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SLCO5A1 Membrane Protein Introduction

Introduction of SLCO5A1

SLCO5A1 is a protein with 12 transmembrane domains encoded by the SLCO5A1 gene. The SLCO5A1 protein contains 848 amino acids and has a molecular weight of 92 kDa. It is a member of the organic anion transport polypeptide (OATP) family that belongs to the superfamily of solute carriers (SLC) and is classified as the gene family SLCO. Eleven OATP family members have been identified in human tissues, which are encoded by a gene called SLCO (Solute Carrier Organic Anion Transporter). Mammalian OATPs are classified according to amino acid sequence homology and can be divided into 6 families, OATP1 to OATP6. Human OATP5A1 (SLCO5A1) is found to be expressed in the epithelium of many cancerous and noncancerous tissues throughout the body. Among the SLCO family members, SLCO5A1 is the only gene located on chromosome 8 (8q13.3).

Basic Information of SLCO5A1
Protein Name Solute carrier organic anion transporter family member 5A1
Gene Name SLCO5A1
Aliases Organic anion transporter polypeptide-related protein 4, Solute carrier family 21 member 15
Organism Homo sapiens (Human)
UniProt ID Q9H2Y9
Transmembrane Times 12
Length (aa) 848
Sequence MDEGTGLQPGAGEQLEAPATAEAVQERCEPETLRSKSLPVLSSASCRPSLSPTSGDANPAFGCVDSSGHQELKQGPNPLAPSPSAPSTSAGLGDCNHRVDLSKTFSVSSALAMLQERRCLYVVLTDSRCFLVCMCFLTFIQALMVSGYLSSVITTIERRYSLKSSESGLLVSCFDIGNLVVVVFVSYFGGRGRRPLWLAVGGLLIAFGAALFALPHFISPPYQIQELNASAPNDGLCQGGNSTATLEPPACPKDSGGNNHWVYVALFICAQILIGMGSTPIYTLGPTYLDDNVKKENSSLYLAIMYVMGALGPAVGYLLGGLLIGFYVDPRNPVHLDQNDPRFIGNWWSGFLLCAIAMFLVIFPMFTFPKKLPPRHKKKKKKKFSVDAVSDDDVLKEKSNNSEQADKKVSSMGFGKDVRDLPRAAVRILSNMTFLFVSLSYTAESAIVTAFITFIPKFIESQFGIPASNASIYTGVIIVPSAGVGIVLGGYIIKKLKLGARESAKLAMICSGVSLLCFSTLFIVGCESINLGGINIPYTTGPSLTMPHRNLTGSCNVNCGCKIHEYEPVCGSDGITYFNPCLAGCVNSGNLSTGIRNYTECTCVQSRQVITPPTVGQRSQLRVVIVKTYLNENGYAVSGKCKRTCNTLIPFLVFLFIVTFITACAQPSAIIVTLRSVEDEERPFALGMQFVLLRTLAYIPTPIYFGAVIDTTCMLWQQECGVQGSCWEYNVTSFRFVYFGLAAGLKFVGFIFIFLAWYSIKYKEDGLQRRRQREFPLSTVSERVGHPDNARTRSCPAFSTQGEFHEETGLQKGIQCAAQTYPGPFPEAISSSADPGLEESPAALEPPS

The Function of SLCO5A1 Membrane Protein

Human SLCO5A1 mRNA is significantly expressed in peripheral blood mononuclear cells (PBMC), monocytes, immature dendritic cells (iDC) and mature dendritic cells (mDC), while macrophages show only very low mRNA expression. The SLCO5A1 expression is strongly increased during differentiation from monocytes to mDCs but decreased during differentiation from monocytes to macrophages. There is no significant difference in the expression of SLCO5A1 in PBMC and monocytes compared with iDC, which indicates that the differential expression of SLCO transporters may play a role in the differentiation of APCs. Compared to the wild-type SLCO5A1, the natural variant L33F of SLCO5A1 shows no difference in its biochemical properties. However, mutations in genes encoding uptake transporters can alter expression in cells and can cause inter-individual variation in drug action. Furthermore, transcriptional analysis of SLCO5A1 and functional studies indicate that SLCO5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization.

The basic membrane topology of the OATP transporter. Members of the OATP family are predicted to have a 12-transmembrane domain topology in which the OATP superfamily signature is located at the junction between the third extracellular loop and the transmembrane domain 6. A conserved cysteine residue is located in the fifth extracellular loop. In addition, three predicted glycosylation sites (Y) are delimited on extracellular loops 2 and 5. Fig.1 The basic membrane topology of the OATP transporter. Members of the OATP family are predicted to have a 12-transmembrane domain topology in which the OATP superfamily signature is located at the junction between the third extracellular loop and the transmembrane domain 6. A conserved cysteine residue is located in the fifth extracellular loop. In addition, three predicted glycosylation sites (Y) are delimited on extracellular loops 2 and 5. (Ronaldson, 2013)

Application of SLCO5A1 Membrane Protein Literature

  1. Sebastian K., et al. Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function. Plos One. 2013, 8(12): e83257. PubMed ID: 24376674

    This article finds that OATP5A1 may be a member of the non-canonical OATP family involved in biological processes that require recombination of cell shapes, such as differentiation and migration.

  2. Kindla J., et al. Expression and localization of the uptake transporters OATP2B1, OATP3A1 and OATP5A1 in non-malignant and malignant breast tissue. Cancer Biology & Therapy. 2011, 11(6): 584-91. PubMed ID: 21278488

    This article suggests that OATP3A1 and OATP5A1 are highly expressed in the plasma membrane and cytoplasm of epithelial cells of lactate tubes in breast cancer, indicating the possibility of OATP-mediated hormone uptake during breast cancer development and the effect of certain OATPs on chemotherapy treatment of cancer.

  3. Isidor B., et al. Mesomelia-Synostoses Syndrome Results from Deletion of SULF1 and SLCO5A1 Genes at 8q13. American Journal of Human Genetics. 2010, 87(1): 95-100. PubMed ID: 20602915

    This article suggests the haploinsufficiency of SULF1 binds to the haploid deficiency of SLCO5A1 (or changes in the expression of adjacent genes by positional effects) may be necessary for the pathogenesis of Mesomelia-synostoses syndrome.

  4. Olszewskihamilton U., et al. Organic Anion Transporting Polypeptide 5A1 (OATP5A1) in Small Cell Lung Cancer (SCLC) Cells: Possible Involvement in Chemoresistance to Satraplatin. Biomark Cancer. 2011, 3: 31-40. PubMed ID: 24179389

    This article reveals that OATP5A1 appears to influence the intracellular transport of drugs and may be involved in the chemical resistance of SCLC by sequestration rather than mediating cellular uptake.

  5. Jang H., et al. Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs. Asian-Australasian Journal of Animal Sciences. 2017, 30(5): 643-652. PubMed ID: 27764917

    This article suggests that the prostaglandin transporters ABCC1, ABCC9, SLCO4C1, and SLCO5A1 may play an important role in the establishment and maintenance of pregnancy by regulating prostaglandin transport in the pig endometrium and placenta.

SLCO5A1 Preparation Options

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Reference

  1. Ronaldson P T and Davis T P. (2013). Targeted Drug Delivery to Treat Pain and Cerebral Hypoxia. Pharmacological Reviews. 65(1): 291.

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