Biology:Surfactant protein C

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the SFTPC gene.

It is a membrane protein.

Structure

Surfactant protein C, N terminal propeptide
Pig SP-C, corresponds to human mature form
Identifiers
Symbol	SP_C-Propep
Pfam	PF08999
InterPro	IPR001729
PROSITE	PDOC00298
OPM superfamily	69
OPM protein	1spf
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

SFTPC is a 197-residue protein made up of two halves: a unique N-terminal propeptide domain and a C-terminal BRICHOS domain. The around 100-aa long propeptide domain actually contains not only the cleaved part, but also the mature peptide. It can be further broken down into a 23-aa helical transmembrane propeptide proper, the mature secreted SP-C (24-58), and a linker (59-89) that connects to the BRICHOS domain.

The propeptide of pulmonary surfactant C has an N-terminal alpha-helical segment whose suggested function was stabilization of the protein structure, since the mature peptide can irreversibly transform from its native alpha-helical structure to beta-sheet aggregates and form amyloid fibrils. The correct intracellular trafficking of proSP-C has also been reported to depend on the propeptide.

The structure of the BRICHOS domain has been solved. Mutations in this domain also lead to amyloid fibrils made up of the mature peptide, suggesting a chaperone activity.

Clinical significance

Mutations are associated with surfactant metabolism dysfunction type 2.

Humans and animals born lacking SP-C tend to develop progressive interstitial lung disease.

Recombinant SP-C is used in Venticute, an artificial lung surfactant.

A process to mass-produce an analogue called rSP-C33Le by fusion with spidroin has been described.

Further reading

• "Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics". Pediatric Pathology & Molecular Medicine 20 (6): 445–69. 2002. doi:10.1080/15227950152625783. PMID 11699574. 
• "Synthesis and post-translational processing of surfactant protein C". Pediatric Pathology & Molecular Medicine 20 (6): 471–500. 2002. doi:10.1080/15227950152625792. PMID 11699575. 
• "Artificial surfactants based on analogues of SP-B and SP-C". Pediatric Pathology & Molecular Medicine 20 (6): 501–18. 2002. doi:10.1080/15227950152625800. PMID 11699576. 
• "Alterations in SP-B and SP-C expression in neonatal lung disease". Annual Review of Physiology 66: 601–23. 2004. doi:10.1146/annurev.physiol.66.032102.134711. PMID 14977415. 
• "Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene". The European Respiratory Journal 24 (1): 30–9. July 2004. doi:10.1183/09031936.04.00000104. PMID 15293602. 
• "Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups". Proceedings of the National Academy of Sciences of the United States of America 87 (8): 2985–9. April 1990. doi:10.1073/pnas.87.8.2985. PMID 2326260. Bibcode: 1990PNAS...87.2985C. 
• "Interaction between perdeuterated dimyristoylphosphatidylcholine and low molecular weight pulmonary surfactant protein SP-C". Biochemistry 29 (24): 5807–14. June 1990. doi:10.1021/bi00476a023. PMID 2383558. 
• "Two SP-C genes encoding human pulmonary surfactant proteolipid". The Journal of Biological Chemistry 263 (21): 10326–31. July 1988. doi:10.1016/S0021-9258(19)81519-3. PMID 2839484. 
• "cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)". The Journal of Biological Chemistry 263 (1): 9–12. January 1988. doi:10.1016/S0021-9258(19)57347-1. PMID 3335510. 
• "Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms". FEBS Letters 232 (1): 61–4. May 1988. doi:10.1016/0014-5793(88)80386-7. PMID 3366248. 
• "Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences". Proceedings of the National Academy of Sciences of the United States of America 84 (22): 7915–9. November 1987. doi:10.1073/pnas.84.22.7915. PMID 3479771. Bibcode: 1987PNAS...84.7915W. 
• "Familial fibrocystic pulmonary dysplasia: a new case in a known affected family". Canadian Medical Association Journal 94 (20): 1059–61. May 1966. PMID 5942662. 
• "Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and characterization of a microsatellite repeat marker that shows frequent loss of heterozygosity in human carcinomas". Genomics 24 (3): 597–600. December 1994. doi:10.1006/geno.1994.1673. PMID 7713515. 
• "Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species". Experimental Lung Research 20 (1): 57–72. 1994. doi:10.3109/01902149409064373. PMID 8181452. 
• "A mutation in the surfactant protein C gene associated with familial interstitial lung disease". The New England Journal of Medicine 344 (8): 573–9. February 2001. doi:10.1056/NEJM200102223440805. PMID 11207353. 
• "Altered stability of pulmonary surfactant in SP-C-deficient mice". Proceedings of the National Academy of Sciences of the United States of America 98 (11): 6366–71. May 2001. doi:10.1073/pnas.101500298. PMID 11344267. Bibcode: 2001PNAS...98.6366G. 

External links

• GeneReviews/NIH/NCBI/UW entry on Pulmonary Fibrosis, Familial
• Pulmonary+Surfactant-Associated+Protein+B at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro: IPR015091