Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Natural resistance-associated macrophage protein 2

Gene

Slc11a2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May serve to import iron into the mitochondria (By similarity). Important in metal transport, in particular iron. Involved in apical iron uptake into duodenal enterocytes. Involved in iron transport from acidified endosomes into the cytoplasm of erythroid precursor cells. May play an important role in hepatic iron accumulation and tissue iron distribution.By similarity2 Publications

Miscellaneous

Nifedipine induces duodenal iron accumulation and mobilizes iron from the liver of iron-overloaded mice.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processIon transport, Iron transport, Transport
LigandIron

Enzyme and pathway databases

ReactomeiR-MMU-425410 Metal ion SLC transporters
R-MMU-917937 Iron uptake and transport

Names & Taxonomyi

Protein namesi
Recommended name:
Natural resistance-associated macrophage protein 2
Short name:
NRAMP 2
Alternative name(s):
Divalent cation transporter 1
Divalent metal transporter 1
Short name:
DMT-1
Solute carrier family 11 member 2
Gene namesi
Name:Slc11a2
Synonyms:Dct1, Dmt1, Nramp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:1345279 Slc11a2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 69CytoplasmicSequence analysisAdd BLAST69
Transmembranei70 – 90HelicalSequence analysisAdd BLAST21
Topological domaini91 – 95ExtracellularSequence analysis5
Transmembranei96 – 117HelicalSequence analysisAdd BLAST22
Topological domaini118 – 154CytoplasmicSequence analysisAdd BLAST37
Transmembranei155 – 175HelicalSequence analysisAdd BLAST21
Topological domaini176 – 179ExtracellularSequence analysis4
Transmembranei180 – 194HelicalSequence analysisAdd BLAST15
Topological domaini195 – 208CytoplasmicSequence analysisAdd BLAST14
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 255ExtracellularSequence analysisAdd BLAST26
Transmembranei256 – 276HelicalSequence analysisAdd BLAST21
Topological domaini277 – 301CytoplasmicSequence analysisAdd BLAST25
Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
Topological domaini323 – 360ExtracellularSequence analysisAdd BLAST38
Transmembranei361 – 381HelicalSequence analysisAdd BLAST21
Topological domaini382 – 408CytoplasmicSequence analysisAdd BLAST27
Transmembranei409 – 429HelicalSequence analysisAdd BLAST21
Topological domaini430 – 440ExtracellularSequence analysisAdd BLAST11
Transmembranei441 – 461HelicalSequence analysisAdd BLAST21
Topological domaini462 – 482CytoplasmicSequence analysisAdd BLAST21
Transmembranei483 – 503HelicalSequence analysisAdd BLAST21
Topological domaini504 – 506ExtracellularSequence analysis3
Transmembranei507 – 527HelicalSequence analysisAdd BLAST21
Topological domaini528 – 568CytoplasmicSequence analysisAdd BLAST41

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Slc11a2 are the cause of microcytic anemia (mk). Homozygous mk/mk mice have hypochromic microcytic anemia due to severe defects in intestinal iron absorption and erythroid iron utilization.

Disruption phenotypei

Mice display no apparent anatomical abnormalities. They are however anemic, show progressive postnatal growth retardation, and at birth have elevated liver iron stores compared with wild-type littermates. None survive for more than 7 days. Heterozygotes appear normal, showing no significant hematological abnormalities. However, by 8 weeks, their liver iron content is lower than in wild-type littermates.1 Publication

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002125951 – 568Natural resistance-associated macrophage protein 2Add BLAST568

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi336N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi349N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei564PhosphoserineCombined sources1
Modified residuei567PhosphoserineCombined sources1
Isoform 1 (identifier: P49282-2)
Modified residuei556PhosphoserineCombined sources1
Isoform 3 (identifier: P49282-3)
Modified residuei586PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.By similarity
Ubiquitinated by WWP2.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49282
MaxQBiP49282
PaxDbiP49282
PeptideAtlasiP49282
PRIDEiP49282

