NRAM2_MOUSE
ID NRAM2_MOUSE Reviewed; 568 AA.
AC P49282; O54903; Q3UFV5; Q8BJL2; Q8BWV3; Q8CFA0; Q8VCU6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Natural resistance-associated macrophage protein 2;
DE Short=NRAMP 2;
DE AltName: Full=Divalent cation transporter 1;
DE AltName: Full=Divalent metal transporter 1;
DE Short=DMT-1;
DE AltName: Full=Solute carrier family 11 member 2;
GN Name=Slc11a2; Synonyms=Dct1, Dmt1, Nramp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=7789986; DOI=10.1016/0888-7543(95)80053-o;
RA Gruenheid S., Cellier M., Vidal S., Gros P.;
RT "Identification and characterization of a second mouse Nramp gene.";
RL Genomics 25:514-525(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=DBA;
RA Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D.,
RA Andrews N.C.;
RT "Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for
RT Nramp2 in endosomal iron transport.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1148-1153(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-80 (ISOFORMS 3/4), AND ALTERNATIVE
RP SPLICING.
RC STRAIN=C57BL/6J; TISSUE=Duodenum;
RX PubMed=12209011; DOI=10.1073/pnas.192423399;
RA Hubert N., Hentze M.W.;
RT "Previously uncharacterized isoforms of divalent metal transporter (DMT)-1:
RT implications for regulation and cellular function.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:12345-12350(2002).
RN [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10361139;
RA Canonne-Hergaux F., Gruenheid S., Ponka P., Gros P.;
RT "Cellular and subcellular localization of the Nramp2 iron transporter in
RT the intestinal brush border and regulation by dietary iron.";
RL Blood 93:4406-4417(1999).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11739192; DOI=10.1182/blood.v98.13.3823;
RA Canonne-Hergaux F., Zhang A.-S., Ponka P., Gros P.;
RT "Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood
RT cells of normal and anemic mk/mk mice.";
RL Blood 98:3823-3830(2001).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15849611; DOI=10.1172/jci200524356;
RA Gunshin H., Fujiwara Y., Custodio A.O., Direnzo C., Robine S.,
RA Andrews N.C.;
RT "Slc11a2 is required for intestinal iron absorption and erythropoiesis but
RT dispensable in placenta and liver.";
RL J. Clin. Invest. 115:1258-1266(2005).
RN [10]
RP NIFEDIPINE TREATMENT.
RX PubMed=17293870; DOI=10.1038/nm1542;
RA Ludwiczek S., Theurl I., Muckenthaler M.U., Jakab M., Mair S.M., Theurl M.,
RA Kiss J., Paulmichl M., Hentze M.W., Ritter M., Weiss G.;
RT "Ca2+ channel blockers reverse iron overload by a new mechanism via
RT divalent metal transporter-1.";
RL Nat. Med. 13:448-454(2007).
RN [11]
RP UBIQUITINATION.
RX PubMed=18776082; DOI=10.1182/blood-2008-04-150953;
RA Foot N.J., Dalton H.E., Shearwin-Whyatt L.M., Dorstyn L., Tan S.S.,
RA Yang B., Kumar S.;
RT "Regulation of the divalent metal ion transporter DMT1 and iron homeostasis
RT by a ubiquitin-dependent mechanism involving Ndfips and WWP2.";
RL Blood 112:4268-4275(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564 AND SER-567, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564 AND SER-567,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556 (ISOFORM 1),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-586 (ISOFORM 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [14]
RP INTERACTION WITH ARRDC4, AND SUBCELLULAR LOCATION.
RX PubMed=27462458; DOI=10.1038/celldisc.2016.11;
RA Mackenzie K., Foot N.J., Anand S., Dalton H.E., Chaudhary N., Collins B.M.,
RA Mathivanan S., Kumar S.;
RT "Regulation of the divalent metal ion transporter via membrane budding.";
RL Cell Discov. 2:16011-16011(2016).
RN [15]
RP VARIANT MK ARG-185.
