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Protein

Natural resistance-associated macrophage protein 2

Gene

SLC11A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. 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. May serve to import iron into the mitochondria.4 Publications

pH dependencei

Optimum pH is 5.5-6.5 for Fe2+ uptake.1 Publication

GO - Molecular functioni

  1. cadmium ion binding Source: Ensembl
  2. cadmium ion transmembrane transporter activity Source: BHF-UCL
  3. cobalt ion binding Source: Ensembl
  4. cobalt ion transmembrane transporter activity Source: UniProtKB
  5. copper ion binding Source: Ensembl
  6. copper ion transmembrane transporter activity Source: BHF-UCL
  7. ferrous iron transmembrane transporter activity Source: BHF-UCL
  8. hydrogen ion transmembrane transporter activity Source: Ensembl
  9. inorganic cation transmembrane transporter activity Source: UniProtKB
  10. iron ion binding Source: Ensembl
  11. lead ion transmembrane transporter activity Source: BHF-UCL
  12. manganese ion binding Source: Ensembl
  13. manganese ion transmembrane transporter activity Source: BHF-UCL
  14. nickel cation binding Source: Ensembl
  15. nickel cation transmembrane transporter activity Source: UniProtKB
  16. solute:proton symporter activity Source: UniProtKB
  17. vanadium ion transmembrane transporter activity Source: UniProtKB
  18. zinc ion binding Source: Ensembl
  19. zinc ion transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. cadmium ion transmembrane transport Source: BHF-UCL
  3. cation transmembrane transport Source: GOC
  4. cellular copper ion homeostasis Source: Ensembl
  5. cellular iron ion homeostasis Source: Reactome
  6. cellular response to hypoxia Source: Ensembl
  7. cellular response to iron ion Source: Ensembl
  8. cellular response to oxidative stress Source: UniProtKB
  9. cellular response to tumor necrosis factor Source: Ensembl
  10. cobalt ion transport Source: UniProtKB
  11. copper ion import into cell Source: Ensembl
  12. copper ion transmembrane transport Source: GOC
  13. copper ion transport Source: BHF-UCL
  14. dendrite morphogenesis Source: Ensembl
  15. detection of oxygen Source: UniProtKB
  16. erythrocyte development Source: Ensembl
  17. ferrous iron import Source: UniProtKB
  18. ferrous iron transport Source: BHF-UCL
  19. heme biosynthetic process Source: Ensembl
  20. lead ion transport Source: BHF-UCL
  21. learning or memory Source: Ensembl
  22. manganese ion transmembrane transport Source: GOC
  23. manganese ion transport Source: BHF-UCL
  24. multicellular organismal iron ion homeostasis Source: BHF-UCL
  25. nickel cation transmembrane transport Source: GOC
  26. nickel cation transport Source: UniProtKB
  27. response to cadmium ion Source: Ensembl
  28. response to hypoxia Source: UniProtKB
  29. response to iron ion Source: UniProtKB
  30. response to lead ion Source: Ensembl
  31. response to manganese ion Source: Ensembl
  32. transmembrane transport Source: Reactome
  33. vanadium ion transport Source: GOC
  34. zinc ion transmembrane transport Source: GOC
Complete GO annotation...

Keywords - Biological processi

Ion transport, Iron transport, Transport

Keywords - Ligandi

Iron

Enzyme and pathway databases

ReactomeiREACT_20547. Metal ion SLC transporters.
REACT_25060. Iron uptake and transport.

Protein family/group databases

TCDBi2.A.55.2.1. the metal ion (mn(2+)-iron) transporter (nramp) family.

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
ORF Names:OK/SW-cl.20
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:10908. SLC11A2.

