Primary Information | |
---|---|
BoMiProt ID | Bomi9387 |
Protein Name | Solute carrier organic anion transporter family member 3A1/Organic anion-transporting polypeptide D |
Organism | Bos taurus |
Uniprot ID | Q8HYW2 |
Milk Fraction | Whey |
Ref Sequence ID | NP_001001134.1 |
Aminoacid Length | 710 |
Molecular Weight | 76555 |
FASTA Sequence | Download |
Gene Name | SLCO3A1/OATP3A1/OATPD/SLC21A11 |
Gene ID | 407132 |
Protein Existence Status | reviewed |
Secondary Information | |
Protein Function | OATP3A1 functions as bile acid efflux transporter that is upregulated as an adaptive response to cholestasis. |
Biochemical Properties | Since it is a member of the OATP family, it was characterized as an uptake transporter with substrate specificity for prostaglandins and thyroxine, but not for bile acids or methotrexate. This separates OATP3A1 from its homologs OATP1B1 and OATP1B3. |
PTMs | N-Acetylation at Meth, Disulfide bond formation,N-Linked Glycosylation at Asn |
Additional Comments | In human cholestasis, expression of the liver-specific proteins OATP1B1 (SLCO1B1 and OATP-C) and OATP1B3 (SLCO1B3 and OATP-8) were significantly decreased, which was thought to be an adaptive response to reduce bile acid accumulation in cholestatic hepatocytes since these transporters mediate bile acid uptake in hepatocytes. |
Linking IDs | Bomi9387 |
Bibliography | 1.Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S, Huang D, Chen Y, Li L, Wang H, Chen W, Cai SY, Boyer JL, Chai J. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology. 2018 Nov;155(5):1578-1592.e16. doi: 10.1053/j.gastro.2018.07.031. Epub 2018 Jul 29. PMID: 30063921; PMCID: PMC6221191. 2.OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.Roth M, Obaidat A, Hagenbuch BBr J Pharmacol. 2012 Mar; 165(5):1260-87. 3.Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain.Huber RD, Gao B, Sidler Pfändler MA, Zhang-Fu W, Leuthold S, Hagenbuch B, Folkers G, Meier PJ, Stieger B Am J Physiol Cell Physiol. 2007 Feb;292(2):C795-806. 4.Molecular characterization of human and rat organic anion transporter OATP-D.Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T Am J Physiol Renal Physiol. 2003 Dec; 285(6):F1188-97. 5.Human organic anion transporter 1B1 and 1B3 function as bidirectional carriers and do not mediate GSH-bile acid cotransport.Mahagita C, Grassl SM, Piyachaturawat P, Ballatori N Am J Physiol Gastrointest Liver Physiol. 2007 Jul; 293(1):G271-8. 6.Recent advances in understanding and managing cholestasis.Wagner M, Trauner M F1000Res. 2016; 5():. 7.Nuclear receptor ligands: rational and effective therapy for chronic cholestatic liver disease? Boyer JL Gastroenterology. 2005 Aug; 129(2):735-40. |
Protein Function | OATP3A1 functions as bile acid efflux transporter that is upregulated as an adaptive response to cholestasis. |
Biochemical Properties | Since it is a member of the OATP family, it was characterized as an uptake transporter with substrate specificity for prostaglandins and thyroxine, but not for bile acids or methotrexate. This separates OATP3A1 from its homologs OATP1B1 and OATP1B3. |
