Myelin oligodendrocyte glycoprotein

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Myelin oligodendrocyte glycoprotein
Crystal structure of rat myelin oligodendrocyte glycoprotein.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MOG ; BTN6; BTNL11; MOGIG2; NRCLP7
External IDs OMIM159465 MGI97435 HomoloGene111009 GeneCards: MOG Gene
Species Human Mouse
Entrez 4340 17441
Ensembl ENSG00000137345 ENSMUSG00000076439
UniProt Q16653 Q61885
RefSeq (mRNA) NM_001008228 NM_010814
RefSeq (protein) NP_001008229 NP_034944
Location (UCSC) Chr 6:
29.66 – 29.67 Mb
Chr 17:
37.01 – 37.02 Mb
PubMed search [2] [3]

Myelin Oligodendrocyte Glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene.[2][3][4] It is speculated to serve as a necessary “adhesion molecule” to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.[5]

Molecular function[edit]

While the primary molecular function of MOG is not yet known, its likely role with the myelin sheath is either in sheath “completion and/or maintenance”.[4] More specifically, MOG is speculated to be “necessary” as an "adhesion molecule" on the myelin sheath of the CNS to provide the structural integrity of the myelin sheath.[5]

MOG’s cDNA coding region in humans have been shown to be “highly homologous”[6] to rats, mice, and bovine, and hence highly conserved. This suggests “an important biological role for this protein”.[4]


The gene for MOG, found on chromosome 6p21.3-p22,[7] was first sequenced in 1995.[4] It is a transmembrane protein expressed on the surface of oligodendrocyte cell and on the outermost surface of myelin sheaths. “MOG is a quantitatively minor type I transmembrane protein,[8] and is found exclusively in the CNS. “A single Ig-domain is exposed to the extracellular space"[8] and consequently allows autoantibodies easy access. and therefore easily accessible for autoantibodies.[4][8] The MOG “primary nuclear transcript … is 15,561 nucleotides in length"[4] and, for humans, it has eight exons which are “separated by seven introns".[4] The introns "contain numerous reptitive [sic] DNA[4]" sequences, among which is "14 Alu sequences within 3 introns",[4] and have a range varying from 242 to 6484 bp.


Because of alternatively spliced from human mRNA of MOG gene forming at least nine isoforms.[9]

The crystal structure of myelin oligodendrocyte glycoprotein was determined by x-ray diffraction at a resolution of 1.45 Angstrom, using protein from the Norway rat. This protein is 139 residues long, and is a member of the immunoglobulin superfamily.[1] The dssp secondary structure of the protein is 6% helical and 43% beta sheet: there are three short helical segments and ten beta strands.[10] The beta strands are within two antiparallel beta sheets that form an immunoglobulin-like beta-sandwich fold.[11] Several features of the protein structure suggest MOG has a role as an "adhesin in the completion and/or compaction of the myelin sheath." There is a "significant strip" of electronegative charge beginning near the N-terminus and running about half the length of the molecule. Also, MOG was shown to dimerize in solution, and the shape complementarity index is high at the dimer interface, suggesting a "biologically relevant MOG dimer."[12]


Developmentally, MOG is formed "very late on oligodendrocytes and the myelin sheath".[5]

Role in disease[edit]

Non-inflammatory demyelinating diseases[edit]

Interest in MOG has centered on its role in demyelinating diseases. Some of them are not-inflammatory, such as adrenoleukodystrophy, vanishing white matter disease, and Rubella induced mental retardation.[13]

anti-MOG in inflammatory demyelinating diseases[edit]

MOG has received much of its laboratory attention in studies dealing with MS. Several studies have shown a role for antibodies against MOG in the pathogenesis of MS.,[5][14] though most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases.

Animal models of MS, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis",[5] but basically explains the part involved in the optic neuritis[15] These models with anti-MOG antibodies have been investigated extensively and are considered the only antibodies with demyelinating capacity[5] but again, EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.

Anti-MOG mediated demyelination has been shown to behave similar to NMO in animal models,[15] and currently it is considered even a biomarker against the MS diagnosis[16][17]

But Anti-MOG autoimmunity has been found to be important for the seronegative NMO[18][19]


