major facilitator superfamily (MFS) transporter facilitates the transport across cytoplasmic or internal membranes of one or more from a variety of substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides
Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse ...
54-591
0e+00
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 cd17460:
Pssm-ID: 475125 [Multi-domain] Cd Length: 479 Bit Score: 698.83 E-value: 0e+00
Solute carrier organic anion transporter 2B subfamily of the Major Facilitator Superfamily of ...
54-591
0e+00
Solute carrier organic anion transporter 2B subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 2B (SLCO2B), also called Organic anion-transporting polypeptide 2B (OATP2B), subfamily has one mammalian member, OATP2B1 (encoded by SLCO2B1). It mediates the Na(+)-independent transport of various organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost. It also mediates the transport of endogenous sex steroid conjugates such as dehydroepiandrosterone sulfate (DHEAS). SLCO2B1 variations result in differential expression and uptake of DHEAS, which impacts subsequent resistance to androgen-deprivation therapy (ADT), the primary treatment of metastatic prostate cancer. The SLCO2B/OATP2B subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341018 [Multi-domain] Cd Length: 479 Bit Score: 698.83 E-value: 0e+00
Organic Anion Transporter Polypeptide (OATP) family; This family consists of several ...
56-650
0e+00
Organic Anion Transporter Polypeptide (OATP) family; This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules). Thus, Tamai et al. initiated the current scheme of using digits for rat OATPs and letters for human ones. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. Note: Members of this family are described (in the Swiss-Prot database) as belonging to the SLC21 family of transporters.
Pssm-ID: 460821 [Multi-domain] Cd Length: 526 Bit Score: 621.91 E-value: 0e+00
sodium-independent organic anion transporter; The Organo Anion Transporter (OAT) Family (TC 2. ...
29-677
7.42e-170
sodium-independent organic anion transporter; The Organo Anion Transporter (OAT) Family (TC 2.A.60)Proteins of the OAT family catalyze the Na+-independent facilitated transport of organic anions such as bromosulfobromophthalein and prostaglandins as well as conjugated and unconjugated bile acids (taurocholate and cholate, respectively). These transporters have been characterized in mammals, but homologues are present in C. elegans and A. thaliana. Some of the mammalian proteins exhibit a high degree of tissue specificity. For example, the rat OAT is found at high levels in liver and kidney and at lower levels in other tissues. These proteins possess 10-12 putative a-helical transmembrane spanners. They may catalyze electrogenic anion uniport or anion exchange.
Pssm-ID: 273279 [Multi-domain] Cd Length: 632 Bit Score: 500.80 E-value: 7.42e-170
Solute carrier organic anion transporter 2B subfamily of the Major Facilitator Superfamily of ...
54-591
0e+00
Solute carrier organic anion transporter 2B subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 2B (SLCO2B), also called Organic anion-transporting polypeptide 2B (OATP2B), subfamily has one mammalian member, OATP2B1 (encoded by SLCO2B1). It mediates the Na(+)-independent transport of various organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost. It also mediates the transport of endogenous sex steroid conjugates such as dehydroepiandrosterone sulfate (DHEAS). SLCO2B1 variations result in differential expression and uptake of DHEAS, which impacts subsequent resistance to androgen-deprivation therapy (ADT), the primary treatment of metastatic prostate cancer. The SLCO2B/OATP2B subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341018 [Multi-domain] Cd Length: 479 Bit Score: 698.83 E-value: 0e+00
Organic Anion Transporter Polypeptide (OATP) family; This family consists of several ...
56-650
0e+00
Organic Anion Transporter Polypeptide (OATP) family; This family consists of several eukaryotic Organic-Anion-Transporting Polypeptides (OATPs). Several have been identified mostly in human and rat. Different OATPs vary in tissue distribution and substrate specificity. Since the numbering of different OATPs in particular species was based originally on the order of discovery, similarly numbered OATPs in humans and rats did not necessarily correspond in function, tissue distribution and substrate specificity (in spite of the name, some OATPs also transport organic cations and neutral molecules). Thus, Tamai et al. initiated the current scheme of using digits for rat OATPs and letters for human ones. Prostaglandin transporter (PGT) proteins are also considered to be OATP family members. In addition, the methotrexate transporter OATK is closely related to OATPs. This family also includes several predicted proteins from Caenorhabditis elegans and Drosophila melanogaster. This similarity was not previously noted. Note: Members of this family are described (in the Swiss-Prot database) as belonging to the SLC21 family of transporters.
