ID FKTN_HUMAN Reviewed; 461 AA. AC O75072; B4DUX9; J3KP13; Q3MIJ1; Q96TE1; Q9P295; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 12-FEB-2003, sequence version 2. DT 27-MAR-2024, entry version 180. DE RecName: Full=Ribitol-5-phosphate transferase FKTN; DE EC=2.7.8.- {ECO:0000269|PubMed:26923585, ECO:0000269|PubMed:29477842}; DE AltName: Full=Fukutin {ECO:0000303|PubMed:9690476}; DE AltName: Full=Fukuyama-type congenital muscular dystrophy protein {ECO:0000303|PubMed:9690476}; DE AltName: Full=Ribitol-5-phosphate transferase {ECO:0000303|PubMed:26923585}; GN Name=FKTN {ECO:0000312|HGNC:HGNC:3622}; GN Synonyms=FCMD {ECO:0000303|PubMed:10545611}; 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] (ISOFORM 1), AND VARIANT GLN-203. RC TISSUE=Brain; RX PubMed=9690476; DOI=10.1038/28653; RA Kobayashi K., Nakahori Y., Miyake M., Matsumura K., Kondo-Iida E., RA Nomura Y., Segawa M., Yoshioka M., Saito K., Osawa M., Hamano K., RA Sakakihara Y., Nonaka I., Nakagome Y., Kanazawa I., Nakamura Y., RA Tokunaga K., Toda T.; RT "An ancient retrotransposal insertion causes Fukuyama-type congenital RT muscular dystrophy."; RL Nature 394:388-392(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11165248; DOI=10.1016/s0014-5793(01)02088-9; RA Kobayashi K., Sasaki J., Kondo-Iida E., Fukuda Y., Kinoshita M., Sunada Y., RA Nakamura Y., Toda T.; RT "Structural organization, complete genomic sequences and mutational RT analyses of the Fukuyama-type congenital muscular dystrophy gene, RT fukutin."; RL FEBS Lett. 489:192-196(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Small intestine; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 DISEASE. RX PubMed=10817652; RX DOI=10.1002/(sici)1096-8628(20000529)92:3<184::aid-ajmg5>3.0.co;2-n; RA Saito K., Osawa M., Wang Z.-P., Ikeya K., Fukuyama Y., Kondo-Iida E., RA Toda T., Ohashi H., Kurosawa K., Wakai S., Kaneko K.; RT "Haplotype-phenotype correlation in Fukuyama congenital muscular RT dystrophy."; RL Am. J. Med. Genet. 92:184-190(2000). RN [7] RP TISSUE SPECIFICITY, AND DISEASE. RX PubMed=11115853; DOI=10.1093/hmg/9.20.3083; RA Sasaki J., Ishikawa K., Kobayashi K., Kondo-Iida E., Fukayama M., RA Mizusawa H., Takashima S., Sakakihara Y., Nakamura Y., Toda T.; RT "Neuronal expression of the fukutin gene."; RL Hum. Mol. Genet. 9:3083-3090(2000). RN [8] RP DISEASE, AND POSSIBLE FUNCTION. RX PubMed=11445638; DOI=10.1212/wnl.57.1.115; RA Hayashi Y.K., Ogawa M., Tagawa K., Noguchi S., Ishihara T., Nonaka I., RA Arahata K.; RT "Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital RT muscular dystrophy."; RL Neurology 57:115-121(2001). RN [9] RP DISEASE. RX PubMed=12601708; DOI=10.1002/ana.10491; RA Silan F., Yoshioka M., Kobayashi K., Simsek E., Tunc M., Alper M., Cam M., RA Guven A., Fukuda Y., Kinoshita M., Kocabay K., Toda T.; RT "A new mutation of the fukutin gene in a non-Japanese patient."; RL Ann. Neurol. 53:392-396(2003). RN [10] RP INVOLVEMENT IN MDDGB4, AND VARIANT ASP-446. RX PubMed=14627679; DOI=10.1136/jmg.40.11.845; RA Beltran-Valero de Bernabe D., van Bokhoven H., van Beusekom E., RA Van den Akker W., Kant S., Dobyns W.B., Cormand B., Currier S., RA Hamel B.C.J., Talim B., Topaloglu H., Brunner H.G.; RT "A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg RT syndrome phenotype."; RL J. Med. Genet. 