref=Rhea:RHEA:66720, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:167456,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:25964343};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66721;
CC Evidence={ECO:0000305|PubMed:25964343};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + folate(in) + H2O = ADP + folate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:66764, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:62501,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15899835};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66765;
CC Evidence={ECO:0000305|PubMed:15899835};
CC -!- ACTIVITY REGULATION: cGMP transport is highly sensitive to inhibitors
CC of cGMP phosphodiesterase, such as zaprinast, trequinsin and
CC sildenafil. {ECO:0000269|PubMed:10893247}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=379 uM for cAMP {ECO:0000269|PubMed:10893247};
CC KM=2.1 uM for cGMP {ECO:0000269|PubMed:10893247};
CC KM=132 uM for cGMP {ECO:0000269|PubMed:17229149};
CC KM=1.0 mM for folate {ECO:0000269|PubMed:15899835};
CC KM=1 mM for N-[(S)-lactoyl]-L-phenylalanine
CC {ECO:0000269|PubMed:25964343};
CC KM=1.9 mM for ZJ43 (glutamate analog) {ECO:0000269|PubMed:26515061};
CC KM=3.5 mM for N-acetylaspartylglutamate (NAAG)
CC {ECO:0000269|PubMed:26515061};
CC KM=1.3 mM for methotrexate {ECO:0000269|PubMed:15899835};
CC Vmax=780 pmol/min/mg enzyme for methotrexate transport
CC {ECO:0000269|PubMed:15899835};
CC Vmax=875 pmol/min/mg enzyme for folate transport
CC {ECO:0000269|PubMed:15899835};
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:24836561}; Multi-pass membrane protein
CC {ECO:0000255}. Golgi apparatus lumen {ECO:0000269|PubMed:24836561}.
CC Endosome membrane {ECO:0000269|PubMed:24836561}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q9R1X5}. Apical cell membrane
CC {ECO:0000269|PubMed:15501592}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In most cells, routes to the basolateral plasma
CC membrane, but in the brain capillary endothelial cells that form the
CC blood-brain barrier, resides in the apical membrane.
CC {ECO:0000269|PubMed:15501592, ECO:0000269|PubMed:24836561}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=O15440-1; Sequence=Displayed;
CC Name=2; Synonyms=SV1;
CC IsoId=O15440-2; Sequence=VSP_043397, VSP_043402;
CC Name=3; Synonyms=SV2;
CC IsoId=O15440-3; Sequence=VSP_043398, VSP_043401, VSP_043402;
CC Name=4; Synonyms=SV3;
CC IsoId=O15440-4; Sequence=VSP_043399, VSP_043400, VSP_043402;
CC Name=5;
CC IsoId=O15440-5; Sequence=VSP_055354;
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Predominant isoform in retinal pigment
CC epithelium, bladder, and stomach. {ECO:0000269|PubMed:17521428}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, but levels in brain and
CC muscle are especially high (PubMed:9827529, PubMed:10438534,
CC PubMed:15501592). All isoforms are equally expressed in retina
CC (PubMed:17521428). {ECO:0000269|PubMed:10438534,
CC ECO:0000269|PubMed:15501592, ECO:0000269|PubMed:17521428,
CC ECO:0000269|PubMed:9827529}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: Although other labs have confirmed the ability of ABCC5
CC to transport cGMP in an ATP-dependent manner, they obtained a much
CC lower affinity for this substrate (PubMed:12637526, PubMed:12695538).
CC The authors conclude that ABCC5 is a low-affinity cyclic nucleotide
CC transporter a major function in cGMP excretion is unlikely
CC (PubMed:12637526, PubMed:12695538). {ECO:0000269|PubMed:12637526,
CC ECO:0000269|PubMed:12695538}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
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DR EMBL; AF104942; AAD04169.1; -; mRNA.
DR EMBL; AF146074; AAD37716.1; -; mRNA.
DR EMBL; AB019002; BAA76608.1; -; mRNA.
