NRAMC_CAEEL
ID NRAMC_CAEEL Reviewed; 560 AA.
AC Q95XG8;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 3.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=NRAMP-like transporter smf-3 {ECO:0000305};
DE AltName: Full=DMT-1 {ECO:0000303|PubMed:23106139};
DE AltName: Full=Divalent metal transporter smf-3 {ECO:0000305};
GN Name=smf-3 {ECO:0000312|WormBase:Y69A2AR.4};
GN ORFNames=Y69A2AR.4 {ECO:0000312|EMBL:CCD74141.1};
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, TISSUE SPECIFICITY, INDUCTION BY BACTERIA, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19785996; DOI=10.1016/j.bbrc.2009.09.082;
RA Bandyopadhyay J., Song H.O., Park B.J., Singaravelu G., Sun J.L., Ahnn J.,
RA Cho J.H.;
RT "Functional assessment of Nramp-like metal transporters and manganese in
RT Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 390:136-141(2009).
RN [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY MANGANESE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=19924247; DOI=10.1371/journal.pone.0007792;
RA Au C., Benedetto A., Anderson J., Labrousse A., Erikson K., Ewbank J.J.,
RA Aschner M.;
RT "SMF-1, SMF-2 and SMF-3 DMT1 orthologues regulate and are regulated
RT differentially by manganese levels in C. elegans.";
RL PLoS ONE 4:E7792-E7792(2009).
RN [4] {ECO:0000305}
RP FUNCTION, INDUCTION BY IRON, AND DISRUPTION PHENOTYPE.
RX PubMed=22194696; DOI=10.1371/journal.pgen.1002394;
RA Romney S.J., Newman B.S., Thacker C., Leibold E.A.;
RT "HIF-1 regulates iron homeostasis in Caenorhabditis elegans by activation
RT and inhibition of genes involved in iron uptake and storage.";
RL PLoS Genet. 7:E1002394-E1002394(2011).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY ALUMINUM,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=23106139; DOI=10.1111/jnc.12072;
RA VanDuyn N., Settivari R., LeVora J., Zhou S., Unrine J., Nass R.;
RT "The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine
RT neuron degeneration.";
RL J. Neurochem. 124:147-157(2013).
CC -!- FUNCTION: Probable divalent metal ion transporter which regulates the
CC uptake of several heavy metals such as Mn(2+), Al(3+) and iron
CC (PubMed:19924247, PubMed:23106139, PubMed:19785996, PubMed:22194696).
CC Plays a role in modulating Al(3+)-induced dopamine (DA) neuron
CC degeneration through the intracellular sequestration of Al(3+)
CC (PubMed:23106139). {ECO:0000269|PubMed:19785996,
CC ECO:0000269|PubMed:19924247, ECO:0000269|PubMed:22194696,
CC ECO:0000269|PubMed:23106139}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:19924247}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:19924247, ECO:0000269|PubMed:23106139}.
CC Note=Translocates to apical cytoplasmic vesicles in intestine in
CC response to high Mn(2+) levels (PubMed:19924247). In dopaminergic
CC neurons, localizes to cytoplasmic vesicles (PubMed:23106139).
CC {ECO:0000269|PubMed:19924247, ECO:0000269|PubMed:23106139}.
CC -!- TISSUE SPECIFICITY: Expressed in dopaminergic neurons (at protein
CC level) (PubMed:23106139). Expressed in intestine with a weaker
CC expression in the most proximal and distal regions (PubMed:19785996,
CC PubMed:19924247). Weakly expressed in the hyp1-6, hyp7 and hyp8-12
CC hypodermis and in head and tail neurons (PubMed:19924247).
CC {ECO:0000269|PubMed:19785996, ECO:0000269|PubMed:19924247,
CC ECO:0000269|PubMed:23106139}.
CC -!- INDUCTION: Induced by pathogenic bacterium S.aureus (PubMed:19785996).
CC Repressed by high levels of Mn(2+) (PubMed:19924247). Repressed by high
CC levels of Al(3+) (PubMed:23106139). Induced by low iron levels
CC (PubMed:22194696). {ECO:0000269|PubMed:19785996,
CC ECO:0000269|PubMed:19924247, ECO:0000269|PubMed:22194696,
CC ECO:0000269|PubMed:23106139}.
CC -!- DISRUPTION PHENOTYPE: Increased survival rate and reduced body levels
CC of iron in response to increasing Mn(2+) levels (PubMed:19924247).
CC Reduced survival rate in response to high Mn(2+) levels or to infection
CC mediated by pathogenic bacterium S.aureus (PubMed:19785996). Reduced
CC CEP neuron death and higher Al(3+) accumulation in the body in response
CC to high Al(3+) levels (PubMed:23106139). Reduced ferritin ftn-1 mRNA
CC levels and Mn(2+) and iron body levels (PubMed:22194696). Increased
CC sfm-1, sfm-2 and sfm-3 mRNA levels (PubMed:19924247).
