Vitronectin binds to integrinalpha-V beta-3 and thus promotes cell adhesion and spreading. It also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpins (serine protease inhibitors). It is a secreted protein and exists in either a single chain form or a clipped, two chain form held together by a disulfide bond.[6] Vitronectin has been speculated to be involved in hemostasis[8] and tumormalignancy.[9][10]
Vitronectin is a 54 kDa glycoprotein, consisting of 478 amino acidresidues. About one-third of the protein's molecular mass is composed of carbohydrates. On occasion, the protein is cleaved after arginine 379, to produce two-chain vitronectin, where the two parts are linked by a disulfide bond. No high-resolution structure has been determined experimentally yet, except for the N-terminal domain.
A central domains with hemopexin homology (131-342)
A C-terminal domain (residues 347-459) also with hemopexin homology.
Several structures has been reported for the Somatomedin B domain. The protein was initially crystallized in complex with one of its physiological binding partners: the Plasminogen activator inhibitor-1 (PAI-1) and the structure solved for this complex.[11] Subsequently two groups reported NMR structures of the domain.[12][13]
The somatomedin B domain is a close-knit disulfide knot, with 4 disulfide bonds within 35 residues. Different disulfide configurations had been reported for this domain[14][15][16] but this ambiguity has been resolved by the crystal structure.[16]
The somatomedin B domain of vitronectin binds to plasminogen activator inhibitor-1 (PAI-1), and stabilizes it.[11] Thus vitronectin serves to regulate proteolysis initiated by plasminogen activation. In addition, vitronectin is a component of platelets and is, thus, involved in hemostasis. Vitronectin contains an RGD (45-47) sequence, which is a binding site for membrane-bound integrins, e.g., the vitronectin receptor, which serve to anchor cells to the extracellular matrix. The Somatomedin B domain interacts with the urokinase receptor, and this interaction has been implicated in cell migration and signal transduction. High plasma levels of both PAI-1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients. Cell adhesion and migration are directly involved in cancer metastasis, which provides a probable mechanistic explanation for this observation.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000109072 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000017344 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Boron, Walter F. and Boulpaep, Emile L. "Medical Physiology". Saunders, 2012, p.1097.
^Jenne D, Stanley KK (Oct 1987). "Nucleotide sequence and organization of the human S-protein gene: repeating peptide motifs in the "pexin" family and a model for their evolution". Biochemistry. 26 (21): 6735–42. doi:10.1021/bi00395a024. PMID 2447940.
^Preissner KT, Seiffert D (Jan 1998). "Role of vitronectin and its receptors in haemostasis and vascular remodeling". Thrombosis Research. 89 (1): 1–21. doi:10.1016/S0049-3848(97)00298-3. PMID 9610756.
^Felding-Habermann B, Cheresh DA (Oct 1993). "Vitronectin and its receptors". Current Opinion in Cell Biology. 5 (5): 864–8. doi:10.1016/0955-0674(93)90036-P. PMID 7694604.
^Hurt, Elaine M.; Chan, King; Serrat, Maria Ana Duhagon; Thomas, Suneetha B.; Veenstra, Timothy D.; Farrar, William L. (2009). "Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation". Stem Cells. 28 (3): 390–8. doi:10.1002/stem.271. PMC3448441. PMID 19998373.
^Kamikubo Y, De Guzman R, Kroon G, Curriden S, Neels JG, Churchill MJ, Dawson P, Ołdziej S, Jagielska A, Scheraga HA, Loskutoff DJ, Dyson HJ (Jun 2004). "Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin". Biochemistry. 43 (21): 6519–34. doi:10.1021/bi049647c. PMID 15157085.
^Mayasundari A, Whittemore NA, Serpersu EH, Peterson CB (Jul 2004). "The solution structure of the N-terminal domain of human vitronectin: proximal sites that regulate fibrinolysis and cell migration". The Journal of Biological Chemistry. 279 (28): 29359–66. doi:10.1074/jbc.M401279200. PMID 15123712.
^Kamikubo Y, Okumura Y, Loskutoff DJ (Jul 2002). "Identification of the disulfide bonds in the recombinant somatomedin B domain of human vitronectin". The Journal of Biological Chemistry. 277 (30): 27109–19. doi:10.1074/jbc.M200354200. PMID 12019263.
^Horn NA, Hurst GB, Mayasundari A, Whittemore NA, Serpersu EH, Peterson CB (Aug 2004). "Assignment of the four disulfides in the N-terminal somatomedin B domain of native vitronectin isolated from human plasma". The Journal of Biological Chemistry. 279 (34): 35867–78. doi:10.1074/jbc.M405716200. PMID 15173163.
^ abcXu D, Baburaj K, Peterson CB, Xu Y (Aug 2001). "Model for the three-dimensional structure of vitronectin: predictions for the multi-domain protein from threading and docking". Proteins. 44 (3): 312–20. doi:10.1002/prot.1096. PMID 11455604. S2CID 24765480.
