LTBP1
Domain
The 8-Cys3 region in the third TB domain mediates the interchain disulfide bond interaction with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1.
Function
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:15184403, PubMed:8617200, PubMed:8939931). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742).
Involvement in disease
Cutis laxa, autosomal recessive, 2E
ARCL2E
A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. ARCL2E patients present with cutis laxa, inguinal hernia, craniofacial dysmorphology, variable heart defects, and prominent skeletal features including craniosynostosis, short stature, brachydactyly, and syndactyly.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Contains hydroxylated asparagine residues.
Isoform Short N-terminus is blocked.
Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.
O-glycosylated on serine residues by POGLUT2 and POGLUT3.
Sequence Similarities
Belongs to the LTBP family.
Tissue Specificity
Expressed in the aorta (at protein level) (PubMed:17293099). Isoform Long: Expressed in fibroblasts (PubMed:17293099).
Cellular localization
- Secreted
- Secreted
- Extracellular space
- Extracellular matrix
Alternative names
Latent-transforming growth factor beta-binding protein 1, LTBP-1, Transforming growth factor beta-1-binding protein 1, TGF-beta1-BP-1, LTBP1