Protein Family Models

The natural resistance-associated macrophage protein (NRAMP) family consists of animal NRAMP1, NRAMP2, yeast proteins Smf1 and Smf2 and bacterial homologues [6-8]. The NRAMP family includes functional related proteins defined by a conserved hydrophobic core of ten transmembrane domains [5]. These membrane proteins are divalent cation transporters which have a high degree of sequence conservation, particularly, the residues contributing to ion interaction are stongly conserved (DPNG and MPH motifs) [6,7]. NRAMP1 is an integral membrane protein expressed exclusively in cells of the immune system and is recruited to the membrane of a phagosome upon phagocytosis, where it plays an essential role in host defense against pathogens [1-6]. Mutations in NRAMP1 may genetically predispose an individual to susceptibility to diseases including leprosy and tuberculosis [1]. NRAMP2 (DMT1) is a multiple divalent cation transporter broadly expressed in the duodenum, kidney, brain, testis and placenta. It transports Fe2+, Mn2+ and Cd+2, whereas Zn2+ is a poor substrate. Ca+2 and Mg+2 are not transported, which is important because their high concentrations in duodenum, where NRAMP2 is expressed at high levels, would interfere with the absorption of Fe2+ [6]. It is the major transferrin-independent iron uptake system in mammals [1,6]. NRAMP related members of this family have substrate specificity for Mn2+ and/or Mg2+, such as the yeast proteins Smf1 and Smf2 [3] and a group of bacterial transporters (NrmT, for Nramp-related magnesium transporter) [8]. [1]. 9719491. Macrophage NRAMP1 and its role in resistance to microbial infections. Govoni. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

This model describes the Nramp metal ion transporter family. Historically, in mammals these proteins have been functionally characterized as proteins involved in the host pathogen resistance, hence the name - NRAMP. At least two isoforms Nramp1 and Nramp2 have been identified. However the exact mechanism of pathogen resistance was unclear, until it was demonstrated by expression cloning and electrophysiological techniques that this protein was a metal ion transporter. It was also independently demonstrated that a microcytic anemia (mk) locus in mouse, encodes a metal ion transporter (DCT1 or Nramp2). The transporter has a broad range of substrate specificity that include Fe+2, Zn+2, Mn+2, Co+2, Cd+2, Cu+2, Ni+2 and Pb+2. The uptake of these metal ions is coupled to proton symport. Metal ions are essential cofactors in a number of biological process including, oxidative phosphorylation, gene regulation and metal ion homeostasis. Nramp1 could confer resistance to infection in one of the two ways. (1) The uptake of Fe+2 can produce toxic hydroxyl radicals via Fenton reaction killing the pathogens in phagosomes or (2) Deplete the metal ion pools in the phagosome and deprive the pathogens of metal ions, which is critical for its survival.

Date:

2024-06-14

Gene:

mntH

Date:

2020-10-26

Nramp (natural resistance-associated macrophage protein) family divalent metal transporters are widely conserved divalent metal transporters, which enables manganese import in bacteria and dietary iron uptake in mammals.

Date:

2022-03-28