MRP8_HUMAN
ID MRP8_HUMAN Reviewed; 1382 AA.
AC Q96J66; Q8TDJ0; Q96JA6; Q9BX80;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ATP-binding cassette sub-family C member 11 {ECO:0000303|PubMed:11483364};
DE EC=7.6.2.2 {ECO:0000269|PubMed:12764137, ECO:0000269|PubMed:15537867, ECO:0000269|PubMed:25896536};
DE EC=7.6.2.3 {ECO:0000269|PubMed:15537867};
DE AltName: Full=Multidrug resistance-associated protein 8 {ECO:0000303|PubMed:11591886};
GN Name=ABCC11 {ECO:0000312|HGNC:HGNC:14639}; Synonyms=MRP8;
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.
RC TISSUE=Testis;
RX PubMed=11483364; DOI=10.1016/s0378-1119(01)00572-8;
RA Tammur J., Prades C., Arnould I., Rzhetsky A., Hutchinson A., Adachi M.,
RA Schuetz J.D., Swoboda K.J., Ptacek L.J., Rosier M., Dean M., Allikmets R.;
RT "Two new genes from the human ATP-binding cassette transporter superfamily,
RT ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12.";
RL Gene 273:89-96(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Liver;
RX PubMed=11688999; DOI=10.1006/bbrc.2001.5865;
RA Yabuuchi H., Shimizu H., Takayanagi S., Ishikawa T.;
RT "Multiple splicing variants of two new human ATP-binding cassette
RT transporters, ABCC11 and ABCC12.";
RL Biochem. Biophys. Res. Commun. 288:933-939(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP GLU-317 AND ARG-1344.
RC TISSUE=Mammary gland;
RX PubMed=11591886; DOI=10.1007/bf03401856;
RA Bera T.K., Lee S., Salvatore G., Lee B.K., Pastan I.H.;
RT "MRP8, a new member of ABC transporter superfamily, identified by EST
RT database mining and gene prediction program, is highly expressed in breast
RT cancer.";
RL Mol. Med. 7:509-516(2001).
RN [4]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=12764137; DOI=10.1074/jbc.m304059200;
RA Guo Y., Kotova E., Chen Z.S., Lee K., Hopper-Borge E., Belinsky M.G.,
RA Kruh G.D.;
RT "MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux
RT pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine
RT and 9'-(2'-phosphonylmethoxyethyl)adenine.";
RL J. Biol. Chem. 278:29509-29514(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15537867; DOI=10.1124/mol.104.007138;
RA Chen Z.S., Guo Y., Belinsky M.G., Kotova E., Kruh G.D.;
RT "Transport of bile acids, sulfated steroids, estradiol 17-beta-D-
RT glucuronide, and leukotriene C4 by human multidrug resistance protein 8
RT (ABCC11).";
RL Mol. Pharmacol. 67:545-557(2005).
RN [6]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16359813; DOI=10.1016/j.neuroscience.2005.10.025;
RA Bortfeld M., Rius M., Koenig J., Herold-Mende C., Nies A.T., Keppler D.;
RT "Human multidrug resistance protein 8 (MRP8/ABCC11), an apical efflux pump
RT for steroid sulfates, is an axonal protein of the CNS and peripheral
RT nervous system.";
RL Neuroscience 137:1247-1257(2006).
RN [7]
RP POLYMORPHISM, VARIANT ARG-180, CHARACTERIZATION OF VARIANT ARG-180, AND
RP FUNCTION IN SECRETION OF EARWAX.