DR EMBL; U83661; AAB71758.2; -; mRNA.
DR EMBL; AY754874; AAW82948.1; -; mRNA.
DR EMBL; AY754875; AAW82949.1; -; mRNA.
DR EMBL; AY754876; AAW82950.1; -; mRNA.
DR EMBL; AY196484; AAO49801.1; -; mRNA.
DR EMBL; AC068644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78307.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78308.1; -; Genomic_DNA.
DR EMBL; BC050744; AAH50744.1; -; mRNA.
DR EMBL; BC140771; AAI40772.1; -; mRNA.
DR EMBL; BC142719; AAI42720.1; -; mRNA.
DR EMBL; AB005659; BAA22887.1; -; mRNA.
DR CCDS; CCDS33898.1; -. [O15440-4]
DR CCDS; CCDS43176.1; -. [O15440-1]
DR PIR; JC5667; JC5667.
DR RefSeq; NP_001018881.1; NM_001023587.2. [O15440-4]
DR RefSeq; NP_001306961.1; NM_001320032.1.
DR RefSeq; NP_005679.2; NM_005688.3. [O15440-1]
DR RefSeq; XP_005247115.1; XM_005247058.4. [O15440-1]
DR RefSeq; XP_005247116.1; XM_005247059.4. [O15440-1]
DR RefSeq; XP_011510616.1; XM_011512314.1. [O15440-1]
DR RefSeq; XP_016860982.1; XM_017005493.1. [O15440-4]
DR RefSeq; XP_016860983.1; XM_017005494.1. [O15440-4]
DR AlphaFoldDB; O15440; -.
DR SMR; O15440; -.
DR BioGRID; 115368; 45.
DR IntAct; O15440; 15.
DR MINT; O15440; -.
DR STRING; 9606.ENSP00000333926; -.
DR BindingDB; O15440; -.
DR ChEMBL; CHEMBL2046258; -.
DR DrugBank; DB00718; Adefovir dipivoxil.
DR DrugBank; DB00770; Alprostadil.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB11672; Curcumin.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB02527; Cyclic adenosine monophosphate.
DR DrugBank; DB00917; Dinoprostone.
DR DrugBank; DB00975; Dipyridamole.
DR DrugBank; DB00544; Fluorouracil.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB08818; Hyaluronic acid.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00495; Zidovudine.
DR DrugCentral; O15440; -.
DR GuidetoPHARMACOLOGY; 783; -.
DR TCDB; 3.A.1.208.15; the atp-binding cassette (abc) superfamily.
DR GlyGen; O15440; 8 sites.
DR iPTMnet; O15440; -.
DR PhosphoSitePlus; O15440; -.
DR BioMuta; ABCC5; -.
DR EPD; O15440; -.
DR jPOST; O15440; -.
DR MassIVE; O15440; -.
DR MaxQB; O15440; -.
DR PaxDb; O15440; -.
DR PeptideAtlas; O15440; -.
DR PRIDE; O15440; -.
DR ProteomicsDB; 48667; -. [O15440-1]
DR ProteomicsDB; 48668; -. [O15440-2]
DR ProteomicsDB; 48669; -. [O15440-3]
DR ProteomicsDB; 48670; -. [O15440-4]
DR ProteomicsDB; 69929; -.
DR Antibodypedia; 18937; 421 antibodies from 38 providers.
DR DNASU; 10057; -.
DR Ensembl; ENST00000265586.10; ENSP00000265586.6; ENSG00000114770.17. [O15440-5]
DR Ensembl; ENST00000334444.11; ENSP00000333926.6; ENSG00000114770.17. [O15440-1]
DR Ensembl; ENST00000382494.6; ENSP00000371934.2; ENSG00000114770.17. [O15440-4]
DR Ensembl; ENST00000392579.6; ENSP00000376358.2; ENSG00000114770.17. [O15440-2]
DR Ensembl; ENST00000443376.5; ENSP00000416840.1; ENSG00000114770.17. [O15440-3]
DR GeneID; 10057; -.
