POMT1 explained

Protein O-mannosyl-transferase 1 is an enzyme that in humans is encoded by the POMT1 gene.^{[1] [2]} It is a member of the dolichyl-phosphate-mannose-protein mannosyltransferases.

Function

O-mannosylation is an important protein modification in eukaryotes that is initiated by an evolutionarily conserved family of protein O-mannosyltransferases. POMT1 shares sequence similarity with protein O-mannosyltransferases of S. cerevisiae. In yeast, these enzymes are located in the endoplasmic reticulum (ER) and are required for cell integrity and cell wall rigidity. POMT1 also shows similarity to the Drosophila 'rotated abdomen' (rt) gene, which when mutated causes defects in myogenesis and muscle structure.[supplied by OMIM]

It is associated with limb-girdle muscular dystrophy type LGMD2K.

In the retina it is known that O-mannosylation of α-DG carried out by POMT1 is crucial for the establishment of proper synapses at the outer plexiform layer and the transmission of visual information from cones and rods to their postsynaptic neurons, i.e. bipolar and horizontal cells.^[3] Lack of POMT1 expression results in a good number of impairments in photoreceptors that have been documented at the proteomic, morphological and physiological levels.^[4]

References

Further reading

• Grewal PK, Hewitt JE . Glycosylation defects: a new mechanism for muscular dystrophy? . Human Molecular Genetics . 12 Spec No 2 . 90002 . R259–64 . October 2003 . 12925572 . 10.1093/hmg/ddg272 . free .
• Beltrán-Valero de Bernabé D, Currier S, Steinbrecher A, Celli J, van Beusekom E, van der Zwaag B, Kayserili H, Merlini L, Chitayat D, Dobyns WB, Cormand B, Lehesjoki AE, Cruces J, Voit T, Walsh CA, van Bokhoven H, Brunner HG . 6 . Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome . American Journal of Human Genetics . 71 . 5 . 1033–43 . November 2002 . 12369018 . 419999 . 10.1086/342975 .
• Sabatelli P, Columbaro M, Mura I, Capanni C, Lattanzi G, Maraldi NM, Beltràn-Valero de Barnabè D, van Bokoven H, Squarzoni S, Merlini L . 6 . Extracellular matrix and nuclear abnormalities in skeletal muscle of a patient with Walker-Warburg syndrome caused by POMT1 mutation . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1638 . 1 . 57–62 . May 2003 . 12757935 . 10.1016/s0925-4439(03)00040-1 . free .
• Manya H, Chiba A, Yoshida A, Wang X, Chiba Y, Jigami Y, Margolis RU, Endo T . 6 . Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity . Proceedings of the National Academy of Sciences of the United States of America . 101 . 2 . 500–5 . January 2004 . 14699049 . 327176 . 10.1073/pnas.0307228101 . 2004PNAS..101..500M . free .
• Kim DS, Hayashi YK, Matsumoto H, Ogawa M, Noguchi S, Murakami N, Sakuta R, Mochizuki M, Michele DE, Campbell KP, Nonaka I, Nishino I . 6 . POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG . Neurology . 62 . 6 . 1009–11 . March 2004 . 15037715 . 10.1212/01.wnl.0000115386.28769.65 . 28864658 .
• Akasaka-Manya K, Manya H, Endo T . Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation . Biochemical and Biophysical Research Communications . 325 . 1 . 75–9 . December 2004 . 15522202 . 10.1016/j.bbrc.2004.10.001 .
• Currier SC, Lee CK, Chang BS, Bodell AL, Pai GS, Job L, Lagae LG, Al-Gazali LI, Eyaid WM, Enns G, Dobyns WB, Walsh CA . 6 . Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome . American Journal of Medical Genetics. Part A . 133A . 1 . 53–7 . February 2005 . 15637732 . 10.1002/ajmg.a.30487 . 16549086 .
• Balci B, Uyanik G, Dincer P, Gross C, Willer T, Talim B, Haliloglu G, Kale G, Hehr U, Winkler J, Topaloğlu H . 6 . An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene . Neuromuscular Disorders . 15 . 4 . 271–5 . April 2005 . 15792865 . 10.1016/j.nmd.2005.01.013 . 23007648 .
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T . 6 . Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries . DNA Research . 12 . 2 . 117–26 . 2007 . 16303743 . 10.1093/dnares/12.2.117 . free .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Akasaka-Manya K, Manya H, Nakajima A, Kawakita M, Endo T . Physical and functional association of human protein O-mannosyltransferases 1 and 2 . The Journal of Biological Chemistry . 281 . 28 . 19339–45 . July 2006 . 16698797 . 10.1074/jbc.M601091200 . free .
• Bouchet C, Vuillaumier-Barrot S, Gonzales M, Boukari S, Bizec CL, Fallet C, Delezoide AL, Moirot H, Laquerriere A, Encha-Razavi F, Durand G, Seta N . 6 . Detection of an Alu insertion in the POMT1 gene from three French Walker Warburg syndrome families . Molecular Genetics and Metabolism . 90 . 1 . 93–6 . January 2007 . 17079174 . 10.1016/j.ymgme.2006.09.005 .

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview

Notes and References

1. Jurado LA, Coloma A, Cruces J . Identification of a human homolog of the Drosophila rotated abdomen gene (POMT1) encoding a putative protein O-mannosyl-transferase, and assignment to human chromosome 9q34.1 . Genomics . 58 . 2 . 171–80 . June 1999 . 10366449 . 10.1006/geno.1999.5819 .
2. Web site: Entrez Gene: POMT1 protein-O-mannosyltransferase 1.
3. Rubio-Fernández M, Uribe ML, Vicente-Tejedor J, Germain F, Susín-Lara C, Quereda C, Montoliu L, de la Villa P, Martín-Nieto J, Cruces J . 6 . Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy . Scientific Reports . 8 . 1 . 8543 . June 2018 . 29867208 . 5986861 . 10.1038/s41598-018-26855-x . 2018NatSR...8.8543R .
4. Uribe ML, Martín-Nieto J, Quereda C, Rubio-Fernández M, Cruces J, Janssen GM, de Ru AH, van Veelen PA, Hensbergen PJ . 6 . Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors . Journal of Proteome Research . 20 . 6 . 3268–3277 . June 2021 . 34027671 . 8280732 . 10.1021/acs.jproteome.1c00126 .