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Conserved domains on  [gi|1622860706|ref|XP_028688644|]
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solute carrier family 22 member 12 isoform X4 [Macaca mulatta]

Protein Classification

MFS transporter( domain architecture ID 1000272)

major facilitator superfamily (MFS) transporter facilitates the transport across cytoplasmic or internal membranes of one or more from a variety of substrates; similar to Drosophila melanogaster organic cation transporter protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
MFS super family cl28910
Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse ...
109-168 1.47e-29

Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides. They do so using the electrochemical potential of the transported substrates. Uniporters transport a single substrate, while symporters and antiporters transport two substrates in the same or in opposite directions, respectively, across membranes. MFS proteins are typically 400 to 600 amino acids in length, and the majority contain 12 transmembrane alpha helices (TMs) connected by hydrophilic loops. The N- and C-terminal halves of these proteins display weak similarity and may be the result of a gene duplication/fusion event. Based on kinetic studies and the structures of a few bacterial superfamily members, GlpT (glycerol-3-phosphate transporter), LacY (lactose permease), and EmrD (multidrug transporter), MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement. Bacterial members function primarily for nutrient uptake, and as drug-efflux pumps to confer antibiotic resistance. Some MFS proteins have medical significance in humans such as the glucose transporter Glut4, which is impaired in type II diabetes, and glucose-6-phosphate transporter (G6PT), which causes glycogen storage disease when mutated.


The actual alignment was detected with superfamily member cd17374:

Pssm-ID: 475125 [Multi-domain]  Cd Length: 341  Bit Score: 118.16  E-value: 1.47e-29
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706 109 SEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASD 168
Cdd:cd17374     1 SEADTEPCVDGWVYDRSKFTSTIVTEWDLVCESQSLKSVAQSIFMAGLLVGALIFGHLSD 60
2A0119 super family cl36765
cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]
11-171 3.63e-24

cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]


The actual alignment was detected with superfamily member TIGR00898:

Pssm-ID: 273328 [Multi-domain]  Cd Length: 505  Bit Score: 105.10  E-value: 3.63e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  11 GGLGRFQVLQTVALMVSIMWLSTQSMLENFSAAVPSHRCWVPLLDNstaqagvpggLTPKALLAVSIPPGPNQGPHQCRR 90
Cdd:TIGR00898   1 GEFGPFQRRTFLLLALPIALLAFHFVLIVFLGATPEHHCRLPDAAN----------LSSRCELNLTLPRLPDGRPESCLR 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  91 FRQPQWQI-----LDPNATaTSWSEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGP 165
Cdd:TIGR00898  71 FMVDQWANpsllgCEPLKL-SDLGLAATEPCLDGWEYSYDTFSSTIVTEWDLVCEDAWKVDLTQSCFFVGVLLGSFVFGY 149

                  ....*.
gi 1622860706 166 ASDSDG 171
Cdd:TIGR00898 150 LSDRFG 155
 
Name Accession Description Interval E-value
MFS_OAT cd17374
Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion ...
109-168 1.47e-29

Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion transporters (OATs) generally display broad substrate specificity and they facilitate the exchange of extracellular with intracellular organic anions (OAs). Several OATs have been characterized including OAT1-10 and urate anion exchanger 1 (URAT1, also called SLC22A12). Many OATs occur in renal proximal tubules, the site of active drug secretion. OATs mediate the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories, and therefore is critical for the survival of the mammalian species. OAT falls into the SLC22 (solute carrier 22) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340932 [Multi-domain]  Cd Length: 341  Bit Score: 118.16  E-value: 1.47e-29
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706 109 SEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASD 168
Cdd:cd17374     1 SEADTEPCVDGWVYDRSKFTSTIVTEWDLVCESQSLKSVAQSIFMAGLLVGALIFGHLSD 60
2A0119 TIGR00898
cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]
11-171 3.63e-24

cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]


Pssm-ID: 273328 [Multi-domain]  Cd Length: 505  Bit Score: 105.10  E-value: 3.63e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  11 GGLGRFQVLQTVALMVSIMWLSTQSMLENFSAAVPSHRCWVPLLDNstaqagvpggLTPKALLAVSIPPGPNQGPHQCRR 90
Cdd:TIGR00898   1 GEFGPFQRRTFLLLALPIALLAFHFVLIVFLGATPEHHCRLPDAAN----------LSSRCELNLTLPRLPDGRPESCLR 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  91 FRQPQWQI-----LDPNATaTSWSEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGP 165
Cdd:TIGR00898  71 FMVDQWANpsllgCEPLKL-SDLGLAATEPCLDGWEYSYDTFSSTIVTEWDLVCEDAWKVDLTQSCFFVGVLLGSFVFGY 149

                  ....*.
gi 1622860706 166 ASDSDG 171
Cdd:TIGR00898 150 LSDRFG 155
 
Name Accession Description Interval E-value
MFS_OAT cd17374
Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion ...
109-168 1.47e-29

Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion transporters (OATs) generally display broad substrate specificity and they facilitate the exchange of extracellular with intracellular organic anions (OAs). Several OATs have been characterized including OAT1-10 and urate anion exchanger 1 (URAT1, also called SLC22A12). Many OATs occur in renal proximal tubules, the site of active drug secretion. OATs mediate the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories, and therefore is critical for the survival of the mammalian species. OAT falls into the SLC22 (solute carrier 22) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340932 [Multi-domain]  Cd Length: 341  Bit Score: 118.16  E-value: 1.47e-29
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706 109 SEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASD 168
Cdd:cd17374     1 SEADTEPCVDGWVYDRSKFTSTIVTEWDLVCESQSLKSVAQSIFMAGLLVGALIFGHLSD 60
2A0119 TIGR00898
cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]
11-171 3.63e-24

cation transport protein; [Transport and binding proteins, Cations and iron carrying compounds]


Pssm-ID: 273328 [Multi-domain]  Cd Length: 505  Bit Score: 105.10  E-value: 3.63e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  11 GGLGRFQVLQTVALMVSIMWLSTQSMLENFSAAVPSHRCWVPLLDNstaqagvpggLTPKALLAVSIPPGPNQGPHQCRR 90
Cdd:TIGR00898   1 GEFGPFQRRTFLLLALPIALLAFHFVLIVFLGATPEHHCRLPDAAN----------LSSRCELNLTLPRLPDGRPESCLR 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622860706  91 FRQPQWQI-----LDPNATaTSWSEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGP 165
Cdd:TIGR00898  71 FMVDQWANpsllgCEPLKL-SDLGLAATEPCLDGWEYSYDTFSSTIVTEWDLVCEDAWKVDLTQSCFFVGVLLGSFVFGY 149

                  ....*.
gi 1622860706 166 ASDSDG 171
Cdd:TIGR00898 150 LSDRFG 155
MFS_SLC22A6_OAT1_like cd17446
Solute carrier family 22 member 6 (also called Organic anion transporter 1) and similar ...
111-171 1.55e-20

Solute carrier family 22 member 6 (also called Organic anion transporter 1) and similar transporters of the Major Facilitator Superfamily; This subfamily includes solute carrier family 22 member 6 (SLC22A6, also called organic anion transporter 1 or OAT1 or para-aminohippurate (PAH) transporter), SLC22A8 (or OAT3), and SLC22A20 (or OAT6). OAT1 and OAT3 are involved in the renal elimination of endogenous and exogenous organic anions (OAs). They function as OA exchangers, coupling the uptake of OAs against an electrochemical gradient with the efflux of intracellular dicarboxylates. SLC22A20 is an OA transporter that mediates the uptake of estrone sulfate. The OAT1-like subfamily belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 341004 [Multi-domain]  Cd Length: 339  Bit Score: 92.48  E-value: 1.55e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622860706 111 ADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17446     1 LATEPCTDGWVYDKSEFPSTIITEWDLVCNHRALRQLAQSIYMAGVLVGAIVFGGLSDRFG 61
MFS_SLC22A4_5_OCTN1_2 cd17376
Solute carrier family 22 members 4 and 5 (also called Organic cation/carnitine transporters 1 ...
109-171 1.11e-13

Solute carrier family 22 members 4 and 5 (also called Organic cation/carnitine transporters 1 and 2) of the Major Facilitator Superfamily of transporters; This subfamily is composed of solute carrier family 22 members 4 (SLC22A4) and 5 (SLC22A5), and similar proteins. SLC22A4 is also called ergothioneine transporter (ETT) or organic cation/carnitine transporter 1 (OCTN1). It is a sodium-ion dependent, low affinity carnitine transporter, and a highly specific transporter for the uptake of ergothioneine (ET), a thiolated derivative of histidine with antioxidant properties. ET is a natural compound produced only by certain fungi and bacteria and must be absorbed from the diet by humans and other vetebrates. SLC22A5, also called organic cation/carnitine transporter 2 (OCTN2), is a sodium-ion dependent, high affinity carnitine transporter involved in the active cellular uptake of carnitine. SLC22A4/5 belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340934 [Multi-domain]  Cd Length: 342  Bit Score: 72.11  E-value: 1.11e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622860706 109 SEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17376     1 TQIEQEPCLDGWEYSQDVYLSTIVTEWNLVCEDDWKVPLTTSLFFVGVLLGSFISGQLSDRFG 63
MFS_SLC22A7_OAT2 cd17447
Solute carrier family 22 member 7 (also called Organic anion transporter 2) of the Major ...
109-171 4.37e-13

