LMAN1

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LMAN1
Protein LMAN1 PDB 1r1z.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases LMAN1, ERGIC-53, ERGIC53, F5F8D, FMFD1, MCFD1, MR60, gp58, lectin, mannose binding 1
External IDs MGI: 1917611 HomoloGene: 4070 GeneCards: LMAN1
Gene location (Human)
Chromosome 18 (human)
Chr. Chromosome 18 (human)[1]
Chromosome 18 (human)
Genomic location for LMAN1
Genomic location for LMAN1
Band 18q21.32 Start 59,327,823 bp[1]
End 59,359,962 bp[1]
RNA expression pattern
PBB GE LMAN1 203294 s at fs.png

PBB GE LMAN1 203293 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
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: 65.98 – 66.02 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[edit]

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[edit]

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

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000074695 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041891 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  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. 
  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. 
  7. ^ a b "Entrez Gene: LMAN1 lectin, mannose-binding, 1". 
  8. ^ a b Khoriaty R, Vasievich MP, Ginsburg D., Blood. 2012 Jul 5;120(1):31-8. doi: 10.1182/blood-2012-01-292086. "The COPII pathway and hematologic disease". www.bloodjournal.org. American Society of Hematology. Retrieved 7 April 2017. 
  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. 
  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[edit]