RX PubMed=16444273; DOI=10.1038/ng1733;
RA Yoshiura K., Kinoshita A., Ishida T., Ninokata A., Ishikawa T., Kaname T.,
RA Bannai M., Tokunaga K., Sonoda S., Komaki R., Ihara M., Saenko V.A.,
RA Alipov G.K., Sekine I., Komatsu K., Takahashi H., Nakashima M.,
RA Sosonkina N., Mapendano C.K., Ghadami M., Nomura M., Liang D.-S., Miwa N.,
RA Kim D.-K., Garidkhuu A., Natsume N., Ohta T., Tomita H., Kaneko A.,
RA Kikuchi M., Russomando G., Hirayama K., Ishibashi M., Takahashi A.,
RA Saitou N., Murray J.C., Saito S., Nakamura Y., Niikawa N.;
RT "A SNP in the ABCC11 gene is the determinant of human earwax type.";
RL Nat. Genet. 38:324-330(2006).
RN [8]
RP VARIANT ARG-180, CHARACTERIZATION OF VARIANTS HIS-19; ARG-180; GLU-317;
RP MET-546; TRP-630; ILE-648; ILE-687; ARG-735; VAL-970 AND ARG-1344,
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT
RP ASN-838 AND ASN-844, POLYMORPHISM, AND MUTAGENESIS OF GLY-180; ASN-838 AND
RP ASN-844.
RX PubMed=19383836; DOI=10.1096/fj.09-129098;
RA Toyoda Y., Sakurai A., Mitani Y., Nakashima M., Yoshiura K., Nakagawa H.,
RA Sakai Y., Ota I., Lezhava A., Hayashizaki Y., Niikawa N., Ishikawa T.;
RT "Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the
RT human ABC transporter ABCC11 gene determine earwax type?";
RL FASEB J. 23:2001-2013(2009).
RN [9]
RP VARIANT ARG-180, CHARACTERIZATION OF VARIANT ARG-180, FUNCTION, TISSUE
RP SPECIFICITY, AND POLYMORPHISM.
RX PubMed=19710689; DOI=10.1038/jid.2009.254;
RA Martin A., Saathoff M., Kuhn F., Max H., Terstegen L., Natsch A.;
RT "A functional ABCC11 allele is essential in the biochemical formation of
RT human axillary odor.";
RL J. Invest. Dermatol. 130:529-540(2010).
RN [10]
RP CHARACTERIZATION OF VARIANTS HIS-19; ARG-180; GLU-317; MET-546; ILE-648 AND
RP ARG-1344, FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=25896536; DOI=10.1038/tpj.2015.27;
RA Arlanov R., Lang T., Jedlitschky G., Schaeffeler E., Ishikawa T.,
RA Schwab M., Nies A.T.;
RT "Functional characterization of common protein variants in the efflux
RT transporter ABCC11 and identification of T546M as functionally damaging
RT variant.";
RL Pharmacogenomics J. 16:193-201(2016).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family that actively extrudes physiological compounds, and xenobiotics
CC from cells. Participates in physiological processes involving bile
CC acids, conjugated steroids and cyclic nucleotides (PubMed:12764137,
CC PubMed:15537867). Stimulates the ATP-dependent uptake of a range of
CC physiological lipophilic anions, including the glutathione S-conjugates
CC leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such
CC as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate,
CC glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the
CC monoanionic bile acids glycocholate and taurocholate, and methotrexate
CC (PubMed:15537867, PubMed:25896536). Enhances also the cellular
CC extrusion of cAMP and cGMP (PubMed:12764137, PubMed:15537867). Confers
CC resistance to anticancer drugs, such as 5-fluorouracil (5-FU) and
CC methotrexate (PubMed:25896536, PubMed:15537867, PubMed:12764137).
CC Probably functions to secrete earwax (PubMed:16444273,
CC PubMed:19383836). Required for the secretion of components contributing
CC to axillary odor formation (PubMed:19710689, PubMed:12764137,
CC PubMed:15537867, PubMed:16444273, PubMed:19383836, PubMed:25896536).
