[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1073/pnas.84.22.7915; PubMed=3479771 [NCBI, ExPASy, EBI, Israel, Japan] Warr R.G., Hawgood S., Buckley D.I., Crisp T.M., Schilling J., Benson B.J., Ballard P.L., Clements J.A., White R.T.; "Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences."; Proc. Natl. Acad. Sci. U.S.A. 84:7915-7919(1987).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 26-42. PubMed=3335510 [NCBI, ExPASy, EBI, Israel, Japan] Glasser S.W., Korfhagen T.R., Weaver T.E., Clark J.C., Pilot-Matias T., Meuth J., Fox J.L., Whitsett J.A.; "cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)."; J. Biol. Chem. 263:9-12(1988).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANT THR-138. PubMed=2839484 [NCBI, ExPASy, EBI, Israel, Japan] Glasser S.W., Korfhagen T.R., Perme C.M., Pilot-Matias T.J., Kister S.E., Whitsett J.A.; "Two SP-C genes encoding human pulmonary surfactant proteolipid."; J. Biol. Chem. 263:10326-10331(1988).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS THR-138 AND SER-186. PubMed=8181452 [NCBI, ExPASy, EBI, Israel, Japan] Hatzis D., Deiter G., deMello D.E., Floros J.; "Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species."; Exp. Lung Res. 20:57-72(1994).
[5]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS THR-138 AND SER-186. Frerking I., Stevens P., Pison U., Witt H.; Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-138 AND SER-186. TISSUE=Lung; DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan] Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; "Complete sequencing and characterization of 21,243 full-length human cDNAs."; Nat. Genet. 36:40-45(2004).
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Yu Z., Zheng Z., Tang T., Fu Y.; "A computer system platform used to predict novel genes."; Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
[8]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-138 AND SER-186. SeattleSNPs variation discovery resource; Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
[9]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS THR-138 AND SER-186. DOI=10.1038/nature04406; PubMed=16421571 [NCBI, ExPASy, EBI, Israel, Japan] Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.; "DNA sequence and analysis of human chromosome 8."; Nature 439:331-335(2006).
[10]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS THR-138 AND SER-186. Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.; Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[11]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). TISSUE=Lung; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[12]	PROTEIN SEQUENCE OF 24-58. DOI=10.1016/0014-5793(88)80386-7; PubMed=3366248 [NCBI, ExPASy, EBI, Israel, Japan] Johansson J., Joernvall H., Eklund A., Christensen N., Robertson B., Curstedt T.; "Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms."; FEBS Lett. 232:61-64(1988).
[13]	PALMITOYLATION AT CYS-28 AND CYS-29. DOI=10.1073/pnas.87.8.2985; PubMed=2326260 [NCBI, ExPASy, EBI, Israel, Japan] Curstedt T., Johansson J., Persson P., Eklund A., Robertson B., Loewenadler B., Joernvall H.; "Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups."; Proc. Natl. Acad. Sci. U.S.A. 87:2985-2989(1990).
[14]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-16, AND MASS SPECTROMETRY. DOI=10.1016/j.cell.2007.11.025; PubMed=18083107 [NCBI, ExPASy, EBI, Israel, Japan] Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."; Cell 131:1190-1203(2007).
[15]	VARIANT SMDP2 GLN-188. PubMed=11991887 [NCBI, ExPASy, EBI, Israel, Japan] Thomas A.Q., Lane K., Phillips J.A. III, Prince M., Markin C., Speer M., Schwartz D.A., Gaddipati R., Marney A., Johnson J., Roberts R., Haines J., Stahlman M., Loyd J.E.; "Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred."; Am. J. Respir. Crit. Care Med. 165:1322-1328(2002).
[16]	VARIANTS SMDP2 THR-73 AND GLN-167. DOI=10.1002/ajmg.a.20670; PubMed=15039969 [NCBI, ExPASy, EBI, Israel, Japan] Tredano M., Griese M., Brasch F., Schumacher S., de Blic J., Marque S., Houdayer C., Elion J., Couderc R., Bahuau M.; "Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease."; Am. J. Med. Genet. A 126:18-26(2004).
[17]	VARIANTS THR-138 AND SER-186, AND INVOLVEMENT IN RDS. DOI=10.1038/sj.ejhg.5201137; PubMed=14735158 [NCBI, ExPASy, EBI, Israel, Japan] Lahti M., Marttila R., Hallman M.; "Surfactant protein C gene variation in the Finnish population -association with perinatal respiratory disease."; Eur. J. Hum. Genet. 12:312-320(2004).
[18]	VARIANT SMDP2 THR-73, AND CHARACTERIZATION OF VARIANT SMDP2 THR-73. DOI=10.1183/09031936.04.00000104; PubMed=15293602 [NCBI, ExPASy, EBI, Israel, Japan] Brasch F., Griese M., Tredano M., Johnen G., Ochs M., Rieger C., Mulugeta S., Mueller K.M., Bahuau M., Beers M.F.; "Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene."; Eur. Respir. J. 24:30-39(2004).
[19]	VARIANT SMDP2 THR-73. DOI=10.1183/09031936.04.00092304; PubMed=15572558 [NCBI, ExPASy, EBI, Israel, Japan] Percopo S., Cameron H.S., Nogee L.M., Pettinato G., Montella S., Santamaria F.; "Variable phenotype associated with SP-C gene mutations: fatal case with the I73T mutation."; Eur. Respir. J. 24:1072-1073(2004).
[20]	VARIANT SURFACTANT PROTEIN C DEFICIENCY ASP-116. DOI=10.1056/NEJM200501133520223; PubMed=15647591 [NCBI, ExPASy, EBI, Israel, Japan] Rosen D.M., Waltz D.A.; "Hydroxychloroquine and surfactant protein C deficiency."; N. Engl. J. Med. 352:207-208(2005).
[21]	VARIANT SMDP2 LYS-66, AND CHARACTERIZATION OF VARIANT SMDP2 LYS-66. DOI=10.1203/01.PDR.0000147567.02473.5A; PubMed=15557112 [NCBI, ExPASy, EBI, Israel, Japan] Stevens P.A., Pettenazzo A., Brasch F., Mulugeta S., Baritussio A., Ochs M., Morrison L., Russo S.J., Beers M.F.; "Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene."; Pediatr. Res. 57:89-98(2005).

