ID FKRP_HUMAN Reviewed; 495 AA. AC Q9H9S5; A8K5G7; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 171. DE RecName: Full=Ribitol 5-phosphate transferase FKRP {ECO:0000305}; DE EC=2.7.8.- {ECO:0000269|PubMed:26923585, ECO:0000269|PubMed:29477842, ECO:0000269|PubMed:31949166}; DE AltName: Full=Fukutin-related protein {ECO:0000303|PubMed:11592034}; DE AltName: Full=Ribitol-5-phosphate transferase {ECO:0000303|PubMed:26923585}; GN Name=FKRP {ECO:0000312|HGNC:HGNC:17997}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS MDDGB5 RP GLY-114; THR-217; CYS-309; ARG-316; SER-328; HIS-339; ASN-401; LEU-448 AND RP SER-465. RC TISSUE=Brain; RX PubMed=11592034; DOI=10.1086/324412; RA Brockington M., Blake D.J., Prandini P., Brown S.C., Torelli S., RA Benson M.A., Ponting C.P., Estournet B., Romero N.B., Mercuri E., Voit T., RA Sewry C.A., Guicheney P., Muntoni F.; RT "Mutations in the fukutin-related protein gene (FKRP) cause a form of RT congenital muscular dystrophy with secondary laminin alpha2 deficiency and RT abnormal glycosylation of alpha-dystroglycan."; RL Am. J. Hum. Genet. 69:1198-1209(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=15213246; DOI=10.1093/jb/mvh086; RA Matsumoto H., Noguchi S., Sugie K., Ogawa M., Murayama K., Hayashi Y.K., RA Nishino I.; RT "Subcellular localization of fukutin and fukutin-related protein in muscle RT cells."; RL J. Biochem. 135:709-712(2004). RN [7] RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS ILE-276 AND LEU-448. RX PubMed=17554798; DOI=10.1002/mus.20833; RA Keramaris-Vrantsis E., Lu P.J., Doran T., Zillmer A., Ashar J., Esapa C.T., RA Benson M.A., Blake D.J., Rosenfeld J., Lu Q.L.; RT "Fukutin-related protein localizes to the Golgi apparatus and mutations RT lead to mislocalization in muscle in vivo."; RL Muscle Nerve 36:455-465(2007). RN [8] RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND CHARACTERIZATION OF VARIANTS RP ILE-276 AND LEU-448. RX PubMed=19900540; DOI=10.1016/j.bbadis.2009.10.016; RA Lu P.J., Zillmer A., Wu X., Lochmuller H., Vachris J., Blake D., Chan Y.M., RA Lu Q.L.; RT "Mutations alter secretion of fukutin-related protein."; RL Biochim. Biophys. Acta 1802:253-258(2010). RN [9] RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-172 AND ASN-209, SUBUNIT, AND RP DISULFIDE BOND. RX PubMed=21886772; DOI=10.1371/journal.pone.0022968; RA Alhamidi M., Kjeldsen Buvang E., Fagerheim T., Brox V., Lindal S., RA Van Ghelue M., Nilssen O.; RT "Fukutin-related protein resides in the Golgi cisternae of skeletal muscle RT fibres and forms disulfide-linked homodimers via an N-Terminal RT interaction."; RL PLoS ONE 6:E22968-E22968(2011). RN [10] RP INVOLVEMENT IN MDDGC5. RX PubMed=23800702; DOI=10.1016/j.nmd.2013.05.010; RA Liang W.C., Hayashi Y.K., Ogawa M., Wang C.H., Huang W.T., Nishino I., RA Jong Y.J.; RT "Limb-girdle muscular dystrophy type 2I is not rare in Taiwan."; RL Neuromuscul. Disord. 23:675-681(2013). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND PATHWAY. RX PubMed=25279699; DOI=10.7554/elife.03941; RA Willer T., Inamori K.I., Venzke D., Harvey C., Morgensen G., Hara Y., RA Beltran Valero de Bernabe D., Yu L., Wright K.M., Campbell K.P.; RT "The glucuronyltransferase B4GAT1 is required for initiation of LARGE- RT mediated alpha-dystroglycan functional glycosylation."; RL Elife 3:0-0(2014). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, MUTAGENESIS OF RP ASP-362, AND VARIANT ASN-307. RX PubMed=26923585; DOI=10.1016/j.celrep.2016.02.017; RA Kanagawa M., Kobayashi K., Tajiri M., Manya H., Kuga A., Yamaguchi Y., RA Akasaka-Manya K., Furukawa J.I., Mizuno M., Kawakami H., Shinohara Y., RA Wada Y., Endo T., Toda T.; RT "Identification of a Post-translational Modification with Ribitol-Phosphate RT and Its Defect in Muscular Dystrophy."; RL Cell Rep. 14:2209-2223(2016). RN [13] RP FUNCTION, AND PATHWAY. RX PubMed=27194101; DOI=10.1038/ncomms11534; RA Gerin I., Ury B., Breloy I., Bouchet-Seraphin C., Bolsee J., Halbout M., RA Graff J., Vertommen D., Muccioli G.G., Seta N., Cuisset J.M., Dabaj I., RA Quijano-Roy S., Grahn A., Van Schaftingen E., Bommer G.T.; RT "ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol RT phosphate onto alpha-dystroglycan."; RL Nat. Commun. 