NRAM2_RAT
ID NRAM2_RAT Reviewed; 568 AA.
AC O54902; O35172;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 167.
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 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 [MRNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=9242408; DOI=10.1038/41343;
RA Gunshin H., Mackenzie B., Berger U.V., Gunshin Y., Romero M.F., Boron W.F.,
RA Nussberger S., Gollan J.L., Hediger M.A.;
RT "Cloning and characterization of a mammalian proton-coupled metal-ion
RT transporter.";
RL Nature 388:482-488(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RA Fleming M.D., Romano M.A., Su M.A., Garrick L.M., Garrick M.D.,
RA Andrews N.C.;
RT "Rat natural resistance associated macrophage protein-2 (Nramp2), C-
RT terminal exon alternative splice variant.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-556 (ISOFORM 1), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP VARIANT B ARG-185.
RX PubMed=9448300; DOI=10.1073/pnas.95.3.1148;
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).
CC -!- FUNCTION: May serve to import iron into the mitochondria (By
CC similarity). Important in metal transport, in particular iron. Can also
CC transport zinc, manganese, cobalt, cadmium, copper, nickel and lead.
CC Involved in apical iron uptake into duodenal enterocytes. Involved in
CC iron 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:9242408}.
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. Interacts with ARRDC1; controls the
CC incorporation of SLC11A2 into extracellular vesicles through an
CC ubiquitination-dependent mechanism. Interacts with ARRDC4; controls the
CC incorporation of SLC11A2 into extracellular vesicles through an
CC ubiquitination-dependent mechanism. {ECO:0000250|UniProtKB:P49281,
CC ECO:0000250|UniProtKB:P49282}.
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:0000250|UniProtKB:P49281}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P49281}. Note=Also found in extracellular
CC vesicles different from exosomes. {ECO:0000250|UniProtKB:P49281}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2; Synonyms=Non-IRE;
CC IsoId=O54902-1; Sequence=Displayed;
CC Name=1; Synonyms=IRE;
CC IsoId=O54902-2; Sequence=VSP_003597;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Ubiquitinated by WWP2. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P49281}.
CC -!- DISEASE: Note=Defects in Slc11a2 are the cause of microcytic anemia
CC (Belgrade or b). Homozygous b/b rats have hypochromic microcytic anemia
CC due to severe defects in intestinal iron absorption and erythroid iron
CC utilization.
CC -!- SIMILARITY: Belongs to the NRAMP family. {ECO:0000305}.
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DR EMBL; AF008439; AAC53319.1; -; mRNA.
DR EMBL; AF029757; AAC24495.1; -; mRNA.
DR RefSeq; NP_037305.2; NM_013173.2.
DR AlphaFoldDB; O54902; -.
DR SMR; O54902; -.
DR BioGRID; 247744; 1.
DR STRING; 10116.ENSRNOP00000026531; -.
DR TCDB; 2.A.55.2.2; the metal ion (mn(2+)-iron) transporter (nramp) family.
DR GlyGen; O54902; 2 sites.
DR iPTMnet; O54902; -.
DR PhosphoSitePlus; O54902; -.
DR jPOST; O54902; -.
DR PaxDb; O54902; -.
DR GeneID; 25715; -.
DR KEGG; rno:25715; -.
DR UCSC; RGD:3684; rat. [O54902-1]
DR CTD; 4891; -.
DR RGD; 3684; Slc11a2.
DR eggNOG; KOG1291; Eukaryota.
DR InParanoid; O54902; -.
DR OrthoDB; 666470at2759; -.
DR PhylomeDB; O54902; -.
DR Reactome; R-RNO-425410; Metal ion SLC transporters.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR PRO; PR:O54902; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; O54902; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0045178; C:basal part of cell; ISO:RGD.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:1903561; C:extracellular vesicle; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISO:RGD.
DR GO; GO:0031902; C:late endosome membrane; IDA:RGD.
DR GO; GO:0005765; C:lysosomal membrane; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0070826; C:paraferritin complex; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0005773; C:vacuole; ISO:RGD.
DR GO; GO:0046870; F:cadmium ion binding; IDA:RGD.
DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0050897; F:cobalt ion binding; IDA:RGD.
DR GO; GO:0015087; F:cobalt ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0005507; F:copper ion binding; IDA:RGD.
DR GO; GO:0005375; F:copper ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IMP:RGD.
DR GO; GO:0022890; F:inorganic cation transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005506; F:iron ion binding; IDA:RGD.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015094; F:lead ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0030145; F:manganese ion binding; IDA:RGD.
DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IDA:RGD.
DR GO; GO:0016151; F:nickel cation binding; IDA:RGD.
DR GO; GO:0015099; F:nickel cation transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015295; F:solute:proton symporter activity; ISO:RGD.
DR GO; GO:0046915; F:transition metal ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015100; F:vanadium ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0070574; P:cadmium ion transmembrane transport; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071281; P:cellular response to iron ion; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0006824; P:cobalt ion transport; ISO:RGD.
DR GO; GO:0098705; P:copper ion import across plasma membrane; IMP:RGD.
DR GO; GO:0006825; P:copper ion transport; ISO:RGD.
DR GO; GO:0048813; P:dendrite morphogenesis; ISO:RGD.
DR GO; GO:0048821; P:erythrocyte development; ISO:RGD.
DR GO; GO:0006783; P:heme biosynthetic process; ISO:RGD.
DR GO; GO:0033212; P:iron import into cell; ISO:RGD.
DR GO; GO:0034755; P:iron ion transmembrane transport; ISO:RGD.
DR GO; GO:0006826; P:iron ion transport; IMP:RGD.
DR GO; GO:0015692; P:lead ion transport; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0006828; P:manganese ion transport; ISO:RGD.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISO:RGD.
DR GO; GO:0015675; P:nickel cation transport; ISO:RGD.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; ISO:RGD.
DR GO; GO:0006778; P:porphyrin-containing compound metabolic process; ISO:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0010042; P:response to manganese ion; IMP:RGD.
DR GO; GO:0000041; P:transition metal ion transport; IDA:RGD.
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_0000212596"
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:0000250|UniProtKB:P49282"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49282"
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 544..568
FT /note="YHLGLTARPEIYLLNTVDAVSLVSR -> VSISKVLLSEDTSGGNTK (in
FT isoform 1)"
FT /evidence="ECO:0000303|PubMed:9242408"
FT /id="VSP_003597"
FT VARIANT 185
FT /note="G -> R (in microcytic anemia)"
FT /evidence="ECO:0000269|PubMed:9448300"
FT MOD_RES O54902-2:556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 568 AA; 62277 MW; C7B77E964E741F4D CRC64;
MVLDPEEKIP DDGASGDHGD SASLGAINPA YSNSSLPHST GDSEEPFTTY FDEKIPIPEE
EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA GFKLLWVLLL ATIVGLLLQR
LAARLGVVTG LHLAEVCHRQ YPKVPRIILW LMVELAIIGS DMQEVIGSAI AINLLSAGRV
PLYGGVLITI ADTFVFLFLD KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLRGM
FVPSCSGCHT PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES
CIALFVSFII NVFVVSVFAE AFFEKTNEQV VEVCRNSSSP HADLFPNDNS TLAVDIYKGG
VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG FLNLKWSRFA RVILTRSIAI
IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL PFALIPILTF TSLRPVMSEF SNGIGWRIAG
GILVLLVCSI NMYFVVVYVQ ELGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGLSFLDC
GRSYHLGLTA RPEIYLLNTV DAVSLVSR