Subcellular locationi

Isoform 2 : Cell membrane 2 Publications; Multi-pass membrane protein Curated. Early endosome 1 Publication
Endosome membrane 3 Publications; Multi-pass membrane protein 1 Publication. Mitochondrion outer membrane 1 Publication; Multi-pass membrane protein. Cell membrane 3 Publications; Multi-pass membrane protein Curated

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6969CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei70 – 9021HelicalSequence AnalysisAdd
BLAST
Topological domaini91 – 966ExtracellularSequence Analysis
Transmembranei97 – 11721HelicalSequence AnalysisAdd
BLAST
Topological domaini118 – 15437CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei155 – 17521HelicalSequence AnalysisAdd
BLAST
Topological domaini176 – 1794ExtracellularSequence Analysis
Transmembranei180 – 20021HelicalSequence AnalysisAdd
BLAST
Topological domaini201 – 2088CytoplasmicSequence Analysis
Transmembranei209 – 22921HelicalSequence AnalysisAdd
BLAST
Topological domaini230 – 25526ExtracellularSequence AnalysisAdd
BLAST
Transmembranei256 – 27621HelicalSequence AnalysisAdd
BLAST
Topological domaini277 – 30125CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei302 – 32221HelicalSequence AnalysisAdd
BLAST
Topological domaini323 – 36038ExtracellularSequence AnalysisAdd
BLAST
Transmembranei361 – 38121HelicalSequence AnalysisAdd
BLAST
Topological domaini382 – 40827CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei409 – 42921HelicalSequence AnalysisAdd
BLAST
Topological domaini430 – 44011ExtracellularSequence AnalysisAdd
BLAST
Transmembranei441 – 46121HelicalSequence AnalysisAdd
BLAST
Topological domaini462 – 48221CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei483 – 50321HelicalSequence AnalysisAdd
BLAST
Topological domaini504 – 5063ExtracellularSequence Analysis
Transmembranei507 – 52721HelicalSequence AnalysisAdd
BLAST
Topological domaini528 – 56841CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical part of cell Source: UniProtKB
  2. apical plasma membrane Source: UniProtKB
  3. basal part of cell Source: UniProtKB
  4. brush border Source: Ensembl
  5. cell surface Source: UniProtKB
  6. cytoplasm Source: BHF-UCL
  7. cytoplasmic vesicle Source: UniProtKB
  8. early endosome Source: UniProtKB
  9. integral component of plasma membrane Source: Ensembl
  10. late endosome Source: UniProtKB
  11. late endosome membrane Source: BHF-UCL
  12. lysosomal membrane Source: UniProtKB
  13. lysosome Source: UniProtKB
  14. membrane Source: UniProtKB
  15. mitochondrial outer membrane Source: UniProtKB-SubCell
  16. nucleus Source: UniProtKB
  17. paraferritin complex Source: UniProtKB
  18. perinuclear region of cytoplasm Source: BHF-UCL
  19. plasma membrane Source: UniProtKB
  20. recycling endosome Source: UniProtKB
  21. trans-Golgi network Source: UniProtKB
  22. vacuole Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Anemia, hypochromic microcytic, with iron overload 1 (AHMIO1)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size. The disorder is due to an error of iron metabolism that results in high serum iron, massive hepatic iron deposition, and absence of sideroblasts and stainable bone marrow iron store. Despite adequate transferrin-iron complex, delivery of iron to the erythroid bone marrow is apparently insufficient for the demands of hemoglobin synthesis.

See also OMIM:206100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti114 – 1141Missing in AHMIO1. 1 Publication
VAR_033011
Natural varianti212 – 2121G → V in AHMIO1. 1 Publication
VAR_033012
Natural varianti399 – 3991E → D in AHMIO1; increased skipping of exon 12. 1 Publication
VAR_033013
Natural varianti416 – 4161R → C in AHMIO1. 1 Publication
VAR_033014