DR KEGG; hsa:10057; -.
DR MANE-Select; ENST00000334444.11; ENSP00000333926.6; NM_005688.4; NP_005679.2.
DR UCSC; uc003fmg.4; human. [O15440-1]
DR CTD; 10057; -.
DR DisGeNET; 10057; -.
DR GeneCards; ABCC5; -.
DR HGNC; HGNC:56; ABCC5.
DR HPA; ENSG00000114770; Tissue enhanced (choroid).
DR MIM; 605251; gene.
DR neXtProt; NX_O15440; -.
DR OpenTargets; ENSG00000114770; -.
DR PharmGKB; PA395; -.
DR VEuPathDB; HostDB:ENSG00000114770; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000155470; -.
DR HOGENOM; CLU_000604_27_3_1; -.
DR InParanoid; O15440; -.
DR OMA; FVKFFGW; -.
DR OrthoDB; 138195at2759; -.
DR PhylomeDB; O15440; -.
DR TreeFam; TF105202; -.
DR BRENDA; 7.6.2.3; 2681.
DR PathwayCommons; O15440; -.
DR Reactome; R-HSA-2142850; Hyaluronan biosynthesis and export.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SignaLink; O15440; -.
DR BioGRID-ORCS; 10057; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; ABCC5; human.
DR GeneWiki; ABCC5; -.
DR GenomeRNAi; 10057; -.
DR Pharos; O15440; Tchem.
DR PRO; PR:O15440; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O15440; protein.
DR Bgee; ENSG00000114770; Expressed in right hemisphere of cerebellum and 199 other tissues.
DR ExpressionAtlas; O15440; baseline and differential.
DR Genevisible; O15440; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005796; C:Golgi lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0043225; F:ATPase-coupled inorganic anion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0034634; F:glutathione transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015232; F:heme transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0015216; F:purine nucleotide transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0070730; P:cAMP transport; IMP:UniProtKB.
DR GO; GO:0070731; P:cGMP transport; IMP:UniProtKB.
DR GO; GO:0140115; P:export across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098838; P:folate transmembrane transport; IMP:UniProtKB.
DR GO; GO:0034775; P:glutathione transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0035351; P:heme transmembrane transport; IMP:UniProtKB.
DR GO; GO:0030213; P:hyaluronan biosynthetic process; TAS:Reactome.
DR GO; GO:0015865; P:purine nucleotide transport; IDA:ARUK-UCL.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; TAS:Reactome.
DR GO; GO:0042908; P:xenobiotic transport; IDA:ARUK-UCL.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR030238; ABCC5.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF196; PTHR24223:SF196; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Endosome; Glycoprotein;
KW Golgi apparatus; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1437
FT /note="ATP-binding cassette sub-family C member 5"
FT /id="PRO_0000093363"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 317..337
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 608..628
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 848..868
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 917..937
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 997..1017
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1018..1038
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1104..1124
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1127..1147
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 179..459
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 562..783
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 859..1155
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1193..1427