Pssm-ID: 460821 [Multi-domain] Cd Length: 526 Bit Score: 621.91 E-value: 0e+00
Solute carrier organic anion transporter 2 family of the Major Facilitator Superfamily of ...
54-591
0e+00
Solute carrier organic anion transporter 2 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 2 (SLCO2) or Organic anion transporting polypeptide 2 (OATP2) family contains two subfamilies: OATP2A and OATP2B, each containing one mammalian member, OATP2A1 and OATP2B1, respectively. OATP2A1 (encoded by SLCO2A1) is a lactate/prostaglandin anion exchanger that mediates the release of newly synthesized prostaglandins (PGD2, PGE1, PGE2, PGF2A and PGI2) from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. OATP2B1 (encoded by SLCO2B1) mediates the Na(+)-independent transport of various organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost, as well as endogenous sex steroid conjugates such as dehydroepiandrosterone sulfate (DHEAS). The SLCO2/OATP2 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340959 [Multi-domain] Cd Length: 440 Bit Score: 613.01 E-value: 0e+00
Solute carrier organic anion transporter 2A subfamily of the Major Facilitator Superfamily of ...
53-591
3.04e-177
Solute carrier organic anion transporter 2A subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 2A (SLCO2A), also called Organic anion-transporting polypeptide 2A (OATP2A), subfamily has one mammalian member, OATP2A1 (encoded by SLCO2A1), which is also called prostaglandin transporter. It is a lactate/prostaglandin anion exchanger that mediates the release of newly synthesized prostaglandins (PGD2, PGE1, PGE2, PGF2A and PGI2) from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Mutations in SLCO2A1 can cause primary hypertrophic osteoarthropathy (PHO), a rare multi-organic disease characterized by digital clubbing, pachydermia and periosteal reaction. The SLCO2A/OATP2A subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341019 [Multi-domain] Cd Length: 474 Bit Score: 513.97 E-value: 3.04e-177
sodium-independent organic anion transporter; The Organo Anion Transporter (OAT) Family (TC 2. ...
29-677
7.42e-170
sodium-independent organic anion transporter; The Organo Anion Transporter (OAT) Family (TC 2.A.60)Proteins of the OAT family catalyze the Na+-independent facilitated transport of organic anions such as bromosulfobromophthalein and prostaglandins as well as conjugated and unconjugated bile acids (taurocholate and cholate, respectively). These transporters have been characterized in mammals, but homologues are present in C. elegans and A. thaliana. Some of the mammalian proteins exhibit a high degree of tissue specificity. For example, the rat OAT is found at high levels in liver and kidney and at lower levels in other tissues. These proteins possess 10-12 putative a-helical transmembrane spanners. They may catalyze electrogenic anion uniport or anion exchange.
Pssm-ID: 273279 [Multi-domain] Cd Length: 632 Bit Score: 500.80 E-value: 7.42e-170
Solute carrier organic anion transporters of the Major Facilitator Superfamily of transporters; ...
54-591
1.83e-130
Solute carrier organic anion transporters of the Major Facilitator Superfamily of transporters; Solute carrier organic anion transporters (SLCOs) are also called organic anion transporting polypeptides (OATPs) or SLC21 (Solute carrier family 21) proteins. They are sodium-independent transporters that mediate the transport of a broad range of endo- as well as xenobiotics. Their substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, although there are a few known neutral or positively charged substrates. These include drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives, and anticancer drugs. SLCOs/OATPs can be classified into 6 families (SLCO1-6 or OATP1-6) and each family may have subfamilies (e.g. OATP1A, OATP1B, OATP1C). Within the subfamilies, individual members are numbered according to the chronology of their identification and if there is already an ortholog known, they are given the same number. For example, the first SLCO identified, is rat OATP1A1 (encoded by the Slco1a1 gene). The second SLCO identified is the first human SLCO from the same subfamily and is called OATP1A2 (encoded by the SLCO1A2 gene). There are 11 human SLCOs/OATPs. SLCOs belong 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: 340894 [Multi-domain] Cd Length: 411 Bit Score: 391.60 E-value: 1.83e-130
Solute carrier organic anion transporter 1C subfamily of the Major Facilitator Superfamily of ...