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi86 – 861D → A: Abolishes ion transport across the cell membrane. 1 Publication
Mutagenesisi89 – 891N → A: Decreases affinity for divalent metal cations. Impairs ion transport across the cell membrane. 1 Publication
Mutagenesisi265 – 2651M → A: Abolishes ion transport across the cell membrane. 1 Publication
Mutagenesisi555 – 5551Y → A: Abolishes localization at early endosomes and leads to localization at late endosomes and lysosomes. 1 Publication
Mutagenesisi557 – 5571L → A: Abolishes localization at early endosomes and leads to localization at late endosomes and lysosomes. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi206100. phenotype.
Orphaneti83642. Microcytic anemia with liver iron overload.
PharmGKBiPA259.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 568568Natural resistance-associated macrophage protein 2PRO_0000212594Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi349 – 3491N-linked (GlcNAc...)Sequence Analysis
Modified residuei564 – 5641PhosphoserineBy similarity
Modified residuei567 – 5671PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP49281.
PaxDbiP49281.
PRIDEiP49281.

PTM databases

PhosphoSiteiP49281.

Expressioni

Tissue specificityi

Ubiquitously expressed. Isoform 1 is highly expressed in brain. Isoform 2 is highly expressed in spleen, thymus and pancreas. Isoform 3 and isoform 4 are abundantly expressed in duodenum and kidney.2 Publications

Gene expression databases

BgeeiP49281.
CleanExiHS_SLC11A2.
ExpressionAtlasiP49281. baseline and differential.
GenevestigatoriP49281.

Organism-specific databases

HPAiHPA032139.
HPA032140.

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.3 Publications

Protein-protein interaction databases

BioGridi110950. 5 interactions.
DIPiDIP-48957N.
IntActiP49281. 1 interaction.
STRINGi9606.ENSP00000262052.

Structurei

3D structure databases

ProteinModelPortaliP49281.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the NRAMP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1914.
GeneTreeiENSGT00390000006526.
HOVERGENiHBG052665.
InParanoidiP49281.
KOiK12347.
OMAiAFHFNGH.
OrthoDBiEOG77127K.
PhylomeDBiP49281.
TreeFamiTF315185.

Family and domain databases

HAMAPiMF_00221. NRAMP.
InterProiIPR001046. NRAMP_fam.
[Graphical view]
PANTHERiPTHR11706. PTHR11706. 1 hit.
PfamiPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSiPR00447. NATRESASSCMP.
TIGRFAMsiTIGR01197. nramp. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: P49281-1) [UniParc]FASTAAdd to basket

Also known as: Non-IRE, DMT1B

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
MVLGPEQKMS DDSVSGDHGE SASLGNINPA YSNPSLSQSP GDSEEYFATY
60 70 80 90 100
FNEKISIPEE EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA
110 120 130 140 150
GFKLLWILLL ATLVGLLLQR LAARLGVVTG LHLAEVCHRQ YPKVPRVILW
160 170 180 190 200
LMVELAIIGS DMQEVIGSAI AINLLSVGRI PLWGGVLITI ADTFVFLFLD
210 220 230 240 250
KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLKGM FVPSCSGCRT
260 270 280 290 300
PQIEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRNNKQEVR EANKYFFIES
310 320 330 340 350
CIALFVSFII NVFVVSVFAE AFFGKTNEQV VEVCTNTSSP HAGLFPKDNS
360 370 380 390 400
TLAVDIYKGG VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG
410 420 430 440 450
FLNLKWSRFA RVVLTRSIAI IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL
460 470 480 490 500
PFALIPILTF TSLRPVMSDF ANGLGWRIAG GILVLIICSI NMYFVVVYVR
510 520 530 540 550
DLGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGMSFLDC GHTCHLGLTA
560
QPELYLLNTM DADSLVSR
Length:568
Mass (Da):62,266
Last modified:May 30, 2000 - v2
Checksum:i4E45D6A448A23263
GO
Isoform 1 (identifier: P49281-2) [UniParc]FASTAAdd to basket

Also known as: IRE

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

Show »
Length:561
Mass (Da):61,456
Checksum:i30020C1DDDF2F8AA
GO
Isoform 3 (identifier: P49281-3) [UniParc]FASTAAdd to basket

Also known as: 1A-IRE

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRKKQLKTEAAPHCELKSYSKNSATQVSTM
     544-568: CHLGLTAQPELYLLNTMDADSLVSR → VSISKGLLTEEATRGYVK

Show »
Length:590
Mass (Da):64,704
Checksum:iE3519A0770B89737
GO
Isoform 4 (identifier: P49281-4) [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 → MRKKQLKTEAAPHCELKSYSKNSATQVSTM

Note: No experimental confirmation available.