PTMs | N-Acetylation at Meth, Disulfide bond formation,N-Linked Glycosylation at Asn |
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation | >sp|Q8HYW2|SO3A1_BOVIN Solute carrier organic anion transporter family member 3A1 OS=Bos taurus OX=9913 GN=SLCO3A1 PE=2 SV=1 MQAKKPGGSSGGGRSGELQGDEAQRNKKKKKKVSCFSNIKIFLVSECALMLAQGTVGAYL VSVLTTLERRFNLQSADVGVIASSFEIGNLALILFVSYFGARGHRPRLIGCGGIVMALGA LLSALPEFLTHQYKYEAGEIRWGAEGRDVCAAN*153GSGGDQGPDPDLICRSRTATNMMYLLL IGAQVLLGIGATPVQPLGVSYIDDHVRRKDSSLYIGILFTMLVFGPACGFILGSFCTKIY VDAVFIDTSNLDITPDDPRWIGAWWGGFLLCGALLFFSSVLMFGFPQSLPPHSDPALESE QAMLPEREYERPKPSNGVLRHPLEPDSSASCFQQLRVIPKVTKHLLSNPVFTCIILAACM EIAVVAGFAAFLGKYLEQQFN*381LTTSSANQLLGMTAIPCACLGIFLGGLLVKKLSLSALGA IRMAMLVNLVSTACYVSFLFLGCDTGPVAGVTVPYGN*457SSTPGSALDPYSSCNKNCECQTD SFTPVCGADGITYLSACFAGCN*502STN*505LTGCACLMTIPPEN*519ATVIPGKCPSPGCQEAFLTFL CVMCVCSMIGAMAQTPSVIILIRTVSPELKSYALGVLFLLLRLLGFIPPPLIFGAGIDST CLFWSTFCGEQGACALYDNVAYRYLYVSIAIALKSFAFLLYTTTWQCLRKNYKRYIKNHE GGLSTSEFFASTLTLDNLGRDPVPANQTHRTKFIYNLEDHEWCENMESVL |
Predicted Disorder Regions | 1-33, 298-319 |
DisProt Annotation | |
TM Helix Prediction | 12TMHs ; (41-63), (78-100), (107-125), (180-202), (213-235), (261-283), (350-372), (391-409), (429-451), (539-561), (574-596), (626-648) |
Additional Comments | In human cholestasis, expression of the liver-specific proteins OATP1B1 (SLCO1B1 and OATP-C) and OATP1B3 (SLCO1B3 and OATP-8) were significantly decreased, which was thought to be an adaptive response to reduce bile acid accumulation in cholestatic hepatocytes since these transporters mediate bile acid uptake in hepatocytes. |
Linking IDs | |
Bibliography | 1.Pan Q, Zhang X, Zhang L, Cheng Y, Zhao N, Li F, Zhou X, Chen S, Li J, Xu S, Huang D, Chen Y, Li L, Wang H, Chen W, Cai SY, Boyer JL, Chai J. Solute Carrier Organic Anion Transporter Family Member 3A1 Is a Bile Acid Efflux Transporter in Cholestasis. Gastroenterology. 2018 Nov;155(5):1578-1592.e16. doi: 10.1053/j.gastro.2018.07.031. Epub 2018 Jul 29. PMID: 30063921; PMCID: PMC6221191. 2.OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.Roth M, Obaidat A, Hagenbuch BBr J Pharmacol. 2012 Mar; 165(5):1260-87. 3.Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain.Huber RD, Gao B, Sidler Pfändler MA, Zhang-Fu W, Leuthold S, Hagenbuch B, Folkers G, Meier PJ, Stieger B Am J Physiol Cell Physiol. 2007 Feb;292(2):C795-806. 4.Molecular characterization of human and rat organic anion transporter OATP-D.Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T Am J Physiol Renal Physiol. 2003 Dec; 285(6):F1188-97. 5.Human organic anion transporter 1B1 and 1B3 function as bidirectional carriers and do not mediate GSH-bile acid cotransport.Mahagita C, Grassl SM, Piyachaturawat P, Ballatori N Am J Physiol Gastrointest Liver Physiol. 2007 Jul; 293(1):G271-8. 6.Recent advances in understanding and managing cholestasis.Wagner M, Trauner M F1000Res. 2016; 5():. 7.Nuclear receptor ligands: rational and effective therapy for chronic cholestatic liver disease? Boyer JL Gastroenterology. 2005 Aug; 129(2):735-40. |