CC {ECO:0000269|PubMed:12764137, ECO:0000269|PubMed:15537867,
CC ECO:0000269|PubMed:16444273, ECO:0000269|PubMed:19383836,
CC ECO:0000269|PubMed:19710689, ECO:0000269|PubMed:25896536}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2; Evidence={ECO:0000269|PubMed:12764137,
CC ECO:0000269|PubMed:15537867, ECO:0000269|PubMed:25896536};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-
CC substituted glutathione(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:456216; EC=7.6.2.3;
CC Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene
CC C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dehydroepiandrosterone 3-sulfate(in) + H2O = ADP +
CC dehydroepiandrosterone 3-sulfate(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:61364, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57905,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15537867,
CC ECO:0000269|PubMed:16359813, ECO:0000269|PubMed:25896536};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61365;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + estrone 3-sulfate(in) + H2O = ADP + estrone 3-
CC sulfate(out) + H(+) + phosphate; Xref=Rhea:RHEA:61348,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:60050, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16359813, ECO:0000269|PubMed:25896536};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61349;
CC Evidence={ECO:0000305|PubMed:25896536};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + taurocholate(in) = ADP + H(+) + phosphate +
CC taurocholate(out); Xref=Rhea:RHEA:50052, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:36257,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50053;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycocholate(in) + H2O = ADP + glycocholate(out) + H(+)
CC + phosphate; Xref=Rhea:RHEA:50056, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29746, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50057;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O =
CC 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + H(+) +
CC phosphate; Xref=Rhea:RHEA:60128, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:82961, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60129;
CC Evidence={ECO:0000305|PubMed:15537867};
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:12764137, ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66185;
CC Evidence={ECO:0000305|PubMed:12764137};
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:12764137, ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66189;
CC Evidence={ECO:0000305|PubMed:12764137};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,4-dinitrophenyl-S-glutathione(in) + ATP + H2O = 2,4-
CC dinitrophenyl-S-glutathione(out) + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:61380, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:133977,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15537867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61381;
CC Evidence={ECO:0000305|PubMed:15537867};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13 uM for DHEAS transport {ECO:0000269|PubMed:15537867};
CC KM=21 uM for DHEAS transport {ECO:0000269|PubMed:16359813};
CC KM=62.9 uM for E(2)17betaG transport {ECO:0000269|PubMed:15537867};
CC KM=957 uM for methotrexate transport {ECO:0000269|PubMed:15537867};
CC Vmax=0.74 pmol/min/mg enzyme for cAMP transport
CC {ECO:0000269|PubMed:15537867};
CC Vmax=0.59 pmol/min/mg enzyme for cGMP transport
CC {ECO:0000269|PubMed:15537867};
CC Vmax=370 pmol/min/mg enzyme for DHEAS transport
CC {ECO:0000269|PubMed:16359813};
CC Vmax=34.9 pmol/min/mg enzyme for DHEAS transport
CC {ECO:0000269|PubMed:15537867};
CC Vmax=62 pmol/min/mg enzyme E(2)17betaG transport
CC {ECO:0000269|PubMed:15537867};
CC Vmax=317 pmol/min/mg enzyme methotrexate
CC {ECO:0000269|PubMed:15537867};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19383836,
CC ECO:0000269|PubMed:25896536}; Multi-pass membrane protein
CC {ECO:0000255}. Vacuole membrane {ECO:0000269|PubMed:19383836}.
CC Cytoplasmic vesicle membrane {ECO:0000269|PubMed:25896536}. Apical cell
CC membrane {ECO:0000269|PubMed:16359813}; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96J66-1; Sequence=Displayed;
CC Name=2; Synonyms=Isoform A;
CC IsoId=Q96J66-2; Sequence=VSP_017351;
CC -!- TISSUE SPECIFICITY: Expressed in ceruminous apocrine gland (at protein
CC level) (PubMed:19383836, PubMed:19710689). Expressed in many tissues.