RX PubMed=9241278; DOI=10.1038/ng0897-383;
RA Fleming M.D., Trenor C.C. III, Su M.A., Foernzler D., Beier D.R.,
RA Dietrich W.F., Andrews N.C.;
RT "Microcytic anaemia mice have a mutation in Nramp2, a candidate iron
RT transporter gene.";
RL Nat. Genet. 16:383-386(1997).
CC -!- FUNCTION: May serve to import iron into the mitochondria (By
CC similarity). Important in metal transport, in particular iron. Involved
CC in apical iron uptake into duodenal enterocytes. Involved in iron
CC transport from acidified endosomes into the cytoplasm of erythroid
CC precursor cells. May play an important role in hepatic iron
CC accumulation and tissue iron distribution.
CC {ECO:0000250|UniProtKB:P49281, ECO:0000269|PubMed:11739192,
CC ECO:0000269|PubMed:15849611}.
CC -!- SUBUNIT: Forms a complex with NDFIP1 and NEDD4L, in cortical neurons,
CC in response to iron and colbalt exposure; this interaction leads to
CC ubiquitination by NEDD4L and proteasome-dependent degradation.
CC Interacts with NDFIP2. Interacts with COX2 and TOM6 at the outer
CC mitochondrion membrane (By similarity). Interacts with ARRDC1; controls
CC the incorporation of SLC11A2 into extracellular vesicles through an
CC ubiquitination-dependent mechanism (By similarity). Interacts with
CC ARRDC4; controls the incorporation of SLC11A2 into extracellular
CC vesicles through an ubiquitination-dependent mechanism
CC (PubMed:27462458). {ECO:0000250|UniProtKB:P49281,
CC ECO:0000269|PubMed:27462458}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:P49281};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P49281}.
CC Mitochondrion outer membrane {ECO:0000250|UniProtKB:P49281}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P49281}. Cell membrane
CC {ECO:0000269|PubMed:27462458}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49281}. Note=Also found in extracellular
CC vesicles different from exosomes. {ECO:0000269|PubMed:27462458}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2; Synonyms=Non-IRE;
CC IsoId=P49282-1; Sequence=Displayed;
CC Name=1; Synonyms=IRE;
CC IsoId=P49282-2; Sequence=VSP_003596;
CC Name=3; Synonyms=1A-IRE;
CC IsoId=P49282-3; Sequence=VSP_038145, VSP_003596;
CC Name=4; Synonyms=1A-Non-IRE;
CC IsoId=P49282-4; Sequence=VSP_038145;
CC -!- TISSUE SPECIFICITY: Isoform 2 is abundantly expressed in erythroid
CC precursor cells (at protein level). Expressed at low levels in most
CC tissues analyzed. Expressed at low levels in small intestine and at
CC higher levels in kidney. {ECO:0000269|PubMed:10361139,
CC ECO:0000269|PubMed:11739192}.
CC -!- INDUCTION: [Isoform 1]: Up-regulated under iron-depletion conditions in
CC the proximal portion of the duodenum where it is abundantly expressed
CC in the brush border of absorptive epithelial cells (at protein level).
CC {ECO:0000269|PubMed:10361139}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P49281}.
CC -!- PTM: Ubiquitinated by WWP2. {ECO:0000269|PubMed:18776082}.
CC -!- DISEASE: Note=Defects in Slc11a2 are the cause of microcytic anemia
CC (mk). Homozygous mk/mk mice have hypochromic microcytic anemia due to
CC severe defects in intestinal iron absorption and erythroid iron
CC utilization.
CC -!- DISRUPTION PHENOTYPE: Mice display no apparent anatomical
CC abnormalities. They are however anemic, show progressive postnatal
CC growth retardation, and at birth have elevated liver iron stores
CC compared with wild-type littermates. None survive for more than 7 days.
CC Heterozygotes appear normal, showing no significant hematological
CC abnormalities. However, by 8 weeks, their liver iron content is lower
CC than in wild-type littermates. {ECO:0000269|PubMed:15849611}.
CC -!- MISCELLANEOUS: Nifedipine induces duodenal iron accumulation and
CC mobilizes iron from the liver of iron-overloaded mice.
CC -!- SIMILARITY: Belongs to the NRAMP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD38518.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L33415; AAC42051.1; -; mRNA.