54-591
3.07e-104
Solute carrier organic anion transporter 1C subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 1C (SLCO1C), also called Organic anion-transporting polypeptide 1C (OATP1C), subfamily contains one mammalian member, OATP1C1 (encoded by SLCO1C1), which is also called thyroxine transporter. It mediates the high affinity transport of the thyroid hormones, T4 (3,5,3',5'tetraiodo-L-thyronine or thyroxine), rT3 (3,3'5'-triiodo-L-thyronine), and T3 (3,5,3'tri-iodo-L-thyronine or triiodothyronine), as well as organic anions such as 17-beta-glucuronosyl estradiol, estrone-3-sulfate, and sulfobromophthalein (BSP), which are transported with much lower efficiency. The SLCO1C/OATP1C subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341017 [Multi-domain] Cd Length: 498 Bit Score: 327.11 E-value: 3.07e-104
Solute carrier organic anion transporter 1A subfamily of the Major Facilitator Superfamily of ...
54-591
2.91e-102
Solute carrier organic anion transporter 1A subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 1A (SLCO1A), also called Organic anion-transporting polypeptide 1A (OATP1A), subfamily is composed of one human member OATP1A2 (encoded by SLCO1A2) and several rodent proteins encoded by the Slco1a1, Slco1a3, Slco1a4, Slco1a5, and Slco1a6 genes. OATP1A2, also known as human OATP-A or OATP1, shows a broad spectrum of substrates including endogenous compounds (such as bile acids, steroid hormones and their conjugates, thyroid hormones) and various drugs (such as fexofenadine, ouabain and the cyanobacterial toxin microcystin). It is expressed in the brain, kidney, intestine, liver, lung, testes, and the eye (ciliary body). The SLCO1A/OATP1A subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341016 [Multi-domain] Cd Length: 527 Bit Score: 322.96 E-value: 2.91e-102
Solute carrier organic anion transporter 4 family of the Major Facilitator Superfamily of ...
54-571
6.21e-98
Solute carrier organic anion transporter 4 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 4 (SLCO4) or Organic anion transporting polypeptide 4 (OATP4) family contains two families: OATP4A and OATP4C, each containing one mammalian member, OATP4A1 and OATP4C1, respectively. OATP4A1 (encoded by SLCO4A1), is ubiquitously expressed and mediates the Na(+)-independent transport of the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and other organic anions such as estrone sulfate and taurocholate. OATP4C1 (encoded by SLCO4C1) is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate, cAMP, and uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs). The SLCO4/OATP4 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340961 [Multi-domain] Cd Length: 420 Bit Score: 308.03 E-value: 6.21e-98
Solute carrier organic anion transporter 5 family of the Major Facilitator Superfamily of ...
55-591
9.27e-94
Solute carrier organic anion transporter 5 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 5 (SLCO5) or Organic anion transporting polypeptide 5 (OATP5) family contains only one subfamily, OATP5A, which contains only one mammalian member OATP5A1 (encoded by SLCO5A1). Deletion of the SLCO5A1 gene has been implicated in the pathogenesis of Mesomelia-synostoses syndrome (MSS), a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations. OATP5A1 may be a non-classical OATP which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration. It seems to affect intracellular transport of drugs and may participate in chemoresistance of small cell lung cancer (SCLC by sequestration), rather than mediating cellular uptake. The SLCO5/OATP5 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340962 [Multi-domain] Cd Length: 425 Bit Score: 297.34 E-value: 9.27e-94
Solute carrier organic anion transporter 3 family of the Major Facilitator Superfamily of ...
54-591
7.90e-90
Solute carrier organic anion transporter 3 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 3 (SLCO3) or Organic anion transporting polypeptide 3 (OATP3) family contains only one subfamily, OATP3A, which contains only one mammalian member OATP3A1 (encoded by SLCO3A1). It mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate, prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123, and vasopressin. SLCO3A1 has been identified as a Crohn's disease (CD)-associated gene, which mediates inflammatory processes in intestinal epithelial cells through NF-kappaB transcription activation, resulting in a higher incidence of bowel perforation in CD patients. The SLCO3/OATP3 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340960 [Multi-domain] Cd Length: 444 Bit Score: 287.60 E-value: 7.90e-90
Solute carrier organic anion transporter 1 family of the Major Facilitator Superfamily of ...
