1ksq

Structural highlights

Disease

LTBP1_HUMAN Autosomal recessive cutis laxa type 1. The disease is caused by variants affecting the gene represented in this entry.

Function

LTBP1_HUMAN Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:2022183, PubMed:8617200, PubMed:8939931). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:8617200, PubMed:8939931, PubMed:15184403). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742).^{[1] [2] [3] [4] [5]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Annes JP, Chen Y, Munger JS, Rifkin DB. Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1. J Cell Biol. 2004 Jun 7;165(5):723-34. PMID:15184403 doi:10.1083/jcb.200312172
2. ↑ Miyazono K, Olofsson A, Colosetti P, Heldin CH. A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1. EMBO J. 1991 May;10(5):1091-101. PMID:2022183 doi:10.1002/j.1460-2075.1991.tb08049.x
3. ↑ Wang R, Zhu J, Dong X, Shi M, Lu C, Springer TA. GARP regulates the bioavailability and activation of TGFbeta. Mol Biol Cell. 2012 Mar;23(6):1129-39. doi: 10.1091/mbc.E11-12-1018. Epub 2012, Jan 25. PMID:22278742 doi:http://dx.doi.org/10.1091/mbc.E11-12-1018
4. ↑ Saharinen J, Taipale J, Keski-Oja J. Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO J. 1996 Jan 15;15(2):245-53 PMID:8617200
5. ↑ Gleizes PE, Beavis RC, Mazzieri R, Shen B, Rifkin DB. Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. J Biol Chem. 1996 Nov 22;271(47):29891-6. PMID:8939931 doi:10.1074/jbc.271.47.29891