CC Not expressed in kidney, spleen and colon. Highly expressed in breast
CC cancer. Expressed at moderate levels in normal breast and testis and at
CC very low levels in liver, brain and placenta (PubMed:11483364,
CC PubMed:11591886, PubMed:19383836, PubMed:19710689). Localizes to axons
CC of the CNS and peripheral nervous system (at protein level)
CC (PubMed:16359813). {ECO:0000269|PubMed:11483364,
CC ECO:0000269|PubMed:11591886, ECO:0000269|PubMed:16359813,
CC ECO:0000269|PubMed:19383836, ECO:0000269|PubMed:19710689}.
CC -!- POLYMORPHISM: Polymorphism in ABCC11 is associated with variation in
CC apocrine gland secretion [MIM:117800]. This determines different ear
CC wax phenotypes, presence or absence of axillary odor, and variation in
CC colostrum secretion. Characteristic of earwax and strength of axillary
CC odor are most likely interconnected. Human earwax is a Mendelian trait
CC consisting of wet and dry types. The wet earwax is brownish and sticky,
CC whereas the dry type lacks cerumen. The wet cerumen phenotype is
CC completely dominant. The dry type is seen frequently (80-95%) among
CC East Asians, but uncommon (0-3%) in populations of European and African
CC origins. Intermediate frequencies (30-50%) of the dry type are seen in
CC populations of Southern Asia, the Pacific Islands, Central Asia and
CC Asia Minor, as well as among the Native North American and Inuit of
CC Asian ancestry. The allele with Arg-180 is responsible for the dry
CC earwax phenotype and lack of axillary odor.
CC {ECO:0000269|PubMed:16444273, ECO:0000269|PubMed:19383836,
CC ECO:0000269|PubMed:19710689}.
CC -!- MISCELLANEOUS: This protein has no ortholog in rodents. {ECO:0000305}.
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=Protein Spotlight; Note=Of earwax and migration
CC - Issue 67 of February 2006;
CC URL="https://web.expasy.org/spotlight/back_issues/067";
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; AY040219; AAK76739.1; -; mRNA.
DR EMBL; AF367202; AAK58869.1; -; mRNA.
DR EMBL; AF411579; AAL99902.1; -; mRNA.
DR EMBL; AF352582; AAK19755.1; -; mRNA.
DR CCDS; CCDS10732.1; -. [Q96J66-1]
DR CCDS; CCDS10733.1; -. [Q96J66-2]
DR RefSeq; NP_115972.2; NM_032583.3. [Q96J66-1]
DR RefSeq; NP_149163.2; NM_033151.3. [Q96J66-1]
DR RefSeq; NP_660187.1; NM_145186.2. [Q96J66-2]
DR RefSeq; XP_016879284.1; XM_017023795.1.
DR RefSeq; XP_016879285.1; XM_017023796.1.
DR RefSeq; XP_016879286.1; XM_017023797.1. [Q96J66-1]
DR RefSeq; XP_016879287.1; XM_017023798.1. [Q96J66-1]
DR RefSeq; XP_016879288.1; XM_017023799.1. [Q96J66-1]
DR RefSeq; XP_016879289.1; XM_017023800.1. [Q96J66-1]
DR AlphaFoldDB; Q96J66; -.
DR SMR; Q96J66; -.
DR BioGRID; 124474; 3.
DR IntAct; Q96J66; 1.
DR STRING; 9606.ENSP00000378230; -.
DR ChEMBL; CHEMBL2073702; -.
DR DrugBank; DB00286; Conjugated estrogens.
DR DrugBank; DB02527; Cyclic adenosine monophosphate.
DR DrugBank; DB00158; Folic acid.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB00563; Methotrexate.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugCentral; Q96J66; -.
DR TCDB; 3.A.1.208.13; the atp-binding cassette (abc) superfamily.
DR GlyGen; Q96J66; 3 sites.
DR iPTMnet; Q96J66; -.
DR PhosphoSitePlus; Q96J66; -.
DR BioMuta; ABCC11; -.