7:11534-11534(2016). RN [14] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FKTN AND RXYLT1, SUBCELLULAR RP LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=29477842; DOI=10.1016/j.bbrc.2018.02.162; RA Nishihara R., Kobayashi K., Imae R., Tsumoto H., Manya H., Mizuno M., RA Kanagawa M., Endo T., Toda T.; RT "Cell endogenous activities of fukutin and FKRP coexist with the ribitol RT xylosyltransferase, TMEM5."; RL Biochem. Biophys. Res. Commun. 497:1025-1030(2018). RN [15] RP TISSUE SPECIFICITY. RX PubMed=29416295; RA Haro C., Uribe M.L., Quereda C., Cruces J., Martin-Nieto J.; RT "Expression in retinal neurons of fukutin and FKRP, the protein products of RT two dystroglycanopathy-causative genes."; RL Mol. Vis. 24:43-58(2018). RN [16] {ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAK, ECO:0007744|PDB:6KAL, ECO:0007744|PDB:6KAM, ECO:0007744|PDB:6KAN, ECO:0007744|PDB:6L7S, ECO:0007744|PDB:6L7T, ECO:0007744|PDB:6L7U} RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 45-495 IN COMPLEXES WITH RP CDP-L-RIBITOL; MAGNESIUM AND ZINC, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION RP AT ASN-172 AND ASN-209, REGION, MUTAGENESIS OF TYR-88; ASP-360; ASP-362; RP ASP-364 AND ASP-416, VARIANT MDDGB5 ARG-221, VARIANT MDDGC5 ILE-276, RP CHARACTERIZATION OF VARIANT MDDGB5 ARG-221, CHARACTERIZATION OF VARIANT RP MDDGC5 ILE-276, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=31949166; DOI=10.1038/s41467-019-14220-z; RA Kuwabara N., Imae R., Manya H., Tanaka T., Mizuno M., Tsumoto H., RA Kanagawa M., Kobayashi K., Toda T., Senda T., Endo T., Kato R.; RT "Crystal structures of fukutin-related protein (FKRP), a ribitol-phosphate RT transferase related to muscular dystrophy."; RL Nat. Commun. 11:303-303(2020). RN [17] RP VARIANTS MDDGC5 143-ARG--GLU-146 DEL; SER-143; ILE-276; CYS-312; ARG-316 RP AND LEU-339. RX PubMed=11741828; DOI=10.1093/hmg/10.25.2851; RA Brockington M., Yuva Y., Prandini P., Brown S.C., Torelli S., Benson M.A., RA Herrmann R., Anderson L.V.B., Bashir R., Burgunder J.-M., Fallet S., RA Romero N., Fardeau M., Straub V., Storey G., Pollitt C., Richard I., RA Sewry C.A., Bushby K., Voit T., Blake D.J., Muntoni F.; RT "Mutations in the fukutin-related protein gene (FKRP) identify limb girdle RT muscular dystrophy 2I as a milder allelic variant of congenital muscular RT dystrophy MDC1C."; RL Hum. Mol. Genet. 10:2851-2859(2001). RN [18] RP VARIANTS MDDGB5 CYS-309; HIS-339 AND LEU-448, AND VARIANTS MDDGC5 ILE-276; RP ASN-307; SER-316; ASN-360 AND SER-462. RX PubMed=12666124; DOI=10.1002/ana.10559; RA Mercuri E., Brockington M., Straub V., Quijano-Roy S., Yuva Y., RA Herrmann R., Brown S.C., Torelli S., Dubowitz V., Blake D.J., Romero N.B., RA Estournet B., Sewry C.A., Guicheney P., Voit T., Muntoni F.; RT "Phenotypic spectrum associated with mutations in the fukutin-related RT protein gene."; RL Ann. Neurol. 53:537-542(2003). RN [19] RP VARIANTS MDDGC5 MET-79; TRP-134; PHE-160; CYS-182; ILE-276; ILE-293; RP ALA-300; MET-300 AND LEU-358. RX PubMed=14647208; DOI=10.1038/sj.ejhg.5201066; RA de Paula F., Vieira N., Starling A., Yamamoto L.U., Lima B., RA de Cassia Pavanello R., Vainzof M., Nigro V., Zatz M.; RT "Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the RT other end of the spectrum."; RL Eur. J. Hum. Genet. 11:923-930(2003). RN [20] RP VARIANTS MDDGB5 ARG-221 AND THR-315. RX PubMed=12654965; DOI=10.1212/01.wnl.0000052996.14099.dc; RA Topaloglu H., Brockington M., Yuva Y., Talim B., Haliloglu G., Blake D.J., RA Torelli S., Brown S.C., Muntoni F.; RT "FKRP gene mutations cause congenital muscular dystrophy, mental RT retardation, and cerebellar cysts."; RL Neurology 60:988-992(2003). RN [21] RP VARIANT MDDGC5 TRP-54. RX PubMed=14523375; DOI=10.1038/sj.ejhg.5201087; RA Harel T., Goldberg Y., Shalev S.A., Chervinski I., Ofir R., Birk O.S.; RT "Limb-girdle muscular dystrophy 2I: phenotypic variability within a large RT consanguineous Bedouin family associated with a novel FKRP mutation."; RL Eur. J. Hum. Genet. 12:38-43(2004). RN [22] RP VARIANTS MDDGA5 ASN-307 AND TYR-318. RX PubMed=15121789; DOI=10.1136/jmg.2003.013870; RA Beltran-Valero de Bernabe D., Voit T., Longman C., Steinbrecher A., RA Straub V., Yuva Y., Herrmann R., Sperner J., Korenke C., Diesen C., RA Dobyns W.B., Brunner H.G., van Bokhoven H., Brockington M., Muntoni F.; RT "Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker- RT Warburg syndrome."; RL J. Med. Genet. 