Solute carrier family 22 member 7 (also called Organic anion transporter 2) of the Major Facilitator Superfamily of transporters; Solute carrier family 22 member 7 (SLC22A7), also called organic anion transporter 2 (OAT2) mediates sodium-independent transport of a variety of organic anions including prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate. It also plays a role in renal uric acid uptake from blood as a first step of tubular secretion. OAT2 belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS)of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 341005 [Multi-domain]  Cd Length: 341  Bit Score: 70.14  E-value: 4.37e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622860706 109 SEADTEPCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17447     1 SDLPVVPCQNGWVYDHSTFSSTIATEWDLVCDRKGLNQATATFFFAGVTMGAVAFGYLSDRFG 63
MFS_SLC22A16_CT2 cd17375
Solute carrier family 22 member 16 (also called Carnitine transporter 2) of the Major ...
115-171 6.99e-11

Solute carrier family 22 member 16 (also called Carnitine transporter 2) of the Major Facilitator Superfamily of transporters; Solute carrier family 22 member 16 (SLC22A16) is also called carnitine transporter 2 (CT2), fly-like putative transporter 2 (FLIPT2), organic cation transporter OKB1, or organic cation/carnitine transporter 6 (OCT6). It is a partially sodium-ion dependent high affinity carnitine transporter. It also transports organic cations such as tetraethylammonium (TEA) and doxorubicin. It is one of several organic cation transporters (OCTs) that falls into the SLC22 (solute carrier 22) family. OCTs are broad-specificity transporters that play a critical role in the excretion and distribution of endogeneous organic cations and for the uptake, elimination and distribution of cationic drugs, toxins, and environmental waste products. SLC22A16 belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340933 [Multi-domain]  Cd Length: 341  Bit Score: 63.62  E-value: 6.99e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622860706 115 PCVDGWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17375     7 SCSDGFVYDQSKWESSIVTDWDLVCDREWLAKLIQPIFMLGVLLGAVIFGDIADRIG 63
MFS_SLC22 cd17317
Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major ...
119-171 3.63e-10

Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily; The Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. The SLC22 family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340875 [Multi-domain]  Cd Length: 331  Bit Score: 61.06  E-value: 3.63e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1622860706 119 GWVYDHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17317     1 GWEFDYSVSESTIVTEWDLVCDRDWLVALVQTIFFLGVLIGSLLFGYLADRFG 53
MFS_SLC22A1_2_3 cd17379
Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, ...
115-171 2.25e-05

Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, and 3) of the Major Facilitator Superfamily of transporters; This sufamily includes solute carrier family 22 member 1 (SLC22A1, also called organic cation transporter 1 or OCT1), SLC22A2 (or OCT2), SLC22A3 (or OCT3), and similar proteins. OCT1-3 have similar basic functional properties: they are able to translocate a variety of structurally different organic cations in both directions across the plasma membrane; to translocate organic cations independently from sodium, chloride or proton gradients; and to function as electrogenic uniporters for cations or as electroneutral cation exchangers. They show overlapping but distinct substrate and inhibitor specificities, and different tissue expression pattern. In humans, OCT1 is strongly expressed in the liver, OCT2 is highly expressed in the kidney where it is localized at the basolateral membrane of renal proximal tubules, and OCT3 is most strongly expressed in skeletal muscle. OCTs are broad-specificity transporters that play a critical role in the excretion and distribution of endogeneous organic cations and for the uptake, elimination and distribution of cationic drugs, toxins, and environmental waste products. The SLC22A1-3 subfamily belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 340937 [Multi-domain]  Cd Length: 340  Bit Score: 46.19  E-value: 2.25e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622860706 115 PCVDGWVYDHSifTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17379     7 PCQDGWVYNTP--RSSIVTEFNLVCEDAWKLDLFQSSLNLGFLIGSIVIGYLADRFG 61
MFS_SLC22A17 cd17445
Solute carrier family 22, member 17 of the Major Facilitator Superfamily; Solute carrier ...
116-171 2.18e-03

Solute carrier family 22, member 17 of the Major Facilitator Superfamily; Solute carrier family 22, member 17 (SLC22A17) is also called 24p3 receptor (24p3R), lipocalin-2 receptor, or neutrophil gelatinase-associated lipocalin (NGAL) receptor (NGALR). It functions as a cell surface receptor for lipocalin-2 (LCN2), also called NGAL or 24p3, which plays a key role in iron homeostasis and transport. LCN2 is a secreted protein of the lipocalin family that induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron-laden bacterial siderophore. Over-expressions of NGAL and NGALR have been found to be correlated with unfavorable clinicopathologic features and poor prognosis of patients with hepatocellular carcinoma. SLC22A17 is a member of the SLC22 family of organic cation/anion/zwitterion transporters, which includes organic cation transporters (OCTs/OCTNs) and organic anion transporters (OATs). It belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.


Pssm-ID: 341003 [Multi-domain]  Cd Length: 346  Bit Score: 40.14  E-value: 2.18e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622860706 116 CVDGWVY-DHSIFTSTIVAKWNLVCDSHALKPMAQSIYLAGILVGAAACGPASDSDG 171
Cdd:cd17445     8 CDAGWNYtGLPGLTNNIVTEWDLVCSRYWLVPLEQVCFILGFASGYLCLGYTADRLG 64
 
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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