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Identification
HMDB Protein ID HMDBP02405
Secondary Accession Numbers
  • 7898
Name Natural resistance-associated macrophage protein 2
Synonyms
  1. DMT-1
  2. Divalent cation transporter 1
  3. Divalent metal transporter 1
  4. NRAMP 2
Gene Name SLC11A2
Protein Type Unknown
Biological Properties
General Function Involved in transporter activity
Specific Function 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
transporter activity
Process
establishment of localization
transport
Cellular Location
  1. Endosome membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 12q13
SNPs SLC11A2
Gene Sequence
>1707 bp
ATGGTGCTGGGTCCTGAACAGAAGATGTCAGATGACAGTGTTTCTGGAGATCATGGGGAG
TCTGCCAGTCTTGGTAACATCAACCCTGCCTATAGTAATCCCTCTCTTTCACAGTCCCCT
GGGGACTCAGAGGAGTACTTCGCCACTTACTTTAATGAGAAGATCTCCATTCCTGAGGAG
GAGTACTCTTGTTTTAGCTTTCGTAAACTCTGGGCTTTCACCGGACCAGGTTTTCTTATG
AGCATTGCCTACCTGGATCCAGGAAATATTGAATCCGATTTGCAGTCTGGAGCAGTGGCT
GGATTTAAGTTGCTCTGGATCCTTCTGTTGGCCACCCTTGTGGGGCTGCTGCTCCAGCGG
CTTGCAGCTAGACTGGGAGTGGTTACTGGGCTGCATCTTGCTGAAGTATGTCACCGTCAG
TATCCCAAGGTCCCACGAGTCATCCTGTGGCTGATGGTGGAGTTGGCTATCATCGGCTCA
GACATGCAAGAAGTCATTGGCTCAGCCATTGCTATCAATCTTCTGTCTGTAGGAAGAATT
CCTCTGTGGGGTGGCGTTCTCATCACCATTGCAGATACTTTTGTATTTCTCTTCTTGGAC
AAATATGGCTTGCGGAAGCTAGAAGCATTTTTTGGCTTTCTCATCACTATTATGGCCCTC
ACATTTGGATATGAGTATGTTACAGTGAAACCCAGCCAGAGCCAGGTACTCAAGGGCATG
TTCGTACCATCCTGTTCAGGCTGTCGCACTCCACAGATTGAACAGGCTGTGGGCATCGTG
GGAGCTGTCATCATGCCACACAACATGTACCTGCATTCTGCCTTAGTCAAGTCTAGACAG
GTAAACCGGAACAATAAGCAGGAAGTTCGAGAAGCCAATAAGTACTTTTTCATTGAATCC
TGCATTGCACTCTTTGTTTCCTTCATCATCAATGTCTTTGTTGTCTCAGTCTTTGCTGAA
GCATTTTTTGGGAAAACCAACGAGCAGGTGGTTGAAGTCTGTACAAATACCAGCAGTCCT
CATGCTGGCCTCTTTCCTAAAGATAACTCGACACTGGCTGTGGACATCTACAAAGGGGGT
GTTGTGCTGGGATGTTACTTTGGGCCTGCTGCACTCTACATTTGGGCAGTGGGGATCCTG
GCTGCAGGACAGAGCTCCACCATGACAGGAACCTATTCTGGCCAGTTTGTCATGGAGGGA
TTCCTGAACCTAAAGTGGTCACGCTTTGCCCGAGTGGTTCTGACTCGCTCTATTGCCATC
ATCCCCACTCTGCTTGTTGCTGTCTTCCAAGATGTAGAGCATCTAACAGGGATGAATGAC
TTTCTGAATGTTCTACAGAGCTTACAGCTTCCCTTTGCTCTCATACCCATCCTCACATTT
ACGAGCTTGCGGCCAGTAATGAGTGACTTTGCCAATGGACTAGGCTGGCGGATTGCAGGA
GGAATCTTGGTCCTTATCATCTGTTCCATCAATATGTACTTTGTAGTGGTTTATGTCCGG
GACCTAGGGCATGTGGCATTATATGTGGTGGCTGCTGTGGTCAGCGTGGCTTATCTGGGC
TTTGTGTTCTACTTGGGTTGGCAATGTTTGATTGCACTGGGCATGTCCTTCCTGGACTGT
GGGCATACGTGCCATCTGGGATTGACAGCTCAGCCTGAACTCTATCTTCTGAACACCATG
GACGCTGACTCACTTGTGTCTAGATGA
Protein Properties
Number of Residues 568
Molecular Weight 62265.2
Theoretical pI 6.0
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 70-90
  • 97-117
  • 155-175
  • 180-200
  • 209-229
  • 256-276
  • 302-322
  • 361-381
  • 409-429
  • 441-461
  • 483-503
  • 507-527
Protein Sequence
>Natural resistance-associated macrophage protein 2
MVLGPEQKMSDDSVSGDHGESASLGNINPAYSNPSLSQSPGDSEEYFATYFNEKISIPEE
EYSCFSFRKLWAFTGPGFLMSIAYLDPGNIESDLQSGAVAGFKLLWILLLATLVGLLLQR
LAARLGVVTGLHLAEVCHRQYPKVPRVILWLMVELAIIGSDMQEVIGSAIAINLLSVGRI
PLWGGVLITIADTFVFLFLDKYGLRKLEAFFGFLITIMALTFGYEYVTVKPSQSQVLKGM
FVPSCSGCRTPQIEQAVGIVGAVIMPHNMYLHSALVKSRQVNRNNKQEVREANKYFFIES
