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P49281

- NRAM2_HUMAN

UniProt

P49281 - NRAM2_HUMAN

Protein

Natural resistance-associated macrophage protein 2

Gene

SLC11A2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 2 (30 May 2000)
      Previous versions | rss
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    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.1 Publication

    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. protein binding Source: UniProtKB
    17. solute:proton symporter activity Source: UniProtKB
    18. vanadium ion transmembrane transporter activity Source: UniProtKB
    19. zinc ion binding Source: Ensembl
    20. 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. cellular iron ion homeostasis Source: Reactome
    4. cellular response to hypoxia Source: Ensembl
    5. cellular response to iron ion Source: Ensembl
    6. cellular response to oxidative stress Source: UniProtKB
    7. cellular response to tumor necrosis factor Source: Ensembl
    8. cobalt ion transport Source: UniProtKB
    9. copper ion transport Source: BHF-UCL
    10. dendrite morphogenesis Source: Ensembl
    11. detection of oxygen Source: UniProtKB
    12. erythrocyte development Source: Ensembl
    13. ferrous iron import Source: UniProtKB
    14. ferrous iron transport Source: BHF-UCL
    15. heme biosynthetic process Source: Ensembl
    16. lead ion transport Source: BHF-UCL
    17. learning or memory Source: Ensembl
    18. manganese ion transmembrane transport Source: GOC
    19. manganese ion transport Source: BHF-UCL
    20. multicellular organismal iron ion homeostasis Source: BHF-UCL
    21. nickel cation transmembrane transport Source: GOC
    22. nickel cation transport Source: UniProtKB
    23. response to cadmium ion Source: Ensembl
    24. response to hypoxia Source: UniProtKB
    25. response to iron ion Source: UniProtKB
    26. response to lead ion Source: Ensembl
    27. response to manganese ion Source: Ensembl
    28. transmembrane transport Source: Reactome
    29. vanadium ion transport Source: GOC
    30. zinc ion transmembrane transport Source: GOC

    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: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:10908. SLC11A2.

    Subcellular locationi

    Endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication

    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. nucleus Source: UniProtKB
    16. paraferritin complex Source: UniProtKB
    17. perinuclear region of cytoplasm Source: BHF-UCL
    18. plasma membrane Source: UniProtKB
    19. recycling endosome Source: UniProtKB
    20. trans-Golgi network Source: UniProtKB
    21. vacuole Source: BHF-UCL

    Keywords - Cellular componenti

    Endosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Anemia, hypochromic microcytic, with iron overload 1 (AHMIO1) [MIM:206100]: A 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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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

    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

    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

    ArrayExpressiP49281.
    BgeeiP49281.
    CleanExiHS_SLC11A2.
    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 NDFIP2.2 Publications

    Protein-protein interaction databases

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

    Structurei

    3D structure databases

    ProteinModelPortaliP49281.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 6969CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini91 – 966ExtracellularSequence Analysis
    Topological domaini118 – 15437CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini176 – 1794ExtracellularSequence Analysis
    Topological domaini201 – 2088CytoplasmicSequence Analysis
    Topological domaini230 – 25526ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini277 – 30125CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini323 – 36038ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini382 – 40827CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini430 – 44011ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini462 – 48221CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini504 – 5063ExtracellularSequence Analysis
    Topological domaini528 – 56841CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei70 – 9021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei97 – 11721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei155 – 17521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei180 – 20021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei209 – 22921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei256 – 27621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei302 – 32221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei361 – 38121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei409 – 42921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei441 – 46121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei483 – 50321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei507 – 52721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the NRAMP family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1914.
    HOVERGENiHBG052665.
    KOiK12347.
    OMAiVMQGFVH.
    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. Align

    Isoform 2 (identifier: P49281-1) [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

