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The SMB domain (yellow) in complex with PAI-1
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols VTN ; V75; VN; VNT
External IDs OMIM193190 MGI98940 HomoloGene532 ChEMBL: 1075314 GeneCards: VTN Gene
RNA expression pattern
PBB GE VTN 204534 at tn.png
More reference expression data
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 [1] [2]

Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.[1][2]

The protein encoded by this gene is a member of the pexin family. Vitronectin is an abundant glycoprotein found in serum, the extracellular matrix and bone[3] and promotes cell adhesion and spreading, 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.[1] Vitronectin has been speculated to be involved in hemostasis[4] and tumor malignancy.[5]


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:

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.[6] Subsequently two groups reported NMR structures of the domain.[7][8]

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[9][10][11] but this ambiguity has been resolved by the crystal structure.[11]

Homology models have been built for the central and C-terminal domains.[11]


The somatomedin B domain of vitronectin binds to plasminogen activator inhibitor-1 (PAI-1), and stabilizes it.[6] 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.


  1. ^ a b "Entrez Gene: M Vitronectin". 
  2. ^ 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. 
  3. ^ Boron, Walter F. and Boulpaep, Emile L. "Medical Physiology". Saunders, 2012, p.1097.
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ Kamikubo Y, De Guzman R, Kroon G, Curriden S, Neels JG, Churchill MJ et al. (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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 

Further reading[edit]

  • 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[edit]