P49281 (NRAM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	SLC11A2
Synonyms:	DCT1, DMT1, NRAMP2
ORF Names:	OK/SW-cl.20

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	568 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Involvement in disease	Hypochromic microcytic anemia (HCMA) [MIM:206100]: Characterized by an abnormal hemoglobin content in the erythrocytes which are reduced in size. It may be hereditary or acquired. Mutations in SLC11A2 are associated with progressive liver iron overload and normal to moderately elevated serum ferritin levels. 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 process	Ion transport Iron transport Transport
Cellular component	Endosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Iron
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay PubMed 18082289. Source: UniProtKB cellular iron ion homeostasis Traceable author statement. Source: Reactome cellular response to oxidative stress Inferred from direct assay PubMed 18082289. Source: UniProtKB dendrite morphogenesis Inferred from electronic annotation. Source: Compara detection of oxygen Inferred from expression pattern PubMed 18419598. Source: UniProtKB erythrocyte development Inferred from electronic annotation. Source: Compara ferrous iron import Inferred from direct assay Ref.12. Source: UniProtKB heme biosynthetic process Inferred from electronic annotation. Source: Compara learning or memory Inferred from electronic annotation. Source: Compara multicellular organismal iron ion homeostasis Inferred from mutant phenotype Ref.16. Source: BHF-UCL 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
Cellular_component	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: Compara cell surface Inferred from direct assay PubMed 12475959. Source: UniProtKB cytoplasmic vesicle Inferred from direct assay PubMed 15880641. Source: UniProtKB early endosome Inferred from direct assay PubMed 15880641PubMed 12475959PubMed 15792797Ref.14. Source: UniProtKB endomembrane system Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from electronic annotation. Source: Compara 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 10751401. Source: BHF-UCL 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.12. Source: UniProtKB recycling endosome Inferred from direct assay PubMed 15880641Ref.14. Source: UniProtKB trans-Golgi network Inferred from direct assay Ref.14. Source: UniProtKB
Molecular_function	cadmium ion transmembrane transporter activity Inferred from direct assay PubMed 12662899. Source: BHF-UCL cobalt ion transmembrane transporter activity Inferred from direct assay Ref.12. Source: UniProtKB 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: Compara lead ion transmembrane transporter activity Inferred from direct assay PubMed 12127992. Source: BHF-UCL manganese ion transmembrane transporter activity Inferred from direct assay Ref.13. Source: BHF-UCL nickel cation transmembrane transporter activity Inferred from direct assay Ref.12. Source: UniProtKB solute:hydrogen 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 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 568	568	Natural resistance-associated macrophage protein 2		PRO_0000212594
Regions
	Topological domain	1 – 69	69	Cytoplasmic Potential
	Transmembrane	70 – 90	21	Helical; Potential
	Topological domain	91 – 96	6	Extracellular Potential
	Transmembrane	97 – 117	21	Helical; Potential
	Topological domain	118 – 154	37	Cytoplasmic Potential
	Transmembrane	155 – 175	21	Helical; Potential
	Topological domain	176 – 179	4	Extracellular Potential
	Transmembrane	180 – 200	21	Helical; Potential
	Topological domain	201 – 208	8	Cytoplasmic Potential
	Transmembrane	209 – 229	21	Helical; Potential
	Topological domain	230 – 255	26	Extracellular Potential
	Transmembrane	256 – 276	21	Helical; Potential
	Topological domain	277 – 301	25	Cytoplasmic Potential
	Transmembrane	302 – 322	21	Helical; Potential
	Topological domain	323 – 360	38	Extracellular Potential
	Transmembrane	361 – 381	21	Helical; Potential
	Topological domain	382 – 408	27	Cytoplasmic Potential
	Transmembrane	409 – 429	21	Helical; Potential
	Topological domain	430 – 440	11	Extracellular Potential
	Transmembrane	441 – 461	21	Helical; Potential
	Topological domain	462 – 482	21	Cytoplasmic Potential
	Transmembrane	483 – 503	21	Helical; Potential
	Topological domain	504 – 506	3	Extracellular Potential
	Transmembrane	507 – 527	21	Helical; Potential
	Topological domain	528 – 568	41	Cytoplasmic Potential
Amino acid modifications
