FKTN_MOUSE
ID FKTN_MOUSE Reviewed; 461 AA.
AC Q8R507; Q8VD64;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Ribitol-5-phosphate transferase FKTN {ECO:0000305};
DE EC=2.7.8.- {ECO:0000250|UniProtKB:O75072};
DE AltName: Full=Fukutin {ECO:0000303|PubMed:12408965};
DE AltName: Full=Fukuyama-type congenital muscular dystrophy protein {ECO:0000250|UniProtKB:O75072};
DE AltName: Full=Ribitol-5-phosphate transferase {ECO:0000250|UniProtKB:O75072};
GN Name=Fktn {ECO:0000312|MGI:MGI:2179507};
GN Synonyms=Fcmd {ECO:0000250|UniProtKB:O75072};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND POSSIBLE FUNCTION.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=12471058; DOI=10.1093/hmg/11.26.3319;
RA Esapa C.T., Benson M.A., Schroeder J.E., Martin-Rendon E., Brockington M.,
RA Brown S.C., Muntoni F., Kroeger S., Blake D.J.;
RT "Functional requirements for fukutin-related protein in the Golgi
RT apparatus.";
RL Hum. Mol. Genet. 11:3319-3331(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=12408965; DOI=10.1006/geno.2002.6853;
RA Horie M., Kobayashi K., Takeda S., Nakamura Y., Lyons G.E., Toda T.;
RT "Isolation and characterization of the mouse ortholog of the Fukuyama-type
RT congenital muscular dystrophy gene.";
RL Genomics 80:482-486(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
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 [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=12670716; DOI=10.1016/s0169-328x(03)00055-x;
RA Henion T.R., Qu Q., Smith F.I.;
RT "Expression of dystroglycan, fukutin and POMGnT1 during mouse cerebellar
RT development.";
RL Brain Res. Mol. Brain Res. 112:177-181(2003).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND PATHWAY.
RX PubMed=19017726; DOI=10.1093/hmg/ddn387;
RA Kanagawa M., Nishimoto A., Chiyonobu T., Takeda S., Miyagoe-Suzuki Y.,
RA Wang F., Fujikake N., Taniguchi M., Lu Z., Tachikawa M., Nagai Y.,
RA Tashiro F., Miyazaki J., Tajima Y., Takeda S., Endo T., Kobayashi K.,
RA Campbell K.P., Toda T.;
RT "Residual laminin-binding activity and enhanced dystroglycan glycosylation
RT by LARGE in novel model mice to dystroglycanopathy.";
RL Hum. Mol. Genet. 18:621-631(2009).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=22922256; DOI=10.1172/jci63004;
RA Beedle A.M., Turner A.J., Saito Y., Lueck J.D., Foltz S.J., Fortunato M.J.,
RA Nienaber P.M., Campbell K.P.;
RT "Mouse fukutin deletion impairs dystroglycan processing and recapitulates
RT muscular dystrophy.";
RL J. Clin. Invest. 122:3330-3342(2012).
RN [8]
RP SUBCELLULAR LOCATION, AND 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).
CC -!- FUNCTION: Catalyzes the transfer of CDP-ribitol to the distal N-
CC acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-
CC acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-
CC 6-)mannose), a carbohydrate structure present in alpha-dystroglycan
CC (DAG1) (PubMed:12471058). This constitutes the first step in the
CC 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 (By
CC similarity). Required for normal location of POMGNT1 in Golgi
CC membranes, and for normal POMGNT1 activity (PubMed:19017726). May
CC interact with and reinforce a large complex encompassing the outside
CC and inside of muscle membranes (PubMed:19017726, PubMed:22922256).
CC Could be involved in brain development (Probable).
CC {ECO:0000250|UniProtKB:O75072, ECO:0000269|PubMed:12471058,
CC ECO:0000269|PubMed:19017726, ECO:0000269|PubMed:22922256,
CC ECO:0000305|PubMed:12670716}.
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:0000250|UniProtKB:O75072};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36552;
CC Evidence={ECO:0000250|UniProtKB:O75072};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:19017726}.
CC -!- SUBUNIT: Forms a complex composed of FKTN/fukutin, FKRP and
CC RXYLT1/TMEM5 (By similarity). Interacts (via transmembrane domain) with
CC POMGNT1; the interaction is direct and is required for normal POMGNT1
CC location in Golgi membranes (By similarity).
CC {ECO:0000250|UniProtKB:O75072}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:12471058}; Single-pass type II membrane protein
CC {ECO:0000305}. Cytoplasm {ECO:0000269|PubMed:29416295}. Nucleus
CC {ECO:0000269|PubMed:29416295}. Endoplasmic reticulum
CC {ECO:0000305|PubMed:29416295}. Note=In retinal tissue, does not
CC localize with the Golgi apparatus. {ECO:0000269|PubMed:29416295}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina, with highest levels found
CC in the inner segments of photoreceptors and the outer plexiform layer
CC (at protein level) (PubMed:29416295). Expressed at lower levels in the
CC inner and outer nuclear layers, the inner plexiform layers, and the
CC ganglion cell layers of the retina (at protein level)
CC (PubMed:29416295). Expressed in the heart, brain, spleen, lung, liver,
CC skeletal muscle, kidney and testis (PubMed:12471058, PubMed:12408965).
CC {ECO:0000269|PubMed:12408965, ECO:0000269|PubMed:12471058,
CC ECO:0000269|PubMed:29416295}.