  1. ^ a b PDB: 1PKO ; Breithaupt C, Schubart A, Zander H, Skerra A, Huber R, Linington C, Jacob U (August 2003). "Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein". Proc. Natl. Acad. Sci. U.S.A. 100 (16): 9446–51. doi:10.1073/pnas.1133443100. PMC 170938. PMID 12874380. 
  2. ^ Pham-Dinh D, Della Gaspera B, Kerlero de Rosbo N, Dautigny A (September 1995). "Structure of the human myelin/oligodendrocyte glycoprotein gene and multiple alternative spliced isoforms". Genomics 29 (2): 345–52. doi:10.1006/geno.1995.9995. PMID 8666381. 
  3. ^ Pham-Dinh D, Jones EP, Pitiot G, Della Gaspera B, Daubas P, Mallet J, Le Paslier D, Fischer Lindahl K, Dautigny A (1995). "Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region". Immunogenetics 42 (5): 386–91. doi:10.1007/bf00179400. PMID 7590972. 
  4. ^ a b c d e f g h Roth MP, Malfroy L, Offer C, Sevin J, Enault G, Borot N, Pontarotti P, Coppin H (July 1995). "The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide sequence and structural characterization". Genomics 28 (2): 241–50. doi:10.1006/geno.1995.1137. PMID 8530032. 
  5. ^ a b c d e f Berger, T., Innsbruck Medical University Dept. of Neurology interviewed by S. Gillooly, Nov. 24, 2008.
  6. ^ Pham-Dinh D, Allinquant B, Ruberg M, Della Gaspera B, Nussbaum JL, Dautigny A (December 1994). "Characterization and expression of the cDNA coding for the human myelin/oligodendrocyte glycoprotein". J. Neurochem. 63 (6): 2353–6. doi:10.1046/j.1471-4159.1994.63062353.x. PMID 7964757. 
  7. ^ Pham-Dinh D, Mattei MG, Nussbaum JL, Roussel G, Pontarotti P, Roeckel N, Mather IH, Artzt K, Lindahl KF, Dautigny A (September 1993). "Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex". Proc. Natl. Acad. Sci. U.S.A. 90 (17): 7990–4. doi:10.1073/pnas.90.17.7990. PMC 47273. PMID 8367453. 
  8. ^ a b c Berger T, Reindl M (August 2007). "Multiple sclerosis: disease biomarkers as indicated by pathophysiology". J. Neurol. Sci. 259 (1-2): 21–6. doi:10.1016/j.jns.2006.05.070. PMID 17367811. 
  9. ^ Boyle LH, Traherne JA, Plotnek G, Ward R, Trowsdale J (September 2007). "Splice variation in the cytoplasmic domains of myelin oligodendrocyte glycoprotein affects its cellular localisation and transport". J. Neurochem. 102 (6): 1853–62. doi:10.1111/j.1471-4159.2007.04687.x. PMC 2156149. PMID 17573820. 
  10. ^ Kabsch W, Sander C (December 1983). "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features". Biopolymers 22 (12): 2577–637. doi:10.1002/bip.360221211. PMID 6667333. 
  11. ^ Murzin AG, Brenner SE, Hubbard T, Chothia C (April 1995). "SCOP: a structural classification of proteins database for the investigation of sequences and structures". J. Mol. Biol. 247 (4): 536–40. doi:10.1016/S0022-2836(05)80134-2. PMID 7723011. 
  12. ^ Clements CS, Reid HH, Beddoe T et al. (September 2003). "The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis". Proc. Natl. Acad. Sci. U.S.A. 100 (19): 11059–64. doi:10.1073/pnas.1833158100. PMC 196926. PMID 12960396. 
  13. ^ Cong H, Jiang Y, Tien P (November 2011). "Identification of the myelin oligodendrocyte glycoprotein as a cellular receptor for rubella virus". J. Virol. 85 (21): 11038–47. doi:10.1128/JVI.05398-11. PMC 3194935. PMID 21880773. 
  14. ^ Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M (July 2003). "Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event". N. Engl. J. Med. 349 (2): 139–45. doi:10.1056/NEJMoa022328. PMID 12853586. 
  15. ^ a b Kezuka et al. Relationship Between NMO-Antibody and Anti–MOG Antibody in Optic Neuritis. Journal of Neuro-Ophthalmology: June 2012 - Volume 32 - Issue 2 - p 107–110 doi: 10.1097/WNO.0b013e31823c9b6c
  16. ^ Immy A Ketelslegers, Daniëlle E Van Pelt, Susanne Bryde, Rinze F Neuteboom, Coriene E Catsman-Berrevoets, Dörte Hamann, and Rogier Q Hintzen Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort Mult Scler 1352458514566666, first published on February 6, 2015 doi:10.1177/1352458514566666
  17. ^ Joanna Kitley, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology September 18, 2012 vol. 79 no. 12 1273-1277. doi: 10.1212/WNL.0b013e31826aac4e
  18. ^ Anne-Katrin Pröbstel et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. Journal of Neuroinflammation Volume 12, 2015, 12:46 doi:10.1186/s12974-015-0256-1
  19. ^ CYNTHIA MCKELVEY, Press Report, What’s the Role of Myelin Oligodendrocyte Glycoprotein in NMO? [1]

External links[edit]