LTBP4
Developmental stage
Very low expression in fetal brain, liver, heart, spleen and thymus.
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. 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.
Involvement in disease
Urban-Rifkin-Davis syndrome
URDS
A syndrome characterized by disrupted pulmonary, gastrointestinal, urinary, musculoskeletal, craniofacial and dermal development. Clinical features include cutis laxa, mild cardiovascular lesions, respiratory distress with cystic and atelectatic changes in the lungs, and diverticulosis, tortuosity and stenosis at various levels of the intestinal tract. Craniofacial features include microretrognathia, flat midface, receding forehead and wide fontanelles.
None
The disease is caused by variants affecting the gene represented in this entry.
Duchenne muscular dystrophy
DMD
Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment.
None
The gene represented in this entry may act as a disease modifier. DMD patients homozygous for the IAAM haplotype consisting of Ile-194, Ala-787, Ala-820 and Met-1141 remain ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype consisting of Val-194, Thr-787, Thr-820 and Thr-1141. This may be due to increased binding to TGFB1, resulting in TGFB1 sequestration in the extracellular matrix and reduced TGFB1 signaling which has been linked to improved muscle function and regeneration.
Post-translational modifications
Contains hydroxylated asparagine residues.
Sequence Similarities
Belongs to the LTBP family.
Tissue Specificity
Highly expressed in heart, skeletal muscle, pancreas, uterus, and small intestine. Weakly expressed in placenta and lung.
Cellular localization
- Secreted
- Extracellular space
- Extracellular matrix
Alternative names
Latent-transforming growth factor beta-binding protein 4, LTBP-4, LTBP4