CC {ECO:0000269|PubMed:19785996, ECO:0000269|PubMed:19924247,
CC ECO:0000269|PubMed:22194696, ECO:0000269|PubMed:23106139}.
CC -!- SIMILARITY: Belongs to the NRAMP family. {ECO:0000305}.
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DR EMBL; BX284604; CCD74141.1; -; Genomic_DNA.
DR RefSeq; NP_500235.4; NM_067834.4.
DR AlphaFoldDB; Q95XG8; -.
DR SMR; Q95XG8; -.
DR STRING; 6239.Y69A2AR.4; -.
DR TCDB; 2.A.55.2.15; the metal ion (mn(2+)-iron) transporter (nramp) family.
DR PaxDb; Q95XG8; -.
DR EnsemblMetazoa; Y69A2AR.4.1; Y69A2AR.4.1; WBGene00004878.
DR EnsemblMetazoa; Y69A2AR.4.2; Y69A2AR.4.2; WBGene00004878.
DR GeneID; 177044; -.
DR KEGG; cel:CELE_Y69A2AR.4; -.
DR UCSC; Y69A2AR.4; c. elegans.
DR CTD; 177044; -.
DR WormBase; Y69A2AR.4; CE46127; WBGene00004878; smf-3.
DR eggNOG; KOG1291; Eukaryota.
DR eggNOG; KOG3923; Eukaryota.
DR HOGENOM; CLU_020088_5_2_1; -.
DR InParanoid; Q95XG8; -.
DR OMA; SPKWLRY; -.
DR OrthoDB; 666470at2759; -.
DR PhylomeDB; Q95XG8; -.
DR Reactome; R-CEL-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-CEL-425410; Metal ion SLC transporters.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-6803544; Ion influx/efflux at host-pathogen interface.
DR PRO; PR:Q95XG8; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004878; Expressed in larva and 1 other tissue.
DR GO; GO:0016324; C:apical plasma membrane; IDA:WormBase.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031090; C:organelle membrane; IDA:WormBase.
DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0046915; F:transition metal ion transmembrane transporter activity; ISS:WormBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0055071; P:manganese ion homeostasis; IMP:WormBase.
DR GO; GO:0010042; P:response to manganese ion; IMP:WormBase.
DR GO; GO:0010038; P:response to metal ion; IGI:WormBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:WormBase.
DR GO; GO:0000041; P:transition metal ion transport; ISS:WormBase.
DR HAMAP; MF_00221; NRAMP; 1.
DR InterPro; IPR001046; NRAMP_fam.
DR PANTHER; PTHR11706; PTHR11706; 1.
DR Pfam; PF01566; Nramp; 1.
DR PRINTS; PR00447; NATRESASSCMP.
DR TIGRFAMs; TIGR01197; nramp; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; Glycoprotein; Ion transport; Iron;
KW Iron transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..560
FT /note="NRAMP-like transporter smf-3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000437466"
FT TOPO_DOM 1..43
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 44..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..71
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..152
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..182
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..229
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..339
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 340..360
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 361..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..420
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 421..441
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 480..486
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 487..507
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..560
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 560 AA; 63186 MW; BCFF0BC8B3055ABC CRC64;
MEGEMKCPIE EIREKPEMRK AQQTYEVQVE VEDTPDTTFS WRKLWAFTGP GFLMSIAYLD
PGNIESDLQA GAISYFKLIW VLLVAHIMGL LLQRLAARLG VVSGKHMAEI AFSYYPKIPR
LVLWMLVESA IVGSDMQEVI GTAISFYLLS NGVIPLWAGV LITICDTFTF LFLEKYGVRK
FEAFFCFLIT CMAITFGYEF GVSAPDAGKM FSGMFVPWCN GCDNNMVMQG VAIIGAVIMP
HNFYLHSALV KSRRVDRRRA EKVTEANKYF FIESAFALFV SFIINTLVIS VFAQGMYGKT
NQDIRDTCYN NTHNGMPDFY KVEFPANNDA AQSDIYHAGI FLGCTFGIFA LYVWAVGILA
AGQSSTMTGT YAGQFAMEGF IQIKLPQWKR ILITRSLAIL PTLAVVIFSG GIDNISSLND
FLNCLQLIQL PFALIPVLTF VSDRNIMHEY KLASVSKVVS IVISLIILFI NFYFLYSWIG
STFGYNAVSI PITIFCAIFY IIFIAYLTYY CLVAMEFISP IQTKWLAEPI YHDFDAPWLE
DSENPSTKNT ISDDELSMRY
