LMAN1 explained

Protein ERGIC-53 also known as ER-Golgi intermediate compartment 53 kDa protein or lectin mannose-binding 1 is a protein that in humans is encoded by the LMAN1 gene.^{[1] [2] [3]}

Function

ERGIC-53 (also named LMAN1) is a type I integral membrane protein localized in the intermediate region (ERGIC) between the endoplasmic reticulum and the Golgi, presumably recycling between the two compartments. The protein is a mannose-specific lectin and is a member of a novel family of plant lectin homologs in the secretory pathway of animal cells. Mutations in the gene are associated with a coagulation defect. Using positional cloning, the gene was identified as the disease gene leading to combined deficiency of factor V-factor VIII, a rare, autosomal recessive disorder in which both coagulation factors V and VIII are diminished.^[4] MCFD2 is the second gene that leads to combined deficiency of factor V-factor VIII.^[5] ERGIC-53 and MCFD2 form a protein complex and serve as a cargo receptor to transport FV and FVIII from the ER to the ERGIC and then the Golgi,^[6] as illustrated here.^[4]

Clinical significance

LMAN1 mutational inactivation is a frequent and early event potentially contributing to colorectal tumorigenesis.^[7]

References

Further reading

• Botos I, Wlodawer A . Proteins that bind high-mannose sugars of the HIV envelope . Prog. Biophys. Mol. Biol. . 88 . 2 . 233–82 . 2005 . 15572157 . 10.1016/j.pbiomolbio.2004.05.001 . free .
• Arar C, Carpentier V, Le Caer JP, etal . ERGIC-53, a membrane protein of the endoplasmic reticulum-Golgi intermediate compartment, is identical to MR60, an intracellular mannose-specific lectin of myelomonocytic cells . J. Biol. Chem. . 270 . 8 . 3551–3 . 1995 . 7876089 . 10.1074/jbc.270.8.3551 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Fiedler K, Simons K . A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins . Cell . 77 . 5 . 625–6 . 1994 . 8205612 . 10.1016/0092-8674(94)90047-7 . 21111364 .
• Schindler R, Itin C, Zerial M, etal . ERGIC-53, a membrane protein of the ER-Golgi intermediate compartment, carries an ER retention motif . Eur. J. Cell Biol. . 61 . 1 . 1–9 . 1993 . 8223692 .
• Haurum JS, Thiel S, Jones IM, etal . Complement activation upon binding of mannan-binding protein to HIV envelope glycoproteins . AIDS . 7 . 10 . 1307–13 . 1994 . 8267903 . 10.1097/00002030-199310000-00002 . 25026640 .
• Senaldi G, Davies ET, Mahalingam M, etal . Circulating levels of mannose binding protein in human immunodeficiency virus infection . J. Infect. . 31 . 2 . 145–8 . 1996 . 8666845 . 10.1016/S0163-4453(95)92185-0 .
• Neerman-Arbez M, Antonarakis SE, Blouin JL, etal . The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103 . Am. J. Hum. Genet. . 61 . 1 . 143–50 . 1997 . 9245995 . 10.1086/513897 . 1715850 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Nichols WC, Terry VH, Wheatley MA, etal . ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families . Blood . 93 . 7 . 2261–6 . 1999 . 10090935 .
• Saifuddin M, Hart ML, Gewurz H, etal . Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1 . J. Gen. Virol. . 81 . Pt 4 . 949–55 . 2000 . 10725420 . 10.1099/0022-1317-81-4-949. free .
• Harris RA, Yang A, Stein RC, etal . Cluster analysis of an extensive human breast cancer cell line protein expression map database . Proteomics . 2 . 2 . 212–23 . 2002 . 11840567 . 10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H . 44946014 .
• Jüliger S, Kremsner PG, Alpers MP, etal . Restricted polymorphisms of the mannose-binding lectin gene in a population of Papua New Guinea . Mutat. Res. . 505 . 1–2 . 87–91 . 2002 . 12175909 . 10.1016/S0027-5107(02)00142-2 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Hart ML, Saifuddin M, Uemura K, etal . High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1 . AIDS Res. Hum. Retroviruses . 18 . 17 . 1311–7 . 2003 . 12487819 . 10.1089/088922202320886352 .
• Hart ML, Saifuddin M, Spear GT . Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin . J. Gen. Virol. . 84 . Pt 2 . 353–60 . 2003 . 12560567 . 10.1099/vir.0.18734-0 . free .
• Gevaert K, Goethals M, Martens L, etal . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nat. Biotechnol. . 21 . 5 . 566–9 . 2004 . 12665801 . 10.1038/nbt810 . 23783563 .
• García-Laorden MI, Rúa-Figueroa I, Pérez-Aciego P, etal . Mannose binding lectin polymorphisms as a disease-modulating factor in women with systemic lupus erythematosus from Canary Islands, Spain . J. Rheumatol. . 30 . 4 . 740–6 . 2003 . 12672193 .

Notes and References

1. Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, Moussalli MJ, Hauri HP, Ciavarella N, Kaufman RJ, Ginsburg D . Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII . Cell . 93 . 1 . 61–70 . May 1998 . 9546392 . 10.1016/S0092-8674(00)81146-0 . 15021770 . free .
2. Arar C, Mignon C, Mattei M, Monsigny M, Roche A, Legrand A . Mapping of the MR60/ERGIC-53 gene to human chromosome 18q21.3-18q22 by in situ hybridization . Mamm Genome . 7 . 10 . 791–2 . Feb 1997 . 8854877 . 10.1007/s003359900238 . 19754504 .
3. Web site: Entrez Gene: LMAN1 lectin, mannose-binding, 1.
4. Khoriaty R, Vasievich MP, Ginsburg D . The COPII pathway and hematologic disease . Blood . 120 . 1 . 31–8 . July 2012 . 22586181 . 3390960 . 10.1182/blood-2012-01-292086 .
5. Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D . Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex . Nat Genet . 34 . 2 . 220–5 . May 2003 . 12717434 . 10.1038/ng1153 . 19281158 .
6. Zhang B, Kaufman RJ, Ginsburg D . LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway . J. Biol. Chem. . 280 . 27 . 25881–6 . 2005 . 15886209 . 10.1074/jbc.M502160200 . free .
7. Roeckel N, Woerner SM, Kloor M, Yuan YP, Patsos G, Gromes R, Kopitz J, Gebert J . High frequency of LMAN1 abnormalities in colorectal tumors with microsatellite instability . Cancer Res. . 69 . 1 . 292–9 . January 2009 . 19118014 . 10.1158/0008-5472.CAN-08-3314 . free .