RXLT1_HUMAN
ID RXLT1_HUMAN Reviewed; 443 AA.
AC Q9Y2B1; A8K017; Q6PKD6;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Ribitol-5-phosphate xylosyltransferase 1 {ECO:0000305};
DE EC=2.4.2.61 {ECO:0000269|PubMed:27733679, ECO:0000269|PubMed:29477842};
DE AltName: Full=Transmembrane protein 5 {ECO:0000305};
DE AltName: Full=UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase {ECO:0000303|PubMed:27733679};
GN Name=RXYLT1 {ECO:0000312|HGNC:HGNC:13530}; Synonyms=TMEM5;
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].
RX PubMed=10072769; DOI=10.1016/s0378-1119(99)00004-9;
RA Yokoyama-Kobayashi M., Yamaguchi T., Sekine S., Kato S.;
RT "Selection of cDNAs encoding putative type II membrane proteins on the cell
RT surface from a human full-length cDNA bank.";
RL Gene 228:161-167(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
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].
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary, and Skin;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [6]
RP INVOLVEMENT IN MDDGA10.
RX PubMed=23519211; DOI=10.1126/science.1233675;
RA Jae L.T., Raaben M., Riemersma M., van Beusekom E., Blomen V.A., Velds A.,
RA Kerkhoven R.M., Carette J.E., Topaloglu H., Meinecke P., Wessels M.W.,
RA Lefeber D.J., Whelan S.P., van Bokhoven H., Brummelkamp T.R.;
RT "Deciphering the glycosylome of dystroglycanopathies using haploid screens
RT for lassa virus entry.";
RL Science 340:479-483(2013).
RN [7]
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 [8]
RP FUNCTION, PATHWAY, VARIANT MDDGA10 ARG-333, CHARACTERIZATION OF VARIANT
RP MDDGA10 ARG-333, AND CATALYTIC ACTIVITY.
RX PubMed=27130732; DOI=10.7554/elife.14473;
RA Praissman J.L., Willer T., Sheikh M.O., Toi A., Chitayat D., Lin Y.Y.,
RA Lee H., Stalnaker S.H., Wang S., Prabhakar P.K., Nelson S.F., Stemple D.L.,
RA Moore S.A., Moremen K.W., Campbell K.P., Wells L.;
RT "The functional O-mannose glycan on alpha-dystroglycan contains a phospho-
RT ribitol primed for matriglycan addition.";
RL Elife 5:0-0(2016).
RN [9]
RP INVOLVEMENT IN MDDGA10.
RX PubMed=27212206; DOI=10.1016/j.nmd.2016.05.003;
RA Astrea G., Pezzini I., Picillo E., Pasquariello R., Moro F., Ergoli M.,
RA D'Ambrosio P., D'Amico A., Politano L., Santorelli F.M.;
RT "TMEM5-associated dystroglycanopathy presenting with CMD and mild limb-
RT girdle muscle involvement.";
RL Neuromuscul. Disord. 26:459-461(2016).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND CHARACTERIZATION OF VARIANTS
RP MDDGA10 CYS-339 AND LEU-340.
RX PubMed=27733679; DOI=10.1074/jbc.m116.751917;
RA Manya H., Yamaguchi Y., Kanagawa M., Kobayashi K., Tajiri M.,
RA Akasaka-Manya K., Kawakami H., Mizuno M., Wada Y., Toda T., Endo T.;
RT "The muscular dystrophy gene TMEM5 encodes a ribitol beta1,4-xylosyltran
RT sferase required for the functional glycosylation of dystroglycan.";
RL J. Biol. Chem. 291:24618-24627(2016).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH FKTN AND FKRP.
RX PubMed=27601598; DOI=10.1074/mcp.m116.062729;
RA Yagi H., Kuo C.W., Obayashi T., Ninagawa S., Khoo K.H., Kato K.;
RT "Direct mapping of additional modifications on phosphorylated O-glycans of
RT alpha-dystroglycan by mass spectrometry analysis in conjunction with
RT knocking out of causative genes for dystroglycanopathy.";
RL Mol. Cell. Proteomics 15:3424-3434(2016).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, IDENTIFICATION IN A COMPLEX WITH
RP FKTN AND FKRP, 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 [13]
RP VARIANTS MDDGA10 CYS-339 AND LEU-340.