41:E61-E61(2004). RN [23] RP VARIANTS MDDGB5 LEU-405 AND ASP-455. RX PubMed=14652796; DOI=10.1007/s10048-003-0165-9; RA Louhichi N., Triki C., Quijano-Roy S., Richard P., Makri S., Meziou M., RA Estournet B., Mrad S., Romero N.B., Ayadi H., Guicheney P., Fakhfakh F.; RT "New FKRP mutations causing congenital muscular dystrophy associated with RT mental retardation and central nervous system abnormalities. Identification RT of a founder mutation in Tunisian families."; RL Neurogenetics 5:27-34(2004). RN [24] RP VARIANT MDDGB5 ASP-463. RX PubMed=17336067; DOI=10.1016/j.nmd.2007.01.005; RA MacLeod H., Pytel P., Wollmann R., Chelmicka-Schorr E., Silver K., RA Anderson R.B., Waggoner D., McNally E.M.; RT "A novel FKRP mutation in congenital muscular dystrophy disrupts the RT dystrophin glycoprotein complex."; RL Neuromuscul. Disord. 17:285-289(2007). RN [25] RP VARIANT MDDGC5 MET-314. RX PubMed=30345904; DOI=10.1152/physiolgenomics.00036.2018; RA Saha M., Reddy H.M., Salih M., Estrella E., Jones M.D., Mitsuhashi S., RA Cho K.A., Suzuki-Hatano S., Rizzo S.A., Hamad M.H., Mukhtar M.M., RA Hamed A.A., Elseed M.A., Lek M., Valkanas E., MacArthur D.G., Kunkel L.M., RA Pacak C.A., Draper I., Kang P.B.; RT "The impact of PYROXD1 deficiency on cellular respiration and correlations RT with genetic analyses of limb-girdle muscular dystrophy in Saudi Arabia and RT Sudan."; RL Physiol. Genomics 50:929-939(2018). CC -!- FUNCTION: Catalyzes the transfer of a ribitol 5-phosphate from CDP-L- CC ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin CC to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine- CC beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a CC carbohydrate structure present in alpha-dystroglycan (DAG1) CC (PubMed:26923585, PubMed:29477842, PubMed:31949166, PubMed:27194101). CC This constitutes the second step in the formation of the ribose 5- CC phosphate tandem repeat which links the phosphorylated O-mannosyl CC trisaccharide to the ligand binding moiety composed of repeats of 3- CC xylosyl-alpha-1,3-glucuronic acid-beta-1 (PubMed:25279699, CC PubMed:26923585, PubMed:29477842, PubMed:31949166, PubMed:27194101). CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:26923585, CC ECO:0000269|PubMed:27194101, ECO:0000269|PubMed:29477842, CC ECO:0000269|PubMed:31949166}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-[Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O- CC 6-P-alpha-D-Man)]-Thr-[protein] + CDP-L-ribitol = 3-O-[Rib-ol-P-Rib- CC ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D- CC Man)]-Thr-[protein] + CMP + H(+); Xref=Rhea:RHEA:39867, Rhea:RHEA- CC COMP:15021, Rhea:RHEA-COMP:17480, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57608, ChEBI:CHEBI:60377, ChEBI:CHEBI:142403, CC ChEBI:CHEBI:177331; Evidence={ECO:0000269|PubMed:26923585, CC ECO:0000269|PubMed:29477842, ECO:0000269|PubMed:31949166}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39868; CC Evidence={ECO:0000269|PubMed:26923585}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:31949166}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:26923585, CC ECO:0000269|PubMed:27194101, ECO:0000269|PubMed:31949166}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:21886772). Tetramer CC (PubMed:31949166). Forms a complex composed of FKRP, FKTN/fukutin, and CC RXYLT1/TMEM5 (PubMed:29477842). Exists also as large multimeric protein CC complexes (PubMed:25279699). May interact with the dystrophin- CC glycoprotein complex (DGC) (By similarity). CC {ECO:0000250|UniProtKB:Q8CG64, ECO:0000269|PubMed:21886772, CC ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:29477842, CC ECO:0000269|PubMed:31949166}. CC -!