Show »
Length:597
Mass (Da):65,514
Checksum:i3B5363A0DA116B40
GO
Isoform 5 (identifier: P49281-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MVLGPEQKMSDD → MSTVDYLN
     544-568: CHLGLTAQPELYLLNTMDADSLVSR → VSISKGLLTEEATRGYVK

Note: No experimental confirmation available.Curated

Show »
Length:557
Mass (Da):61,048
Checksum:iFF774A7FDD434B25
GO

Sequence cautioni

The sequence AAH02592.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAA34374.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti58 – 592PE → GM in AAA79219 (PubMed:7613023).Curated
Sequence conflicti81 – 811S → T in AAA79219 (PubMed:7613023).Curated
Sequence conflicti119 – 1191Q → K in AAI00015 (PubMed:15489334).Curated
Sequence conflicti124 – 1241R → K in AAA79219 (PubMed:7613023).Curated
Sequence conflicti462 – 4632SL → YV in AAA79219 (PubMed:7613023).Curated
Sequence conflicti476 – 4761W → C in AAA79219 (PubMed:7613023).Curated
Isoform 5 (identifier: P49281-5)
Sequence conflicti6 – 61Y → S in BAG59096 (PubMed:14702039).Curated
Sequence conflicti6 – 61Y → S in BAH14878 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti48 – 481A → T in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036434
Natural varianti114 – 1141Missing in AHMIO1. 1 Publication
VAR_033011
Natural varianti212 – 2121G → V in AHMIO1. 1 Publication
VAR_033012
Natural varianti399 – 3991E → D in AHMIO1; increased skipping of exon 12. 1 Publication
VAR_033013
Natural varianti416 – 4161R → C in AHMIO1. 1 Publication
VAR_033014
Natural varianti435 – 4351L → I.1 Publication
Corresponds to variant rs144863268 [ dbSNP | Ensembl ].
VAR_008882

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1212MVLGP…KMSDD → MSTVDYLN in isoform 5. 1 PublicationVSP_046058Add
BLAST
Alternative sequencei1 – 11M → MRKKQLKTEAAPHCELKSYS KNSATQVSTM in isoform 3 and isoform 4. 2 PublicationsVSP_038144
Alternative sequencei544 – 56825CHLGL…SLVSR → VSISKGLLTEEATRGYVK in isoform 1, isoform 3 and isoform 5. 6 PublicationsVSP_003595Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004857 mRNA. Translation: BAA24933.1.
AB015355 Genomic DNA. Translation: BAA34374.1. Sequence problems.
AF064482
, AF064476, AF064477, AF064478, AF064479, AF064480, AF064481 Genomic DNA. Translation: AAC21460.1.
AF064483
, AF064476, AF064477, AF064478, AF064479, AF064480, AF064481, AF064482 Genomic DNA. Translation: AAC21461.1.
AF064484 mRNA. Translation: AAC21459.1.
AJ493662 mRNA. Translation: CAD38517.1.
AF046997 mRNA. Translation: AAC18078.1.
AK094735 mRNA. Translation: BAG52920.1.
AK296445 mRNA. Translation: BAG59096.1.
AK316507 mRNA. Translation: BAH14878.1.
AB062284 mRNA. Translation: BAB93467.1.
AC087884 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58159.1.
BC002592 mRNA. Translation: AAH02592.1. Different initiation.
BC100014 mRNA. Translation: AAI00015.1.
L37347 mRNA. Translation: AAA79219.1.
CCDSiCCDS53791.1. [P49281-5]
CCDS53792.1. [P49281-1]
CCDS53793.1. [P49281-3]
CCDS8805.1. [P49281-2]
PIRiI57022.
RefSeqiNP_000608.1. NM_000617.2. [P49281-2]
NP_001167596.1. NM_001174125.1. [P49281-3]
NP_001167597.1. NM_001174126.1. [P49281-1]
NP_001167598.1. NM_001174127.1. [P49281-1]
NP_001167599.1. NM_001174128.1. [P49281-2]
NP_001167600.1. NM_001174129.1. [P49281-2]
NP_001167601.1. NM_001174130.1. [P49281-5]
XP_005268968.1. XM_005268911.1. [P49281-4]
UniGeneiHs.505545.