CIALFVSFIINVFVVSVFAEAFFGKTNEQVVEVCTNTSSPHAGLFPKDNSTLAVDIYKGG
VVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVVLTRSIAI
IPTLLVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSDFANGLGWRIAG
GILVLIICSINMYFVVVYVRDLGHVALYVVAAVVSVAYLGFVFYLGWQCLIALGMSFLDC
GHTCHLGLTAQPELYLLNTMDADSLVSR
GenBank ID Protein 295293169
UniProtKB/Swiss-Prot ID P49281
UniProtKB/Swiss-Prot Entry Name NRAM2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001174126.1
GeneCard ID SLC11A2
GenAtlas ID SLC11A2
HGNC ID HGNC:10908
References
General References
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  3. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  4. Kishi F, Tabuchi M: Complete nucleotide sequence of human NRAMP2 cDNA. Mol Immunol. 1997 Aug-Sep;34(12-13):839-42. [PubMed:9464519 ]
  5. Kishi F, Tabuchi M: Human natural resistance-associated macrophage protein 2: gene cloning and protein identification. Biochem Biophys Res Commun. 1998 Oct 29;251(3):775-83. [PubMed:9790986 ]
  6. Lee PL, Gelbart T, West C, Halloran C, Beutler E: The human Nramp2 gene: characterization of the gene structure, alternative splicing, promoter region and polymorphisms. Blood Cells Mol Dis. 1998 Jun;24(2):199-215. [PubMed:9642100 ]
  7. Hubert N, Hentze MW: Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12345-50. Epub 2002 Sep 3. [PubMed:12209011 ]
  8. Vidal S, Belouchi AM, Cellier M, Beatty B, Gros P: Cloning and characterization of a second human NRAMP gene on chromosome 12q13. Mamm Genome. 1995 Apr;6(4):224-30. [PubMed:7613023 ]
  9. Mackenzie B, Takanaga H, Hubert N, Rolfs A, Hediger MA: Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1). Biochem J. 2007 Apr 1;403(1):59-69. [PubMed:17109629 ]
  10. Ludwiczek S, Theurl I, Muckenthaler MU, Jakab M, Mair SM, Theurl M, Kiss J, Paulmichl M, Hentze MW, Ritter M, Weiss G: Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med. 2007 Apr;13(4):448-54. Epub 2007 Feb 11. [PubMed:17293870 ]
  11. Foot NJ, Dalton HE, Shearwin-Whyatt LM, Dorstyn L, Tan SS, Yang B, Kumar S: Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2. Blood. 2008 Nov 15;112(10):4268-75. doi: 10.1182/blood-2008-04-150953. Epub 2008 Sep 5. [PubMed:18776082 ]
  12. Howitt J, Putz U, Lackovic J, Doan A, Dorstyn L, Cheng H, Yang B, Chan-Ling T, Silke J, Kumar S, Tan SS: Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons. Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15489-94. doi: 10.1073/pnas.0904880106. Epub 2009 Aug 25. [PubMed:19706893 ]
  13. Mims MP, Guan Y, Pospisilova D, Priwitzerova M, Indrak K, Ponka P, Divoky V, Prchal JT: Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood. 2005 Feb 1;105(3):1337-42. Epub 2004 Sep 30. [PubMed:15459009 ]
  14. Iolascon A, d'Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C: Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood. 2006 Jan 1;107(1):349-54. Epub 2005 Sep 13. [PubMed:16160008 ]
  15. Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G: Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood. 2006 May 15;107(10):4168-70. Epub 2006 Jan 26. [PubMed:16439678 ]