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P49281 (NRAM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC11A2
Synonyms:DCT1, DMT1, NRAMP2
ORF Names:OK/SW-cl.20
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length568 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12

Subunit structure

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. Ref.14 Ref.15

Subcellular location

Endosome membrane; Multi-pass membrane protein Ref.14.

Tissue specificity

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. Ref.3 Ref.4

Post-translational modification

Ubiquitinated by WWP2 By similarity. HAMAP-Rule MF_00221

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.17 Ref.18

Miscellaneous

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

Sequence similarities

Belongs to the NRAMP family.

Biophysicochemical properties

pH dependence:

Optimum pH is 5.5-6.5 for Fe2+ uptake. Ref.13

Sequence caution

The sequence AAH02592.1 differs from that shown. Reason: Erroneous initiation.

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

Ontologies

Keywords
   Biological processIon transport
Iron transport
Transport
   Cellular componentEndosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandIron
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 18082289. Source: UniProtKB

cadmium ion transmembrane transport

Inferred from direct assay PubMed 12662899. Source: BHF-UCL

cellular iron ion homeostasis

Traceable author statement. Source: Reactome

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to iron ion

Inferred from electronic annotation. Source: Ensembl

cellular response to oxidative stress

Inferred from direct assay PubMed 18082289. Source: UniProtKB

cellular response to tumor necrosis factor

Inferred from electronic annotation. Source: Ensembl

cobalt ion transport

Inferred from direct assay Ref.12. Source: UniProtKB

copper ion transport

Inferred from direct assay PubMed 12734107. Source: BHF-UCL

dendrite morphogenesis

Inferred from electronic annotation. Source: Ensembl

detection of oxygen

Inferred from expression pattern PubMed 18419598. Source: UniProtKB

erythrocyte development

Inferred from electronic annotation. Source: Ensembl

ferrous iron import

Inferred from direct assay Ref.12. Source: UniProtKB

ferrous iron transport

Inferred from direct assay PubMed 12734107Ref.13. Source: BHF-UCL

heme biosynthetic process

Inferred from electronic annotation. Source: Ensembl

lead ion transport

Inferred from direct assay PubMed 12127992. Source: BHF-UCL

learning or memory

Inferred from electronic annotation. Source: Ensembl

manganese ion transmembrane transport

Inferred from direct assay Ref.12. Source: GOC

manganese ion transport

Inferred from direct assay Ref.13. Source: BHF-UCL

multicellular organismal iron ion homeostasis

Inferred from mutant phenotype Ref.16. Source: BHF-UCL

nickel cation transmembrane transport

Inferred from direct assay Ref.12. Source: GOC

nickel cation transport

Inferred from direct assay Ref.12. Source: UniProtKB

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from expression pattern PubMed 18419598PubMed 18419598. Source: UniProtKB

response to iron ion

Inferred from expression pattern PubMed 12734107Ref.12PubMed 15792797PubMed 18082289. Source: UniProtKB

response to lead ion

Inferred from electronic annotation. Source: Ensembl

response to manganese ion

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

vanadium ion transport

Inferred from direct assay Ref.12. Source: GOC

zinc ion transmembrane transport

Inferred from direct assay Ref.12. Source: GOC

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 15880641. Source: UniProtKB

apical plasma membrane

Inferred from direct assay PubMed 15880641PubMed 12475959PubMed 12475959PubMed 15792797. Source: UniProtKB

basal part of cell

Inferred from direct assay PubMed 15880641. Source: UniProtKB

brush border

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from direct assay PubMed 12475959. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 11891802. Source: BHF-UCL

cytoplasmic vesicle

Inferred from direct assay PubMed 15880641. Source: UniProtKB

early endosome

Inferred from direct assay PubMed 15880641PubMed 12475959PubMed 15792797Ref.14. Source: UniProtKB

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from direct assay PubMed 18876082PubMed 12475959PubMed 15792797Ref.14. Source: UniProtKB

late endosome membrane

Inferred from direct assay PubMed 10751401. Source: BHF-UCL

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

lysosome

Inferred from direct assay PubMed 12475959. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 15880641PubMed 18419598PubMed 18419598. Source: UniProtKB

paraferritin complex

Inferred from direct assay PubMed 11842004. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 10751401. Source: BHF-UCL

plasma membrane

Inferred from direct assay Ref.12PubMed 15792797. Source: UniProtKB

recycling endosome

Inferred from direct assay PubMed 15880641Ref.14. Source: UniProtKB

trans-Golgi network

Inferred from direct assay Ref.14. Source: UniProtKB

vacuole

Inferred from mutant phenotype PubMed 17932044. Source: BHF-UCL

   Molecular_functioncadmium ion binding

Inferred from electronic annotation. Source: Ensembl

cadmium ion transmembrane transporter activity

Inferred from direct assay PubMed 12662899. Source: BHF-UCL

cobalt ion binding

Inferred from electronic annotation. Source: Ensembl

cobalt ion transmembrane transporter activity

Inferred from direct assay Ref.12. Source: UniProtKB

copper ion binding

Inferred from electronic annotation. Source: Ensembl

copper ion transmembrane transporter activity

Inferred from direct assay PubMed 12734107. Source: BHF-UCL

ferrous iron transmembrane transporter activity

Inferred from direct assay PubMed 12734107Ref.13. Source: BHF-UCL

hydrogen ion transmembrane transporter activity

Inferred from electronic annotation. Source: Ensembl

inorganic cation transmembrane transporter activity

Inferred from genetic interaction PubMed 12475959PubMed 12475959. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: Ensembl

