Protein ERGIC-53 (LMAN1)
The protein contains 510 amino acids for an estimated molecular weight of 57549 Da.
Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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Biological Process
Blood coagulation
COPII vesicle coating
Endoplasmic reticulum organization
Endoplasmic reticulum to Golgi vesicle-mediated transport
Golgi organization
Negative regulation of protein targeting to mitochondrion
Positive regulation of organelle organization
Protein folding
Protein N-linked glycosylation via asparagine
Protein transport
Cellular Component
Collagen-containing extracellular matrix
COPII-coated ER to Golgi transport vesicle
Cytosol
Endoplasmic reticulum
Endoplasmic reticulum membrane
Endoplasmic reticulum-Golgi intermediate compartment
Endoplasmic reticulum-Golgi intermediate compartment membrane
ER to Golgi transport vesicle membrane
Extracellular exosome
Golgi membrane
Host cell perinuclear region of cytoplasm
Integral component of membrane
Membrane
Sarcomere
The reference OMIM entry for this protein is 227300
Factor v and factor viii, combined deficiency of, 1; f5f8d1
Familial multiple coagulation factor deficiency i; fmfd1
Fmfd i
Multiple coagulation factor deficiency i; mcfd1
A number sign (#) is used with this entry because combined deficiency of factor V and factor VIII type 1 can be caused by homozygous mutation in the mannose-binding lectin-1 gene (LMAN1; 601567) on chromosome 18.
DESCRIPTION
Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). - Genetic Heterogeneity of Combined Deficiency of Factor V and Factor VIII Another form of combined deficiency of factor V and factor VII (F5F8D2; 613625) is caused by mutation in the MCFD2 gene (607788) on chromosome 2.CLINICAL FEATURES
Oeri et al. (1954) presented relatively convincing laboratory data for the existence of a combined deficiency of factors V and VIII. Affected patients demonstrated a moderate bleeding tendency in association with plasma levels of FV and FVIII between 5% and 30%. Nichols et al. (1997) stated that at least 89 patients with F5F8D belonging to 58 families had been identified.INHERITANCE
Consanguinity in several reported families with F5F8D supported autosomal recessive inheritance (Seibert et al., 1958; Jones et al., 1962). Smit Sibinga et al. (1972) studied an extensive family with combined F5F8D. They concluded that inheritance is most likely autosomal recessive with variable expression and partial penetrance in heterozygotes. However, Tuddenham (1997) pointed out that heterozygotes have normal factor V and factor VIII levels. Cimo et al. (1977) reported an affected male whose parents were first cousins from the northwestern coast of Spain.POPULATION GENETICS
Seligsohn et al. (1982) counted 26 separate reported families including those described in their report. Populations from the Mediterranean basin accounted for most cases: Spanish, Italian, Yugoslavian, Greek, Algerian, Oriental Jewish, and Sephardic Jewish. Ashkenazi Jews had not been affected. Seligsohn et al. (1982) related the difference in frequency of the disease in the 2 main branches of Jewry to historical differences in the Diaspora. The highest frequency of F5F8D was found in Jews of Sephardic and Middle Eastern origin living in Israel with an estimated frequency of 1 in 100,000.MAPPING
Nichols et al. (1997) used a positional cloning approach to identify the gene mutant in F5F8D. Of 14 affected individuals from 8 unrelated Jewish patients, 12 were offspring of first-cousin marriages. After a genomewide search using 241 highly polymorphic short tandem repeat (STR) markers, 13 of the 14 affected patients were found to be homozygous for 2 closely linked 18q markers. Patients and all available family members were genotyped for 11 additional STRs spanning approximately 11 cM on 18q. Multipoint linkage analysis yielded a maximum lod score of 13.22. Haplotype analysis identified a number of recombinant individuals and established a minimum candidate interval of 2.5 cM for the gene responsible for combined factors V and VIII deficiency. Nichols et al. (1997) commented that the product of this locus is likely to oper ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 227300 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).