ID SC5AB_HUMAN Reviewed; 675 AA. AC Q8WWX8; Q6PF02; Q6ZUW3; Q86Y55; Q96PP5; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 16-DEC-2008, entry version 38. DE RecName: Full=Sodium/myo-inositol cotransporter 2; DE AltName: Full=Na+/myo-inositol cotransporter 2; DE AltName: Full=Sodium/glucose cotransporter KST1; DE AltName: Full=Sodium-dependent glucose cotransporter; DE AltName: Full=Solute carrier family 5 member 11; GN Name=SLC5A11; Synonyms=KST1, SLGTX, SMIT2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND RP VARIANTS ALA-182; LEU-258 AND ILE-526. RC TISSUE=Brain; RX MEDLINE=22035362; PubMed=12039040; DOI=10.1016/S0378-1119(02)00416-X; RA Roll P., Massacrier A., Pereira S., Robaglia-Schlupp A., Cau P., RA Szepetowski P.; RT "New human sodium/glucose cotransporter gene (KST1): identification, RT characterization, and mutation analysis in ICCA (infantile convulsions RT and choreoathetosis) and BFIC (benign familial infantile convulsions) RT families."; RL Gene 285:141-148(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-182. RA Mount D.B.; RT "Cloning of the human ortholog of RKST1, a member of the SGLT gene RT family of sodium-coupled cotransporters."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Kidney; RA Bruss M., Bonisch H.; RT "Cloning and functional characterization of a new human sugar RT transporter in kidney."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT RP ALA-182. RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT RP ARG-452. RC TISSUE=Hypothalamus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, AND VARIANT ALA-182. RX PubMed=15172003; DOI=10.1016/j.ymgme.2004.03.007; RA Groenen P.M.W., Klootwijk R., Schijvenaars M.M.V.A.P., Straatman H., RA Mariman E.C.M., Franke B., Steegers-Theunissen R.P.M.; RT "Spina bifida and genetic factors related to myo-inositol, glucose, RT and zinc."; RL Mol. Genet. Metab. 82:154-161(2004). RN [8] RP POSSIBLE ROLE IN SLE. RX PubMed=18069935; DOI=10.1111/j.1399-0039.2007.00975.x; RA Tsai L.-J., Hsiao S.-H., Tsai L.-M., Lin C.-Y., Tsai J.-J., RA Liou D.-M., Lan J.-L.; RT "The sodium-dependent glucose cotransporter SLC5A11 as an autoimmune RT modifier gene in SLE."; RL Tissue Antigens 71:114-126(2008). CC -!- FUNCTION: Involved in the sodium-dependent cotransport of myo- CC inositol (MI) with a Na(+):MI stoichiometry of 2:1. Exclusively CC responsible for apical MI transport and absorption in intestine. CC Also can transport D-chiro-inositol (DCI) but not L-fructose. CC Exhibits stereospecific cotransport of both D-glucose and D- CC xylose. May induce apoptosis through the TNF-alpha, PDCD1 pathway. CC May play a role in the regulation of MI concentration in serum, CC involving reabsorption in at least the proximal tubule of the CC kidney. CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein (By CC similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8WWX8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WWX8-2; Sequence=VSP_052790; CC Name=3; CC IsoId=Q8WWX8-3; Sequence=VSP_052789; CC Note=No experimental confirmation available; CC Name=4; CC IsoId=Q8WWX8-4; Sequence=VSP_033259; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Highest expression in heart, skeletal muscle, CC kidney, liver and placenta. Weaker expression in brain, colon, CC spleen, lung and peripheral blood leukocytes. CC -!- MISCELLANEOUS: Acts as an autoimmune modifier in systemic lupus CC erythematosus (SLE) as it is significantly associated with low CC complement component 4 (C4), anti-Smith antibody, serositis, and CC alopecia. CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) CC (TC 2.A.21) family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY044906; AAK97784.1; -; mRNA. DR EMBL; AF292385; AAK97053.1; -; mRNA. DR EMBL; AJ305237; CAC83728.1; -; mRNA. DR EMBL; AK125267; BAC86105.1; -; mRNA. DR EMBL; CH471145; EAW55781.1; -; Genomic_DNA. DR EMBL; BC057780; AAH57780.1; -; mRNA. DR RefSeq; NP_443176.2; -. DR UniGene; Hs.164118; -. DR PRIDE; Q8WWX8; -. DR Ensembl; ENSG00000158865; Homo sapiens. DR GeneID; 115584; -. DR KEGG; hsa:115584; -. DR GeneCards; GC16P024765; -. DR HGNC; HGNC:23091; SLC5A11. DR MIM; 610238; gene. DR PharmGKB; PA134923660; -. DR HOVERGEN; Q8WWX8; -. DR NextBio; 79624; -. DR ArrayExpress; Q8WWX8; -. DR CleanEx; HS_SLC5A11; -. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0031402; F:sodium ion binding; IEA:UniProtKB-KW. DR GO; GO:0005351; F:sugar:hydrogen symporter activity; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptosis; IEA:UniProtKB-KW. DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW. DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW. DR InterPro; IPR001734; Na/solut_symport. DR PANTHER; PTHR11819; Na/solut_symport; 1. DR Pfam; PF00474; SSF; 1. DR TIGRFAMs; TIGR00813; sss; 1. DR PROSITE; PS00456; NA_SOLUT_SYMP_1; FALSE_NEG. DR PROSITE; PS00457; NA_SOLUT_SYMP_2; FALSE_NEG. DR PROSITE; PS50283; NA_SOLUT_SYMP_3; 1. PE 2: Evidence at transcript level; KW Alternative splicing; Apoptosis; Ion transport; Membrane; KW Polymorphism; Sodium; Sodium transport; Sugar transport; Symport; KW Transmembrane; Transport. FT CHAIN 1 675 Sodium/myo-inositol cotransporter 2. FT /FTId=PRO_0000331568. FT TOPO_DOM 1 27 Extracellular (Potential). FT TRANSMEM 28 48 Potential. FT TOPO_DOM 49 65 Cytoplasmic (Potential). FT TRANSMEM 66 88 Potential. FT TOPO_DOM 89 102 Extracellular (Potential). FT TRANSMEM 103 123 Potential. FT TOPO_DOM 124 135 Cytoplasmic (Potential). FT TRANSMEM 136 156 Potential. FT TOPO_DOM 157 180 Extracellular (Potential). FT TRANSMEM 181 201 Potential. FT TOPO_DOM 202 208 Cytoplasmic (Potential). FT TRANSMEM 209 229 Potential. FT TOPO_DOM 230 272 Extracellular (Potential). FT TRANSMEM 273 293 Potential. FT TOPO_DOM 294 308 Cytoplasmic (Potential). FT TRANSMEM 309 329 Potential. FT TOPO_DOM 330 375 Extracellular (Potential). FT TRANSMEM 376 396 Potential. FT TOPO_DOM 397 418 Cytoplasmic (Potential). FT TRANSMEM 419 439 Potential. FT TOPO_DOM 440 446 Extracellular (Potential). FT TRANSMEM 447 467 Potential. FT TOPO_DOM 468 479 Cytoplasmic (Potential). FT TRANSMEM 480 500 Potential. FT TOPO_DOM 501 521 Extracellular (Potential). FT TRANSMEM 522 542 Potential. FT TOPO_DOM 543 654 Cytoplasmic (Potential). FT TRANSMEM 655 675 Potential. FT VAR_SEQ 1 64 Missing (in isoform 3). FT /FTId=VSP_052789. FT VAR_SEQ 45 45 W -> WVGSPSVAQGTRTQWWQSWLTPASTSWAQVILSPRL FT PDTEEVLSTRNRLSPDTKPLGALILNFQVSRI (in FT isoform 4). FT /FTId=VSP_033259. FT VAR_SEQ 125 159 Missing (in isoform 2). FT /FTId=VSP_052790. FT VARIANT 47 47 T -> P (in dbSNP:rs36048966). FT /FTId=VAR_052494. FT VARIANT 182 182 V -> A (reduces serum myo-inositol FT concentration; dbSNP:rs11074656). FT /FTId=VAR_042896. FT VARIANT 258 258 F -> L (in dbSNP:rs35993597). FT /FTId=VAR_042897. FT VARIANT 452 452 Q -> R (in dbSNP:rs17854935). FT /FTId=VAR_042898. FT VARIANT 526 526 M -> I. FT /FTId=VAR_042899. FT CONFLICT 41 41 A -> T (in Ref. 2; AAK97053). FT CONFLICT 371 371 T -> P (in Ref. 3; CAC83728). FT CONFLICT 547 547 S -> P (in Ref. 5; BAC86105). SQ SEQUENCE 675 AA; 74036 MW; 44F7BA6D2FE92335 CRC64; MESGTSSPQP PQLDPLDAFP QKGLEPGDIA VLVLYFLFVL AVGLWSTVKT KRDTVKGYFL AGGDMVWWPV GASLFASNVG SGHFIGLAGS GAATGISVSA YELNGLFSVL MLAWIFLPIY IAGQVTTMPE YLRKRFGGIR IPIILAVLYL FIYIFTKISV DMYAGAIFIQ QSLHLDLYLA IVGLLAITAV YTVAGGLAAV IYTDALQTLI MLIGALTLMG YSFAAVGGME GLKEKYFLAL ASNRSENSSC GLPREDAFHI FRDPLTSDLP WPGVLFGMSI PSLWYWCTDQ VIVQRTLAAK NLSHAKGGAL MAAYLKVLPL FIMVFPGMVS RILFPDQVAC ADPEICQKIC SNPSGCSDIA YPKLVLELLP TGLRGLMMAV MVAALMSSLT SIFNSASTIF TMDLWNHLRP RASEKELMIV GRVFVLLLVL VSILWIPVVQ ASQGGQLFIY IQSISSYLQP PVAVVFIMGC FWKRTNEKGA FWGLISGLLL GLVRLVLDFI YVQPRCDQPD ERPVLVKSIH YLYFSMILST VTLITVSTVS WFTEPPSKEM VSHLTWFTRH DPVVQKEQAP PAAPLSLTLS QNGMPEASSS SSVQFEMVQE NTSKTHSCDM TPKQSKVVKA ILWLCGIQEK GKEELPARAE AIIVSLEENP LVKTLLDVNL IFCVSCAIFI WGYFA //