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Conserved domains on  [gi|1255287627|ref|NP_001343881|]
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natural resistance-associated macrophage protein 2 isoform 3 [Mus musculus]

Protein Classification

SLC5/6 family protein( domain architecture ID 124)

SLC5/6 (solute carrier 5/6) family protein may function as a transporter

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SLC5-6-like_sbd super family cl00456
Solute carrier families 5 and 6-like; solute binding domain; This superfamily includes the ...
 1-203 1.77e-98

Solute carrier families 5 and 6-like; solute binding domain; This superfamily includes the solute-binding domain of SLC5 proteins (also called the sodium/glucose cotransporters or solute sodium symporters), SLC6 proteins (also called the sodium- and chloride-dependent neurotransmitter transporters or Na+/Cl--dependent transporters), and nucleobase-cation-symport-1 (NCS1) transporters. SLC5s co-transport Na+ with sugars, amino acids, inorganic ions or vitamins. SLC6s include Na+/Cl--dependent plasma membrane transporters for the monoamine neurotransmitters serotonin, dopamine, and norepinephrine, and the amino acid neurotransmitters GABA and glycine. NCS1s are essential components of salvage pathways for nucleobases and related metabolites; their known substrates include allantoin, uracil, thiamine, and nicotinamide riboside. Members of this superfamily are important in human physiology and disease. They contain a functional core of 10 transmembrane helices (TMs): an inverted structural repeat, TMs1-5 and TMs6-10; TMs numbered to conform to the SLC6 Aquifex aeolicus LeuT.


The actual alignment was detected with superfamily member TIGR01197:

Pssm-ID: 444915  Cd Length: 390  Bit Score: 294.71  E-value: 1.77e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRANKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNKQVVEVcknnssphADL 80
Cdd:TIGR01197 196 MPHSLYLHSALVQSRLVDRDVKEGVSEANMYRPIEAAIALSVSFSINEFVIALFTAALFVNTNILVVAG--------ATL 267

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 FPSDNSTLAVDIYKGGVVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:TIGR01197 268 FNSNNNADAADLFSIGVLLGCLFSPAAGYIFAVGLLAAGQSSGMVGTYSGQFVMEGFLNWRWSPWLRRLITRAIAIIPCL 347

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVM 203
Cdd:TIGR01197 348 LVAAFGGREGLTGALNASQVVLSLLLPFALIPLIMFTSSKKIM 390
 
Name Accession Description Interval E-value
nramp TIGR01197
NRAMP (natural resistance-associated macrophage protein) metal ion transporters; This model ...
 1-203 1.77e-98

NRAMP (natural resistance-associated macrophage protein) metal ion transporters; 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. [Transport and binding proteins, Cations and iron carrying compounds]


Pssm-ID: 162246  Cd Length: 390  Bit Score: 294.71  E-value: 1.77e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRANKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNKQVVEVcknnssphADL 80
Cdd:TIGR01197 196 MPHSLYLHSALVQSRLVDRDVKEGVSEANMYRPIEAAIALSVSFSINEFVIALFTAALFVNTNILVVAG--------ATL 267

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 FPSDNSTLAVDIYKGGVVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:TIGR01197 268 FNSNNNADAADLFSIGVLLGCLFSPAAGYIFAVGLLAAGQSSGMVGTYSGQFVMEGFLNWRWSPWLRRLITRAIAIIPCL 347

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVM 203
Cdd:TIGR01197 348 LVAAFGGREGLTGALNASQVVLSLLLPFALIPLIMFTSSKKIM 390
Nramp pfam01566
Natural resistance-associated macrophage protein; The natural resistance-associated macrophage ...
 1-210 1.19e-48

Natural resistance-associated macrophage protein; The natural resistance-associated macrophage protein (NRAMP) family consists of Nramp1, Nramp2, and yeast proteins Smf1 and Smf2. The NRAMP family is a novel family of functional related proteins defined by a conserved hydrophobic core of ten transmembrane domains. This family of membrane proteins are divalent cation transporters. 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. By controlling divalent cation concentrations Nramp1 may regulate the interphagosomal replication of bacteria. Mutations in Nramp1 may genetically predispose an individual to susceptibility to diseases including leprosy and tuberculosis conversely this might however provide protection form rheumatoid arthritis. Nramp2 is a multiple divalent cation transporter for Fe2+, Mn2+ and Zn2+ amongst others it is expressed at high levels in the intestine; and is major transferrin-independent iron uptake system in mammals. The yeast proteins Smf1 and Smf2 may also transport divalent cations.