	Modified residue	21	1	Phosphoserine By similarity
	Modified residue	564	1	Phosphoserine By similarity
	Modified residue	567	1	Phosphoserine By similarity
	Glycosylation	336	1	N-linked (GlcNAc...) Potential
	Glycosylation	349	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 12	12	MVLGP…KMSDD → MSTVDYLN in isoform 5.		VSP_046058
	Alternative sequence	1	1	M → MRKKQLKTEAAPHCELKSYS KNSATQVSTM in isoform 3 and isoform 4.		VSP_038144
	Alternative sequence	544 – 568	25	CHLGL…SLVSR → VSISKGLLTEEATRGYVK in isoform 1, isoform 3 and isoform 5.		VSP_003595
	Natural variant	48	1	A → T in a colorectal cancer sample; somatic mutation. Ref.19		VAR_036434
	Natural variant	114	1	Missing in HCMA. Ref.18		VAR_033011
	Natural variant	212	1	G → V in HCMA. Ref.18		VAR_033012
	Natural variant	399	1	E → D in HCMA; increased skipping of exon 12. Ref.16		VAR_033013
	Natural variant	416	1	R → C in HCMA. Ref.17		VAR_033014
	Natural variant	435	1	L → I. Ref.3		VAR_008882
Experimental info
	Sequence conflict	58 – 59	2	PE → GM in AAA79219. Ref.11
	Sequence conflict	81	1	S → T in AAA79219. Ref.11
	Sequence conflict	119	1	Q → K in AAI00015. Ref.10
	Sequence conflict	124	1	R → K in AAA79219. Ref.11
	Sequence conflict	462 – 463	2	SL → YV in AAA79219. Ref.11
	Sequence conflict	476	1	W → C in AAA79219. Ref.11
Isoform 5:
	Sequence conflict	6	1	Y → S in BAG59096. Ref.6
	Sequence conflict	6	1	Y → S in BAH14878. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Non-IRE) [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 4E45D6A448A23263	FASTA	568	62,266
	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
	Isoform 1 (IRE) [UniParc]. Checksum: 30020C1DDDF2F8AA	FASTA	561	61,456
	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 GHTVSISKGL LTEEATRGYV K
	Isoform 3 (1A-IRE) [UniParc]. Checksum: E3519A0770B89737	FASTA	590	64,704
	10 20 30 40 50 60 MRKKQLKTEA APHCELKSYS KNSATQVSTM VLGPEQKMSD DSVSGDHGES ASLGNINPAY 70 80 90 100 110 120 SNPSLSQSPG DSEEYFATYF NEKISIPEEE YSCFSFRKLW AFTGPGFLMS IAYLDPGNIE 130 140 150 160 170 180 SDLQSGAVAG FKLLWILLLA TLVGLLLQRL AARLGVVTGL HLAEVCHRQY PKVPRVILWL 190 200 210 220 230 240 MVELAIIGSD MQEVIGSAIA INLLSVGRIP LWGGVLITIA DTFVFLFLDK YGLRKLEAFF 250 260 270 280 290 300 GFLITIMALT FGYEYVTVKP SQSQVLKGMF VPSCSGCRTP QIEQAVGIVG AVIMPHNMYL 310 320 330 340 350 360 HSALVKSRQV NRNNKQEVRE ANKYFFIESC IALFVSFIIN VFVVSVFAEA FFGKTNEQVV 370 380 390 400 410 420 EVCTNTSSPH AGLFPKDNST LAVDIYKGGV VLGCYFGPAA LYIWAVGILA AGQSSTMTGT 430 440 450 460 470 480 YSGQFVMEGF LNLKWSRFAR VVLTRSIAII PTLLVAVFQD VEHLTGMNDF LNVLQSLQLP 490 500 510 520 530 540 FALIPILTFT SLRPVMSDFA NGLGWRIAGG ILVLIICSIN MYFVVVYVRD LGHVALYVVA 550 560 570 580 590 AVVSVAYLGF VFYLGWQCLI ALGMSFLDCG HTVSISKGLL TEEATRGYVK
	Isoform 4 (1A-Non-IRE) [UniParc]. Checksum: 3B5363A0DA116B40	FASTA	597	65,514
	10 20 30 40 50 60 MRKKQLKTEA APHCELKSYS KNSATQVSTM VLGPEQKMSD DSVSGDHGES ASLGNINPAY 70 80 90 100 110 120 SNPSLSQSPG DSEEYFATYF NEKISIPEEE YSCFSFRKLW AFTGPGFLMS IAYLDPGNIE 130 140 150 160 170 180 SDLQSGAVAG FKLLWILLLA TLVGLLLQRL AARLGVVTGL HLAEVCHRQY PKVPRVILWL 190 200 210 220 230 240 MVELAIIGSD MQEVIGSAIA INLLSVGRIP LWGGVLITIA DTFVFLFLDK YGLRKLEAFF 250 260 270 280 290 300 GFLITIMALT FGYEYVTVKP SQSQVLKGMF VPSCSGCRTP QIEQAVGIVG AVIMPHNMYL 310 320 330 340 350 360 HSALVKSRQV NRNNKQEVRE ANKYFFIESC IALFVSFIIN VFVVSVFAEA FFGKTNEQVV 370 380 390 400 410 420 EVCTNTSSPH AGLFPKDNST LAVDIYKGGV VLGCYFGPAA LYIWAVGILA AGQSSTMTGT 430 440 450 460 470 480 YSGQFVMEGF LNLKWSRFAR VVLTRSIAII PTLLVAVFQD VEHLTGMNDF LNVLQSLQLP 490 500 510 520 530 540 FALIPILTFT SLRPVMSDFA NGLGWRIAGG ILVLIICSIN MYFVVVYVRD LGHVALYVVA 550 560 570 580 590 AVVSVAYLGF VFYLGWQCLI ALGMSFLDCG HTCHLGLTAQ PELYLLNTMD ADSLVSR
	Isoform 5 [UniParc]. Checksum: FF774A7FDD434B25	FASTA	557	61,048
	10 20 30 40 50 60 MSTVDYLNSV SGDHGESASL GNINPAYSNP SLSQSPGDSE EYFATYFNEK ISIPEEEYSC 70 80 90 100 110 120 FSFRKLWAFT GPGFLMSIAY LDPGNIESDL QSGAVAGFKL LWILLLATLV GLLLQRLAAR 130 140 150 160 170 180 LGVVTGLHLA EVCHRQYPKV PRVILWLMVE LAIIGSDMQE VIGSAIAINL LSVGRIPLWG 190 200 210 220 230 240 GVLITIADTF VFLFLDKYGL RKLEAFFGFL ITIMALTFGY EYVTVKPSQS QVLKGMFVPS 250 260 270 280 290 300 CSGCRTPQIE QAVGIVGAVI MPHNMYLHSA LVKSRQVNRN NKQEVREANK YFFIESCIAL 310 320 330 340 350 360 FVSFIINVFV VSVFAEAFFG KTNEQVVEVC TNTSSPHAGL FPKDNSTLAV DIYKGGVVLG 370 380 390 400 410 420 CYFGPAALYI WAVGILAAGQ SSTMTGTYSG QFVMEGFLNL KWSRFARVVL TRSIAIIPTL 430 440 450 460 470 480 LVAVFQDVEH LTGMNDFLNV LQSLQLPFAL IPILTFTSLR PVMSDFANGL GWRIAGGILV 490 500 510 520 530 540 LIICSINMYF VVVYVRDLGH VALYVVAAVV SVAYLGFVFY LGWQCLIALG MSFLDCGHTV 550 SISKGLLTEE ATRGYVK