Further readingedit
Singh B, Su YC, Riesbeck K (2010). "Vitronectin in bacterial pathogenesis: a host protein used in complement escape and cellular invasion". Mol. Microbiol. 78 (3): 545–60. doi:10.1111/j.1365-2958.2010.07373.x. PMID 20807208. S2CID 24516528.
Singh B, Jalalvand F, Mörgelin M, Zipfel P, Blom AM, Riesbeck K (2011). "Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex". Mol. Microbiol. 81 (1): 80–98. doi:10.1111/j.1365-2958.2011.07678.x. PMID 21542857. S2CID 26484037.
Su YC, Jalalvand F, Mörgelin M, Blom AM, Singh B, Riesbeck K (2013). "Haemophilus influenzae acquires vitronectin via the ubiquitous Protein F to subvert host innate immunity". Mol. Microbiol. 87 (6): 1245–66. doi:10.1111/mmi.12164. PMID 23387957. S2CID 26923730.
vitronectin, redirects, here, other, uses, disambiguation, glycoprotein, hemopexin, family, which, synthesized, excreted, liver, abundantly, found, serum, extracellular, matrix, bone, humans, encoded, gene, vtnavailable, structurespdbortholog, search, pdbe, rc. Vnt redirects here For other uses see VNT disambiguation Vitronectin VTN or VN is a glycoprotein of the hemopexin family which is synthesized and excreted by the liver and abundantly found in serum the extracellular matrix and bone 5 In humans it is encoded by the VTN gene 6 7 VTNAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1OC0 1S4G 1SSU 2JQ8 3BT1 3BT2 4K24IdentifiersAliasesVTN V75 VN VNT vitronectinExternal IDsOMIM 193190 MGI 98940 HomoloGene 532 GeneCards VTNGene location Human Chr Chromosome 17 human 1 Band17q11 2Start28 367 284 bp 1 End28 373 091 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 B5 11 46 74 cMStart78 389 917 bp 2 End78 393 150 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lobe of liverright adrenal glandleft adrenal glandgallbladderleft ventricleplacentaislet of Langerhansbody of pancreasduodenumright coronary arteryTop expressed inleft lobe of livergallbladderoptic nerveretinal pigment epitheliumsexually immature organismpia materolfactory bulbciliary bodysupraoptic nucleussuperior frontal gyrusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein binding scavenger receptor activity heparin binding extracellular matrix binding polysaccharide binding integrin binding identical protein binding collagen binding extracellular matrix structural constituentCellular componentalphav beta3 integrin vitronectin complex extracellular exosome blood microparticle Golgi lumen basement membrane rough endoplasmic reticulum lumen cytoplasm extracellular matrix extracellular space endoplasmic reticulum intracellular membrane bounded organelle extracellular region collagen containing extracellular matrixBiological processreceptor mediated endocytosis positive regulation of protein binding cell adhesion positive regulation of cell substrate adhesion extracellular matrix organization smooth muscle cell matrix adhesion regulation of complement activation positive regulation of smooth muscle cell migration negative regulation of endopeptidase activity positive regulation of peptidyl tyrosine phosphorylation positive regulation of vascular endothelial growth factor receptor signaling pathway immune response endodermal cell differentiation positive regulation of wound healing positive regulation of receptor mediated endocytosis negative regulation of blood coagulation oligodendrocyte differentiation cell adhesion mediated by integrin cell matrix adhesion protein polymerization liver regeneration cell population proliferation cell migration vesicle mediated transport endocytosisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez744822370EnsemblENSG00000109072ENSMUSG00000017344UniProtP04004P29788RefSeq mRNA NM 000638NM 011707RefSeq protein NP 000629NP 035837Location UCSC Chr 17 28 37 28 37 MbChr 11 78 39 78 39 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseVitronectin binds to integrin alpha V beta 3 and thus promotes cell adhesion and spreading It also inhibits the membrane damaging effect of the terminal cytolytic complement pathway and binds to several serpins serine protease inhibitors It is a secreted protein and exists in either a single chain form or a clipped two chain form held together by a disulfide bond 6 Vitronectin has been speculated to be involved in hemostasis 8 and tumor malignancy 9 10 Contents 1 Structure 2 Function 3 References 4 Further reading 5 External linksStructure editVitronectin is a 54 kDa glycoprotein consisting of 478 amino acid residues About one third of the protein s molecular mass is composed of carbohydrates On occasion the protein is cleaved after arginine 379 to produce two chain vitronectin where the two parts are linked by a disulfide bond No high resolution structure has been determined experimentally yet except for the N terminal domain The protein consists of three domains The N terminal Somatomedin B domain 1 39 A central domains with hemopexin homology 131 342 A C terminal domain residues 347 459 also with hemopexin homology Several structures has been reported for the Somatomedin B domain The protein