Genome annotation databases

EnsembliENST00000262051; ENSP00000262051; ENSG00000110911. [P49281-1]
ENST00000262052; ENSP00000262052; ENSG00000110911. [P49281-2]
ENST00000394904; ENSP00000378364; ENSG00000110911. [P49281-3]
ENST00000541174; ENSP00000444542; ENSG00000110911. [P49281-2]
ENST00000545993; ENSP00000442810; ENSG00000110911. [P49281-5]
ENST00000546636; ENSP00000449008; ENSG00000110911. [P49281-1]
ENST00000547198; ENSP00000446769; ENSG00000110911. [P49281-1]
ENST00000547688; ENSP00000449200; ENSG00000110911. [P49281-3]
GeneIDi4891.
KEGGihsa:4891.
UCSCiuc001rxc.4. human. [P49281-1]
uc001rxh.2. human. [P49281-2]
uc001rxk.2. human. [P49281-3]

Polymorphism databases

DMDMi8247934.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004857 mRNA. Translation: BAA24933.1.
AB015355 Genomic DNA. Translation: BAA34374.1. Sequence problems.
AF064482
, AF064476, AF064477, AF064478, AF064479, AF064480, AF064481 Genomic DNA. Translation: AAC21460.1.
AF064483
, AF064476, AF064477, AF064478, AF064479, AF064480, AF064481, AF064482 Genomic DNA. Translation: AAC21461.1.
AF064484 mRNA. Translation: AAC21459.1.
AJ493662 mRNA. Translation: CAD38517.1.
AF046997 mRNA. Translation: AAC18078.1.
AK094735 mRNA. Translation: BAG52920.1.
AK296445 mRNA. Translation: BAG59096.1.
AK316507 mRNA. Translation: BAH14878.1.
AB062284 mRNA. Translation: BAB93467.1.
AC087884 Genomic DNA. No translation available.
CH471111 Genomic DNA. Translation: EAW58159.1.
BC002592 mRNA. Translation: AAH02592.1. Different initiation.
BC100014 mRNA. Translation: AAI00015.1.
L37347 mRNA. Translation: AAA79219.1.
CCDSiCCDS53791.1. [P49281-5]
CCDS53792.1. [P49281-1]
CCDS53793.1. [P49281-3]
CCDS8805.1. [P49281-2]
PIRiI57022.
RefSeqiNP_000608.1. NM_000617.2. [P49281-2]
NP_001167596.1. NM_001174125.1. [P49281-3]
NP_001167597.1. NM_001174126.1. [P49281-1]
NP_001167598.1. NM_001174127.1. [P49281-1]
NP_001167599.1. NM_001174128.1. [P49281-2]
NP_001167600.1. NM_001174129.1. [P49281-2]
NP_001167601.1. NM_001174130.1. [P49281-5]
XP_005268968.1. XM_005268911.1. [P49281-4]
UniGeneiHs.505545.

