ID   NRAM1_RAT               Reviewed;         507 AA.
AC   P70553; Q496Z6;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2006, sequence version 3.
DT   24-JAN-2024, entry version 130.
DE   RecName: Full=Natural resistance-associated macrophage protein 1;
DE            Short=NRAMP 1;
DE   AltName: Full=Solute carrier family 11 member 1;
GN   Name=Slc11a1; Synonyms=Bcg, Nramp1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 336-507.
RC   STRAIN=Lewis;
RX   PubMed=8875897; DOI=10.1007/s003359900251;
RA   Ge L., Remmers E.F., Du Y., Wilder R.L.;
RT   "Genomic cloning and genetic mapping of the rat Nramp1 (Bcg) gene on
RT   chromosome 9.";
RL   Mamm. Genome 7:856-857(1996).
CC   -!- FUNCTION: Macrophage-specific antiporter that fluxes metal ions in
CC       either direction against a proton gradient. Localized to late endosomal
CC       lysosomal membranes, delivers bivalent cations from the cytosol into
CC       these acidic compartments where they may directly affect antimicrobial
CC       activity. Involved in iron metabolism and host natural resistance to
CC       infection with intracellular parasites. Pathogen resistance involves
CC       sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and
CC       eukaryotic catalases and superoxide dismutases, not only to protect the
CC       macrophage against its own generation of reactive oxygen species, but
CC       to deny the cations to the pathogen for synthesis of its protective
CC       enzymes. {ECO:0000250|UniProtKB:P49279}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(out) + Zn(2+)(in) = H(+)(in) + Zn(2+)(out);
CC         Xref=Rhea:RHEA:28839, ChEBI:CHEBI:15378, ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P49279};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Fe(2+)(in) + H(+)(out) = Fe(2+)(out) + H(+)(in);
CC         Xref=Rhea:RHEA:29439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000250|UniProtKB:P49279};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H(+)(out) + Mn(2+)(in) = H(+)(in) + Mn(2+)(out);
CC         Xref=Rhea:RHEA:73063, ChEBI:CHEBI:15378, ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P49279};
CC   -!- SUBCELLULAR LOCATION: Late endosome membrane
CC       {ECO:0000250|UniProtKB:P49279}; Multi-pass membrane protein
CC       {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:P49279}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the NRAMP family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB49833.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; BC100653; AAI00654.1; -; mRNA.
DR   EMBL; U53822; AAB49833.1; ALT_INIT; Genomic_DNA.
DR   RefSeq; NP_001026828.1; NM_001031658.1.
DR   AlphaFoldDB; P70553; -.
DR   SMR; P70553; -.
DR   STRING; 10116.ENSRNOP00000054282; -.
DR   GlyCosmos; P70553; 2 sites, No reported glycans.
DR   GlyGen; P70553; 2 sites.
DR   PhosphoSitePlus; P70553; -.
DR   PaxDb; 10116-ENSRNOP00000054282; -.
DR   GeneID; 316519; -.
DR   KEGG; rno:316519; -.
DR   UCSC; RGD:1601463; rat.
DR   AGR; RGD:1601463; -.
DR   CTD; 6556; -.
DR   RGD; 1601463; Slc11a1.
DR   eggNOG; KOG1291; Eukaryota.
DR   InParanoid; P70553; -.
DR   OrthoDB; 1093299at2759; -.
DR   Reactome; R-RNO-1222556; ROS and RNS production in phagocytes.
DR   Reactome; R-RNO-425410; Metal ion SLC transporters.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-6803544; Ion influx/efflux at host-pathogen interface.
DR   PRO; PR:P70553; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR   GO; GO:0005770; C:late endosome; ISO:RGD.
DR   GO; GO:0031902; C:late endosome membrane; ISO:RGD.
DR   GO; GO:0005765; C:lysosomal membrane; ISO:RGD.
DR   GO; GO:0005764; C:lysosome; ISO:RGD.
DR   GO; GO:0030670; C:phagocytic vesicle membrane; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0070821; C:tertiary granule membrane; ISO:RGD.
DR   GO; GO:0015086; F:cadmium ion transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0005381; F:iron ion transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0005384; F:manganese ion transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0051139; F:metal cation:proton antiporter activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR   GO; GO:0046915; F:transition metal ion transmembrane transporter activity; ISO:RGD.
DR   GO; GO:0048002; P:antigen processing and presentation of peptide antigen; ISO:RGD.
DR   GO; GO:0070574; P:cadmium ion transmembrane transport; ISO:RGD.