RX PubMed=23217329; DOI=10.1016/j.ajhg.2012.10.009;
RA Vuillaumier-Barrot S., Bouchet-Seraphin C., Chelbi M., Devisme L.,
RA Quentin S., Gazal S., Laquerriere A., Fallet-Bianco C., Loget P., Odent S.,
RA Carles D., Bazin A., Aziza J., Clemenson A., Guimiot F., Bonniere M.,
RA Monnot S., Bole-Feysot C., Bernard J.P., Loeuillet L., Gonzales M.,
RA Socha K., Grandchamp B., Attie-Bitach T., Encha-Razavi F., Seta N.;
RT "Identification of mutations in TMEM5 and ISPD as a cause of severe
RT cobblestone lissencephaly.";
RL Am. J. Hum. Genet. 91:1135-1143(2012).
CC -!- FUNCTION: Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-
CC xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to
CC ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-
CC mannosyl glycan (PubMed:27733679, PubMed:29477842) (Probable).
CC Participates in the biosynthesis of the phosphorylated O-mannosyl
CC trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-
CC (phosphate-6-)mannose), a carbohydrate structure present in alpha-
CC dystroglycan (DAG1), which is required for binding laminin G-like
CC domain-containing extracellular proteins with high affinity
CC (PubMed:25279699, PubMed:27601598, PubMed:27733679) (Probable).
CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:27601598,
CC ECO:0000269|PubMed:27733679, ECO:0000269|PubMed:29477842,
CC ECO:0000305|PubMed:27130732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-GlcNAc-
CC (1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + UDP-alpha-D-xylose = 3-O-
CC [beta-D-Xyl-(1->4)-Rib-ol-P-Rib-ol-P-3-beta-D-GalNAc-(1->3)-beta-D-
CC GlcNAc-(1->4)-(O-6-P-alpha-D-Man)]-Thr-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:57880, Rhea:RHEA-COMP:15021, Rhea:RHEA-COMP:15023,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:142403, ChEBI:CHEBI:142405; EC=2.4.2.61;
CC Evidence={ECO:0000269|PubMed:27130732, ECO:0000269|PubMed:27733679,
CC ECO:0000269|PubMed:29477842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57881;
CC Evidence={ECO:0000269|PubMed:29477842, ECO:0000305|PubMed:27733679};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:27130732,
CC ECO:0000269|PubMed:27733679, ECO:0000269|PubMed:29477842}.
CC -!- SUBUNIT: Forms a complex composed of FKTN/fukutin, FKRP and
CC RXYLT1/TMEM5. {ECO:0000269|PubMed:27601598,
CC ECO:0000269|PubMed:29477842}.
CC -!- INTERACTION:
CC Q9Y2B1; Q8WZA1: POMGNT1; NbExp=4; IntAct=EBI-3914763, EBI-3912424;
CC Q9Y2B1; O76024: WFS1; NbExp=3; IntAct=EBI-3914763, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:29477842}; Single-pass
CC type II membrane protein {ECO:0000305}.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain
CC and eye anomalies A10 (MDDGA10) [MIM:615041]: 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:23217329, ECO:0000269|PubMed:23519211,
CC ECO:0000269|PubMed:27130732, ECO:0000269|PubMed:27212206,
CC ECO:0000269|PubMed:27733679}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RXYLT1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02596.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={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; AB015633; BAA76500.1; -; mRNA.
DR EMBL; AK289382; BAF82071.1; -; mRNA.
DR EMBL; CH471054; EAW97121.1; -; Genomic_DNA.
DR EMBL; BC002596; AAH02596.1; ALT_SEQ; mRNA.
DR EMBL; BC013152; AAH13152.1; -; mRNA.
DR CCDS; CCDS8966.1; -.
DR RefSeq; NP_001265166.1; NM_001278237.1.
DR RefSeq; NP_055069.1; NM_014254.2.
DR AlphaFoldDB; Q9Y2B1; -.
DR BioGRID; 115612; 19.
DR IntAct; Q9Y2B1; 16.
DR STRING; 9606.ENSP00000261234; -.
DR GlyGen; Q9Y2B1; 1 site.
DR iPTMnet; Q9Y2B1; -.
DR PhosphoSitePlus; Q9Y2B1; -.
DR BioMuta; TMEM5; -.
DR EPD; Q9Y2B1; -.
DR jPOST; Q9Y2B1; -.
DR MassIVE; Q9Y2B1; -.
DR MaxQB; Q9Y2B1; -.
DR PaxDb; Q9Y2B1; -.
DR PeptideAtlas; Q9Y2B1; -.
DR PRIDE; Q9Y2B1; -.
DR ProteomicsDB; 85717; -.
DR Antibodypedia; 29125; 157 antibodies from 24 providers.
DR DNASU; 10329; -.
DR Ensembl; ENST00000261234.11; ENSP00000261234.6; ENSG00000118600.13.
