MRP5_CAEEL
ID MRP5_CAEEL Reviewed; 1427 AA.
AC G5EE72;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Multidrug resistance-associated protein 5 {ECO:0000312|WormBase:F14F4.3};
DE AltName: Full=ATP-binding cassette sub-family C member mrp-5 {ECO:0000305};
GN Name=mrp-5 {ECO:0000312|WormBase:F14F4.3};
GN ORFNames=F14F4.3 {ECO:0000312|WormBase:F14F4.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
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 [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28581477; DOI=10.1038/ncb3539;
RA Sinclair J., Pinter K., Samuel T., Beardsley S., Yuan X., Zhang J.,
RA Meng K., Yun S., Krause M., Hamza I.;
RT "Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.";
RL Nat. Cell Biol. 19:799-807(2017).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29562169; DOI=10.1016/j.celrep.2018.02.100;
RA Na H., Ponomarova O., Giese G.E., Walhout A.J.M.;
RT "C. elegans MRP-5 Exports Vitamin B12 from Mother to Offspring to Support
RT Embryonic Development.";
RL Cell Rep. 22:3126-3133(2018).
CC -!- FUNCTION: Heme transporter required for the export of intestinal heme
CC to different tissues and subcellular compartments (PubMed:24836561,
CC PubMed:28581477). Also, required for the export of vitamin B12 from the
CC intestine of the mother to the embryo to support embryonic development
CC (PubMed:29562169). {ECO:0000269|PubMed:24836561,
CC ECO:0000269|PubMed:28581477, ECO:0000269|PubMed:29562169}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:24836561}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the intestine and pharynx
CC (PubMed:24836561, PubMed:29562169). Expressed at low levels in the
CC hypodermis and in some neurons (PubMed:24836561).
CC {ECO:0000269|PubMed:24836561, ECO:0000269|PubMed:29562169}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development.
CC {ECO:0000269|PubMed:24836561}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in larvae does not result
CC in any obvious developmental defects and animals are able to reach the
CC adult gravid stage and lay eggs (PubMed:24836561). However, 80% of the
CC eggs laid fail to hatch, and the animals that hatch do not survive
CC beyond the L1 larval stage (PubMed:24836561). RNAi-mediated knockdown
CC in larvae results in the heme accumulation in the intestine under low
CC heme conditions (PubMed:28581477). RNAi-mediated knockdown in larvae
CC results in an accumulation of vitamin B12 in the intestine and
CC defective vitamin B12 transport from mother to dead embryos
CC (PubMed:29562169). Furthermore, embryos of RNAi-treated mothers also
CC have defects in vitamin B12 metabolism and have reduced levels of
CC methionine and S-adenosylmethionine (PubMed:29562169). Double RNAi-
CC mediated knockdown with hrg-7 in larvae results in defective heme
CC sensing (PubMed:28581477). {ECO:0000269|PubMed:24836561,
CC ECO:0000269|PubMed:28581477, ECO:0000269|PubMed:29562169}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC Conjugate transporter (TC 3.A.1.208) subfamily. {ECO:0000305}.
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DR EMBL; BX284606; CAB54225.1; -; Genomic_DNA.
DR PIR; T20903; T20903.
DR PIR; T20904; T20904.
DR RefSeq; NP_510479.1; NM_078078.1.
DR AlphaFoldDB; G5EE72; -.
DR SMR; G5EE72; -.
DR STRING; 6239.F14F4.3b; -.
DR EPD; G5EE72; -.
DR PaxDb; G5EE72; -.
DR PeptideAtlas; G5EE72; -.
DR EnsemblMetazoa; F14F4.3.1; F14F4.3.1; WBGene00003411.
DR GeneID; 181587; -.
DR KEGG; cel:CELE_F14F4.3; -.
DR CTD; 181587; -.
DR WormBase; F14F4.3; CE23650; WBGene00003411; mrp-5.
DR eggNOG; KOG0054; Eukaryota.
DR InParanoid; G5EE72; -.
DR OMA; IPKMWAM; -.
DR OrthoDB; 138195at2759; -.
DR PhylomeDB; G5EE72; -.
DR Reactome; R-CEL-2142850; Hyaluronan biosynthesis and export.
DR Reactome; R-CEL-382556; ABC-family proteins mediated transport.
DR Reactome; R-CEL-9748787; Azathioprine ADME.
DR Reactome; R-CEL-9753281; Paracetamol ADME.
