• Purity

  >95%, by SDS-PAGE with silver staining

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by the ability of the immobilized protein to support the adhesion of HFL1 human fetal lung fibroblast cells. The ED    ₅₀ for this effect is 0.5-2.5 μg/mL.

• Source

  Human embryonic kidney cell, HEK293-derived Met1-Ala1624, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Multiple starts between Met1 & Ser273

• Predicted Molecular Mass

  174 kDa

• SDS-PAGE

  155-205 kDa, reducing conditions

Background: Latent TGF-beta bp4

Latent TGF? beta Binding Protein?4 (LTBP?4) is a widely expressed 170?230 kDa secreted glycoprotein within the LTBP/fibrillin family (1?3). LTBPs contain a conserved pattern of eight-cysteine motifs (8Cys) and EGF?like (EGFL) domains (2?4). The 1624 amino acid (aa) human LTBP?4 (L isoform) includes a signal sequence (aa 1?27), a heparin-binding N?terminal domain (aa 28?460) with two EGFL, one hybrid and one 8?Cys motif, a protease-sensitive hinge region, a central region with 10 EGFL motifs, and a C?terminal domain (aa 1180?1624) with two EGFL and two 8Cys (1?4). The first C?terminal 8Cys motif is responsible for covalent association with the latency associated peptide (LAP) of latent TGF? beta 1 (1?4). Unlike LTBP-1 and ?3, LTBP?4 does not bind TGF? beta 2 or TGF? beta 3 LAPs (4). LTBP?4 also binds fibronectin, which mediates targeting to extracellular matrix (ECM), fibrillin-1 which mediates binding to microfibrils, and the cytokine midkine (1, 5, 6). Mature human LTBP?4 (LTBP?4L) shares 87% and 90% aa sequence identity with mouse and rat LTBP?4, respectively. A variant that lacks the TGF?binding 8Cys motif is reported to be widely expressed along with LTBP?4L (3). Other differentially expressed human splice isoforms of 1557 (LTBP?4S), 1587 and 636 aa have alternate N?termini through aa 69, 151, and 919 (also lacking aa 1005?1090), respectively (1, 7). LTBP?4 is involved in the assembly, secretion and targeting of latent TGF? beta 1 to sites where it can be activated. Deletion or mutation in humans can cause Urban?Rifkin?Davis syndrome (URDS), a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal and dermal development mediated by enhanced TGF? beta 1 activity (8). Similar defects are found in mice deleted for LTBP?4 (9?11). Impaired LTBP?4 expression enhances susceptibility to colon cancer (8). LTBP-4 is also down?regulated in breast cancer tissues (5).

• References:

1. Kantola, A.K. et al. (2008) Exp. Cell Res. 314:2488.

2. Saharinen, J. et al. (1998) J. Biol. Chem. 273:18459.

3. Koli, K. et al. (2001) J. Cell Sci. 114:2869.

4. Saharinen, J. and J. Keski-Oja (2000) Mol. Biol. Cell 11:2691.

5. Takahashi, Y. et al. (2012) Breast Cancer 19:46.

6. Yan, Q. et al. (2012) Hepatobiliary Pancreat. Dis. Int. 11:272.

7. Kantola, A.K. et al. (2010) J. Cell Physiol. 223:727.

8. Urban, Z. et al. (2009) Am. J. Hum. Genet. 85:593.

9. Sterner-Kock, A. et al. (2002) Genes Dev. 16:2264.

10. Dabovic, B. et al. (2009) J. Cell Physiol. 219:14.

11. Koli, K. et al. (2004) J. Cell Biol. 167:123.

• Entrez Gene IDs:

  8425 (Human)

• Alternate Names:

  Latent TGFbeta bp4; Latent TGF-beta bp4; latent transforming growth factor beta binding protein 4; LTBP4; LTBP-4; LTBP4L; LTBP4S