40:845-848(2003). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH POMGNT1, AND RP CHARACTERIZATION OF VARIANT MDDGA4 CYS-371. RX PubMed=17034757; DOI=10.1016/j.bbrc.2006.09.129; RA Xiong H., Kobayashi K., Tachikawa M., Manya H., Takeda S., Chiyonobu T., RA Fujikake N., Wang F., Nishimoto A., Morris G.E., Nagai Y., Kanagawa M., RA Endo T., Toda T.; RT "Molecular interaction between fukutin and POMGnT1 in the glycosylation RT pathway of alpha-dystroglycan."; RL Biochem. Biophys. Res. Commun. 350:935-941(2006). RN [12] RP INVOLVEMENT IN MDDGB4, AND VARIANT SER-125. RX PubMed=18177472; DOI=10.1111/j.1399-0004.2007.00936.x; RA Cotarelo R.P., Valero M.C., Prados B., Pena A., Rodriguez L., Fano O., RA Marco J.J., Martinez-Frias M.L., Cruces J.; RT "Two new patients bearing mutations in the fukutin gene confirm the RT relevance of this gene in Walker-Warburg syndrome."; RL Clin. Genet. 73:139-145(2008). RN [13] RP INVOLVEMENT IN MDDGA4. RX PubMed=22958903; DOI=10.1016/j.ajhg.2012.07.009; RA Manzini M.C., Tambunan D.E., Hill R.S., Yu T.W., Maynard T.M., RA Heinzen E.L., Shianna K.V., Stevens C.R., Partlow J.N., Barry B.J., RA Rodriguez J., Gupta V.A., Al-Qudah A.K., Eyaid W.M., Friedman J.M., RA Salih M.A., Clark R., Moroni I., Mora M., Beggs A.H., Gabriel S.B., RA Walsh C.A.; RT "Exome sequencing and functional validation in zebrafish identify GTDC2 RT mutations as a cause of Walker-Warburg syndrome."; RL Am. J. Hum. Genet. 91:541-547(2012). RN [14] 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 [15] 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 [16] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, VARIANT RP GLN-307, AND MUTAGENESIS OF MET-133 AND ASP-317. 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 [17] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, IDENTIFICATION IN A COMPLEX WITH RP FKRP AND RXYLT1, AND SUBCELLULAR LOCATION. 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 [18] 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 [19] RP VARIANT MDDGA4 GLY-250. RX PubMed=10545611; DOI=10.1093/hmg/8.12.2303; RA Kondo-Iida E., Kobayashi K., Watanabe M., Sasaki J., Kumagai T., Koide H., RA Saito K., Osawa M., Nakamura Y., Toda T.; RT "Novel mutations and genotype-phenotype relationships in 107 families with RT Fukuyama-type congenital muscular dystrophy (FCMD)."; RL Hum. Mol. Genet. 8:2303-2309(1999). RN [20] RP VARIANTS CMD1X THR-179 AND PRO-358. RX PubMed=17036286; DOI=10.1002/ana.20973; RA Murakami T., Hayashi Y.K., Noguchi S., Ogawa M., Nonaka I., Tanabe Y., RA Ogino M., Takada F., Eriguchi M., Kotooka N., Campbell K.P., Osawa M., RA Nishino I.; RT "Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle RT weakness."; RL Ann. Neurol. 