DR PRO; PR:G5EE72; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00003411; Expressed in material anatomical entity and 5 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IC:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0015420; F:ABC-type vitamin B12 transporter activity; IMP:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015889; P:cobalamin transport; IMP:WormBase.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
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; IPR027417; P-loop_NTPase.
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 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Glycoprotein; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1427
FT /note="Multidrug resistance-associated protein 5"
FT /id="PRO_0000449291"
FT TOPO_DOM 1..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 169..185
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 207..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 290
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 291..311
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 312..375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 397..399
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 421..770
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 771..791
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 792..833
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 834..854
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 855..909
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 910..930
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 931
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 932..952
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 953..1022
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1023..1043
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 1044..1049
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1050..1070
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00441"
FT TOPO_DOM 1071..1427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 151..432
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 486..707
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 783..1078
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1117..1351
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1361..1427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1366..1381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1382..1420
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 518..525
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1151..1158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 817
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 1427 AA; 158686 MW; 81DA0FBC90961FAE CRC64;
MPSDSEEVCL QQSGTGVYEN VVYSKETSDR AKRYAGDTNR KTIGRYSAAV QNLIPLRTTE
RNKNNGGSRI DDAGLFSFVT YSWVFPYLYQ AVRGKLDRNQ VWGCSFYDSC GLNMARLEVL
WEDEKKANAK SPSLFKVIYR FISTRLWFSC AVFFFCLIFG FIGPTCFIRR LIAFAENPER
DEQSRIVYSY GIALVAAISV VEFARVLSYG ATWAVSYRTG IRVRGAVLAL LYKNVLNSKD
LCGKTESDVI NIFANDGQRL FDAVTFAPLV LVGPLVLVGG IGYLLMVIGR WSLLGILVFF
VFDVIQFGLG KSMVACRNLA IVKTEKRISM MAEIIKYIRI VKMNGWEQIF SAKIDQFRKE
EKVQIRKSGY AQSLAIACGP VVPVVAAILT FVGVVLAGND LLASDAFSAI TVYFVMLFGI
RMIPYGSRYL AEAVVAMRRI QEYLLLEQYA PYPVTNAEDV VLDCQGATYT YQPKAAKAPV
DETKEPTENE VIVVETPVFT CSFDKLSIKR GEHIAVIGAV GCGKSAILKA ISGHMFTTDD
ALSVDRSQTV YVPQKAWIFN GTVQDNILFG DKMNSERYYK AVNGCQLTED LTTLSVGDRT
EVGERGATLS GGQKARVALA RAVFQTKNLY LFDDIFASLD KKVANKIHEE IIQKLLKKKA
LMMVTNNMEL LHHFDRVLFV EGGNIVADGN HDILYEKNDA YKTFVDACET YQATSGATSP
CGDGPAQPAP LDAEILRNSS EDLKGDADKL ISDEEDMGNS TIAWRIYKQY IHAAGGWPIW
TCLVIGFIVN VVSNIFSTYW LSRWLKKGHD ETTTITNGTE FLEMKTSLAD SPVTGFYAAV
YLVALVVLTI SGLFKACVFV KVSLTAATRL HDRMFQAVIH GATSFFDSTP TGRILNRFSK
DMDEIDVKLP FTAEVFLQNM ITCLGFLVVI TSVFPYFLLF AIPLFVVFVV FVSCFRAGIR
NLKRSEHISR SPLYDHVSAS LEGITTIHTF QQSNRFLEVL KKHLDCNSGA IFMFQSAMRW
LAVWLDLLVV VMTAIVALLT VMLTGTVSPA DAGMAIAFAV QMSGIFQFAV RTQTELEAKM
TSVERVSYYA DNIPEDGEWN TRQGLDIESS WPANGQINFS EVNLRYRKSH PLALNDITFE
IKGGEKVGII GRTGSGKSSL ANLIFRLYPV TNGTIYIDGV DIRTVGLVKL RRGISAIAQD
PSLFSGTVRF NLDPSLEYSD SMIWEALEKC HLKTLVQSLD KKLEADVSHG GNNFSVGERQ
LFCLARALLM KSRIVILDEA TASVDAGTDK LIQEVIKTVF ADATVIIIAH RLDNVRNMDR
IMHLKNGKLI NFTTPQEMFK DDWSVYKLED KDDDQHSAVV VGENSEHSME KSSQGSSQES
DDIVKVENEQ KDSSDDVVHI ESGDDDVKAD SSEVKETSSD TDIEVVQ