PTM databases

iPTMnetiP49282
PhosphoSitePlusiP49282
SwissPalmiP49282

Expressioni

Tissue specificityi

Isoform 2 is abundantly expressed in erythroid precursor cells (at protein level). Expressed at low levels in most tissues analyzed. Expressed at low levels in small intestine and at higher levels in kidney.2 Publications

Inductioni

Isoform 1 is up-regulated under iron-depletion conditions in the proximal portion of the duodenum where it is abundantly expressed in the brush border of absorptive epithelial cells (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000023030 Expressed in 267 organ(s), highest expression level in cardiac ventricle
ExpressionAtlasiP49282 baseline and differential
GenevisibleiP49282 MM

Interactioni

Subunit structurei

Forms a complex with NDFIP1 and NEDD4L, in cortical neurons, in response to iron and colbalt exposure; this interaction leads to ubiquitination by NEDD4L and proteasome-dependent degradation. Interacts with NDFIP2. Interacts with COX2 and TOM6 at the outer mitochondrion membrane (By similarity). Interacts with ARRDC1; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity). Interacts with ARRDC4; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458).By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000023774

Structurei

3D structure databases

ProteinModelPortaliP49282
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NRAMP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1291 Eukaryota
COG1914 LUCA
GeneTreeiENSGT00390000006526
HOVERGENiHBG052665
InParanoidiP49282
KOiK21398
OMAiSLRPVMN
OrthoDBiEOG091G05M9
PhylomeDBiP49282
TreeFamiTF315185

Family and domain databases

HAMAPiMF_00221 NRAMP, 1 hit
InterProiView protein in InterPro
IPR001046 NRAMP_fam
PANTHERiPTHR11706 PTHR11706, 1 hit
PfamiView protein in Pfam
PF01566 Nramp, 1 hit
PRINTSiPR00447 NATRESASSCMP
TIGRFAMsiTIGR01197 nramp, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.iShow all

Isoform 2 (identifier: P49282-1) [UniParc]FASTAAdd to basket
Also known as: Non-IRE

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MVLDPKEKMP DDGASGDHGD SASLGAINPA YSNSSLPHST GDSEEPFTTY
60 70 80 90 100
FDEKIPIPEE EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA
110 120 130 140 150
GFKLLWVLLL ATIVGLLLQR LAARLGVVTG LHLAEVCHRQ YPKVPRIILW
160 170 180 190 200
LMVELAIIGS DMQEVIGSAI AINLLSAGRV PLWGGVLITI ADTFVFLFLD
210 220 230 240 250
KYGLRKLEAF FGFLITIMAL TFGYEYITVK PSQSQVLRGM FVPSCPGCRT
260 270 280 290 300
PQVEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRANKQEVR EANKYFFIES
310 320 330 340 350
CIALFVSFII NVFVVSVFAE AFFEKTNKQV VEVCKNNSSP HADLFPSDNS
360 370 380 390 400
TLAVDIYKGG VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG
410 420 430 440 450
FLNLKWSRFA RVILTRSIAI IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL
460 470 480 490 500
PFALIPILTF TSLRPVMSEF SNGIGWRIAG GILVLIVCSI NMYFVVVYVQ
510 520 530 540 550
ELGHVALYVV AAVVSVAYLT FVFYLGWQCL IALGLSFLDC GRSYRLGLTA
560
QPELYLLNTV DADSVVSR
Length:568
Mass (Da):62,368
Last modified:September 22, 2009 - v2
Checksum:i603AAF697AAD3C74
GO
Isoform 1 (identifier: P49282-2) [UniParc]FASTAAdd to basket
Also known as: IRE

The sequence of this isoform differs from the canonical sequence as follows:
     544-568: YRLGLTAQPELYLLNTVDADSVVSR → VSISKVLLSEDTSGGNIK

Show »
Length:561
Mass (Da):61,421
Checksum:iD2FAA52B8F73FFBC
GO
Isoform 3 (identifier: P49282-3) [UniParc]FASTAAdd to basket
Also known as: 1A-IRE

