FKRP_HUMAN
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 03-AUG-2022, entry version 163.
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 ---------------------------------------------------------------------------
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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; 39.
DR IntAct; Q9H9S5; 20.
DR MINT; Q9H9S5; -.
DR STRING; 9606.ENSP00000326570; -.
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; Q9H9S5; -.
DR PeptideAtlas; Q9H9S5; -.
DR PRIDE; Q9H9S5; -.
DR ProteomicsDB; 81360; -.
DR Antibodypedia; 57230; 256 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 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; 1115738at2759; -.
DR PhylomeDB; Q9H9S5; -.
DR TreeFam; TF324064; -.
DR BioCyc; MetaCyc:ENSG00000181027-MON; -.
DR PathwayCommons; Q9H9S5; -.
DR SignaLink; Q9H9S5; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 79147; 16 hits in 1081 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 157 other tissues.
DR ExpressionAtlas; Q9H9S5; baseline and differential.
DR Genevisible; Q9H9S5; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0002162; F:dystroglycan binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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: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 InterPro; IPR007074; LicD_fam.
DR Pfam; PF04991; LicD; 1.
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; unknown pathological
FT significance; 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 5-
FT 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; unknown pathological
FT significance; dbSNP:rs563033008)"
FT /evidence="ECO:0000269|PubMed:14647208"
FT /id="VAR_065061"
FT VARIANT 307
FT /note="Y -> N (in MDDGC5 and MDDGA5; muscle-eye-brain
FT disease, decrease in ribitol-5-phosphate transferase
FT activity.; 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; unknown pathological
FT significance; 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