3D structure databases

ProteinModelPortaliP49281.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110950. 5 interactions.
DIPiDIP-48957N.
IntActiP49281. 1 interaction.
STRINGi9606.ENSP00000262052.

Chemistry

BindingDBiP49281.
ChEMBLiCHEMBL1932895.

Protein family/group databases

TCDBi2.A.55.2.1. the metal ion (mn(2+)-iron) transporter (nramp) family.

PTM databases

PhosphoSiteiP49281.

Polymorphism databases

DMDMi8247934.

Proteomic databases

MaxQBiP49281.
PaxDbiP49281.
PRIDEiP49281.

Protocols and materials databases

DNASUi4891.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262051; ENSP00000262051; ENSG00000110911. [P49281-1]
ENST00000262052; ENSP00000262052; ENSG00000110911. [P49281-2]
ENST00000394904; ENSP00000378364; ENSG00000110911. [P49281-3]
ENST00000541174; ENSP00000444542; ENSG00000110911. [P49281-2]
ENST00000545993; ENSP00000442810; ENSG00000110911. [P49281-5]
ENST00000546636; ENSP00000449008; ENSG00000110911. [P49281-1]
ENST00000547198; ENSP00000446769; ENSG00000110911. [P49281-1]
ENST00000547688; ENSP00000449200; ENSG00000110911. [P49281-3]
GeneIDi4891.
KEGGihsa:4891.
UCSCiuc001rxc.4. human. [P49281-1]
uc001rxh.2. human. [P49281-2]
uc001rxk.2. human. [P49281-3]

Organism-specific databases

CTDi4891.
GeneCardsiGC12M051375.
HGNCiHGNC:10908. SLC11A2.
HPAiHPA032139.
HPA032140.
MIMi206100. phenotype.
600523. gene.
neXtProtiNX_P49281.
Orphaneti83642. Microcytic anemia with liver iron overload.
PharmGKBiPA259.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1914.
GeneTreeiENSGT00390000006526.
HOVERGENiHBG052665.
InParanoidiP49281.
KOiK12347.
OMAiAFHFNGH.
OrthoDBiEOG77127K.
PhylomeDBiP49281.
TreeFamiTF315185.

Enzyme and pathway databases

ReactomeiREACT_20547. Metal ion SLC transporters.
REACT_25060. Iron uptake and transport.

Miscellaneous databases

ChiTaRSiSLC11A2. human.
GeneWikiiDMT1.
GenomeRNAii4891.
NextBioi18825.
PROiP49281.
SOURCEiSearch...

Gene expression databases

BgeeiP49281.
CleanExiHS_SLC11A2.
ExpressionAtlasiP49281. baseline and differential.
GenevestigatoriP49281.

Family and domain databases

HAMAPiMF_00221. NRAMP.
InterProiIPR001046. NRAMP_fam.
[Graphical view]
PANTHERiPTHR11706. PTHR11706. 1 hit.
PfamiPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSiPR00447. NATRESASSCMP.
TIGRFAMsiTIGR01197. nramp. 1 hit.
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Publicationsi