lead ion transmembrane transporter activity

Inferred from direct assay PubMed 12127992. Source: BHF-UCL

manganese ion binding

Inferred from electronic annotation. Source: Ensembl

manganese ion transmembrane transporter activity

Inferred from direct assay Ref.13. Source: BHF-UCL

nickel cation binding

Inferred from electronic annotation. Source: Ensembl

nickel cation transmembrane transporter activity

Inferred from direct assay Ref.12. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 15880641Ref.14. Source: UniProtKB

solute:proton symporter activity

Inferred from direct assay Ref.12. Source: UniProtKB

vanadium ion transmembrane transporter activity

Inferred from direct assay Ref.12. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

zinc ion transmembrane transporter activity

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: P49281-1)

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.
Isoform 1 (identifier: P49281-2)

Also known as: IRE;

The sequence of this isoform differs from the canonical sequence as follows:
     544-568: CHLGLTAQPELYLLNTMDADSLVSR → VSISKGLLTEEATRGYVK
Isoform 3 (identifier: P49281-3)

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
Isoform 4 (identifier: P49281-4)

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.
Isoform 5 (identifier: P49281-5)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 568568Natural resistance-associated macrophage protein 2 HAMAP-Rule MF_00221
PRO_0000212594

Regions

Topological domain1 – 6969Cytoplasmic Potential
Transmembrane70 – 9021Helical; Potential
Topological domain91 – 966Extracellular Potential
Transmembrane97 – 11721Helical; Potential
Topological domain118 – 15437Cytoplasmic Potential
Transmembrane155 – 17521Helical; Potential
Topological domain176 – 1794Extracellular Potential
Transmembrane180 – 20021Helical; Potential
Topological domain201 – 2088Cytoplasmic Potential
Transmembrane209 – 22921Helical; Potential
Topological domain230 – 25526Extracellular Potential
Transmembrane256 – 27621Helical; Potential
Topological domain277 – 30125Cytoplasmic Potential
Transmembrane302 – 32221Helical; Potential
Topological domain323 – 36038Extracellular Potential
Transmembrane361 – 38121Helical; Potential
Topological domain382 – 40827Cytoplasmic Potential
Transmembrane409 – 42921Helical; Potential
Topological domain430 – 44011Extracellular Potential
Transmembrane441 – 46121Helical; Potential
Topological domain462 – 48221Cytoplasmic Potential
Transmembrane483 – 50321Helical; Potential
Topological domain504 – 5063Extracellular Potential
Transmembrane507 – 52721Helical; Potential
Topological domain528 – 56841Cytoplasmic Potential

Amino acid modifications

Modified residue5641Phosphoserine By similarity
Modified residue5671Phosphoserine By similarity
Glycosylation3361N-linked (GlcNAc...) Potential
Glycosylation3491N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1212MVLGP…KMSDD → MSTVDYLN in isoform 5.
VSP_046058
Alternative sequence11M → MRKKQLKTEAAPHCELKSYS KNSATQVSTM in isoform 3 and isoform 4.
VSP_038144
Alternative sequence544 – 56825CHLGL…SLVSR → VSISKGLLTEEATRGYVK in isoform 1, isoform 3 and isoform 5.
VSP_003595
Natural variant481A → T in a colorectal cancer sample; somatic mutation. Ref.19
VAR_036434
Natural variant1141Missing in AHMIO1. Ref.18
VAR_033011
Natural variant2121G → V in AHMIO1. Ref.18
VAR_033012
Natural variant3991E → D in AHMIO1; increased skipping of exon 12. Ref.16
VAR_033013
Natural variant4161R → C in AHMIO1. Ref.17
VAR_033014
Natural variant4351L → I. Ref.3
Corresponds to variant rs144863268 [ dbSNP | Ensembl ].
VAR_008882

Experimental info

Sequence conflict58 – 592PE → GM in AAA79219. Ref.11
Sequence conflict811S → T in AAA79219. Ref.11
Sequence conflict1191Q → K in AAI00015. Ref.10
Sequence conflict1241R → K in AAA79219. Ref.11
Sequence conflict462 – 4632SL → YV in AAA79219. Ref.11
Sequence conflict4761W → C in AAA79219. Ref.11
Isoform 5:
Sequence conflict61Y → S in BAG59096. Ref.6
Sequence conflict61Y → S in BAH14878. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 (Non-IRE) [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 4E45D6A448A23263

FASTA56862,266
        10         20         30         40         50         60 
MVLGPEQKMS DDSVSGDHGE SASLGNINPA YSNPSLSQSP GDSEEYFATY FNEKISIPEE 

