NRAMA_CAEEL
ID NRAMA_CAEEL Reviewed; 562 AA.
AC Q21434; Q65ZJ5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=NRAMP-like transporter smf-1 {ECO:0000305};
DE AltName: Full=Divalent metal transporter smf-1 {ECO:0000305};
GN Name=smf-1; ORFNames=K11G12.4;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
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]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION BY BACTERIA, AND
RP DISRUPTION 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]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY MANGANESE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19801673; DOI=10.1074/jbc.m109.051409;
RA Settivari R., Levora J., Nass R.;
RT "The divalent metal transporter homologues SMF-1/2 mediate dopamine neuron
RT sensitivity in caenorhabditis elegans models of manganism and parkinson
RT disease.";
RL J. Biol. Chem. 284:35758-35768(2009).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY MANGANESE, AND DISRUPTION
RP 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).
CC -!- FUNCTION: Probable divalent metal ion transporter which regulates
CC Mn(2+) uptake. {ECO:0000269|PubMed:19801673,
CC ECO:0000269|PubMed:19924247}.
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}.
CC -!- TISSUE SPECIFICITY: Expressed in dopaminergic neurons (at protein
CC level) (PubMed:19801673). Expressed predominantly in anterior and
CC posterior intestine, rectal gland cell, H-shaped excretory cell, vulva
CC cells, proximal uterus and spermatheca in adults (PubMed:19924247,
CC PubMed:19785996). Weakly expressed in hyp7 hypodermis, pharyngeal
CC muscles and some anterior sensory, ring and posterior head neurons in
CC adults (PubMed:19924247, PubMed:19785996). Expressed in the anchor cell
CC at the larval stage (PubMed:19924247). {ECO:0000269|PubMed:19785996,
CC ECO:0000269|PubMed:19801673, ECO:0000269|PubMed:19924247}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the embryonic comma stage and
CC throughout larval and adult stages. {ECO:0000269|PubMed:19785996}.
CC -!- INDUCTION: Induced by pathogenic bacterium S.aureus (PubMed:19785996).
CC Repressed by high levels of Mn(2+) (PubMed:19801673, PubMed:19924247).
CC {ECO:0000269|PubMed:19785996, ECO:0000269|PubMed:19801673,
CC ECO:0000269|PubMed:19924247}.
CC -!- DISRUPTION PHENOTYPE: Higher iron levels in their body compared to
CC wild-type. Increased survival rate and reduced iron levels in their
CC body in response to increasing Mn(2+) levels (PubMed:19924247). Reduced
CC survival rate in response to high Mn(2+) levels or to infection
CC mediated by pathogenic bacterium S.aureus (PubMed:19785996). Increased
CC smf-2 mRNA levels (PubMed:19924247). RNAi-mediated knockdown increases
CC resistance to Mn(2+)-induced CEP neuron death and prevents CEP neuron
CC death-mediated by the neurotoxin 6-hydroxy dopamine (6-OHDA)
CC (PubMed:19801673). {ECO:0000269|PubMed:19785996,
CC ECO:0000269|PubMed:19801673, ECO:0000269|PubMed:19924247}.
CC -!- SIMILARITY: Belongs to the NRAMP family. {ECO:0000305}.
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DR EMBL; FO081325; CCD70800.1; -; Genomic_DNA.
DR PIR; T16619; T16619.
DR RefSeq; NP_001024792.2; NM_001029621.4.
DR AlphaFoldDB; Q21434; -.
DR SMR; Q21434; -.
DR STRING; 6239.K11G12.4a; -.
DR TCDB; 2.A.55.2.16; the metal ion (mn(2+)-iron) transporter (nramp) family.
DR EPD; Q21434; -.
DR PaxDb; Q21434; -.
DR EnsemblMetazoa; K11G12.4a.1; K11G12.4a.1; WBGene00004876.
DR GeneID; 180939; -.
DR KEGG; cel:CELE_K11G12.4; -.
DR UCSC; K11G12.4b; c. elegans.
DR CTD; 180939; -.
DR WormBase; K11G12.4a; CE41828; WBGene00004876; smf-1.
DR eggNOG; KOG1291; Eukaryota.
DR GeneTree; ENSGT00940000170016; -.
DR HOGENOM; CLU_020088_5_2_1; -.
DR InParanoid; Q21434; -.
DR OMA; IATFVNS; -.
DR OrthoDB; 666470at2759; -.
DR PhylomeDB; Q21434; -.
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 Reactome; R-CEL-917937; Iron uptake and transport.
DR PRO; PR:Q21434; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004876; Expressed in embryo and 3 other tissues.
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: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:0055072; P:iron ion homeostasis; IMP:WormBase.
DR GO; GO:0055071; P:manganese ion homeostasis; IMP:WormBase.
DR GO; GO:1905803; P:negative regulation of cellular response to manganese ion; IMP:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:UniProtKB.
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: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; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..562
FT /note="NRAMP-like transporter smf-1"
FT /id="PRO_0000212607"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..83
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..164
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..241
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 263..287
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 288..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..347
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 348..368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 369..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 399..419
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..428
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 450..462
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 463..483
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 484..496
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 497..517
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..562
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 562 AA; 63104 MW; 6C49AFB160285FF5 CRC64;
MASSNNDGPI EPEAEPWRIT QNDHLEQDLL EEDAESQERV DIPVDDVEKA FSFKKLWAFT
GPGFLMSIAY LDPGNIESDL QSGAQAAYKL LWVLLSAHII GMLLQRMSAR LGVVSGKHMA
EVAYQFYPRL PRIILWLMIE IAIVCSDMQE VIGTAIAIFL LSKGFVPLYV GVFITILDTF
TFLLIDRYGI RKLELIFGFL ILTMTVSFGY EFVVVKPPIG EVISGMVVPW CAGCGKGEFM
QAISVVGAVI MPHNLYLHSA LVKSRRVDRK DRRRVAEANK YFTLESAIAL FLSFFINLFV
VAVFAHGLYQ KTNADVREMC IARHDIPDAD IFPNNTEPVE VDIYKGGIYL GCQFGAIAMF
IWGIGIFAAG QSSTMTGTYT GQFVMEGFVK IEWPKWKRVL ITRAIAITPT LVLTFYSQGV
QNLTGMNDFL NCVQMIQLPF ALIPIITFTS SRKIMHDFRS SKVFQIFALI TSALILSINV
YFISDYVFSR LGSEWYIIMV LAPITFAYVL FVLYLALYCL VSCEIIPDTV SIRGFSFNKS
YENDAPWLAV DSSAVHDNAG YQ
