• receptor-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 • cellular proliferation • cell migration • vesicle-mediated transport • endocytosis
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
7448
22370
Ensembl
ENSG00000109072
ENSMUSG00000017344
UniProt
P04004
P29788
RefSeq (mRNA)
NM_000638
NM_011707
RefSeq (protein)
NP_000629
NP_035837
Location (UCSC)
Chr 17: 28.37 – 28.37 Mb
Chr 11: 78.5 – 78.5 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone.[5] In humans it is encoded by the VTN gene.[6][7]
Vitronectin 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
1Structure
2Function
3References
4Further reading
5External links
Structure
Vitronectin is a 75 kDa glycoprotein, consisting of 459 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
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.
References
^ 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.
^ ab"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: N/A–N/A. doi:10.1002/stem.271. PMC 3448441. 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.
Further reading
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.
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.
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.
External links
Vitronectin at the US National Library of Medicine Medical Subject Headings (MeSH)
v
t
e
PDB gallery
1oc0: PLASMINOGEN ACTIVATOR INHIBITOR-1 COMPLEX WITH SOMATOMEDIN B DOMAIN OF VITRONECTIN
1s4g: Somatomedin-B Domain of human plasma vitronectin.
1ssu: Structural and biochemical evidence for disulfide bond heterogeneity in active forms of the somatomedin B domain of human vitronectin
v
t
e
Protein, glycoconjugate: glycoproteins and glycopeptides
Mucoproteins
Mucin
CD43
CD164
MUC1
MUC2
MUC3A
MUC3B
MUC4
MUC5AC
MUC5B
MUC6
MUC7
MUC8
MUC12
MUC13
MUC15
MUC16
MUC17
MUC19
MUC20
Other
Haptoglobin
Intrinsic factor
Orosomucoid
Peptidoglycan
Phytohaemagglutinin
Ovomucin
Proteoglycans
CS/DS
Decorin
Biglycan
Versican
HS/CS
Testican
Perlecan
CS
Chondroitin sulfate proteoglycans: Aggrecan
Neurocan
Brevican
CD44
CSPG4
CSPG5
Platelet factor 4
Structural maintenance of chromosomes 3
KS
Fibromodulin
Lumican
Keratocan
HS
Syndecan 1
Other
Activin and inhibin
ADAM
Alpha 1-antichymotrypsin
Apolipoprotein H
CD70
Asialoglycoprotein
Avidin
B-cell activating factor
4-1BB ligand
Cholesterylester transfer protein
Clusterin
Colony-stimulating factor
Hemopexin
Lactoferrin
Membrane glycoproteins
Myelin protein zero
Osteonectin
Protein C
Protein S
Serum amyloid P component
Sialoglycoprotein
CD43
Glycophorin
Glycophorin C
Thrombopoietin
Thyroglobulin
Thyroxine-binding proteins
Transcortin
Tumor necrosis factor alpha
Uteroglobin
Vitronectin
v
t
e
Protein: scleroproteins
Extracellular matrix
Collagen
Fibril forming
type I
COL1A1
COL1A2
type II (COL2A1)
type III
type V
COL5A1
COL5A2
COL5A3
COL24A1
COL26A1
Other
FACIT: type IX
COL9A1
COL9A2
COL9A3
type XII (COL12A1)
COL14A1
COL16A1
COL19A1
COL20A1
COL21A1
COL22A1
basement membrane: type IV
COL4A1
COL4A2
COL4A3
COL4A4
COL4A5
COL4A6
multiplexin: COL15A1
type XVIII
COL18A1
Endostatin
transmembrane: COL13A1
COL17A1
COL23A1
COL25A1
other: type VI
COL6A1
COL6A2
COL6A3
COL6A5
type VII (COL7A1)
type VIII
COL8A1
COL8A2
type X (COL10A1)
type XI
COL11A1
COL11A2
COL27A1
COL28A1
Enzymes
Prolyl hydroxylase/Lysyl hydroxylase
Cartilage associated protein/Leprecan
ADAMTS2
Procollagen peptidase
Lysyl oxidase
Laminin
alpha
LAMA1
LAMA2
LAMA3
LAMA4
LAMA5
beta
LAMB1
LAMB2
LAMB3
LAMB4
gamma
LAMC1
LAMC2
LAMC3
Other
ALCAM
Elastin
Tropoelastin
Vitronectin
FRAS1
FREM2
Decorin
FAM20C
ECM1
Matrix gla protein
Tectorin
TECTA
TECTB
Other
Keratin/Cytokeratin
Gelatin
Reticulin
Cartilage oligomeric matrix protein
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
The effect of human platelet lysate on the differentiation ability of human adipose-derived stem cells cultured on ECM-coated surfaces.
Gao Y, Ku NJ, Sung TC, Higuchi A, Hung CS, Lee HH, Ling QD, Cheng NC, Umezawa A, Barro L, Burnouf T, Ye Q, Chen H.
Journal of materials chemistry. B. 2019 Dec;7(45)7110-7119.
Human mesenchymal stem cells (hMSCs), such as human adipose-derived stem cells (hADSCs), present heterogeneous characteristics, including varying differentiation abilities and genotypes. hADSCs isolated under different conditions exhibit differences in stemness. We isolated hADSCs from human fat tis
The combined effects of hierarchical scaffolds and mechanical stimuli on ex vivo expansion of haematopoietic stem/progenitor cells.
Kim JE, Lee EJ, Wu Y, Kang YG, Shin JW.
Artificial cells, nanomedicine, and biotechnology. 2019 Dec;47(1)586-593.
We describe the ex vivo expansion of haematopoietic stem/progenitor cells (HSPCs) with consideration of their eventual in-vivo niche. We firstly fabricated hierarchically structured scaffolds (lattices derived via three-dimensional plotting combined with electrospun submicron fibers coated with vitr
Identification of second arginine-glycine-aspartic acid motif of ovine vitronectin as the complement C9 binding site and its implication in bacterial infection
Vitronectin is a glycoprotein present in plasma and tissues. Together with fibronectin, vitronectin is one of the major cell adhesion proteins in plasma.
Defined, Xeno-Free Cell Attachment Factor that Supports the Growth and Differentiation of Human Pluripotent Stem Cells Under Serum-Free, Feeder-Free Conditions ... Vitronectin XF , developed and manufactured by Primorigen ...