DR GeneID; 10329; -.
DR KEGG; hsa:10329; -.
DR MANE-Select; ENST00000261234.11; ENSP00000261234.6; NM_014254.3; NP_055069.1.
DR UCSC; uc001srq.3; human.
DR CTD; 10329; -.
DR DisGeNET; 10329; -.
DR GeneCards; RXYLT1; -.
DR HGNC; HGNC:13530; RXYLT1.
DR HPA; ENSG00000118600; Low tissue specificity.
DR MalaCards; RXYLT1; -.
DR MIM; 605862; gene.
DR MIM; 615041; phenotype.
DR neXtProt; NX_Q9Y2B1; -.
DR OpenTargets; ENSG00000118600; -.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA37796; -.
DR VEuPathDB; HostDB:ENSG00000118600; -.
DR eggNOG; ENOG502QT2E; Eukaryota.
DR GeneTree; ENSGT00390000003526; -.
DR HOGENOM; CLU_040812_0_0_1; -.
DR InParanoid; Q9Y2B1; -.
DR OMA; PVVEPSW; -.
DR OrthoDB; 912057at2759; -.
DR PhylomeDB; Q9Y2B1; -.
DR TreeFam; TF328717; -.
DR BioCyc; MetaCyc:ENSG00000118600-MON; -.
DR BRENDA; 2.4.2.61; 2681.
DR PathwayCommons; Q9Y2B1; -.
DR SignaLink; Q9Y2B1; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 10329; 6 hits in 1075 CRISPR screens.
DR ChiTaRS; TMEM5; human.
DR GenomeRNAi; 10329; -.
DR Pharos; Q9Y2B1; Tbio.
DR PRO; PR:Q9Y2B1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9Y2B1; protein.
DR Bgee; ENSG00000118600; Expressed in corpus epididymis and 215 other tissues.
DR ExpressionAtlas; Q9Y2B1; baseline and differential.
DR Genevisible; Q9Y2B1; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0120053; F:ribitol beta-1,4-xylosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0035269; P:protein O-linked mannosylation; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Congenital muscular dystrophy; Disease variant; Dystroglycanopathy;
KW Golgi apparatus; Lissencephaly; Membrane; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..443
FT /note="Ribitol-5-phosphate xylosyltransferase 1"
FT /id="PRO_0000072587"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..443
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 35..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..76
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 333
FT /note="G -> R (in MDDGA10; unknown pathological
FT significance; loss of binding activity of alpha-
FT dystroglycan (DAG1) for the ligand laminin in fibroblasts
FT from patients; loss of alpha-dystroglycan functional
FT glycosylation in fibroblasts from patients; does not affect
FT Golgi apparatus localization; dbSNP:rs777596548)"
FT /evidence="ECO:0000269|PubMed:27130732"
FT /id="VAR_085411"
FT VARIANT 339
FT /note="Y -> C (in MDDGA10; abolishes xylosyltransferase
FT activity; dbSNP:rs150736997)"
FT /evidence="ECO:0000269|PubMed:23217329,
FT ECO:0000269|PubMed:27733679"
FT /id="VAR_069738"
FT VARIANT 340
FT /note="R -> L (in MDDGA10; abolishes xylosyltransferase
FT activity; dbSNP:rs397514544)"
FT /evidence="ECO:0000269|PubMed:23217329,
FT ECO:0000269|PubMed:27733679"
FT /id="VAR_069739"
SQ SEQUENCE 443 AA; 51146 MW; 07BBD23A91973A52 CRC64;
MRLTRKRLCS FLIALYCLFS LYAAYHVFFG RRRQAPAGSP RGLRKGAAPA RERRGREQST
LESEEWNPWE GDEKNEQQHR FKTSLQILDK STKGKTDLSV QIWGKAAIGL YLWEHIFEGL
LDPSDVTAQW REGKSIVGRT QYSFITGPAV IPGYFSVDVN NVVLILNGRE KAKIFYATQW
LLYAQNLVQI QKLQHLAVVL LGNEHCDNEW INPFLKRNGG FVELLFIIYD SPWINDVDVF
QWPLGVATYR NFPVVEASWS MLHDERPYLC NFLGTIYENS SRQALMNILK KDGNDKLCWV
SAREHWQPQE TNESLKNYQD ALLQSDLTLC PVGVNTECYR IYEACSYGSI PVVEDVMTAG
NCGNTSVHHG APLQLLKSMG APFIFIKNWK ELPAVLEKEK TIILQEKIER RKMLLQWYQH
FKTELKMKFT NILESSFLMN NKS