DR DMDM; 74762666; -.
DR jPOST; Q96J66; -.
DR MassIVE; Q96J66; -.
DR MaxQB; Q96J66; -.
DR PaxDb; Q96J66; -.
DR PeptideAtlas; Q96J66; -.
DR PRIDE; Q96J66; -.
DR ProteomicsDB; 76891; -. [Q96J66-1]
DR ProteomicsDB; 76892; -. [Q96J66-2]
DR Antibodypedia; 28152; 333 antibodies from 34 providers.
DR DNASU; 85320; -.
DR Ensembl; ENST00000353782.9; ENSP00000311326.6; ENSG00000121270.16. [Q96J66-2]
DR Ensembl; ENST00000356608.7; ENSP00000349017.2; ENSG00000121270.16. [Q96J66-1]
DR Ensembl; ENST00000394747.5; ENSP00000378230.1; ENSG00000121270.16. [Q96J66-1]
DR Ensembl; ENST00000394748.5; ENSP00000378231.1; ENSG00000121270.16. [Q96J66-1]
DR GeneID; 85320; -.
DR KEGG; hsa:85320; -.
DR MANE-Select; ENST00000356608.7; ENSP00000349017.2; NM_001370497.1; NP_001357426.1.
DR UCSC; uc002eff.1; human. [Q96J66-1]
DR CTD; 85320; -.
DR DisGeNET; 85320; -.
DR GeneCards; ABCC11; -.
DR HGNC; HGNC:14639; ABCC11.
DR HPA; ENSG00000121270; Tissue enriched (breast).
DR MalaCards; ABCC11; -.
DR MIM; 117800; phenotype.
DR MIM; 607040; gene.
DR neXtProt; NX_Q96J66; -.
DR OpenTargets; ENSG00000121270; -.
DR PharmGKB; PA24393; -.
DR VEuPathDB; HostDB:ENSG00000121270; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000162968; -.
DR HOGENOM; CLU_000604_27_1_1; -.
DR InParanoid; Q96J66; -.
DR OMA; MKNKMCV; -.
DR PhylomeDB; Q96J66; -.
DR TreeFam; TF352085; -.
DR PathwayCommons; Q96J66; -.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR SABIO-RK; Q96J66; -.
DR SignaLink; Q96J66; -.
DR BioGRID-ORCS; 85320; 14 hits in 1063 CRISPR screens.
DR ChiTaRS; ABCC11; human.
DR GeneWiki; ABCC11; -.
DR GenomeRNAi; 85320; -.
DR Pharos; Q96J66; Tbio.
DR PRO; PR:Q96J66; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96J66; protein.
DR Bgee; ENSG00000121270; Expressed in right lobe of liver and 86 other tissues.
DR ExpressionAtlas; Q96J66; baseline and differential.
DR Genevisible; Q96J66; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015432; F:ABC-type bile acid transporter activity; IDA:UniProtKB.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; IDA:UniProtKB.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0008514; F:organic anion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015216; F:purine nucleotide transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015721; P:bile acid and bile salt transport; IDA:UniProtKB.
DR GO; GO:0071716; P:leukotriene transport; IDA:UniProtKB.
DR GO; GO:0015711; P:organic anion transport; IDA:UniProtKB.
DR GO; GO:0015865; P:purine nucleotide transport; IDA:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0042908; P:xenobiotic transport; IDA:UniProtKB.
