Defective pro-SFTPC does not translocate from ER membrane to multivesicle body

Stable Identifier
Reaction [transition]
Homo sapiens
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Surfactant proteins (SFTPs) are trafficked from the ER membrane to lamellar bodies (LBs) via the multi-vesicle body (MVB). The pro-SFTPs B and C are cleaved here to produce functional SFTPs. Defects in the SFTPC gene result in protein misfolding, misrouting and/or misprocessing resulting in accumulation of partially-processed, inactive pro-SFTPC in alveoli causing cell toxicity. Defects in SFTPC can cause pulmonary surfactant metabolism dysfunction 2 (SMDP2; MIM:610913), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Cellular responses to the misfolded pro-SFTPC products include ER stress, the activation of reactive oxygen species and autophagy. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450). Mutations causing RDS that arrest the pro-protein in the ER include P30L and P115L (Thurm et al. 2013).
Literature References
PubMed ID Title Journal Year
23701443 SFTPC mutations cause SP-C degradation and aggregate formation without increasing ER stress

Zarbock, R, Griese, M, Thurm, T, Kern, S, Kaltenborn, E

Eur. J. Clin. Invest. 2013
Normal reaction
Functional status

Loss of function of pro-SFTPC mutants [endoplasmic reticulum membrane]

Name Identifier Synonyms
newborn respiratory distress syndrome DOID:12716 Neonatal respiratory Distress syndrome, hyaline membrane disease, HMD - Hyaline membrane disease, pulmonary hypoperfusion syndrome of newborn, respiratory distress syndrome of newborn, pulmonary hyaline membrane disease
interstitial lung disease DOID:3082 ILD
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