Pssm-ID: 426327 [Multi-domain]  Cd Length: 356  Bit Score: 165.43  E-value: 1.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRaNKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNKQVVEvcknnssphadl 80
Cdd:pfam01566 171 MPHNLFLHSSLVQERGWTI-DRDEEDEALRYSRIDTIIALIVAGLVNAAILIVAAAAFHGSGGIDVAT------------ 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlAVDIYKggvVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:pfam01566 238 --------LADAAA---ALEPLLGKAAAVLFALGLLAAGLSSTITGTLAGQYVMEGFLGWRIPLWLRRLITRAIAFYPAL 306

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGI 210
Cdd:pfam01566 307 AVILLGGAPGVVQLLVLSQVVLSLQLPFALIPLLLLTSDRKLMGEFVNSR 356
PRK00701 PRK00701
divalent metal cation transporter MntH;
1-238 6.29e-43

divalent metal cation transporter MntH;


Pssm-ID: 234815  Cd Length: 439  Bit Score: 152.30  E-value: 6.29e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRANKqEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFektnkqvvevcKNNSSPHADL 80
Cdd:PRK00701  226 MPHNLYLHSSLVQTRVVGRTGE-EKREALRFTRIDSAIALTIAGFVNAAMLILAAAAFH-----------ASGHTDVADI 293

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlaVDIYKGgvvLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:PRK00701  294 ---------EDAYLL---LSPLLGAAAATLFGIALLASGLSSTVVGTLAGQIVMEGFLRLRIPLWVRRLITRGLAMVPAL 361

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGIGWRIAGGILVLIVCSINMYFVVVYVQEL 238
Cdd:PRK00701  362 IVILLGGELDPTRLLVLSQVVLSFGLPFALIPLLLFTSDRKLMGELVNPRWVKIIAWIIAVLIVALNIYLLYQTFTGL 439
MntH COG1914
Mn2+ or Fe2+ transporter, NRAMP family [Inorganic ion transport and metabolism];
1-232 2.11e-31

Mn2+ or Fe2+ transporter, NRAMP family [Inorganic ion transport and metabolism];


Pssm-ID: 441518 [Multi-domain]  Cd Length: 405  Bit Score: 120.63  E-value: 2.11e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRankqevREANKYFFIESCIALFVSFIINVFVVSVFAEAFFeKTNKQVVEvcknnssphadl 80
Cdd:COG1914   199 MPYNLFLHSSLVQEKGWTG------KEDLRYARLDTVVGMLLAGLVNLAILLLAAAVLH-GTGIGVDS------------ 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlAVDIYKggvVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARV--ILTRSIAIIP 158
Cdd:COG1914   260 --------AAQAAQ---ALEPLLGEWAAILFALGLLAAGFSSTITATLAGAYVMAGFLGWRIGLWLRRfyLVTRLLTLIG 328

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1255287627 159 TLLVAVFQDveHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGIGWRIAGGILVLIVCSINMYFVV 232
Cdd:COG1914   329 ALIVLLLGG--DPVKLLVLSQVLNGLLLPFALIPLLLLTNDKDLMGEYRNGRWLNVLGWLIVLLIVVLNLYLLV 400
 
Name Accession Description Interval E-value
nramp TIGR01197
NRAMP (natural resistance-associated macrophage protein) metal ion transporters; This model ...
 1-203 1.77e-98

NRAMP (natural resistance-associated macrophage protein) metal ion transporters; 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. [Transport and binding proteins, Cations and iron carrying compounds]


Pssm-ID: 162246  Cd Length: 390  Bit Score: 294.71  E-value: 1.77e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRANKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNKQVVEVcknnssphADL 80
Cdd:TIGR01197 196 MPHSLYLHSALVQSRLVDRDVKEGVSEANMYRPIEAAIALSVSFSINEFVIALFTAALFVNTNILVVAG--------ATL 267

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 FPSDNSTLAVDIYKGGVVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:TIGR01197 268 FNSNNNADAADLFSIGVLLGCLFSPAAGYIFAVGLLAAGQSSGMVGTYSGQFVMEGFLNWRWSPWLRRLITRAIAIIPCL 347