DR EMBL; AF029758; AAC24496.1; -; mRNA.
DR EMBL; AK049856; BAC33960.1; -; mRNA.
DR EMBL; AK083478; BAC38930.1; -; mRNA.
DR EMBL; AK148276; BAE28454.1; -; mRNA.
DR EMBL; CH466550; EDL04090.1; -; Genomic_DNA.
DR EMBL; BC019137; AAH19137.1; -; mRNA.
DR EMBL; AJ493663; CAD38518.1; ALT_FRAME; mRNA.
DR CCDS; CCDS37211.1; -. [P49282-1]
DR CCDS; CCDS49733.1; -. [P49282-2]
DR PIR; A56852; A56852.
DR RefSeq; NP_001139633.1; NM_001146161.1. [P49282-2]
DR RefSeq; NP_032758.2; NM_008732.2. [P49282-1]
DR RefSeq; XP_006520640.1; XM_006520577.3. [P49282-1]
DR RefSeq; XP_006520641.1; XM_006520578.3. [P49282-1]
DR RefSeq; XP_011243789.1; XM_011245487.2. [P49282-4]
DR AlphaFoldDB; P49282; -.
DR SMR; P49282; -.
DR STRING; 10090.ENSMUSP00000023774; -.
DR GlyGen; P49282; 2 sites.
DR iPTMnet; P49282; -.
DR PhosphoSitePlus; P49282; -.
DR SwissPalm; P49282; -.
DR EPD; P49282; -.
DR jPOST; P49282; -.
DR MaxQB; P49282; -.
DR PaxDb; P49282; -.
DR PeptideAtlas; P49282; -.
DR PRIDE; P49282; -.
DR ProteomicsDB; 253101; -. [P49282-1]
DR ProteomicsDB; 253102; -. [P49282-2]
DR ProteomicsDB; 253103; -. [P49282-3]
DR ProteomicsDB; 253104; -. [P49282-4]
DR Antibodypedia; 26282; 377 antibodies from 31 providers.
DR DNASU; 18174; -.
DR Ensembl; ENSMUST00000023774; ENSMUSP00000023774; ENSMUSG00000023030. [P49282-1]
DR Ensembl; ENSMUST00000138843; ENSMUSP00000116463; ENSMUSG00000023030. [P49282-2]
DR GeneID; 18174; -.
DR KEGG; mmu:18174; -.
DR UCSC; uc007xrc.2; mouse. [P49282-1]
DR UCSC; uc007xrd.2; mouse. [P49282-2]
DR CTD; 4891; -.
DR MGI; MGI:1345279; Slc11a2.
DR VEuPathDB; HostDB:ENSMUSG00000023030; -.
DR eggNOG; KOG1291; Eukaryota.
DR GeneTree; ENSGT00940000155330; -.
DR HOGENOM; CLU_020088_5_2_1; -.
DR InParanoid; P49282; -.
DR OMA; IATFVNS; -.
DR OrthoDB; 666470at2759; -.
DR PhylomeDB; P49282; -.
DR TreeFam; TF315185; -.
DR Reactome; R-MMU-425410; Metal ion SLC transporters.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 18174; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Slc11a2; mouse.
DR PRO; PR:P49282; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P49282; protein.
DR Bgee; ENSMUSG00000023030; Expressed in epithelium of small intestine and 242 other tissues.
DR ExpressionAtlas; P49282; baseline and differential.
DR Genevisible; P49282; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0045178; C:basal part of cell; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; IGI:BHF-UCL.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:1903561; C:extracellular vesicle; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0070826; C:paraferritin complex; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI.
DR GO; GO:0005773; C:vacuole; ISO:MGI.
DR GO; GO:0046870; F:cadmium ion binding; ISS:UniProtKB.
DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0050897; F:cobalt ion binding; ISO:MGI.
DR GO; GO:0015087; F:cobalt ion transmembrane transporter activity; IDA:MGI.
DR GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0022890; F:inorganic cation transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; ISO:MGI.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015094; F:lead ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0030145; F:manganese ion binding; ISO:MGI.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0016151; F:nickel cation binding; ISO:MGI.
