FKTN_HUMAN
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 03-AUG-2022, entry version 171.
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 -!- 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}.
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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. [O75072-1]
DR RefSeq; XP_016869957.1; XM_017014468.1. [O75072-1]
DR AlphaFoldDB; O75072; -.
DR BioGRID; 108512; 13.
DR IntAct; O75072; 3.
DR STRING; 9606.ENSP00000223528; -.
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; O75072; -.
DR PeptideAtlas; O75072; -.
DR PRIDE; O75072; -.
DR ProteomicsDB; 49738; -. [O75072-1]
DR Antibodypedia; 2319; 175 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 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; WPVDEWD; -.
DR OrthoDB; 1115738at2759; -.
DR PhylomeDB; O75072; -.
DR TreeFam; TF319633; -.
DR BioCyc; MetaCyc:ENSG00000106692-MON; -.
DR PathwayCommons; O75072; -.
DR SignaLink; O75072; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 2218; 12 hits in 1080 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 190 other tissues.
DR ExpressionAtlas; O75072; baseline and differential.
DR Genevisible; O75072; HS.
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:0030173; C:integral component of 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; PTHR15407; 1.
DR Pfam; PF19737; FKTN_N; 1.
DR Pfam; PF04991; LicD; 1.
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
