Alternative titles; symbols
HGNC Approved Gene Symbol: MMRN1
Cytogenetic location: 4q22.1 Genomic coordinates (GRCh38): 4:89,879,511-89,954,614 (from NCBI)
Multimerin, a soluble protein with a unique cDNA sequence, is found in platelets and endothelium, but not in plasma (Hayward et al., 1991; Hayward et al., 1993; Hayward and Kelton, 1995). The large size of multimerin, its tissue distribution, its binding to activated platelets, and its structure suggests a possible role in hemostasis. Hayward et al. (1995) reported the cDNA sequence of human endothelial cell multimerin. The gene encodes a 1,228-amino acid polypeptide with an RGDS motif and probable coiled-coil structure.
By in situ hybridization, Leimeister et al. (2002) observed expression of multimerin as a faint stripe on both sides of mouse embryos at day 9.5. At later stages, multimerin was expressed in a speckled pattern throughout the embryos. Prominent expression was seen in lung and was often associated with blood vessels. In embryonic liver, multimerin expression was restricted to megakaryocytes.
Hayward et al. (1995) demonstrated that multimerin is a specific factor V/Va (612309) binding protein that is complexed with platelet, but not plasma, factor V. Although factor V was found to colocalize with multimerin during storage in resting platelets, major differences were observed in the distribution of multimerin and factor V after thrombin activation. Based on their association during storage, Hayward et al. (1996) considered that multimerin might function as a carrier protein for platelet factor V, analogous to the role of von Willebrand factor (613160) as a carrier protein for factor VIII (300841).
The report of an unusual bleeding disorder, designated factor V Quebec (601709), affecting the platelet stores of factor V (Tracy et al., 1984) led Hayward et al. (1996) to investigate these individuals for a possible defect in multimerin. They indeed found a deficiency in multimerin in patients with factor V Quebec. Both analyses of the platelet glycoprotein in factor V Quebec patients indicated that platelet thrombospondin (188060), von Willebrand factor, and fibrinogen (see 134820) had evidence of proteolytic degradation despite normal antigen levels. The platelet counts of family members with bleeding symptoms ranged from mildly cytothrombopenic to low normal, and tests of their platelet function indicated an additional defect in epinephrine aggregation.
Leimeister et al. (2002) determined that the multimerin gene contains 8 exons and spans 60 kb.
Leimeister et al. (2002) stated that the multimerin gene maps to chromosome 4q22.1.
Hayward, C. P. M., Bainton, D. F., Smith, J. W., Horsewood, P., Stead, R. H., Podor, T. J., Warkentin, T. E., Kelton, J. G. Multimerin is found in the alpha-granules of resting platelets and is synthesized by a megakaryocytic cell line. J. Clin. Invest. 91: 2630-2639, 1993. [PubMed: 8514871] [Full Text: https://doi.org/10.1172/JCI116502]
Hayward, C. P. M., Furmaniak-Kazmierczak, E., Cieutat, A.-M., Moore, J. C., Bainton, D. F., Nesheim, M. E., Kelton, J. G., Cote, G. Factor V is complexed with multimerin in resting platelet lysates and colocalizes with multimerin within platelet alpha granules. J. Biol. Chem. 270: 19217-19224, 1995. [PubMed: 7642592] [Full Text: https://doi.org/10.1074/jbc.270.33.19217]
Hayward, C. P. M., Hassell, J. A., Denomme, G. A., Rachubinski, R. A., Brown, C., Kelton, J. G. The cDNA sequence of human endothelial cell multimerin: a unique protein with RGDS, coiled-coil, and EGF-like domains and a carboxyl-terminus similar to the globular domain of complement Clq and collagens type VIII and X. J. Biol. Chem. 270: 18246-18251, 1995. [PubMed: 7629143] [Full Text: https://doi.org/10.1074/jbc.270.31.18246]
Hayward, C. P. M., Kelton, J. G. Multimerin. Curr. Opin. Hemat. 2: 339-344, 1995. [PubMed: 9372017] [Full Text: https://doi.org/10.1097/00062752-199502050-00003]
Hayward, C. P. M., Rivard, G. E., Kane, W. H., Drouin, J., Zheng, S., Moore, J. C., Kelton, J. G. An autosomal dominant, qualitative platelet disorder associated with multimerin deficiency, abnormalities in platelet factor V, thrombospondin, von Willebrand factor, and fibrinogen and an epinephrine aggregation defect. Blood 87: 4967-4978, 1996. [PubMed: 8652809]
Hayward, C. P. M., Smith, J. W., Horsewood, P., Warkentin, T. E., Keltoin, J. G. p-155, a multimeric platelet protein that is expressed on activated platelets. J. Biol. Chem. 266: 7114-7120, 1991. [PubMed: 2016319]
Leimeister, C., Steidl, C., Schumacher, N., Erhard, S., Gessler, M. Developmental expression and biochemical characterization of Emu family members. Dev. Biol. 249: 204-218, 2002. [PubMed: 12221002] [Full Text: https://doi.org/10.1006/dbio.2002.0764]
Tracy, P. B., Giles, A. R., Mann, K. G., Eide, L. L., Hoogendoorn, H., Rivard, G. E. Factor V (Quebec): a bleeding diathesis associated with a qualitative platelet factor V deficiency. J. Clin. Invest. 74: 1221-1228, 1984. [PubMed: 6480825] [Full Text: https://doi.org/10.1172/JCI111531]