54-591
1.64e-83
Solute carrier organic anion transporter 1 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 1 (SLCO1) or Organic anion transporting polypeptide 1 (OATP1) family contains three subfamilies: OATP1A, OATP1B, and OATP1C. OATP1A contains one human member, OATP1A2, which shows a broad spectrum of substrates including endogenous compounds (such as bile acids, steroid hormones and their conjugates, thyroid hormones) and various drugs (such as fexofenadine, ouabain and the cyanobacterial toxin microcystin). OATP1B contains two human proteins, OATP1B1 and OATP1B3, which can both accept a wide variety of structurally-unrelated compounds as substrates including clinically-important drugs such as hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statins), angiotensin II receptor blockers (sartans), angiotensin converting enzyme (ACE) inhibitors, and anti-diabetes drugs (glinides). OATP1C contains one mammalian member, OATP1C1, which is also called thyroxine transporter. It mediates the high affinity transport of the thyroid hormones, T4 (3,5,3',5'tetraiodo-L-thyronine or thyroxine), rT3 (3,3'5'-triiodo-L-thyronine), and T3 (3,5,3'tri-iodo-L-thyronine or triiodothyronine). The SLCO1/OATP1 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340958 [Multi-domain] Cd Length: 436 Bit Score: 270.94 E-value: 1.64e-83
Solute carrier organic anion transporter 1B subfamily of the Major Facilitator Superfamily of ...
54-591
4.39e-83
Solute carrier organic anion transporter 1B subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 1B (SLCO1B), also called organic anion-transporting polypeptide 1B (OATP1B), subfamily is composed of two human proteins, OATP1B1 (encoded by SLCO1B1) and OATP1B3 (encoded by SLCO1B3), and one rodent member, OATP1B2 (encoded by Slco1b2). OATP1B1 and OATP1B3 are almost exclusively expressed on the basal side of hepatocytes in normal human organs. They both can accept a wide variety of structurally-unrelated compounds as substrates including clinically-important drugs such as hydroxymethylglutaryl (HMG)-CoA reductase inhibitors (statins), angiotensin II receptor blockers (sartans), angiotensin converting enzyme (ACE) inhibitors, and anti-diabetes drugs (glinides). Loss-of-function mutations in both SLCO1B1 and SLCO1B3 genes result in the Rotor syndrome, a hereditary hyperbilirubinemia. The SLCO1B/OATP1B subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341015 [Multi-domain] Cd Length: 455 Bit Score: 270.17 E-value: 4.39e-83
Solute carrier organic anion transporter 4A subfamily of the Major Facilitator Superfamily of ...
47-591
1.95e-71
Solute carrier organic anion transporter 4A subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 4A (SLCO4A), also called Organic anion-transporting polypeptide 4A (OATP4A), subfamily has one mammalian member, OATP4A1 (encoded by SLCO4A1). It is ubiquitously expressed and it mediates the Na(+)-independent transport of the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and other organic anions such as estrone sulfate and taurocholate. OATP4A1 is the most abundantly expressed transporter colorectal cancer (CRC) and its role in the transport of estrone sulfate, which is used in hormone replacement therapy (HRT), affects the outcome of the treatment. The SLCO4A/OATP4A subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341020 [Multi-domain] Cd Length: 427 Bit Score: 238.58 E-value: 1.95e-71
Solute carrier organic anion transporter 4C subfamily of the Major Facilitator Superfamily of ...
55-591
1.11e-68
Solute carrier organic anion transporter 4C subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 4C (SLCO4C), also called Organic anion-transporting polypeptide 4C (OATP4C), subfamily has one mammalian member, OATP4C1 (encoded by SLCO4C1). It is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. It is the only OATP expressed at the basolateral side of proximal tubular cells in human kidney and it mediates the excretion of uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Overexpression of human SLCO4C1 in rat kidney promotes the renal excretion of uremic toxins and reduces hypertension, cardiomegaly, and renal inflammation in renal failure. The SLCO4C/OATP4C subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 341021 [Multi-domain] Cd Length: 429 Bit Score: 231.17 E-value: 1.11e-68
Solute carrier organic anion transporter 6 family of the Major Facilitator Superfamily of ...