DR   GO; GO:0098849; P:cellular detoxification of cadmium ion; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR   GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
DR   GO; GO:0051649; P:establishment of localization in cell; ISO:RGD.
DR   GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR   GO; GO:0006879; P:intracellular iron ion homeostasis; ISO:RGD.
DR   GO; GO:0006826; P:iron ion transport; ISS:UniProtKB.
DR   GO; GO:1903826; P:L-arginine transmembrane transport; ISO:RGD.
DR   GO; GO:0042116; P:macrophage activation; ISO:RGD.
DR   GO; GO:0006828; P:manganese ion transport; ISS:UniProtKB.
DR   GO; GO:0030001; P:metal ion transport; ISO:RGD.
DR   GO; GO:0045342; P:MHC class II biosynthetic process; ISO:RGD.
DR   GO; GO:0048255; P:mRNA stabilization; ISO:RGD.
DR   GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; ISO:RGD.
DR   GO; GO:0001818; P:negative regulation of cytokine production; ISO:RGD.
DR   GO; GO:0015707; P:nitrite transport; ISO:RGD.
DR   GO; GO:0006909; P:phagocytosis; ISO:RGD.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR   GO; GO:0002606; P:positive regulation of dendritic cell antigen processing and presentation; ISO:RGD.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR   GO; GO:0050766; P:positive regulation of phagocytosis; ISO:RGD.
DR   GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; ISO:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; ISO:RGD.
DR   GO; GO:0045730; P:respiratory burst; ISO:RGD.
DR   GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR   GO; GO:0034341; P:response to type II interferon; ISO:RGD.
DR   GO; GO:0002309; P:T cell proliferation involved in immune response; ISO:RGD.
DR   GO; GO:0007035; P:vacuolar acidification; ISO:RGD.
DR   GO; GO:0042060; P:wound healing; ISO:RGD.
DR   HAMAP; MF_00221; NRAMP; 1.
DR   InterPro; IPR001046; NRAMP_fam.
DR   NCBIfam; TIGR01197; nramp; 1.
DR   NCBIfam; NF037982; Nramp_1; 1.
DR   PANTHER; PTHR11706:SF52; NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 1; 1.
DR   PANTHER; PTHR11706; SOLUTE CARRIER PROTEIN FAMILY 11 MEMBER; 1.
DR   Pfam; PF01566; Nramp; 1.
DR   PRINTS; PR00447; NATRESASSCMP.
PE   2: Evidence at transcript level;
KW   Endosome; Glycoprotein; Ion transport; Iron; Iron transport; Lysosome;
KW   Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..507
FT                   /note="Natural resistance-associated macrophage protein 1"
FT                   /id="PRO_0000212591"
FT   TOPO_DOM        1..39
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        40..60
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        61..123
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        124..144
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        145..152
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        153..173
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        174..199
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        200..220
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        221..245
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        246..266
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        267..305
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        306..326
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        327..353
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        354..374
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        375..391
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        392..412
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        413..422
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        423..443
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        444..451
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        452..472
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        473..507
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..36
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        280
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        404
FT                   /note="T -> S (in Ref. 2; AAB49833)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        409
FT                   /note="P -> S (in Ref. 2; AAB49833)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   507 AA;  55922 MW;  0A052B5EF53D1C64 CRC64;
     MIRDKNPQRV NRPSYGSISS LPSPAPQPEP SRNTYLSEKI PIPSTEQLLW VLLWATVLGL
     LCQRLAARLG VVTGKDLGEI CHLYYPKVPR ILLWLTIELA IVGSDMQEVI GTAISFNLLS
     AGRIPLWGGV LITIVDTFFF LFLDNYGLRK LEAFFGFLVT IMALTFGYEY VVARPSQGAL
     LKGLFLPSCP GCGQPELLQA VGIVGAIIMP HNIYLHSALV KSREVDRTRR GDVREANMYF
     LTEATIALFV SFIINLFVMA VFGQAFYQQT NEEAFNICAN SSLHNYAKIF PRDNNTVSVD
     IYQGGVILGC LFGPAALYIW AVGLLAAGQS STMTGTYAGQ FVMEGFLKLR WSRFARVLLT
     RSCAILPTVL VAVFRDLRDL SGLNDLLNVL QSLLLPFAVL PILTFTSMPA VMQEFANGWL
     SKVITSCIMA LVCAINLYFV ISYLPSLPHP AYFGLVALLA IGYLGLTAYL AWTCCIAHGA
     KFLTHSSHQR FLYGLPIEEQ EGREGSG
//