CC -!- DEVELOPMENTAL STAGE: Wide distribution of expression throughout
CC embryonic development, most predominantly in the central and peripheral
CC nervous systems. High expression in the ventricular zone of
CC proliferating neurons at 13.5 dpc. Broadly expressed in late embryonic
CC and early postnatal cerebellar neurons, including premigratory granule
CC neurons of the external granule cell layer. Expression is maintained in
CC neurons of the internal granule cell layer after migration is complete.
CC Intense expression in Purkinje cells throughout development. A unique
CC pattern of intense expression in irregularly spaced cell bodies that do
CC not appear to correlate with known parasagittal stripes. Expressed in
CC Bergmann glial scaffolds used by granule cells during early posnatal
CC radial migration. {ECO:0000269|PubMed:12670716}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality (PubMed:19017726). However,
CC when human FCMD disease-causing retrotransposon is introduced into the
CC mouse fukutin gene, alpha-dystroglycan/DAG1 is hypoglycosylated in
CC muscles as is seen in FCMD (congenital muscular dystrophy Fukuyama)
CC patients. Transfer of normal fukutin gene into these knockin mice
CC restores glycosylation of alpha-dystroglycan (PubMed:19017726).
CC Conditional knockout in muscle results in near absence of glycosylated
CC dystroglycan within 18 days of gene deletion. 20 week-old knockout mice
CC show clear dystrophic histopathology and defects in glycosylation near
CC the dystroglycan O-mannose phosphate when excision driven by muscle-
CC specific promoters takes place at 8 dpc or 17 dpc. Earlier gene
CC deletion causes more severe phenotypes (PubMed:22922256).
CC {ECO:0000269|PubMed:19017726, ECO:0000269|PubMed:22922256}.
CC -!- SIMILARITY: Belongs to the LicD transferase family. {ECO:0000305}.
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DR EMBL; AJ511807; CAD54302.1; -; mRNA.
DR EMBL; AB077383; BAB87769.1; -; mRNA.
DR EMBL; AK085931; BAC39572.1; -; mRNA.
DR EMBL; BC017538; AAH17538.1; -; mRNA.
DR CCDS; CCDS18191.1; -.
DR RefSeq; NP_647470.1; NM_139309.4.
DR AlphaFoldDB; Q8R507; -.
DR STRING; 10090.ENSMUSP00000114699; -.
DR GlyGen; Q8R507; 1 site.
DR PhosphoSitePlus; Q8R507; -.
DR MaxQB; Q8R507; -.
DR PaxDb; Q8R507; -.
DR PRIDE; Q8R507; -.
DR ProteomicsDB; 266853; -.
DR Antibodypedia; 2319; 175 antibodies from 32 providers.
DR DNASU; 246179; -.
DR Ensembl; ENSMUST00000061771; ENSMUSP00000061489; ENSMUSG00000028414.
DR Ensembl; ENSMUST00000128667; ENSMUSP00000114699; ENSMUSG00000028414.
DR GeneID; 246179; -.
DR KEGG; mmu:246179; -.
DR UCSC; uc008sxe.1; mouse.
DR CTD; 2218; -.
DR MGI; MGI:2179507; Fktn.
DR VEuPathDB; HostDB:ENSMUSG00000028414; -.
DR eggNOG; ENOG502QUDN; Eukaryota.
DR GeneTree; ENSGT00390000014471; -.
DR HOGENOM; CLU_047572_0_0_1; -.
DR InParanoid; Q8R507; -.
DR OMA; WPVDEWD; -.
DR PhylomeDB; Q8R507; -.
DR TreeFam; TF319633; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 246179; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Fktn; mouse.
DR PRO; PR:Q8R507; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8R507; protein.
DR Bgee; ENSMUSG00000028414; Expressed in epithelium of lens and 234 other tissues.
DR ExpressionAtlas; Q8R507; baseline and differential.
DR Genevisible; Q8R507; MM.
DR GO; GO:0005801; C:cis-Golgi network; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0016780; F:phosphotransferase activity, for other substituted phosphate groups; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:BHF-UCL.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:BHF-UCL.
DR GO; GO:0001764; P:neuron migration; NAS:BHF-UCL.
DR GO; GO:0006486; P:protein glycosylation; IBA:GO_Central.
DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0035269; P:protein O-linked mannosylation; ISS: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 Cytoplasm; Endoplasmic reticulum; Glycoprotein; Golgi apparatus; 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_0000204722"
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:0000250|UniProtKB:O75072"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 38
FT /note="P -> L (in Ref. 4; AAH17538)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 461 AA; 53579 MW; 1E1E0C5F187FCC39 CRC64;
MSRINKNVVL ALLTLTSSAF LLFQLYYYKH YLSARNGPGS SKSKGNRVGF DSTQWRAVKK
FIMLTSSQNV PVFLIDPWIL ESINKNFEQV KNASQGPASE CRFFCVPRDF TAFALQYHLW
KNEDGWFRIA ENMGFQCLKT ESKDPRLDGI DSLSGTEIPL HYVCKLTTHA IHLVVFHERS
GNYLWHGHLR LKGHMDRKFV PFRKLQFGRY PGAFDRPELQ QVTVDGLDML IPKDPGRFLE
EVPHSRFIEC RYKEARAFLQ QYIDDNTVDA MVFRKRAKEL LQLAAKTLKD LGVPFWLSSG
TCLGWYRQCG IIPYSKDVDL GIFIQDYKPD IILAFQEAGL PLKHKFGKVE DSLELSFQGK
NDVKLDIFFF YEEADHLWNG GTQARTGKKF KYLFPKFTLC WTEFVDIKVH VPCETVDYIE
ANYGKTWKIP IKTWDWKSSP PNVQPNGIWP ISEWDEVIQL Y