« Hide 'large scale' publications
  1. "Complete nucleotide sequence of human NRAMP2 cDNA."
    Kishi F., Tabuchi M.
    Mol. Immunol. 34:839-842(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Human natural resistance-associated macrophage protein 2: gene cloning and protein identification."
    Kishi F., Tabuchi M.
    Biochem. Biophys. Res. Commun. 251:775-783(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  3. "The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms."
    Lee P.L., Gelbart T., West C., Halloran C., Beutler E.
    Blood Cells Mol. Dis. 24:199-215(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANT ILE-435.
  4. "Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function."
    Hubert N., Hentze M.W.
    Proc. Natl. Acad. Sci. U.S.A. 99:12345-12350(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 1-583 (ISOFORM 3), ALTERNATIVE SPLICING (ISOFORMS 2 AND 4), TISSUE SPECIFICITY.
  5. "Cloning and functional expression of the full length human NRAMP2 iron transporter."
    Worthington M.T., Battle E., Luo R.Q.
    Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
  6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
    Tissue: Brain, Thalamus and Trachea.
  7. "Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients."
    Shichijo S., Itoh K.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Colon adenocarcinoma.
  8. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
    Tissue: Hypothalamus and Neuroblastoma.
  11. "Cloning and characterization of a second human NRAMP gene on chromosome 12q13."
    Vidal S., Belouchi A.-M., Cellier M., Beatty B., Gros P.
    Mamm. Genome 6:224-230(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-568 (ISOFORM 1).
    Tissue: Liver.
  12. "Alternative splicing regulates the subcellular localization of divalent metal transporter 1 isoforms."
    Tabuchi M., Tanaka N., Nishida-Kitayama J., Ohno H., Kishi F.
    Mol. Biol. Cell 13:4371-4387(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, MUTAGENESIS OF TYR-555.
  13. "Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)."
    Mackenzie B., Takanaga H., Hubert N., Rolfs A., Hediger M.A.
    Biochem. J. 403:59-69(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1."
    Ludwiczek S., Theurl I., Muckenthaler M.U., Jakab M., Mair S.M., Theurl M., Kiss J., Paulmichl M., Hentze M.W., Ritter M., Weiss G.
    Nat. Med. 13:448-454(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES, NIFEDIPINE TREATMENT.
  15. "Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2."
    Foot N.J., Dalton H.E., Shearwin-Whyatt L.M., Dorstyn L., Tan S.S., Yang B., Kumar S.
    Blood 112:4268-4275(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NDFIP1; NDFIP2 AND WWP2, SUBCELLULAR LOCATION.
  16. "Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons."
    Howitt J., Putz U., Lackovic J., Doan A., Dorstyn L., Cheng H., Yang B., Chan-Ling T., Silke J., Kumar S., Tan S.S.
    Proc. Natl. Acad. Sci. U.S.A. 106:15489-15494(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NDFIP1 AND NEDD4L.
  17. "Inhibition of iron uptake by ferristatin II is exerted through internalization of DMT1 at the plasma membrane."
    Yanatori I., Yasui Y., Noguchi Y., Kishi F.
    Cell Biol. Int. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, FUNCTION, GLYCOSYLATION.
  18. "Evidence for mitochondrial localization of divalent metal transporter 1 (DMT1)."
    Wolff N.A., Ghio A.J., Garrick L.M., Garrick M.D., Zhao L., Fenton R.A., Thevenod F.
    FASEB J. 28:2134-2145(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH COX2 AND TOM6.
  19. "Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport."
    Ehrnstorfer I.A., Geertsma E.R., Pardon E., Steyaert J., Dutzler R.
    Nat. Struct. Mol. Biol. 21:990-996(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-86; ASN-89 AND MET-265.
  20. "Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload."
    Mims M.P., Guan Y., Pospisilova D., Priwitzerova M., Indrak K., Ponka P., Divoky V., Prchal J.T.
    Blood 105:1337-1342(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AHMIO1 ASP-399.
  21. "Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2)."
    Iolascon A., d'Apolito M., Servedio V., Cimmino F., Piga A., Camaschella C.
    Blood 107:349-354(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AHMIO1 CYS-416.
  22. "Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload."
    Beaumont C., Delaunay J., Hetet G., Grandchamp B., de Montalembert M., Tchernia G.
    Blood 107:4168-4170(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS AHMIO1 VAL-114 DEL AND VAL-212.
  23. Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-48.

Entry informationi

Entry nameiNRAM2_HUMAN
AccessioniPrimary (citable) accession number: P49281
Secondary accession number(s): B3KT08
, B4DK84, F5H741, O43288, O60932, O94801, Q498Z5, Q8IUD7, Q96J35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 30, 2000
Last modified: April 1, 2015
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

NRAMP2-mediated iron uptake is markedly stimulated by nifedipine in a concentration-dependent manner.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.