LMAN1

LMAN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A4U, 3LCP, 3WHT, 3WHU, 3WNX, 4GKX, 4GKY, 4YGC, 4YGD, 4YGE, 4YGB
Identifiers
Aliases	LMAN1 , ERGIC-53, ERGIC53, F5F8D, FMFD1, MCFD1, MR60, gp58, lectin, mannose binding 1
External IDs	OMIM: 601567; MGI: 1917611; HomoloGene: 4070; GeneCards: LMAN1; OMA:LMAN1 - orthologs
Gene location (Human) Chr. Chromosome 18 (human) [1] Band 18q21.32 Start 59,327,823 bp [1] End 59,359,265 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18|18 E1 Start 66,113,809 bp [2] End 66,155,651 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in germinal epithelium jejunal mucosa gingival epithelium corpus epididymis caput epididymis epithelium of nasopharynx secondary oocyte tibia cardia seminal vesicula Top expressed in lacrimal gland calvaria salivary gland islet of Langerhans seminal vesicula submandibular gland retinal pigment epithelium ciliary body parotid gland human fetus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function unfolded protein binding metal ion binding protein binding mannose binding carbohydrate binding Cellular component integral component of membrane Golgi apparatus Golgi membrane sarcomere host cell perinuclear region of cytoplasm endoplasmic reticulum ER to Golgi transport vesicle membrane extracellular exosome endoplasmic reticulum membrane endoplasmic reticulum-Golgi intermediate compartment membrane endoplasmic reticulum-Golgi intermediate compartment membrane COPII-coated ER to Golgi transport vesicle Biological process Golgi organization early endosome to Golgi transport blood coagulation positive regulation of organelle organization protein N-linked glycosylation via asparagine COPII vesicle coating protein exit from endoplasmic reticulum protein folding protein transport vesicle-mediated transport endoplasmic reticulum to Golgi vesicle-mediated transport endoplasmic reticulum organization transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3998 70361 Ensembl ENSG00000074695 ENSMUSG00000041891 UniProt P49257 Q9D0F3 RefSeq (mRNA) NM_005570 NM_001172062 NM_027400 RefSeq (protein) NP_005561 NP_001165533 NP_081676 Location (UCSC) Chr 18: 59.33 – 59.36 Mb Chr 18: 66.11 – 66.16 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[5] [6] [7]}

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. ^{[8] [7]} MCFD2 is the second gene that leads to combined deficiency of factor V-factor VIII. ^[9] 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, ^[10] as illustrated here. ^[8]

Clinical significance

LMAN1 mutational inactivation is a frequent and early event potentially contributing to colorectal tumorigenesis. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000074695 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041891 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nichols WC, Seligsohn U, Zivelin A, Terry VH, Hertel CE, Wheatley MA, Moussalli MJ, Hauri HP, Ciavarella N, Kaufman RJ, Ginsburg D (May 1998). "Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII". Cell. 93 (1): 61–70. doi: 10.1016/S0092-8674(00)81146-0 . PMID   9546392. S2CID   15021770.
6. Arar C, Mignon C, Mattei M, Monsigny M, Roche A, Legrand A (Feb 1997). "Mapping of the MR60/ERGIC-53 gene to human chromosome 18q21.3-18q22 by in situ hybridization". Mamm Genome. 7 (10): 791–2. doi:10.1007/s003359900238. PMID   8854877. S2CID   19754504.
7. "Entrez Gene: LMAN1 lectin, mannose-binding, 1".
8. Khoriaty R, Vasievich MP, Ginsburg D (July 2012). "The COPII pathway and hematologic disease". Blood. 120 (1): 31–8. doi:10.1182/blood-2012-01-292086. PMC   3390960 . PMID   22586181.
9. 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 (May 2003). "Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex". Nat Genet. 34 (2): 220–5. doi:10.1038/ng1153. PMID   12717434. S2CID   19281158.
10. Zhang B, Kaufman RJ, Ginsburg D (2005). "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. doi: 10.1074/jbc.M502160200 . PMID   15886209.
11. Roeckel N, Woerner SM, Kloor M, Yuan YP, Patsos G, Gromes R, Kopitz J, Gebert J (January 2009). "High frequency of LMAN1 abnormalities in colorectal tumors with microsatellite instability". Cancer Res. 69 (1): 292–9. doi: 10.1158/0008-5472.CAN-08-3314 . PMID   19118014.

Further reading

• Botos I, Wlodawer A (2005). "Proteins that bind high-mannose sugars of the HIV envelope". Prog. Biophys. Mol. Biol. 88 (2): 233–82. doi: 10.1016/j.pbiomolbio.2004.05.001 . PMID   15572157.
• Arar C, Carpentier V, Le Caer JP, et al. (1995). "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. doi: 10.1074/jbc.270.8.3551 . PMID   7876089.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Fiedler K, Simons K (1994). "A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins". Cell. 77 (5): 625–6. doi:10.1016/0092-8674(94)90047-7. PMID   8205612. S2CID   21111364.
• Schindler R, Itin C, Zerial M, et al. (1993). "ERGIC-53, a membrane protein of the ER-Golgi intermediate compartment, carries an ER retention motif". Eur. J. Cell Biol. 61 (1): 1–9. PMID   8223692.
• Haurum JS, Thiel S, Jones IM, et al. (1994). "Complement activation upon binding of mannan-binding protein to HIV envelope glycoproteins". AIDS. 7 (10): 1307–13. doi:10.1097/00002030-199310000-00002. PMID   8267903. S2CID   25026640.
• Senaldi G, Davies ET, Mahalingam M, et al. (1996). "Circulating levels of mannose binding protein in human immunodeficiency virus infection". J. Infect. 31 (2): 145–8. doi:10.1016/S0163-4453(95)92185-0. PMID   8666845.
• Neerman-Arbez M, Antonarakis SE, Blouin JL, et al. (1997). "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. doi:10.1086/513897. PMC   1715850 . PMID   9245995.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Nichols WC, Terry VH, Wheatley MA, et al. (1999). "ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families". Blood. 93 (7): 2261–6. PMID   10090935.
• Saifuddin M, Hart ML, Gewurz H, et al. (2000). "Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1". J. Gen. Virol. 81 (Pt 4): 949–55. doi: 10.1099/0022-1317-81-4-949 . PMID   10725420.
• Harris RA, Yang A, Stein RC, et al. (2002). "Cluster analysis of an extensive human breast cancer cell line protein expression map database". Proteomics. 2 (2): 212–23. doi:10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H. PMID   11840567. S2CID   44946014.
• Jüliger S, Kremsner PG, Alpers MP, et al. (2002). "Restricted polymorphisms of the mannose-binding lectin gene in a population of Papua New Guinea". Mutat. Res. 505 (1–2): 87–91. doi:10.1016/S0027-5107(02)00142-2. PMID   12175909.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Hart ML, Saifuddin M, Uemura K, et al. (2003). "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. doi:10.1089/088922202320886352. PMID   12487819.
• Hart ML, Saifuddin M, Spear GT (2003). "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. doi: 10.1099/vir.0.18734-0 . PMID   12560567.
• Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID   12665801. S2CID   23783563.
• García-Laorden MI, Rúa-Figueroa I, Pérez-Aciego P, et al. (2003). "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. PMID   12672193.