60:597-602(2006). RN [21] RP VARIANT MDDGC4 GLN-307, AND CHARACTERIZATION OF VARIANT MDDGC4 GLN-307. RX PubMed=17044012; DOI=10.1002/ana.21006; RA Godfrey C., Escolar D., Brockington M., Clement E.M., Mein R., RA Jimenez-Mallebrera C., Torelli S., Feng L., Brown S.C., Sewry C.A., RA Rutherford M., Shapira Y., Abbs S., Muntoni F.; RT "Fukutin gene mutations in steroid-responsive limb girdle muscular RT dystrophy."; RL Ann. Neurol. 60:603-610(2006). RN [22] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-225 AND ASN-225. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [23] RP VARIANT MDDGB4 GLN-307. RX PubMed=19299310; DOI=10.1212/01.wnl.0000346518.68110.60; RA Mercuri E., Messina S., Bruno C., Mora M., Pegoraro E., Comi G.P., RA D'Amico A., Aiello C., Biancheri R., Berardinelli A., Boffi P., RA Cassandrini D., Laverda A., Moggio M., Morandi L., Moroni I., Pane M., RA Pezzani R., Pichiecchio A., Pini A., Minetti C., Mongini T., Mottarelli E., RA Ricci E., Ruggieri A., Saredi S., Scuderi C., Tessa A., Toscano A., RA Tortorella G., Trevisan C.P., Uggetti C., Vasco G., Santorelli F.M., RA Bertini E.; RT "Congenital muscular dystrophies with defective glycosylation of RT dystroglycan: a population study."; RL Neurology 72:1802-1809(2009). RN [24] RP VARIANTS MDDGA4 GLU-170 AND CYS-371, AND VARIANTS MDDGB4 GLY-246 AND RP GLN-307. RX PubMed=19179078; DOI=10.1016/j.nmd.2008.12.005; RA Vuillaumier-Barrot S., Quijano-Roy S., Bouchet-Seraphin C., Maugenre S., RA Peudenier S., Van den Bergh P., Marcorelles P., Avila-Smirnow D., RA Chelbi M., Romero N.B., Carlier R.Y., Estournet B., Guicheney P., Seta N.; RT "Four Caucasian patients with mutations in the fukutin gene and variable RT clinical phenotype."; RL Neuromuscul. Disord. 19:182-188(2009). RN [25] RP VARIANTS MDDGC4 THR-114 AND SER-176. RX PubMed=19342235; DOI=10.1016/j.nmd.2009.03.001; RA Puckett R.L., Moore S.A., Winder T.L., Willer T., Romansky S.G., RA Covault K.K., Campbell K.P., Abdenur J.E.; RT "Further evidence of Fukutin mutations as a cause of childhood onset limb- RT girdle muscular dystrophy without mental retardation."; RL Neuromuscul. Disord. 19:352-356(2009). RN [26] RP INVOLVEMENT IN MDDGA4. RX PubMed=24530477; DOI=10.1016/j.gene.2014.01.070; RA Ismail S., Schaffer A.E., Rosti R.O., Gleeson J.G., Zaki M.S.; RT "Novel mutation in the fukutin gene in an Egyptian family with Fukuyama RT congenital muscular dystrophy and microcephaly."; RL Gene 539:279-282(2014). CC -!- FUNCTION: Catalyzes the transfer of a ribitol-phosphate from CDP- CC ribitol to the distal N-acetylgalactosamine of the phosphorylated O- CC mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N- CC acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate CC structure present in alpha-dystroglycan (DAG1) (PubMed:26923585, CC PubMed:29477842, PubMed:27194101). This constitutes the first step in CC the formation of the ribitol 5-phosphate tandem repeat which links the CC phosphorylated O-mannosyl trisaccharide to the ligand binding moiety CC composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1 CC (PubMed:17034757, PubMed:25279699, PubMed:26923585, PubMed:29477842, CC PubMed:27194101). Required for normal location of POMGNT1 in Golgi CC membranes, and for normal POMGNT1 activity (PubMed:17034757). May CC interact with and reinforce a large complex encompassing the outside CC and inside of muscle membranes (PubMed:25279699). Could be involved in CC brain development (Probable). {ECO:0000269|PubMed:17034757, CC ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:26923585, CC ECO:0000269|PubMed:27194101, ECO:0000269|PubMed:29477842, CC ECO:0000305|PubMed:11115853}. CC -!