- INTERACTION: CC Q9H9S5; Q9H9S5: FKRP; NbExp=3; IntAct=EBI-21505709, EBI-21505709; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:17554798, ECO:0000269|PubMed:21886772, CC ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:29477842, CC ECO:0000305|PubMed:26923585}; Single-pass type II membrane protein CC {ECO:0000305}. Secreted {ECO:0000269|PubMed:19900540}. Cell membrane, CC sarcolemma {ECO:0000250|UniProtKB:Q8CG64}. Rough endoplasmic reticulum CC {ECO:0000269|PubMed:15213246}. Cytoplasm CC {ECO:0000250|UniProtKB:Q8CG64}. Note=According to some studies the N- CC terminal hydrophobic domain is cleaved after translocation to the Golgi CC apparatus and the protein is secreted (PubMed:19900540). Localization CC at the cell membrane may require the presence of dystroglycan (By CC similarity). At the Golgi apparatus localizes to the middle-to-trans- CC cisternae, as assessed by MG160 colocalization. Detected in rough CC endoplasmic reticulum in myocytes (PubMed:17554798, PubMed:21886772). CC In general, mutants associated with severe clinical phenotypes are CC retained within the endoplasmic reticulum (PubMed:15213246). CC {ECO:0000250|UniProtKB:Q8CG64, ECO:0000269|PubMed:15213246, CC ECO:0000269|PubMed:17554798, ECO:0000269|PubMed:19900540, CC ECO:0000269|PubMed:21886772}. CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level) CC (PubMed:29416295). Expressed predominantly in skeletal muscle, CC placenta, and heart and relatively weakly in brain, lung, liver, CC kidney, and pancreas (PubMed:11592034). {ECO:0000269|PubMed:11592034, CC ECO:0000269|PubMed:29416295}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19900540, CC ECO:0000269|PubMed:21886772}. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain CC and eye anomalies A5 (MDDGA5) [MIM:613153]: An autosomal recessive CC disorder characterized by congenital muscular dystrophy associated with CC cobblestone lissencephaly and other brain anomalies, eye malformations, CC profound intellectual disability, and death usually in the first years CC of life. Included diseases are the more severe Walker-Warburg syndrome CC and the slightly less severe muscle-eye-brain disease. CC {ECO:0000269|PubMed:15121789}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with or CC without impaired intellectual development B5 (MDDGB5) [MIM:606612]: A CC congenital muscular dystrophy characterized by a severe phenotype with CC inability to walk, muscle hypertrophy, marked elevation of serum CC creatine kinase, secondary deficiency of laminin alpha2, and a marked CC reduction in alpha-dystroglycan expression. Only a subset of affected CC individuals have brain involvements. {ECO:0000269|PubMed:11592034, CC ECO:0000269|PubMed:12654965, ECO:0000269|PubMed:12666124, CC ECO:0000269|PubMed:14652796, ECO:0000269|PubMed:17336067, CC ECO:0000269|PubMed:31949166}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C5 (MDDGC5) CC [MIM:607155]: An autosomal recessive degenerative myopathy with age of CC onset ranging from childhood to adult life, and variable severity. CC Clinical features include proximal muscle weakness, waddling gait, calf CC hypertrophy, cardiomyopathy and respiratory insufficiency. A reduction CC of alpha-dystroglycan and laminin alpha-2 expression can be observed on CC skeletal muscle biopsy from MDDGC5 patients. CC {ECO:0000269|PubMed:11741828, ECO:0000269|PubMed:12666124, CC ECO:0000269|PubMed:14523375, ECO:0000269|PubMed:14647208, CC ECO:0000269|PubMed:23800702, ECO:0000269|PubMed:30345904, CC ECO:0000269|PubMed:31949166}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the LicD transferase family. {ECO:0000305}. 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; AJ314847; CAC85633.1; -; mRNA. DR EMBL; AK022638; BAB14146.1; -; mRNA. DR EMBL; AK095497; BAG53071.1; -; mRNA. DR EMBL; AK291282; BAF83971.1; -; mRNA. DR EMBL; AC008622; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471126; EAW57444.1; -; Genomic_DNA. DR EMBL; BC002612; AAH02612.1; -; mRNA. DR CCDS; CCDS12691.1; -. DR RefSeq; NP_001034974.1; NM_001039885.2. DR RefSeq; NP_077277.1; NM_024301.4. DR RefSeq; XP_005259304.1; XM_005259247.2. DR RefSeq; XP_005259305.1; XM_005259248.2. DR RefSeq; XP_005259306.1; XM_005259249.4. DR RefSeq; XP_011525608.1; XM_011527306.1. DR RefSeq; XP_011525609.1; XM_011527307.1. DR RefSeq; XP_016882786.1; XM_017027297.1. DR PDB; 6KAJ; X-ray; 2.22 A; A/B/C/D=45-495. DR PDB; 6KAK; X-ray; 2.06 A; A/B/C/D=45-495. DR PDB; 6KAL; X-ray; 2.60 A; A/B/C/D=45-495. DR PDB; 6KAM; X-ray; 2.46 A; A/B/C/D=45-495. DR PDB; 6KAN; X-ray; 2.25 A; A/B/C/D=45-495. DR PDB; 6L7S; X-ray; 2.41 A; A/B/C/D=45-495. DR PDB; 6L7T; X-ray; 2.41 A; A/B/C/D=45-495. DR PDB; 