DR GO; GO:0015099; F:nickel cation transmembrane transporter activity; ISO:MGI.
DR GO; GO:1905394; F:retromer complex binding; ISO:MGI.
DR GO; GO:0015295; F:solute:proton symporter activity; ISO:MGI.
DR GO; GO:0046915; F:transition metal ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015100; F:vanadium ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0070574; P:cadmium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI.
DR GO; GO:0006824; P:cobalt ion transport; IDA:MGI.
DR GO; GO:0098705; P:copper ion import across plasma membrane; ISO:MGI.
DR GO; GO:0006825; P:copper ion transport; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0048821; P:erythrocyte development; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:MGI.
DR GO; GO:0033212; P:iron import into cell; IMP:MGI.
DR GO; GO:0034755; P:iron ion transmembrane transport; ISO:MGI.
DR GO; GO:0006826; P:iron ion transport; IMP:MGI.
DR GO; GO:0015692; P:lead ion transport; ISO:MGI.
DR GO; GO:0007611; P:learning or memory; IMP:MGI.
DR GO; GO:0006828; P:manganese ion transport; ISO:MGI.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; IMP:MGI.
DR GO; GO:0015675; P:nickel cation transport; ISO:MGI.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; IMP:MGI.
DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; IMP:MGI.
DR GO; GO:0001666; P:response to hypoxia; IBA:GO_Central.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; ISO:MGI.
DR GO; GO:0000041; P:transition metal ion transport; ISO:MGI.
DR GO; GO:0015676; P:vanadium ion transport; ISO:MGI.
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 Alternative splicing; Cell membrane; Disease variant; Endosome;
KW Glycoprotein; Ion transport; Iron; Iron transport; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..568
FT /note="Natural resistance-associated macrophage protein 2"
FT /id="PRO_0000212595"
FT TOPO_DOM 1..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..179
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..255
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 323..360
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..408
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 430..440
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..506
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 507..527
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 528..568
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT CARBOHYD 336
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1
FT /note="M -> MGKKQPRAAAAAPNCELKSYSKSTDPQVSTM (in isoform 3
FT and isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_038145"
FT VAR_SEQ 544..568
FT /note="YRLGLTAQPELYLLNTVDADSVVSR -> VSISKVLLSEDTSGGNIK (in
FT isoform 1 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT /id="VSP_003596"
FT VARIANT 185
FT /note="G -> R (in microcytic anemia)"
FT /evidence="ECO:0000269|PubMed:9241278"
FT CONFLICT 6
FT /note="K -> E (in Ref. 3; BAE28454 and 6; CAD38518)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="R -> S (in Ref. 2; AAC24496)"
FT /evidence="ECO:0000305"
FT CONFLICT 69..70
FT /note="Missing (in Ref. 6; CAD38518)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="P -> R (in Ref. 3; BAC38930)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="L -> V (in Ref. 1; AAC42051)"
FT /evidence="ECO:0000305"
FT MOD_RES P49282-2:556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES P49282-3:586
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 568 AA; 62368 MW; 603AAF697AAD3C74 CRC64;
MVLDPKEKMP DDGASGDHGD SASLGAINPA YSNSSLPHST GDSEEPFTTY FDEKIPIPEE
EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA GFKLLWVLLL ATIVGLLLQR
LAARLGVVTG LHLAEVCHRQ YPKVPRIILW LMVELAIIGS DMQEVIGSAI AINLLSAGRV
PLWGGVLITI ADTFVFLFLD KYGLRKLEAF FGFLITIMAL TFGYEYITVK PSQSQVLRGM
FVPSCPGCRT PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES
CIALFVSFII NVFVVSVFAE AFFEKTNKQV VEVCKNNSSP HADLFPSDNS TLAVDIYKGG
VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG FLNLKWSRFA RVILTRSIAI
IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL PFALIPILTF TSLRPVMSEF SNGIGWRIAG
GILVLIVCSI NMYFVVVYVQ ELGHVALYVV AAVVSVAYLT FVFYLGWQCL IALGLSFLDC
GRSYRLGLTA QPELYLLNTV DADSVVSR