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; IPR030251; ABCC11.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF168; PTHR24223:SF168; 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; Cytoplasmic vesicle;
KW Glycoprotein; Lipid transport; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..1382
FT /note="ATP-binding cassette sub-family C member 11"
FT /id="PRO_0000225594"
FT TOPO_DOM 1..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 384..404
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 439..806
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 807..827
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 864..884
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 931..951
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1050..1070
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1071..1382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 163..443
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 508..732
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 806..1105
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1141..1375
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 504..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 544..551
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1175..1182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 838
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:19383836"
FT CARBOHYD 844
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:19383836"
FT CARBOHYD 992
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1261..1298
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11688999"
FT /id="VSP_017351"
FT VARIANT 19
FT /note="R -> H (no effect on glycosylation; no effect on
FT transport activity; no effect on plasma membrane
FT localization; dbSNP:rs16945988)"
FT /evidence="ECO:0000269|PubMed:19383836,
FT ECO:0000269|PubMed:25896536"
FT /id="VAR_025437"
FT VARIANT 180
FT /note="G -> R (in dry earwax and lack of axillary odor
FT phenotype; loss of N-glycosylation; strongly reduced plasma
FT membrane localization; no DHEAS transport and largely
FT reduced estrone 3-sulfate transport; decreased protein
FT concentration in axillary sweat; dbSNP:rs17822931)"
FT /evidence="ECO:0000269|PubMed:16444273,
FT ECO:0000269|PubMed:19383836, ECO:0000269|PubMed:19710689,
FT ECO:0000269|PubMed:25896536"
FT /id="VAR_025438"
FT VARIANT 317
FT /note="A -> E (no effect on glycosylation; no effect on
FT transport activity; no effect on plasma membrane
FT localization; dbSNP:rs11863236)"
FT /evidence="ECO:0000269|PubMed:11591886,
FT ECO:0000269|PubMed:19383836, ECO:0000269|PubMed:25896536"
FT /id="VAR_048144"
FT VARIANT 546
FT /note="T -> M (significantly decreased transport activity
FT of DHEAS and estrone 3-sulfate; no effect on glycosylation;
FT reduced ATP-dependent 5-FdUMP transport; no effect on
FT plasma membrane localization; dbSNP:rs17822471)"
FT /evidence="ECO:0000269|PubMed:19383836,
FT ECO:0000269|PubMed:25896536"
FT /id="VAR_048145"
FT VARIANT 630
FT /note="R -> W (no effect on glycosylation;
FT dbSNP:rs41282045)"
FT /evidence="ECO:0000269|PubMed:19383836"
FT /id="VAR_077575"
FT VARIANT 648
FT /note="V -> I (no effect on glycosylation; no effect on
FT transport activity; no effect on plasma membrane
FT localization; dbSNP:rs16945930)"
FT /evidence="ECO:0000269|PubMed:19383836,
FT ECO:0000269|PubMed:25896536"
FT /id="VAR_048146"
FT VARIANT 687
FT /note="V -> I (no effect on glycosylation;
FT dbSNP:rs16945928)"
FT /evidence="ECO:0000269|PubMed:19383836"
FT /id="VAR_048147"
FT VARIANT 735
FT /note="K -> R (no effect on glycosylation;
FT dbSNP:rs16945926)"
FT /evidence="ECO:0000269|PubMed:19383836"
FT /id="VAR_048148"
FT VARIANT 970
FT /note="M -> V (no effect on glycosylation;
FT dbSNP:rs41280943)"
FT /evidence="ECO:0000269|PubMed:19383836"
FT /id="VAR_077576"
FT VARIANT 1344
FT /note="H -> R (no effect on glycosylation; no effect on
FT transport activity; no effect on plasma membrane
FT localization; dbSNP:rs16945916)"
FT /evidence="ECO:0000269|PubMed:11591886,
FT ECO:0000269|PubMed:19383836, ECO:0000269|PubMed:25896536"
FT /id="VAR_048149"
FT MUTAGEN 180
FT /note="G->A,P: Does not affect N-glycosylation."