6L7U; X-ray; 2.24 A; A/B/C/D=45-495. DR PDBsum; 6KAJ; -. DR PDBsum; 6KAK; -. DR PDBsum; 6KAL; -. DR PDBsum; 6KAM; -. DR PDBsum; 6KAN; -. DR PDBsum; 6L7S; -. DR PDBsum; 6L7T; -. DR PDBsum; 6L7U; -. DR AlphaFoldDB; Q9H9S5; -. DR SMR; Q9H9S5; -. DR BioGRID; 122565; 42. DR ComplexPortal; CPX-7722; Fukutin-FKRP-TMEM5 multienzyme complex. DR IntAct; Q9H9S5; 22. DR MINT; Q9H9S5; -. DR STRING; 9606.ENSP00000326570; -. DR GlyCosmos; Q9H9S5; 2 sites, No reported glycans. DR GlyGen; Q9H9S5; 2 sites. DR iPTMnet; Q9H9S5; -. DR PhosphoSitePlus; Q9H9S5; -. DR SwissPalm; Q9H9S5; -. DR BioMuta; FKRP; -. DR DMDM; 46395992; -. DR EPD; Q9H9S5; -. DR MassIVE; Q9H9S5; -. DR MaxQB; Q9H9S5; -. DR PaxDb; 9606-ENSP00000326570; -. DR PeptideAtlas; Q9H9S5; -. DR ProteomicsDB; 81360; -. DR Pumba; Q9H9S5; -. DR Antibodypedia; 57230; 281 antibodies from 26 providers. DR DNASU; 79147; -. DR Ensembl; ENST00000318584.10; ENSP00000326570.4; ENSG00000181027.11. DR Ensembl; ENST00000391909.7; ENSP00000375776.2; ENSG00000181027.11. DR GeneID; 79147; -. DR KEGG; hsa:79147; -. DR MANE-Select; ENST00000318584.10; ENSP00000326570.4; NM_024301.5; NP_077277.1. DR UCSC; uc002pfn.3; human. DR AGR; HGNC:17997; -. DR CTD; 79147; -. DR DisGeNET; 79147; -. DR GeneCards; FKRP; -. DR HGNC; HGNC:17997; FKRP. DR HPA; ENSG00000181027; Low tissue specificity. DR MalaCards; FKRP; -. DR MIM; 606596; gene. DR MIM; 606612; phenotype. DR MIM; 607155; phenotype. DR MIM; 613153; phenotype. DR neXtProt; NX_Q9H9S5; -. DR OpenTargets; ENSG00000181027; -. DR Orphanet; 370959; Congenital muscular dystrophy with cerebellar involvement. DR Orphanet; 370968; Congenital muscular dystrophy with intellectual disability. DR Orphanet; 370980; Congenital muscular dystrophy without intellectual disability. DR Orphanet; 34515; FKRP-related limb-girdle muscular dystrophy R9. DR Orphanet; 588; Muscle-eye-brain disease. DR Orphanet; 899; Walker-Warburg syndrome. DR PharmGKB; PA134976709; -. DR VEuPathDB; HostDB:ENSG00000181027; -. DR eggNOG; ENOG502QV4Y; Eukaryota. DR GeneTree; ENSGT00390000017583; -. DR HOGENOM; CLU_041755_1_0_1; -. DR InParanoid; Q9H9S5; -. DR OMA; DNEGFYW; -. DR OrthoDB; 5387048at2759; -. DR PhylomeDB; Q9H9S5; -. DR TreeFam; TF324064; -. DR BioCyc; MetaCyc:ENSG00000181027-MONOMER; -. DR PathwayCommons; Q9H9S5; -. DR SignaLink; Q9H9S5; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 79147; 20 hits in 1165 CRISPR screens. DR GenomeRNAi; 79147; -. DR Pharos; Q9H9S5; Tbio. DR PRO; PR:Q9H9S5; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9H9S5; Protein. DR Bgee; ENSG00000181027; Expressed in left ventricle myocardium and 159 other cell types or tissues. DR ExpressionAtlas; Q9H9S5; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell. DR GO; GO:0098723; C:skeletal muscle myofibril; IEA:Ensembl. DR GO; GO:0002162; F:dystroglycan binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043236; F:laminin binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; IDA:UniProtKB. DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl. DR GO; GO:0071711; P:basement membrane organization; IEA:Ensembl. DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl. DR GO; GO:0061448; P:connective tissue development; IEA:Ensembl. DR GO; GO:0097709; P:connective tissue replacement; IEA:Ensembl. DR GO; GO:0006600; P:creatine metabolic process; IEA:Ensembl. DR GO; GO:0060539; P:diaphragm development; IEA:Ensembl. DR GO; GO:0036058; P:filtration diaphragm assembly; IEA:Ensembl. DR GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl. DR GO; GO:0006096; P:glycolytic process; IEA:Ensembl. DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl. DR GO; GO:0051674; P:localization of cell; IEA:Ensembl. DR GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; IEA:Ensembl. DR GO; GO:0006936; P:muscle contraction; IEA:Ensembl. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0072592; P:oxygen metabolic process; IEA:Ensembl. DR GO; GO:0019519; P:pentitol metabolic process; IEA:Ensembl. DR GO; GO:0019321; P:pentose metabolic process; IEA:Ensembl. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0017038; P:protein import; IEA:Ensembl. DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:UniProtKB. DR GO; GO:0016485; P:protein processing; IEA:Ensembl. DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB. DR GO; GO:0038026; P:reelin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0022414; P:reproductive process; IEA:Ensembl. DR GO; GO:0003016; P:respiratory system process; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0097305; P:response to alcohol; IEA:Ensembl. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0098528; P:skeletal muscle fiber differentiation; IEA:Ensembl. DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEA:Ensembl. DR InterPro; IPR007074; LicD_fam. DR PANTHER; PTHR13627; FUKUTIN RELATED PROTEIN; 1. DR PANTHER; PTHR13627:SF31; RIBITOL 5-PHOSPHATE TRANSFERASE FKRP; 1. DR Pfam; PF04991; LicD; 1. DR Genevisible; Q9H9S5; HS. PE 1: Evidence at protein level; KW 3D-structure; Cardiomyopathy; Cell membrane; Congenital muscular dystrophy; KW Cytoplasm; Disease variant; Disulfide bond; Dystroglycanopathy; KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; KW Limb-girdle muscular dystrophy; Lissencephaly; Magnesium; Membrane; KW Metal-binding; Reference proteome; Secreted; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix; Zinc. FT CHAIN 1..495 FT /note="Ribitol 5-phosphate transferase FKRP" FT /id="PRO_0000204723" FT TOPO_DOM 1..6 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 7..29 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 30..495 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 289..318 FT /note="Zinc finger loop" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 289 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 296 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 317 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 318 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 345 FT /ligand="CDP-L-ribitol" FT /ligand_id="ChEBI:CHEBI:57608" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAM" FT BINDING 352 FT /ligand="CDP-L-ribitol" FT /ligand_id="ChEBI:CHEBI:57608" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAM" FT BINDING 359..364 FT /ligand="CDP-L-ribitol" FT /ligand_id="ChEBI:CHEBI:57608" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAM" FT BINDING 360 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ" FT BINDING 362 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAL" FT BINDING 364 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAL" FT BINDING 437..438 FT /ligand="CDP-L-ribitol" FT /ligand_id="ChEBI:CHEBI:57608" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAM" FT BINDING 480..482 FT /ligand="CDP-L-ribitol" FT /ligand_id="ChEBI:CHEBI:57608" FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAM" FT CARBOHYD 172 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21886772, FT ECO:0000269|PubMed:31949166, ECO:0007744|PDB:6KAJ, FT ECO:0007744|PDB:6KAK, ECO:0007744|PDB:6KAL, FT ECO:0007744|PDB:6KAM, ECO:0007744|PDB:6KAN, FT ECO:0007744|PDB:6L7S, ECO:0007744|PDB:6L7T, FT ECO:0007744|PDB:6L7U" FT CARBOHYD 209 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21886772, FT ECO:0000269|PubMed:31949166, ECO:0007744|PDB:6KAJ, FT ECO:0007744|PDB:6KAK, ECO:0007744|PDB:6KAL, FT ECO:0007744|PDB:6KAM, ECO:0007744|PDB:6KAN, FT ECO:0007744|PDB:6L7S, ECO:0007744|PDB:6L7T, FT ECO:0007744|PDB:6L7U" FT DISULFID 6 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:21886772" FT DISULFID 168..191 FT /evidence="ECO:0000269|PubMed:31949166, FT ECO:0007744|PDB:6KAJ, ECO:0007744|PDB:6KAK, FT ECO:0007744|PDB:6KAM, ECO:0007744|PDB:6KAN, FT ECO:0007744|PDB:6L7S, ECO:0007744|PDB:6L7T, FT ECO:0007744|PDB:6L7U" FT VARIANT 54 FT /note="R -> W (in MDDGC5; dbSNP:rs28937905)" FT /evidence="ECO:0000269|PubMed:14523375" FT /id="VAR_019272" FT VARIANT 79 FT /note="V -> M (in MDDGC5; dbSNP:rs104894683)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065055" FT VARIANT 114 FT /note="A -> G (in MDDGB5; uncertain significance; FT dbSNP:rs143793528)" FT /evidence="ECO:0000269|PubMed:11592034" FT /id="VAR_018280" FT VARIANT 134 FT /note="R -> W (in MDDGC5; dbSNP:rs104894690)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065056" FT VARIANT 143..146 FT /note="Missing (in MDDGC5)" FT /evidence="ECO:0000269|PubMed:11741828" FT /id="VAR_018281" FT VARIANT 143 FT /note="R -> S (in MDDGC5; dbSNP:rs148206382)" FT /evidence="ECO:0000269|PubMed:11741828" FT /id="VAR_018282" FT VARIANT 160 FT /note="V -> F (in MDDGC5)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065057" FT VARIANT 182 FT /note="Y -> C (in MDDGC5; dbSNP:rs543163491)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065058" FT VARIANT 217 FT /note="P -> T (in MDDGB5)" FT /evidence="ECO:0000269|PubMed:11592034" FT /id="VAR_018283" FT VARIANT 221 FT /note="S -> R (in MDDGB5; severe form; brain involvement; FT intellectual disability and cerebellar cysts on cranial FT MRI; affects tetramer assembly; decreases the ribitol FT 5-phosphate transferase activity of about 95%; FT dbSNP:rs28937902)" FT /evidence="ECO:0000269|PubMed:12654965, FT ECO:0000269|PubMed:31949166" FT /id="VAR_018284" FT VARIANT 276 FT /note="L -> I (in MDDGC5; reduced secretion to the medium; FT localizes mainly to the Golgi apparatus; affects tetramer FT assembly; decreases the ribitol-5-phosphate transferase FT activity of about 50%; dbSNP:rs28937900)" FT /evidence="ECO:0000269|PubMed:11741828, FT ECO:0000269|PubMed:12666124, ECO:0000269|PubMed:14647208, FT ECO:0000269|PubMed:17554798, ECO:0000269|PubMed:19900540, FT ECO:0000269|PubMed:31949166" FT /id="VAR_018285" FT VARIANT 293 FT /note="T -> I (in MDDGC5)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065059" FT VARIANT 300 FT /note="V -> A (in MDDGC5; dbSNP:rs104894691)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065060" FT VARIANT 300 FT /note="V -> M (in MDDGC5; uncertain significance; FT dbSNP:rs563033008)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065061" FT VARIANT 307 FT /note="Y -> N (in MDDGC5 and MDDGA5; decrease in FT ribitol-5-phosphate transferase activity; FT dbSNP:rs104894692)" FT /evidence="ECO:0000269|PubMed:12666124, FT ECO:0000269|PubMed:15121789, ECO:0000269|PubMed:26923585" FT /id="VAR_022850" FT VARIANT 309 FT /note="Y -> C (in MDDGB5; dbSNP:rs104894679)" FT /evidence="ECO:0000269|PubMed:11592034, FT ECO:0000269|PubMed:12666124" FT /id="VAR_018286" FT VARIANT 312 FT /note="R -> C (in MDDGC5)" FT /evidence="ECO:0000269|PubMed:11741828" FT /id="VAR_018287" FT VARIANT 314 FT /note="T -> M (in MDDGC5; dbSNP:rs398124395)" FT /evidence="ECO:0000269|PubMed:30345904" FT /id="VAR_081096" FT VARIANT 315 FT /note="P -> T (in MDDGB5; severe form; brain involvement; FT intellectual disability and cerebellar cysts on cranial FT MRI)" FT /evidence="ECO:0000269|PubMed:12654965" FT /id="VAR_018288" FT VARIANT 316 FT /note="P -> R (in MDDGB5 and MDDGC5; dbSNP:rs752582904)" FT /evidence="ECO:0000269|PubMed:11592034, FT ECO:0000269|PubMed:11741828" FT /id="VAR_018289" FT VARIANT 316 FT /note="P -> S (in MDDGC5; dbSNP:rs28937901)" FT /evidence="ECO:0000269|PubMed:12666124" FT /id="VAR_022851" FT VARIANT 318 FT /note="C -> Y (in MDDGA5; severe Walker-Warburg syndrome; FT dbSNP:rs104894684)" FT /evidence="ECO:0000269|PubMed:15121789" FT /id="VAR_022852" FT VARIANT 328 FT /note="Y -> S (in MDDGB5)" FT /evidence="ECO:0000269|PubMed:11592034" FT /id="VAR_018290" FT VARIANT 339 FT /note="R -> H (in MDDGB5)" FT /evidence="ECO:0000269|PubMed:11592034, FT ECO:0000269|PubMed:12666124" FT /id="VAR_018292" FT VARIANT 339 FT /note="R -> L (in MDDGC5; dbSNP:rs1450841129)" FT /evidence="ECO:0000269|PubMed:11741828" FT /id="VAR_018291" FT VARIANT 358 FT /note="P -> L (in MDDGC5; uncertain significance; FT dbSNP:rs143031195)" FT /evidence="ECO:0000269|PubMed:14647208" FT /id="VAR_065062" FT VARIANT 360 FT /note="D -> N (in MDDGC5; dbSNP:rs770195088)" FT /evidence="ECO:0000269|PubMed:12666124" FT /id="VAR_022853" FT VARIANT 401 FT /note="D -> N (in MDDGB5; dbSNP:rs1555739117)" FT /evidence="ECO:0000269|PubMed:11592034" FT /id="VAR_018293" FT VARIANT 405 FT /note="V -> L (in MDDGB5; severe form; brain involvement; FT intellectual disability and cerebellar cysts on cranial FT MRI; dbSNP:rs28937904)" FT /evidence="ECO:0000269|PubMed:14652796" FT /id="VAR_022854" FT VARIANT 448 FT /note="P -> L (in MDDGB5; strongly reduced secretion to the FT medium; localizes mainly to the ER compartment; FT dbSNP:rs104894681)" FT /evidence="ECO:0000269|PubMed:11592034, FT ECO:0000269|PubMed:12666124, ECO:0000269|PubMed:17554798, FT ECO:0000269|PubMed:19900540" FT /id="VAR_018294" FT VARIANT 455 FT /note="A -> D (in MDDGB5; severe form; brain involvement; FT intellectual