- CATALYTIC ACTIVITY: CC Reaction=3-O-[beta-D-GalNAc-(1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D- CC Man)]-Thr-[protein] + CDP-L-ribitol = 3-O-[Rib-ol-P-3-beta-D-GalNAc- CC (1->3)-beta-D-GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + CMP CC + H(+); Xref=Rhea:RHEA:36551, Rhea:RHEA-COMP:13309, Rhea:RHEA- CC COMP:17480, ChEBI:CHEBI:15378, ChEBI:CHEBI:57608, ChEBI:CHEBI:60377, CC ChEBI:CHEBI:136710, ChEBI:CHEBI:177331; CC Evidence={ECO:0000269|PubMed:26923585, ECO:0000269|PubMed:29477842}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36552; CC Evidence={ECO:0000269|PubMed:26923585}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:26923585, CC ECO:0000269|PubMed:27194101, ECO:0000269|PubMed:29477842}. CC -!- SUBUNIT: Forms a complex composed of FKTN/fukutin, FKRP and CC RXYLT1/TMEM5 (PubMed:29477842). Interacts (via transmembrane domain) CC with POMGNT1; the interaction is direct and is required for normal CC POMGNT1 location in Golgi membranes (PubMed:17034757). CC {ECO:0000269|PubMed:17034757, ECO:0000269|PubMed:29477842}. CC -!- INTERACTION: CC O75072; Q9Y2B1: RXYLT1; NbExp=4; IntAct=EBI-21511782, EBI-3914763; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:29477842, CC ECO:0000305|PubMed:26923585}; Single-pass type II membrane protein CC {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:Q8R507}. Nucleus CC {ECO:0000250|UniProtKB:Q8R507}. Note=In retinal tissue, does not CC localize with the Golgi apparatus. {ECO:0000250|UniProtKB:Q8R507}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75072-1; Sequence=Displayed; CC Name=2; CC IsoId=O75072-2; Sequence=VSP_045961; CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level) CC (PubMed:29416295). Widely expressed with highest expression in brain, CC heart, pancreas and skeletal muscle (PubMed:11115853). Expressed at CC similar levels in control fetal and adult brain (PubMed:11115853). CC Expressed in migrating neurons, including Cajar-Retzius cells and adult CC cortical neurons, as well as hippocampal pyramidal cells and cerebellar CC Purkinje cells (PubMed:11115853). No expression observed in the glia CC limitans, the subpial astrocytes (which contribute to basement membrane CC formation) or other glial cells (PubMed:11115853). CC {ECO:0000269|PubMed:11115853, ECO:0000269|PubMed:29416295}. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain CC and eye anomalies A4 (MDDGA4) [MIM:253800]: 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:10545611, ECO:0000269|PubMed:17034757, CC ECO:0000269|PubMed:19179078, ECO:0000269|PubMed:22958903, CC ECO:0000269|PubMed:24530477}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital without CC impaired intellectual development B4 (MDDGB4) [MIM:613152]: An CC autosomal recessive disorder characterized by congenital muscular CC dystrophy and evidence of dystroglycanopathy. Features included CC increased serum creatine kinase, generalized weakness, mild white CC matter changes on brain MRI, and absence of intellectual disability. CC {ECO:0000269|PubMed:14627679, ECO:0000269|PubMed:18177472, CC ECO:0000269|PubMed:19179078, ECO:0000269|PubMed:19299310}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C4 (MDDGC4) CC [MIM:611588]: An autosomal recessive degenerative myopathy CC characterized by progressive weakness of the pelvic and shoulder girdle CC muscles, and elevated serum creatine kinase. MDDGC4 has no brain CC involvement and a remarkable clinical response to corticosteroids. CC {ECO:0000269|PubMed:17044012, ECO:0000269|PubMed:19342235}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cardiomyopathy, dilated, 1X (CMD1X) [MIM:611615]: A disorder CC characterized by ventricular dilation and impaired systolic function, CC resulting in congestive heart failure and arrhythmia. Patients are at CC risk of premature death. {ECO:0000269|PubMed:17036286}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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; AB008226; BAA32000.1; -; mRNA. DR EMBL; AB038490; BAA94082.1; -; Genomic_DNA. DR EMBL; AK300840; BAG62491.1; -; mRNA. DR EMBL; AL158070; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC101808; AAI01809.1; -; mRNA. DR EMBL; BC112038; AAI12039.1; -; mRNA. DR EMBL; BC117699; AAI17700.1; -; mRNA. DR CCDS; CCDS6766.1; -. [O75072-1] DR RefSeq; NP_001073270.1; NM_001079802.1. [O75072-1] DR RefSeq; NP_001185892.1; NM_001198963.1. [O75072-2] DR RefSeq; NP_006722.2; NM_006731.2. [O75072-1] DR RefSeq; XP_016869955.1; XM_017014466.1. DR RefSeq; XP_016869956.1; XM_017014467.1. DR RefSeq; XP_016869957.1; XM_017014468.1. DR AlphaFoldDB; O75072; -. DR BioGRID; 108512; 14. DR ComplexPortal; CPX-7722; Fukutin-FKRP-TMEM5 multienzyme complex. DR IntAct; O75072; 4. DR STRING; 9606.ENSP00000223528; -. DR GlyCosmos; O75072; 1 site, No reported glycans. DR GlyGen; O75072; 1 site. DR iPTMnet; O75072; -. DR PhosphoSitePlus; O75072; -. DR BioMuta; FKTN; -. DR EPD; O75072; -. DR jPOST; O75072; -. DR MassIVE; O75072; -. DR MaxQB; O75072; -. DR PaxDb; 9606-ENSP00000223528; -. DR PeptideAtlas; O75072; -. DR ProteomicsDB; 49738; -. [O75072-1] DR Antibodypedia; 2319; 197 antibodies from 32 providers. DR DNASU; 2218; -. DR Ensembl; ENST00000223528.6; ENSP00000223528.2; ENSG00000106692.15. [O75072-1] DR Ensembl; ENST00000357998.10; ENSP00000350687.6; ENSG00000106692.15. [O75072-1] DR Ensembl; ENST00000448551.6; ENSP00000399140.2; ENSG00000106692.15. [O75072-2] DR GeneID; 2218; -. DR KEGG; hsa:2218; -. DR MANE-Select; ENST00000357998.10; ENSP00000350687.6; NM_001079802.2; NP_001073270.1. DR UCSC; uc004bcr.4; human. [O75072-1] DR AGR; HGNC:3622; -. DR CTD; 2218; -. DR DisGeNET; 2218; -. DR GeneCards; FKTN; -. DR GeneReviews; FKTN; -. DR HGNC; HGNC:3622; FKTN. DR HPA; ENSG00000106692; Low tissue specificity. DR MalaCards; FKTN; -. DR MIM; 253800; phenotype. DR MIM; 607440; gene. DR MIM; 611588; phenotype. DR MIM; 611615; phenotype. DR MIM; 613152; phenotype. DR neXtProt; NX_O75072; -. DR OpenTargets; ENSG00000106692; -. DR Orphanet; 370980; Congenital muscular dystrophy without intellectual disability. DR Orphanet; 272; Congenital muscular dystrophy, Fukuyama type. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 206554; Fukutin-related limb-girdle muscular dystrophy R13. DR Orphanet; 588; Muscle-eye-brain disease. DR Orphanet; 899; Walker-Warburg syndrome. DR PharmGKB; PA162388669; -. DR VEuPathDB; HostDB:ENSG00000106692; -. DR eggNOG; ENOG502QUDN; Eukaryota. DR GeneTree; ENSGT00390000014471; -. DR HOGENOM; CLU_047572_0_0_1; -. DR InParanoid; O75072; -. DR OMA; MQRINKN; -. DR OrthoDB; 2897239at2759; -. DR PhylomeDB; O75072; -. DR TreeFam; TF319633; -. DR BioCyc; MetaCyc:ENSG00000106692-MONOMER; -. DR PathwayCommons; O75072; -. DR SignaLink; O75072; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 2218; 12 hits in 1160 CRISPR screens. DR ChiTaRS; FKTN; human. DR GeneWiki; Fukutin; -. DR GenomeRNAi; 2218; -. DR Pharos; O75072; Tbio. DR PRO; PR:O75072; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O75072; Protein. DR Bgee; ENSG00000106692; Expressed in calcaneal tendon and 191 other cell types or tissues. DR ExpressionAtlas; O75072; baseline and differential. DR GO; GO:0005801; C:cis-Golgi network; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; IDA:UniProtKB. DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0046329; P:negative regulation of JNK cascade; IMP:BHF-UCL. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0006486; P:protein glycosylation; IBA:GO_Central. DR GO; GO:0006493; P:protein O-linked glycosylation; IMP:UniProtKB. DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:UniProtKB. DR GO; GO:0060049; P:regulation of protein glycosylation; NAS:BHF-UCL. DR InterPro; IPR009644; FKTN-related. DR InterPro; IPR045587; FKTN_N. DR InterPro; IPR007074; LicD_fam. DR PANTHER; PTHR15407; FUKUTIN-RELATED; 1. DR PANTHER; PTHR15407:SF28; RIBITOL-5-PHOSPHATE TRANSFERASE FKTN; 1. DR Pfam; PF19737; FKTN_N; 1. DR Pfam; PF04991; LicD; 1. DR Genevisible; O75072; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cardiomyopathy; Congenital muscular dystrophy; KW Cytoplasm; Disease variant; Dystroglycanopathy; Glycoprotein; KW Golgi apparatus; Limb-girdle muscular dystrophy; Lissencephaly; Membrane; KW Nucleus; Reference proteome; Signal-anchor; Transferase; Transmembrane; KW Transmembrane helix. FT CHAIN 1..461 FT /note="Ribitol-5-phosphate transferase FKTN" FT /id="PRO_0000204720" FT TOPO_DOM 1..7 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 8..28 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 29..461 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 6..27 FT /note="Required and sufficient for interaction with FT POMGNT1" FT /evidence="ECO:0000269|PubMed:17034757" FT CARBOHYD 92 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 426..461 FT /note="TWKIPVKTWDWKRSPPNVQPNGIWPISEWDEVIQLY -> NQQGA (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045961" FT VARIANT 56 FT /note="R -> C (in dbSNP:rs41277797)" FT /id="VAR_061296" FT VARIANT 114 FT /note="A -> T (in MDDGC4; dbSNP:rs119463995)" FT /evidence="ECO:0000269|PubMed:19342235" FT /id="VAR_065050" FT VARIANT 125 FT /note="G -> S (in a patient diagnosed with Walker-Warburg FT syndrome; dbSNP:rs34006675)" FT /evidence="ECO:0000269|PubMed:18177472" FT /id="VAR_033926" FT VARIANT 170 FT /note="A -> E (in MDDGA4; dbSNP:rs119464997)" FT /evidence="ECO:0000269|PubMed:19179078" FT /id="VAR_065051" FT VARIANT 176 FT /note="F -> S (in MDDGC4; dbSNP:rs119463996)" FT /evidence="ECO:0000269|PubMed:19342235" FT /id="VAR_065052" FT VARIANT 179 FT /note="R -> T (in CMD1X; dbSNP:rs119463994)" FT /evidence="ECO:0000269|PubMed:17036286" FT /id="VAR_039287" FT VARIANT 203 FT /note="R -> Q (in dbSNP:rs34787999)" FT /evidence="ECO:0000269|PubMed:9690476" FT /id="VAR_033927" FT VARIANT 225 FT /note="D -> E (in a breast cancer sample; somatic mutation; FT dbSNP:rs779298204)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036334" FT VARIANT 225 FT /note="D -> N (in a breast cancer sample; somatic mutation; FT dbSNP:rs1298422772)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036335" FT VARIANT 246 FT /note="R -> G (in MDDGB4)" FT /evidence="ECO:0000269|PubMed:19179078" FT /id="VAR_065053" FT VARIANT 250 FT /note="C -> G (in MDDGA4)" FT /evidence="ECO:0000269|PubMed:10545611" FT /id="VAR_018278" FT VARIANT 307 FT /note="R -> Q (in MDDGB4 and MDDGC4; the mutant protein is FT expressed and localized correctly within the cell, decrease FT in ribitol-5-phosphate transferase activity.; FT dbSNP:rs119463992)" FT /evidence="ECO:0000269|PubMed:17044012, FT ECO:0000269|PubMed:19179078, ECO:0000269|PubMed:19299310, FT ECO:0000269|PubMed:26923585" FT /id="VAR_039288" FT VARIANT 358 FT /note="Q -> P (in CMD1X; dbSNP:rs119463993)" FT /evidence="ECO:0000269|PubMed:17036286" FT /id="VAR_039289" FT VARIANT 371 FT /note="Y -> C (in MDDGA4; loss of normal location in Golgi FT membranes; dbSNP:rs119464998)" FT /evidence="ECO:0000269|PubMed:17034757, FT ECO:0000269|PubMed:19179078" FT /id="VAR_065054" FT VARIANT 446 FT /note="N -> D (in dbSNP:rs41313301)" FT /evidence="ECO:0000269|PubMed:14627679" FT /id="VAR_018279" FT MUTAGEN 133 FT /note="M->T: Decrease in ribitol-5-phosphate transferase FT activity." FT /evidence="ECO:0000269|PubMed:26923585" FT MUTAGEN 317 FT /note="D->A: Decrease in ribitol-5-phosphate transferase FT activity." FT /evidence="ECO:0000269|PubMed:26923585" FT CONFLICT 414 FT /note="E -> K (in Ref. 3; BAG62491)" FT /evidence="ECO:0000305" SQ SEQUENCE 461 AA; 53724 MW; 2D11F28E4BCCD858 CRC64; MSRINKNVVL ALLTLTSSAF LLFQLYYYKH YLSTKNGAGL SKSKGSRIGF DSTQWRAVKK FIMLTSNQNV PVFLIDPLIL ELINKNFEQV KNTSHGSTSQ CKFFCVPRDF TAFALQYHLW KNEEGWFRIA ENMGFQCLKI ESKDPRLDGI DSLSGTEIPL HYICKLATHA IHLVVFHERS GNYLWHGHLR LKEHIDRKFV PFRKLQFGRY PGAFDRPELQ QVTVDGLEVL IPKDPMHFVE EVPHSRFIEC RYKEARAFFQ QYLDDNTVEA VAFRKSAKEL LQLAAKTLNK LGVPFWLSSG TCLGWYRQCN IIPYSKDVDL GIFIQDYKSD IILAFQDAGL PLKHKFGKVE DSLELSFQGK DDVKLDVFFF YEETDHMWNG GTQAKTGKKF KYLFPKFTLC WTEFVDMKVH VPCETLEYIE ANYGKTWKIP VKTWDWKRSP PNVQPNGIWP ISEWDEVIQL Y //