    MVLGPEQKMS DDSVSGDHGE SASLGNINPA YSNPSLSQSP GDSEEYFATY    50
    FNEKISIPEE EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA 100
    GFKLLWILLL ATLVGLLLQR LAARLGVVTG LHLAEVCHRQ YPKVPRVILW 150
    LMVELAIIGS DMQEVIGSAI AINLLSVGRI PLWGGVLITI ADTFVFLFLD 200
    KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLKGM FVPSCSGCRT 250
    PQIEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRNNKQEVR EANKYFFIES 300
    CIALFVSFII NVFVVSVFAE AFFGKTNEQV VEVCTNTSSP HAGLFPKDNS 350
    TLAVDIYKGG VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG 400
    FLNLKWSRFA RVVLTRSIAI IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL 450
    PFALIPILTF TSLRPVMSDF ANGLGWRIAG GILVLIICSI NMYFVVVYVR 500
    DLGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGMSFLDC GHTCHLGLTA 550
    QPELYLLNTM DADSLVSR 568
    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.
    The sequence BAA34374.1 differs from that shown. Reason: Erroneous gene model prediction.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS53791.1. [P49281-5 ]
    CCDS53792.1. [P49281-1 ]
    CCDS53793.1. [P49281-3 ]
    CCDS8805.1. [P49281-2 ]
    PIRi I57022.
    RefSeqi NP_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 ]
    UniGenei Hs.505545.

    3D structure databases

    ProteinModelPortali P49281.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110950. 5 interactions.
    DIPi DIP-48957N.
    IntActi P49281. 1 interaction.
    STRINGi 9606.ENSP00000262052.

    Chemistry

    BindingDBi P49281.
    ChEMBLi CHEMBL1932895.

    Protein family/group databases

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

    PTM databases

    PhosphoSitei P49281.

    Polymorphism databases

    DMDMi 8247934.

    Proteomic databases

    MaxQBi P49281.
    PaxDbi P49281.
    PRIDEi P49281.

    Protocols and materials databases

    DNASUi 4891.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000262051 ; 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 ]
    GeneIDi 4891.
    KEGGi hsa:4891.
    UCSCi uc001rxc.4. human. [P49281-1 ]
    uc001rxh.2. human. [P49281-2 ]
    uc001rxk.2. human. [P49281-3 ]

    Organism-specific databases

    CTDi 4891.
    GeneCardsi GC12M051375.
    HGNCi HGNC:10908. SLC11A2.
    HPAi HPA032139.
    HPA032140.
    MIMi 206100. phenotype.
    600523. gene.
    neXtProti NX_P49281.
    Orphaneti 83642. Microcytic anemia with liver iron overload.
    PharmGKBi PA259.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1914.
    HOVERGENi HBG052665.
    KOi K12347.
    OMAi VMQGFVH.
    OrthoDBi EOG77127K.
    PhylomeDBi P49281.
    TreeFami TF315185.

    Enzyme and pathway databases

    Reactomei REACT_20547. Metal ion SLC transporters.
    REACT_25060. Iron uptake and transport.

    Miscellaneous databases

    ChiTaRSi SLC11A2. human.
    GeneWikii DMT1.
    GenomeRNAii 4891.
    NextBioi 18825.
    PROi P49281.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49281.
    Bgeei P49281.
    CleanExi HS_SLC11A2.
    Genevestigatori P49281.

    Family and domain databases

    HAMAPi MF_00221. NRAMP.
    InterProi IPR001046. NRAMP_fam.
    [Graphical view ]
    PANTHERi PTHR11706. PTHR11706. 1 hit.
    Pfami PF01566. Nramp. 1 hit.
    [Graphical view ]
    PRINTSi PR00447. NATRESASSCMP.
    TIGRFAMsi TIGR01197. nramp. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Complete nucleotide sequence of human NRAMP2 cDNA."
      Kishi F., Tabuchi M.
      Mol. Immunol. 34:839-842(1997) [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(1998) [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(1998) [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(2002) [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 (FEB-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(2004) [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 (MAY-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(2006) [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(2004) [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(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-568 (ISOFORM 1).
      Tissue: Liver.
    12. "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(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "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(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, NIFEDIPINE TREATMENT.
    14. "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(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDFIP1; NDFIP2 AND WWP2, SUBCELLULAR LOCATION.
    15. "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(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NDFIP1 AND NEDD4L.
    16. "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(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHMIO1 ASP-399.
    17. "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(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHMIO1 CYS-416.
    18. "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(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHMIO1 VAL-114 DEL AND VAL-212.
    19. 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: October 1, 2014
    This is version 140 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