disability and cerebellar cysts on cranial FT MRI; dbSNP:rs28937903)" FT /evidence="ECO:0000269|PubMed:14652796" FT /id="VAR_022855" FT VARIANT 462 FT /note="P -> S (in MDDGC5; dbSNP:rs768606230)" FT /evidence="ECO:0000269|PubMed:12666124" FT /id="VAR_022856" FT VARIANT 463 FT /note="N -> D (in MDDGB5; dbSNP:rs121908110)" FT /evidence="ECO:0000269|PubMed:17336067" FT /id="VAR_065063" FT VARIANT 465 FT /note="Y -> S (in MDDGB5; dbSNP:rs1057520772)" FT /evidence="ECO:0000269|PubMed:11592034" FT /id="VAR_018295" FT MUTAGEN 88 FT /note="Y->F: Affects the tetramer assembly. Decreases the FT ribitol-5-phosphate transferase activity of about 80%." FT /evidence="ECO:0000269|PubMed:31949166" FT MUTAGEN 360 FT /note="D->A: Does not affect protein expression. Loss of FT ribitol-5-phosphate transferase activity." FT /evidence="ECO:0000269|PubMed:31949166" FT MUTAGEN 362 FT /note="D->A: Decrease in ribitol-5-phosphate transferase FT activity. Does not affect protein expression. Loss of FT ribitol-5-phosphate transferase activity." FT /evidence="ECO:0000269|PubMed:26923585, FT ECO:0000269|PubMed:31949166" FT MUTAGEN 364 FT /note="D->A: Does not affect protein expression. Loss of FT ribitol-5-phosphate transferase activity." FT /evidence="ECO:0000269|PubMed:31949166" FT MUTAGEN 416 FT /note="D->A: Does not affect protein expression. Loss of FT ribitol-5-phosphate transferase activity." FT /evidence="ECO:0000269|PubMed:31949166" FT STRAND 49..53 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 63..73 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 79..85 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 99..103 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 112..115 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 117..120 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 123..128 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 140..150 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 154..160 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 162..165 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 167..174 FT /evidence="ECO:0007829|PDB:6KAK" FT TURN 175..178 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 179..184 FT /evidence="ECO:0007829|PDB:6KAK" FT TURN 186..189 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 190..203 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 204..207 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 218..228 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 233..235 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 251..272 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 276..279 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:6L7U" FT HELIX 306..309 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 316..336 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 344..353 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 363..368 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 369..374 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 376..383 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 393..396 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 398..401 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 403..410 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 414..428 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 443..446 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 447..454 FT /evidence="ECO:0007829|PDB:6KAK" FT STRAND 457..464 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 465..473 FT /evidence="ECO:0007829|PDB:6KAK" FT TURN 475..479 FT /evidence="ECO:0007829|PDB:6KAK" FT HELIX 486..492 FT /evidence="ECO:0007829|PDB:6KAK" SQ SEQUENCE 495 AA; 54568 MW; 8D47756C28C6F578 CRC64; MRLTRCQAAL AAAITLNLLV LFYVSWLQHQ PRNSRARGPR RASAAGPRVT VLVREFEAFD NAVPELVDSF LQQDPAQPVV VAADTLPYPP LALPRIPNVR LALLQPALDR PAAASRPETY VATEFVALVP DGARAEAPGL LERMVEALRA GSARLVAAPV ATANPARCLA LNVSLREWTA RYGAAPAAPR CDALDGDAVV LLRARDLFNL SAPLARPVGT SLFLQTALRG WAVQLLDLTF AAARQPPLAT AHARWKAERE GRARRAALLR ALGIRLVSWE GGRLEWFGCN KETTRCFGTV VGDTPAYLYE ERWTPPCCLR ALRETARYVV GVLEAAGVRY WLEGGSLLGA ARHGDIIPWD YDVDLGIYLE DVGNCEQLRG AEAGSVVDER GFVWEKAVEG DFFRVQYSES NHLHVDLWPF YPRNGVMTKD TWLDHRQDVE FPEHFLQPLV PLPFAGFVAQ APNNYRRFLE LKFGPGVIEN PQYPNPALLS LTGSG //