        70         80         90        100        110        120 
EYSCFSFRKL WAFTGPGFLM SIAYLDPGNI ESDLQSGAVA GFKLLWILLL ATLVGLLLQR 

       130        140        150        160        170        180 
LAARLGVVTG LHLAEVCHRQ YPKVPRVILW LMVELAIIGS DMQEVIGSAI AINLLSVGRI 

       190        200        210        220        230        240 
PLWGGVLITI ADTFVFLFLD KYGLRKLEAF FGFLITIMAL TFGYEYVTVK PSQSQVLKGM 

       250        260        270        280        290        300 
FVPSCSGCRT PQIEQAVGIV GAVIMPHNMY LHSALVKSRQ VNRNNKQEVR EANKYFFIES 

       310        320        330        340        350        360 
CIALFVSFII NVFVVSVFAE AFFGKTNEQV VEVCTNTSSP HAGLFPKDNS TLAVDIYKGG 

       370        380        390        400        410        420 
VVLGCYFGPA ALYIWAVGIL AAGQSSTMTG TYSGQFVMEG FLNLKWSRFA RVVLTRSIAI 

       430        440        450        460        470        480 
IPTLLVAVFQ DVEHLTGMND FLNVLQSLQL PFALIPILTF TSLRPVMSDF ANGLGWRIAG 

       490        500        510        520        530        540 
GILVLIICSI NMYFVVVYVR DLGHVALYVV AAVVSVAYLG FVFYLGWQCL IALGMSFLDC 

       550        560 
GHTCHLGLTA QPELYLLNTM DADSLVSR 

« Hide

Isoform 1 (IRE) [UniParc].

Checksum: 30020C1DDDF2F8AA
Show »

FASTA56161,456
Isoform 3 (1A-IRE) [UniParc].

Checksum: E3519A0770B89737
Show »

FASTA59064,704
Isoform 4 (1A-Non-IRE) [UniParc].

Checksum: 3B5363A0DA116B40
Show »

FASTA59765,514
Isoform 5 [UniParc].

Checksum: FF774A7FDD434B25
Show »

FASTA55761,048

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-48.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB004857 mRNA. Translation: BAA24933.1.
AB015355 Genomic DNA. Translation: BAA34374.1. Sequence problems.
AF064482 expand/collapse EMBL AC list , AF064476, AF064477, AF064478, AF064479, AF064480, AF064481 Genomic DNA. Translation: AAC21460.1.
AF064483 expand/collapse EMBL AC list , 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.
CCDSCCDS53791.1. [P49281-5]
CCDS53792.1. [P49281-1]
CCDS53793.1. [P49281-3]
CCDS8805.1. [P49281-2]
PIRI57022.
RefSeqNP_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]
UniGeneHs.505545.

3D structure databases

ProteinModelPortalP49281.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110950. 5 interactions.
DIPDIP-48957N.
IntActP49281. 1 interaction.
STRING9606.ENSP00000262052.

Chemistry

BindingDBP49281.
ChEMBLCHEMBL1932895.

Protein family/group databases

TCDB2.A.55.2.1. the metal ion (mn(2+)-iron) transporter (nramp) family.

PTM databases

PhosphoSiteP49281.

Polymorphism databases

DMDM8247934.

Proteomic databases

MaxQBP49281.
PaxDbP49281.
PRIDEP49281.

Protocols and materials databases

DNASU4891.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262051; 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]
GeneID4891.
KEGGhsa:4891.
UCSCuc001rxc.4. human. [P49281-1]
uc001rxh.2. human. [P49281-2]
uc001rxk.2. human. [P49281-3]

Organism-specific databases

CTD4891.
GeneCardsGC12M051375.
HGNCHGNC:10908. SLC11A2.
HPAHPA032139.
HPA032140.
MIM206100. phenotype.
600523. gene.
neXtProtNX_P49281.
Orphanet83642. Microcytic anemia with liver iron overload.
PharmGKBPA259.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1914.
HOVERGENHBG052665.
KOK12347.
OMAVMQGFVH.
OrthoDBEOG77127K.
PhylomeDBP49281.
TreeFamTF315185.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP49281.
BgeeP49281.
CleanExHS_SLC11A2.
GenevestigatorP49281.

Family and domain databases

HAMAPMF_00221. NRAMP.
InterProIPR001046. NRAMP-like.
[Graphical view]
PANTHERPTHR11706. PTHR11706. 1 hit.
PfamPF01566. Nramp. 1 hit.
[Graphical view]
PRINTSPR00447. NATRESASSCMP.
TIGRFAMsTIGR01197. nramp. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC11A2. human.
GeneWikiDMT1.
GenomeRNAi4891.
NextBio18825.
PROP49281.
SOURCESearch...

Entry information

Entry nameNRAM2_HUMAN
AccessionPrimary (citable) accession number: P49281
Secondary accession number(s): B3KT08 expand/collapse secondary AC list , B4DK84, F5H741, O43288, O60932, O94801, Q498Z5, Q8IUD7, Q96J35
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 30, 2000
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM