MFGE8

MFGE8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2L9L
Identifiers
Aliases	MFGE8 , milk fat globule-EGF factor 8 protein, BA46, EDIL1, HMFG, HsT19888, MFG-E8, MFGM, OAcGD3S, SED1, SPAG10, hP47, milk fat globule EGF and factor V/VIII domain containing
External IDs	OMIM: 602281; MGI: 102768; HomoloGene: 4334; GeneCards: MFGE8; OMA:MFGE8 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q26.1 Start 88,898,683 bp [1] End 88,913,468 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 D2|7 44.9 cM Start 78,783,516 bp [2] End 78,798,808 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Descending thoracic aorta ascending aorta right coronary artery left coronary artery popliteal artery tibial arteries stromal cell of endometrium left uterine tube apex of heart body of uterus Top expressed in lactiferous gland mesenteric lymph nodes tunica media of zone of aorta entorhinal cortex choroid plexus of fourth ventricle perirhinal cortex lacrimal gland ascending aorta molar neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatidylserine binding phosphatidylethanolamine binding integrin binding extracellular matrix structural constituent Cellular component external side of plasma membrane extrinsic component of plasma membrane extracellular region extracellular exosome extracellular matrix extracellular vesicle membrane extracellular space endoplasmic reticulum lumen collagen-containing extracellular matrix Biological process phagocytosis, recognition angiogenesis positive regulation of phagocytosis positive regulation of apoptotic cell clearance phagocytosis, engulfment cell adhesion single fertilization viral process post-translational protein modification apoptotic cell clearance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4240 17304 Ensembl ENSG00000140545 ENSMUSG00000030605 UniProt Q08431 P21956 RefSeq (mRNA) NM_001114614 NM_001310319 NM_001310320 NM_001310321 NM_005928 NM_001045489 NM_008594 RefSeq (protein) NP_001108086 NP_001297248 NP_001297249 NP_001297250 NP_005919 NP_001038954 NP_032620 Location (UCSC) Chr 15: 88.9 – 88.91 Mb Chr 7: 78.78 – 78.8 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein that in humans is encoded by the MFGE8 gene. ^{[5] [6]}

Species distribution

Mfge8 is a secreted protein found in vertebrates, including mammals as well as birds.

Function

MFGE8 may function as a cell adhesion protein to connect smooth muscle to elastic fibers in arteries. ^[7] An amyloid fragment of MFGE8 known as medin accumulates in the aorta with aging. ^[8] MFGE8 in the vasculature of adults can induce recovery from ischemia by facilitating angiogenesis. ^[9] It has been suggested that antagonizing MFGE8-induced angiogenesis could be a way of fighting cancer. ^[10]

MFGE8 contains a phosphatidylserine (PS) binding domain, as well as an arginine-glycine-aspartic acid motif, which enables the binding to integrins. MFGE8 binds PS, which is exposed on the surface of apoptotic cells. ^[11] Opsonization of the apoptotic cells and binding to integrins on the surface of phagocytic cells, mediates the engulfment of the dead cell.

References

1. GRCh38: Ensembl release 89: ENSG00000140545 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030605 – 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. "Entrez Gene: MFGE8 milk fat globule-EGF factor 8 protein".
6. Collins C, Nehlin JO, Stubbs JD, Kowbel D, Kuo WL, Parry G (January 1997). "Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25". Genomics. 39 (1): 117–8. doi:10.1006/geno.1996.4425. PMID   9027496.
7. Larsson A, Peng S, Persson H, Rosenbloom J, Abrams WR, Wassberg E, Thelin S, Sletten K, Gerwins P, Westermark P (June 2006). "Lactadherin binds to elastin--a starting point for medin amyloid formation?". Amyloid. 13 (2): 78–85. doi:10.1080/13506120600722530. PMID   16911961. S2CID   22755686.
8. Peng S, Glennert J, Westermark P (June 2005). "Medin-amyloid: a recently characterized age-associated arterial amyloid form affects mainly arteries in the upper part of the body". Amyloid. 12 (2): 96–102. doi:10.1080/13506120500107006. PMID   16011985. S2CID   23351552.
9. Silvestre JS, Théry C, Hamard G, Boddaert J, Aguilar B, Delcayre A, Houbron C, Tamarat R, Blanc-Brude O, Heeneman S, Clergue M, Duriez M, Merval R, Lévy B, Tedgui A, Amigorena S, Mallat Z (May 2005). "Lactadherin promotes VEGF-dependent neovascularization". Nat. Med. 11 (5): 499–506. doi:10.1038/nm1233. PMID   15834428. S2CID   9154352.
10. Raymond A, Ensslin MA, Shur BD (April 2009). "SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions". J. Cell. Biochem. 106 (6): 957–66. doi:10.1002/jcb.22076. PMC   2742659 . PMID   19204935.
11. Aguzzi A, Kranich J, Krautler NJ (2014). "Follicular dendritic cells: origin, phenotype, and function in health and disease". Trends in Immunology . 35 (3): 105–113. doi:10.1016/j.it.2013.11.001. PMID   24315719.