References

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[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]	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. , 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 HCMA 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 HCMA 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 HCMA 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. , 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 , 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.
IPI	IPI00394753. IPI00465037. IPI00793358. IPI00795148. IPI00944520.
PIR	I57022.
RefSeq	NP_000608.1. NM_000617.2. NP_001167596.1. NM_001174125.1. NP_001167597.1. NM_001174126.1. NP_001167598.1. NM_001174127.1. NP_001167599.1. NM_001174128.1. NP_001167600.1. NM_001174129.1. NP_001167601.1. NM_001174130.1.
UniGene	Hs.505545.
3D structure databases
ProteinModelPortal	P49281.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48957N.
IntAct	P49281. 1 interaction.
STRING	9606.ENSP00000262052.
Protein family/group databases
TCDB	2.A.55.2.1. metal ion (Mn2+-iron) transporter (Nramp) family.
PTM databases
PhosphoSite	P49281.
Polymorphism databases
DMDM	8247934.
Proteomic databases
PaxDb	P49281.
PRIDE	P49281.
Protocols and materials databases
DNASU	4891.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262051; ENSP00000262051; ENSG00000110911. ENST00000262052; ENSP00000262052; ENSG00000110911. ENST00000394904; ENSP00000378364; ENSG00000110911. ENST00000541174; ENSP00000444542; ENSG00000110911. ENST00000545993; ENSP00000442810; ENSG00000110911. ENST00000546636; ENSP00000449008; ENSG00000110911. ENST00000547198; ENSP00000446769; ENSG00000110911. ENST00000547688; ENSP00000449200; ENSG00000110911.
GeneID	4891.
KEGG	hsa:4891.
UCSC	uc001rxc.4. human. uc001rxh.2. human. uc001rxk.2. human.
Organism-specific databases
CTD	4891.
GeneCards	GC12M051375.
HGNC	HGNC:10908. SLC11A2.
HPA	HPA032139. HPA032140.
MIM	206100. phenotype. 600523. gene.
neXtProt	NX_P49281.
Orphanet	83642. Microcytic anemia with liver iron overload.
PharmGKB	PA259.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1914.
HOVERGEN	HBG052665.
KO	K12347.
OMA	ERYSATK.
OrthoDB	EOG4RFKSH.
PhylomeDB	P49281.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P49281.
Bgee	P49281.
CleanEx	HS_SLC11A2.
Genevestigator	P49281.
GermOnline	ENSG00000110911. Homo sapiens.
Family and domain databases
InterPro	IPR001046. Nat-R-assoc-macro_Nramp. [Graphical view]
PANTHER	PTHR11706. PTHR11706. 1 hit.
Pfam	PF01566. Nramp. 1 hit. [Graphical view]
PRINTS	PR00447. NATRESASSCMP.
TIGRFAMs	TIGR01197. nramp. 1 hit.
ProtoNet	Search...
Other
BindingDB	P49281.
ChEMBL	CHEMBL1932895.
ChiTaRS	SLC11A2. human.
GenomeRNAi	4891.
NextBio	18825.
SOURCE	Search...

Entry information

Entry name

NRAM2_HUMAN

Accession

Primary (citable) accession number: P49281
Secondary accession number(s): B3KT08 , 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:	May 1, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.