FT /evidence="ECO:0000269|PubMed:19383836"
FT MUTAGEN 180
FT /note="G->L,H,D,E: Loss of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:19383836"
FT MUTAGEN 838
FT /note="N->Q: Loss of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:19383836"
FT MUTAGEN 844
FT /note="N->Q: Loss of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:19383836"
FT CONFLICT 199
FT /note="V -> A (in Ref. 2; AAK58869/AAL99902)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="L -> P (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="K -> E (in Ref. 2; AAK58869/AAL99902)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="T -> A (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="L -> P (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
FT CONFLICT 688
FT /note="L -> Q (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
FT CONFLICT 702
FT /note="I -> V (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
FT CONFLICT 982
FT /note="K -> E (in Ref. 3; AAK19755)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1382 AA; 154301 MW; 0F3C17DC69AE97F4 CRC64;
MTRKRTYWVP NSSGGLVNRG IDIGDDMVSG LIYKTYTLQD GPWSQQERNP EAPGRAAVPP
WGKYDAALRT MIPFRPKPRF PAPQPLDNAG LFSYLTVSWL TPLMIQSLRS RLDENTIPPL
SVHDASDKNV QRLHRLWEEE VSRRGIEKAS VLLVMLRFQR TRLIFDALLG ICFCIASVLG
PILIIPKILE YSEEQLGNVV HGVGLCFALF LSECVKSLSF SSSWIINQRT AIRFRAAVSS
FAFEKLIQFK SVIHITSGEA ISFFTGDVNY LFEGVCYGPL VLITCASLVI CSISSYFIIG
YTAFIAILCY LLVFPLAVFM TRMAVKAQHH TSEVSDQRIR VTSEVLTCIK LIKMYTWEKP
FAKIIEDLRR KERKLLEKCG LVQSLTSITL FIIPTVATAV WVLIHTSLKL KLTASMAFSM
LASLNLLRLS VFFVPIAVKG LTNSKSAVMR FKKFFLQESP VFYVQTLQDP SKALVFEEAT
LSWQQTCPGI VNGALELERN GHASEGMTRP RDALGPEEEG NSLGPELHKI NLVVSKGMML
GVCGNTGSGK SSLLSAILEE MHLLEGSVGV QGSLAYVPQQ AWIVSGNIRE NILMGGAYDK
ARYLQVLHCC SLNRDLELLP FGDMTEIGER GLNLSGGQKQ RISLARAVYS DRQIYLLDDP
LSAVDAHVGK HIFEECIKKT LRGKTVVLVT HQLQYLEFCG QIILLENGKI CENGTHSELM
QKKGKYAQLI QKMHKEATSD MLQDTAKIAE KPKVESQALA TSLEESLNGN AVPEHQLTQE
EEMEEGSLSW RVYHHYIQAA GGYMVSCIIF FFVVLIVFLT IFSFWWLSYW LEQGSGTNSS
RESNGTMADL GNIADNPQLS FYQLVYGLNA LLLICVGVCS SGIFTKVTRK ASTALHNKLF
NKVFRCPMSF FDTIPIGRLL NCFAGDLEQL DQLLPIFSEQ FLVLSLMVIA VLLIVSVLSP
YILLMGAIIM VICFIYYMMF KKAIGVFKRL ENYSRSPLFS HILNSLQGLS SIHVYGKTED
FISQFKRLTD AQNNYLLLFL SSTRWMALRL EIMTNLVTLA VALFVAFGIS STPYSFKVMA
VNIVLQLASS FQATARIGLE TEAQFTAVER ILQYMKMCVS EAPLHMEGTS CPQGWPQHGE
IIFQDYHMKY RDNTPTVLHG INLTIRGHEV VGIVGRTGSG KSSLGMALFR LVEPMAGRIL
IDGVDICSIG LEDLRSKLSV IPQDPVLLSG TIRFNLDPFD RHTDQQIWDA LERTFLTKAI
SKFPKKLHTD VVENGGNFSV GERQLLCIAR AVLRNSKIIL IDEATASIDM ETDTLIQRTI
REAFQGCTVL VIAHRVTTVL NCDHILVMGN GKVVEFDRPE VLRKKPGSLF AALMATATSS
LR