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGKKQPRAAAAAPNCELKSYSKSTDPQVSTM
     544-568: YRLGLTAQPELYLLNTVDADSVVSR → VSISKVLLSEDTSGGNIK

Note: No experimental confirmation available.Combined sources
Show »
Length:591
Mass (Da):64,568
Checksum:iF8119C955315B2F6
GO
Isoform 4 (identifier: P49282-4) [UniParc]FASTAAdd to basket
Also known as: 1A-Non-IRE

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGKKQPRAAAAAPNCELKSYSKSTDPQVSTM

Note: No experimental confirmation available.
Show »
Length:598
Mass (Da):65,515
Checksum:iED4B62ED656BAEBE
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z314D3Z314_MOUSE
Natural resistance-associated macro...
Slc11a2
170Annotation score:
F6ZM31F6ZM31_MOUSE
Natural resistance-associated macro...
Slc11a2
220Annotation score:
D3Z0R6D3Z0R6_MOUSE
Natural resistance-associated macro...
Slc11a2
110Annotation score:
D3YXP3D3YXP3_MOUSE
Natural resistance-associated macro...
Slc11a2
50Annotation score:
D6RGP0D6RGP0_MOUSE
Natural resistance-associated macro...
Slc11a2
68Annotation score:

Sequence cautioni

The sequence CAD38518 differs from that shown. Reason: Frameshift at position 69.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6K → E in BAE28454 (PubMed:16141072).Curated1
Sequence conflicti6K → E in CAD38518 (PubMed:12209011).Curated1
Sequence conflicti68R → S in AAC24496 (Ref. 2) Curated1
Sequence conflicti69 – 70Missing in CAD38518 (PubMed:12209011).Curated2
Sequence conflicti142P → R in BAC38930 (PubMed:16141072).Curated1
Sequence conflicti182L → V in AAC42051 (PubMed:7789986).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti185G → R in microcytic anemia. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0381451M → MGKKQPRAAAAAPNCELKSY SKSTDPQVSTM in isoform 3 and isoform 4. Curated1
Alternative sequenceiVSP_003596544 – 568YRLGL…SVVSR → VSISKVLLSEDTSGGNIK in isoform 1 and isoform 3. 2 PublicationsAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33415 mRNA Translation: AAC42051.1
AF029758 mRNA Translation: AAC24496.1
AK049856 mRNA Translation: BAC33960.1
AK083478 mRNA Translation: BAC38930.1
AK148276 mRNA Translation: BAE28454.1
CH466550 Genomic DNA Translation: EDL04090.1
BC019137 mRNA Translation: AAH19137.1
AJ493663 mRNA Translation: CAD38518.1 Frameshift.
CCDSiCCDS37211.1 [P49282-1]
CCDS49733.1 [P49282-2]
PIRiA56852
RefSeqiNP_001139633.1, NM_001146161.1 [P49282-2]
NP_032758.2, NM_008732.2 [P49282-1]
XP_006520640.1, XM_006520577.3 [P49282-1]
XP_006520641.1, XM_006520578.3 [P49282-1]
XP_011243789.1, XM_011245487.2 [P49282-4]
UniGeneiMm.234608

Genome annotation databases

EnsembliENSMUST00000023774; ENSMUSP00000023774; ENSMUSG00000023030 [P49282-1]
ENSMUST00000138843; ENSMUSP00000116463; ENSMUSG00000023030 [P49282-2]
GeneIDi18174
KEGGimmu:18174
UCSCiuc007xrc.2 mouse [P49282-1]
uc007xrd.2 mouse [P49282-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNRAM2_MOUSE
AccessioniPrimary (citable) accession number: P49282
Secondary accession number(s): O54903
, Q3UFV5, Q8BJL2, Q8BWV3, Q8CFA0, Q8VCU6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 22, 2009
Last modified: September 12, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again