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2.A.55.2.3
Macrophage and intestinal divalent cation (Mn2+ > Fe2+):H+ antiporter (catalyzes divalent cation efflux and regulates cation homeostasis), NRAMP1, scavenger receptor-BI (SR-BI) or Slc11a2.  (Techau et al., 2007). The C-terminal cytoplasmic PDZ-interacting domain and the C-terminal transmembrane domains are both necessary for HDL signaling. Direct binding of cholesterol to the C-terminal transmembrane domain has been demonstrated (Assanasen et al. 2005). Thus, HDL signaling requires cholesterol binding and efflux as well as the C-terminal domains of SR-BI; thus, SR-BI serves as a cholesterol sensor on the plasma membrane. The G212V mutation leads to microcytic anemia and liver iron overload (Bardou-Jacquet et al., 2011). Multiple targeting motifs direct NRAMP1 into lysosomes (Cheng and Wang, 2012). The structure and topology has been studied revealing a symmetric but inversely oriented arrangement (Li et al., 2012). Structural modeling and molecular dynamics simulations of the caprine and bovine orthologs led to mechanistic predictions (Triantaphyllopoulos et al. 2019).

Accession Number:P49279
Protein Name:NRAMP1
Length:550
Molecular Weight:59872.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Mn2+, Fe2+, H+

Cross database links:

Genevestigator: P49279 P49279
eggNOG: prNOG11368 COG1914
HEGENOM: HBG312498 HOG000152203
RefSeq: NP_000569.3   
Entrez Gene ID: 6556   
Pfam: PF01566   
OMIM: 600266  gene
607948  phenotype
610446  phenotype
KEGG: hsa:6556    hsa:6556   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005770 C:late endosome
GO:0005764 C:lysosome
GO:0030670 C:phagocytic vesicle membrane
GO:0070821 C:tertiary granule membrane
GO:0005384 F:manganese ion transmembrane transporter act...
GO:0051139 F:metal ion:hydrogen antiporter activity
GO:0042803 F:protein homodimerization activity
GO:0032147 P:activation of protein kinase activity
GO:0048002 P:antigen processing and presentation of pept...
GO:0070574 P:cadmium ion transmembrane transport
GO:0006876 P:cellular cadmium ion homeostasis
GO:0006879 P:cellular iron ion homeostasis
GO:0050829 P:defense response to Gram-negative bacterium
GO:0042832 P:defense response to protozoan
GO:0070839 P:divalent metal ion export
GO:0006954 P:inflammatory response
GO:0032623 P:interleukin-2 production
GO:0032632 P:interleukin-3 production
GO:0006826 P:iron ion transport
GO:0043091 P:L-arginine import
GO:0042116 P:macrophage activation
GO:0006828 P:manganese ion transport
GO:0045342 P:MHC class II biosynthetic process
GO:0048255 P:mRNA stabilization
GO:0060586 P:multicellular organismal iron ion homeostasis
GO:0001818 P:negative regulation of cytokine production
GO:0015707 P:nitrite transport
GO:0006909 P:phagocytosis
GO:0002606 P:positive regulation of dendritic cell antig...
GO:0032729 P:positive regulation of interferon-gamma pro...
GO:0050766 P:positive regulation of phagocytosis
GO:0002827 P:positive regulation of T-helper 1 type immu...
GO:0045944 P:positive regulation of transcription from R...
GO:0000060 P:protein import into nucleus, translocation
GO:0045730 P:respiratory burst
GO:0034341 P:response to interferon-gamma
GO:0032496 P:response to lipopolysaccharide
GO:0002369 P:T cell cytokine production
GO:0002309 P:T cell proliferation during immune response
GO:0007035 P:vacuolar acidification
GO:0042060 P:wound healing
GO:0009279 C:cell outer membrane
GO:0031902 C:late endosome membrane
GO:0005384 F:manganese ion transmembrane transporter activity
GO:0048002 P:antigen processing and presentation of peptide antigen
GO:0002606 P:positive regulation of dendritic cell antigen processing and presentation
GO:0032729 P:positive regulation of interferon-gamma production
GO:0002827 P:positive regulation of T-helper 1 type immune response
GO:0045944 P:positive regulation of transcription from RNA polymerase II promoter
GO:0002309 P:T cell proliferation involved in immune response

References (18)

[1] “Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression.”  Cellier M.et.al.   7964458
[2] “Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes.”  Kishi F.et.al.   8537108
[3] “Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35.”  Marquet S.et.al.   10967134
[4] “Isolation and characterization of human Nramp cDNA.”  Kishi F.et.al.   7980580
[5] “Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism.”  Blackwell J.M.et.al.   8529098
[6] “Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.”  Yu L.-R.et.al.   17924679
[7] “Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene.”  Liu J.et.al.   7717395
[8] “Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease.”  Malik S.et.al.   16103355
[9] “Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.”  Stienstra Y.et.al.   16395392
[10] “Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression.”  Cellier M.et.al.   7964458
[11] “Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes.”  Kishi F.et.al.   8537108
[12] “Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35.”  Marquet S.et.al.   10967134
[13] “Isolation and characterization of human Nramp cDNA.”  Kishi F.et.al.   7980580
[14] “Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism.”  Blackwell J.M.et.al.   8529098
[15] “Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.”  Yu L.-R.et.al.   17924679
[16] “Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene.”  Liu J.et.al.   7717395
[17] “Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease.”  Malik S.et.al.   16103355
[18] “Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.”  Stienstra Y.et.al.   16395392

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTGDKGPQRL SGSSYGSISS PTSPTSPGPQ QAPPRETYLS EKIPIPDTKP GTFSLRKLWA 
61:	FTGPGFLMSI AFLDPGNIES DLQAGAVAGF KLLWVLLWAT VLGLLCQRLA ARLGVVTGKD 
121:	LGEVCHLYYP KVPRTVLWLT IELAIVGSDM QEVIGTAIAF NLLSAGRIPL WGGVLITIVD 
181:	TFFFLFLDNY GLRKLEAFFG LLITIMALTF GYEYVVARPE QGALLRGLFL PSCPGCGHPE 
241:	LLQAVGIVGA IIMPHNIYLH SALVKSREID RARRADIREA NMYFLIEATI ALSVSFIINL 
301:	FVMAVFGQAF YQKTNQAAFN ICANSSLHDY AKIFPMNNAT VAVDIYQGGV ILGCLFGPAA 
361:	LYIWAIGLLA AGQSSTMTGT YAGQFVMEGF LRLRWSRFAR VLLTRSCAIL PTVLVAVFRD 
421:	LRDLSGLNDL LNVLQSLLLP FAVLPILTFT SMPTLMQEFA NGLLNKVVTS SIMVLVCAIN 
481:	LYFVVSYLPS LPHPAYFGLA ALLAAAYLGL STYLVWTCCL AHGATFLAHS SHHHFLYGLL 
541:	EEDQKGETSG