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 15..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..41
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 799..827
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 595..602
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1227..1234
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 513
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CARBOHYD 494
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 636
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 684
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 890
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 897
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1044
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 198..225
FT /note="AFMVKHLLEYTQATESNLQYSLLLVLGL -> PSFGDCSISAEVCGNRLHCT
FT AILLSCFT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17521428"
FT /id="VSP_043397"
FT VAR_SEQ 198..212
FT /note="AFMVKHLLEYTQATE -> LAWCCQDLDLGGVSL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17521428"
FT /id="VSP_043398"
FT VAR_SEQ 198..208
FT /note="AFMVKHLLEYT -> NFQDGCILRSE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17521428"
FT /id="VSP_043399"
FT VAR_SEQ 209..225
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:17521428"
FT /id="VSP_043400"
FT VAR_SEQ 213..225
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17521428"
FT /id="VSP_043401"
FT VAR_SEQ 226..1437
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17521428"
FT /id="VSP_043402"
FT VAR_SEQ 1033..1075
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_055354"
FT CONFLICT 176
FT /note="R -> P (in Ref. 3; BAA76608)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="S -> G (in Ref. 1; AAD04169)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="I -> V (in Ref. 2; AAD37716)"
FT /evidence="ECO:0000305"
FT CONFLICT 1383
FT /note="T -> N (in Ref. 3; BAA76608 and 8; BAA22887)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1437 AA; 160660 MW; 00558076B3BB4C00 CRC64;
MKDIDIGKEY IIPSPGYRSV RERTSTSGTH RDREDSKFRR TRPLECQDAL ETAARAEGLS
LDASMHSQLR ILDEEHPKGK YHHGLSALKP IRTTSKHQHP VDNAGLFSCM TFSWLSSLAR
VAHKKGELSM EDVWSLSKHE SSDVNCRRLE RLWQEELNEV GPDAASLRRV VWIFCRTRLI
LSIVCLMITQ LAGFSGPAFM VKHLLEYTQA TESNLQYSLL LVLGLLLTEI VRSWSLALTW
ALNYRTGVRL RGAILTMAFK KILKLKNIKE KSLGELINIC SNDGQRMFEA AAVGSLLAGG
PVVAILGMIY NVIILGPTGF LGSAVFILFY PAMMFASRLT AYFRRKCVAA TDERVQKMNE
VLTYIKFIKM YAWVKAFSQS VQKIREEERR ILEKAGYFQS ITVGVAPIVV VIASVVTFSV
HMTLGFDLTA AQAFTVVTVF NSMTFALKVT PFSVKSLSEA SVAVDRFKSL FLMEEVHMIK
NKPASPHIKI EMKNATLAWD SSHSSIQNSP KLTPKMKKDK RASRGKKEKV RQLQRTEHQA
VLAEQKGHLL LDSDERPSPE EEEGKHIHLG HLRLQRTLHS IDLEIQEGKL VGICGSVGSG
KTSLISAILG QMTLLEGSIA ISGTFAYVAQ QAWILNATLR DNILFGKEYD EERYNSVLNS
CCLRPDLAIL PSSDLTEIGE RGANLSGGQR QRISLARALY SDRSIYILDD PLSALDAHVG
NHIFNSAIRK HLKSKTVLFV THQLQYLVDC DEVIFMKEGC ITERGTHEEL MNLNGDYATI
FNNLLLGETP PVEINSKKET SGSQKKSQDK GPKTGSVKKE KAVKPEEGQL VQLEEKGQGS
VPWSVYGVYI QAAGGPLAFL VIMALFMLNV GSTAFSTWWL SYWIKQGSGN TTVTRGNETS
VSDSMKDNPH MQYYASIYAL SMAVMLILKA IRGVVFVKGT LRASSRLHDE LFRRILRSPM
KFFDTTPTGR ILNRFSKDMD EVDVRLPFQA EMFIQNVILV FFCVGMIAGV FPWFLVAVGP
LVILFSVLHI VSRVLIRELK RLDNITQSPF LSHITSSIQG LATIHAYNKG QEFLHRYQEL
LDDNQAPFFL FTCAMRWLAV RLDLISIALI TTTGLMIVLM HGQIPPAYAG LAISYAVQLT
GLFQFTVRLA SETEARFTSV ERINHYIKTL SLEAPARIKN KAPSPDWPQE GEVTFENAEM
RYRENLPLVL KKVSFTIKPK EKIGIVGRTG SGKSSLGMAL FRLVELSGGC IKIDGVRISD
IGLADLRSKL SIIPQEPVLF SGTVRSNLDP FNQYTEDQIW DALERTHMKE CIAQLPLKLE
SEVMENGDNF SVGERQLLCI ARALLRHCKI LILDEATAAM DTETDLLIQE TIREAFADCT
MLTIAHRLHT VLGSDRIMVL AQGQVVEFDT PSVLLSNDSS RFYAMFAAAE NKVAVKG