54-591
1.12e-30
Solute carrier organic anion transporter 6 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 6 (SLCO6) or Organic anion transporting polypeptide 6 (OATP6) family contains only one subfamily, OATP6A, which contains only one human member OATP6A1 (encoded by SLCO6A1). The OATP6 family is the most diverged of the OATPs. OATP6A1 is also called cancer/testis antigen 48 (CT48) or gonad-specific transporter. It is strongly expressed only in normal testis, and weakly in spleen, brain, fetal brain, and placenta. It is found in tumor samples (lung, bladder, and esophageal) and cancer cell lines (lung), and may be of potential use as a target for therapy for a variety of tumor types. The SLCO6/OATP6 family belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Pssm-ID: 340963 [Multi-domain] Cd Length: 428 Bit Score: 125.35 E-value: 1.12e-30
The kazal-type serine protease inhibitor domain has been detected in an extracellular loop ...
488-545
4.97e-16
The kazal-type serine protease inhibitor domain has been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The KAZAL_SLC21 domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.
Pssm-ID: 238650 [Multi-domain] Cd Length: 54 Bit Score: 72.34 E-value: 4.97e-16
Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse ...
62-444
1.07e-07
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.
Pssm-ID: 349949 [Multi-domain] Cd Length: 378 Bit Score: 54.74 E-value: 1.07e-07
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
495-544
1.75e-04
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.
Pssm-ID: 400135 Cd Length: 50 Bit Score: 39.78 E-value: 1.75e-04
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
500-544
3.66e-03
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.
Pssm-ID: 238052 [Multi-domain] Cd Length: 41 Bit Score: 35.71 E-value: 3.66e-03
Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; ...
71-438
4.39e-03
Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; The protein spinster family includes Drosophila protein spinster, its vertebrate homologs, and similar proteins. Humans contain three homologs called protein spinster homologs 1 (SPNS1), 2 (SPNS2), and 3 (SPNS3). Protein spinster and its homologs may be sphingolipid transporters that play central roles in endosomes and/or lysosomes storage. SPNS2 is also called sphingosine 1-phosphate (S1P) transporter and is required for migration of myocardial precursors. S1P is a secreted lipid mediator that plays critical roles in cardiovascular, immunological, and neural development and function. The spinster-like 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: 340886 [Multi-domain] Cd Length: 405 Bit Score: 39.91 E-value: 4.39e-03
bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator ...
84-432
8.75e-03
bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator Superfamily of transporters; This family is composed of eukaryotic solute carrier 18 (SLC18) family transporters and related bacterial multidrug resistance (MDR) transporters including several proteins from Escherichia coli such as multidrug resistance protein MdtG, from Bacillus subtilis such as multidrug resistance proteins 1 (Bmr1) and 2 (Bmr2), and from Staphylococcus aureus such as quinolone resistance protein NorA. The family also includes Escherichia coli arabinose efflux transporters YfcJ and YhhS. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. The SLC18 transporter family includes vesicular monoamine transporters (VAT1 and VAT2), vesicular acetylcholine transporter (VAChT), and SLC18B1, which is proposed to be a vesicular polyamine transporter (VPAT). The MdtG/SLC18 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: 340883 [Multi-domain] Cd Length: 375 Bit Score: 39.10 E-value: 8.75e-03
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.
of the residues that compose this conserved feature have been mapped to the query sequence.
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of your query sequence and the protein sequences used to curate the domain model,
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The thumbnail image, if present, provides an approximate view of the feature's location in 3 dimensions.
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Functional characterization of the conserved domain architecture found on the query.
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This image shows a graphical summary of conserved domains identified on the query sequence.
The Show Concise/Full Display button at the top of the page can be used to select the desired level of detail: only top scoring hits
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Domains are color coded according to superfamilies
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if a domain or superfamily has been annotated with functional sites (conserved features),
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click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.
The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores.
Click on the domain model's accession number to view the multiple sequence alignment of the proteins used to develop the corresponding domain model.
To view your query sequence embedded in that multiple sequence alignment, click on the colored bars in the Graphical Summary portion of the search results page,
or click on the triangles, if present, that represent functional sites (conserved features)
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Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence.
(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
(labeled illustration) Full Display shows all domain models, in each hit category below, that meet or exceed the RPS-BLAST threshold for statistical significance.
(labeled illustration) Four types of hits can be shown, as available,
for each region on the query sequence:
specific hits meet or exceed a domain-specific e-value threshold
(illustrated example)
and represent a very high confidence that the query sequence belongs to the same protein family as the sequences use to create the domain model
non-specific hits
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the domain superfamily to which the specific and non-specific hits belong
multi-domain models that were computationally detected and are likely to contain multiple single domains
Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool
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