was initially crystallized in complex with one of its physiological binding partners the Plasminogen activator inhibitor 1 PAI 1 and the structure solved for this complex 11 Subsequently two groups reported NMR structures of the domain 12 13 The somatomedin B domain is a close knit disulfide knot with 4 disulfide bonds within 35 residues Different disulfide configurations had been reported for this domain 14 15 16 but this ambiguity has been resolved by the crystal structure 16 Homology models have been built for the central and C terminal domains 16 Function editThe somatomedin B domain of vitronectin binds to plasminogen activator inhibitor 1 PAI 1 and stabilizes it 11 Thus vitronectin serves to regulate proteolysis initiated by plasminogen activation In addition vitronectin is a component of platelets and is thus involved in hemostasis Vitronectin contains an RGD 45 47 sequence which is a binding site for membrane bound integrins e g the vitronectin receptor which serve to anchor cells to the extracellular matrix The Somatomedin B domain interacts with the urokinase receptor and this interaction has been implicated in cell migration and signal transduction High plasma levels of both PAI 1 and the urokinase receptor have been shown to correlate with a negative prognosis for cancer patients Cell adhesion and migration are directly involved in cancer metastasis which provides a probable mechanistic explanation for this observation References edit a b c GRCh38 Ensembl release 89 ENSG00000109072 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000017344 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Boron Walter F and Boulpaep Emile L Medical Physiology Saunders 2012 p 1097 a b Entrez Gene M Vitronectin Jenne D Stanley KK Oct 1987 Nucleotide sequence and organization of the human S protein gene repeating peptide motifs in the pexin family and a model for their evolution Biochemistry 26 21 6735 42 doi 10 1021 bi00395a024 PMID 2447940 Preissner KT Seiffert D Jan 1998 Role of vitronectin and its receptors in haemostasis and vascular remodeling Thrombosis Research 89 1 1 21 doi 10 1016 S0049 3848 97 00298 3 PMID 9610756 Felding Habermann B Cheresh DA Oct 1993 Vitronectin and its receptors Current Opinion in Cell Biology 5 5 864 8 doi 10 1016 0955 0674 93 90036 P PMID 7694604 Hurt Elaine M Chan King Serrat Maria Ana Duhagon Thomas Suneetha B Veenstra Timothy D Farrar William L 2009 Identification of Vitronectin as an Extrinsic Inducer of Cancer Stem Cell Differentiation and Tumor Formation Stem Cells 28 3 390 8 doi 10 1002 stem 271 PMC 3448441 PMID 19998373 a b Zhou A Huntington JA Pannu NS Carrell RW Read RJ Jul 2003 How vitronectin binds PAI 1 to modulate fibrinolysis and cell migration Nature Structural Biology 10 7 541 4 doi 10 1038 nsb943 PMID 12808446 S2CID 26086796 Kamikubo Y De Guzman R Kroon G Curriden S Neels JG Churchill MJ Dawson P Oldziej S Jagielska A Scheraga HA Loskutoff DJ Dyson HJ Jun 2004 Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin Biochemistry 43 21 6519 34 doi 10 1021 bi049647c PMID 15157085 Mayasundari A Whittemore NA Serpersu EH Peterson CB Jul 2004 The solution structure of the N terminal domain of human vitronectin proximal sites that regulate fibrinolysis and cell migration The Journal of Biological Chemistry 279 28 29359 66 doi 10 1074 jbc M401279200 PMID 15123712 Kamikubo Y Okumura Y Loskutoff DJ Jul 2002 Identification of the disulfide bonds in the recombinant somatomedin B domain of human vitronectin The Journal of Biological Chemistry 277 30 27109 19 doi 10 1074 jbc M200354200 PMID 12019263 Horn NA Hurst GB Mayasundari A Whittemore NA Serpersu EH Peterson CB Aug 2004 Assignment of the four disulfides in the N terminal somatomedin B domain of native vitronectin isolated from human plasma The Journal of Biological Chemistry 279 34 35867 78 doi 10 1074 jbc M405716200 PMID 15173163 a b c Xu D Baburaj K Peterson CB Xu Y Aug 2001 Model for the three dimensional structure of vitronectin predictions for the multi domain protein from threading and docking Proteins 44 3 312 20 doi 10 1002 prot 1096 PMID 11455604 S2CID 24765480 Further reading editSingh B Su YC Riesbeck K 2010 Vitronectin in bacterial pathogenesis a host protein used in complement escape and cellular invasion Mol Microbiol 78 3 545 60 doi 10 1111 j 1365 2958 2010 07373 x PMID 20807208 S2CID 24516528 Singh B Jalalvand F Morgelin M Zipfel P Blom AM Riesbeck K 2011 Haemophilus influenzae protein E recognizes the C terminal domain of vitronectin and modulates the membrane attack complex Mol Microbiol 81 1 80 98 doi 10 1111 j 1365 2958 2011 07678 x PMID 21542857 S2CID 26484037 Su YC Jalalvand F Morgelin M Blom AM Singh B Riesbeck K 2013 Haemophilus influenzae acquires vitronectin via the ubiquitous Protein F to subvert host innate immunity Mol Microbiol 87 6 1245 66 doi 10 1111 mmi 12164 PMID 23387957 S2CID 26923730 External links editVitronectin at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Vitronectin amp oldid 1191577285, wikipedia, wiki, book, books, library,