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVM 203
Cdd:TIGR01197 348 LVAAFGGREGLTGALNASQVVLSLLLPFALIPLIMFTSSKKIM 390
Nramp pfam01566
Natural resistance-associated macrophage protein; The natural resistance-associated macrophage ...
 1-210 1.19e-48

Natural resistance-associated macrophage protein; The natural resistance-associated macrophage protein (NRAMP) family consists of Nramp1, Nramp2, and yeast proteins Smf1 and Smf2. The NRAMP family is a novel family of functional related proteins defined by a conserved hydrophobic core of ten transmembrane domains. This family of membrane proteins are divalent cation transporters. 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. By controlling divalent cation concentrations Nramp1 may regulate the interphagosomal replication of bacteria. Mutations in Nramp1 may genetically predispose an individual to susceptibility to diseases including leprosy and tuberculosis conversely this might however provide protection form rheumatoid arthritis. Nramp2 is a multiple divalent cation transporter for Fe2+, Mn2+ and Zn2+ amongst others it is expressed at high levels in the intestine; and is major transferrin-independent iron uptake system in mammals. The yeast proteins Smf1 and Smf2 may also transport divalent cations.


Pssm-ID: 426327 [Multi-domain]  Cd Length: 356  Bit Score: 165.43  E-value: 1.19e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRaNKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFEKTNKQVVEvcknnssphadl 80
Cdd:pfam01566 171 MPHNLFLHSSLVQERGWTI-DRDEEDEALRYSRIDTIIALIVAGLVNAAILIVAAAAFHGSGGIDVAT------------ 237

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlAVDIYKggvVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:pfam01566 238 --------LADAAA---ALEPLLGKAAAVLFALGLLAAGLSSTITGTLAGQYVMEGFLGWRIPLWLRRLITRAIAFYPAL 306

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGI 210
Cdd:pfam01566 307 AVILLGGAPGVVQLLVLSQVVLSLQLPFALIPLLLLTSDRKLMGEFVNSR 356
PRK00701 PRK00701
divalent metal cation transporter MntH;
1-238 6.29e-43

divalent metal cation transporter MntH;


Pssm-ID: 234815  Cd Length: 439  Bit Score: 152.30  E-value: 6.29e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRANKqEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFektnkqvvevcKNNSSPHADL 80
Cdd:PRK00701  226 MPHNLYLHSSLVQTRVVGRTGE-EKREALRFTRIDSAIALTIAGFVNAAMLILAAAAFH-----------ASGHTDVADI 293

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlaVDIYKGgvvLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVILTRSIAIIPTL 160
Cdd:PRK00701  294 ---------EDAYLL---LSPLLGAAAATLFGIALLASGLSSTVVGTLAGQIVMEGFLRLRIPLWVRRLITRGLAMVPAL 361

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1255287627 161 LVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGIGWRIAGGILVLIVCSINMYFVVVYVQEL 238
Cdd:PRK00701  362 IVILLGGELDPTRLLVLSQVVLSFGLPFALIPLLLFTSDRKLMGELVNPRWVKIIAWIIAVLIVALNIYLLYQTFTGL 439
MntH COG1914
Mn2+ or Fe2+ transporter, NRAMP family [Inorganic ion transport and metabolism];
1-232 2.11e-31

Mn2+ or Fe2+ transporter, NRAMP family [Inorganic ion transport and metabolism];


Pssm-ID: 441518 [Multi-domain]  Cd Length: 405  Bit Score: 120.63  E-value: 2.11e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627   1 MPHNMYLHSALVKSRQVNRankqevREANKYFFIESCIALFVSFIINVFVVSVFAEAFFeKTNKQVVEvcknnssphadl 80
Cdd:COG1914   199 MPYNLFLHSSLVQEKGWTG------KEDLRYARLDTVVGMLLAGLVNLAILLLAAAVLH-GTGIGVDS------------ 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1255287627  81 fpsdnstlAVDIYKggvVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARV--ILTRSIAIIP 158
Cdd:COG1914   260 --------AAQAAQ---ALEPLLGEWAAILFALGLLAAGFSSTITATLAGAYVMAGFLGWRIGLWLRRfyLVTRLLTLIG 328

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1255287627 159 TLLVAVFQDveHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSEFSNGIGWRIAGGILVLIVCSINMYFVV 232
Cdd:COG1914   329 ALIVLLLGG--DPVKLLVLSQVLNGLLLPFALIPLLLLTNDKDLMGEYRNGRWLNVLGWLIVLLIVVLNLYLLV 400
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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