Further reading

• Peterson JA, Scallan CD, Ceriani RL, Hamosh M (2002). "Structural and Functional Aspects of Three Major Glycoproteins of the Human Milk Fat Globule Membrane". Bioactive Components of Human Milk. Advances in Experimental Medicine and Biology. Vol. 501. pp. 179–87. doi:10.1007/978-1-4615-1371-1_23. ISBN   978-1-4613-5521-2. PMID   11787681.
• Larocca D, Peterson JA, Urrea R, et al. (1991). "A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains". Cancer Res. 51 (18): 4994–8. PMID   1909932.
• 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.
• Couto JR, Taylor MR, Godwin SG, et al. (1996). "Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain". DNA Cell Biol. 15 (4): 281–6. doi:10.1089/dna.1996.15.281. PMID   8639264.
• Collins C, Nehlin JO, Stubbs JD, et al. (1997). "Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25". Genomics. 39 (1): 117–8. doi:10.1006/geno.1996.4425. PMID   9027496.
• Aoki N, Ishii T, Ohira S, et al. (1997). "Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, beta-casein". Biochim. Biophys. Acta. 1334 (2–3): 182–90. doi:10.1016/s0304-4165(96)00091-8. PMID   9101712.
• Taylor MR, Couto JR, Scallan CD, et al. (1997). "Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell adhesion". DNA Cell Biol. 16 (7): 861–9. doi:10.1089/dna.1997.16.861. PMID   9260929.
• 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.
• Giuffrida MG, Cavaletto M, Giunta C, et al. (1998). "Isolation and characterization of full and truncated forms of human breast carcinoma protein BA46 from human milk fat globule membranes". J. Protein Chem. 17 (2): 143–8. doi:10.1023/A:1022531500370. PMID   9535276. S2CID   36987464.
• Newburg DS, Peterson JA, Ruiz-Palacios GM, et al. (1998). "Role of human-milk lactadherin in protection against symptomatic rotavirus infection". Lancet. 351 (9110): 1160–4. doi:10.1016/S0140-6736(97)10322-1. PMID   9643686. S2CID   25702042.
• Peterson JA, Hamosh M, Scallan CD, et al. (1998). "Milk fat globule glycoproteins in human milk and in gastric aspirates of mother's milk-fed preterm infants". Pediatr. Res. 44 (4): 499–506. doi: 10.1203/00006450-199810000-00006 . PMID   9773837.
• Häggqvist B, Näslund J, Sletten K, et al. (1999). "Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8669–74. Bibcode:1999PNAS...96.8669H. doi: 10.1073/pnas.96.15.8669 . PMC   17574 . PMID   10411933.
• Oshima K, Aoki N, Kato T, et al. (2002). "Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles". Eur. J. Biochem. 269 (4): 1209–18. doi: 10.1046/j.1432-1033.2002.02758.x . PMID   11856354.
• Hanayama R, Tanaka M, Miwa K, et al. (2002). "Identification of a factor that links apoptotic cells to phagocytes". Nature. 417 (6885): 182–7. Bibcode:2002Natur.417..182H. doi:10.1038/417182a. PMID   12000961. S2CID   4429707.
• 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.
• Lee SH, Seo GS, Park PH, et al. (2003). "Increased expression of O-acetyl disialoganglioside synthase during rat liver fibrogenesis relates to stellate cell activation". Biochem. Biophys. Res. Commun. 303 (3): 954–61. Bibcode:2003BBRC..303..954L. doi:10.1016/S0006-291X(03)00448-0. PMID   12670504.
• Rehman KS, Yin S, Mayhew BA, et al. (2004). "Human myometrial adaptation to pregnancy: cDNA microarray gene expression profiling of myometrium from non-pregnant and pregnant women". Mol. Hum. Reprod. 9 (11): 681–700. doi: 10.1093/molehr/gag078 . PMID   14561811.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Reches M, Gazit E (2005). "Amyloidogenic hexapeptide fragment of medin: homology to functional islet amyloid polypeptide fragments". Amyloid. 11 (2): 81–9. doi:10.1080/13506120412331272287. PMID   15478463. S2CID   22673832.