Comments

FUNCTION: Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.
SUBCELLULAR LOCATION: Secreted, extracellular space, surface film.
ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name 1

Isoform ID P11686-1

This is the isoform sequence displayed in this entry.

Name 2

Synonyms C1

Isoform ID P11686-2

Features which should be applied to build the isoform sequence: VSP_006311.
DISEASE: Polymorphisms in the SFTPC gene are important determinants for predisposition to respiratory distress syndrome (RDS) in premature infants [MIM:267450]. RDS in the newborn is the main cause of mortality and morbidity in premature infants. RDS is characterized by deficient gas exchange that is caused by diffuse atelectasis and high-permeability lung edema that results in fibrin-rich alveolar deposits called 'hyaline membranes'. The risk of bronchopulmonary dysplasia increases with the severity of RDS.
DISEASE: Defects in SFTPC are the cause of pulmonary surfactant metabolism dysfunction type 2 (SMDP2) [MIM:610913]; also called pulmonary alveolar proteinosis due to surfactant protein C deficiency. SMDP2 is a rare autosomal dominant disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course. The pathophysiology of the disorder is postulated to involve intracellular accumulation of a structurally defective SFTPC protein. Some patients who survive to adulthood manifest features of pulmonary fibrosis such as shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees in inflammation, fibrosis, or both on biopsy. Pulmonary surfactant metabolism disorders are genetically heterogeneous and associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular non-specific interstitial pneumonitis (NSIP).
DISEASE: Genetic variations in SFTPC are associated with respiratory distress syndrome in premature infants (RDS) [MIM:267450]; also known as RDS in prematurity. RDS in the newborn is the main cause of mortality and morbidity in premature infants. RDS is characterized by deficient gas exchange that is caused by diffuse atelectasis and high-permeability lung edema that results in fibrin-rich alveolar deposits called 'hyaline membranes'. The risk of bronchopulmonary dysplasia increases with the severity of RDS.
MISCELLANEOUS: Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).
SIMILARITY: Contains 1 BRICHOS domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=SFTPC";.
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/sftpc/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

J03553; AAA36631.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J03517; AAA36634.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J03890; AAC32022.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
J03890; AAC32023.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U02948; AAB60332.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY357924; AAQ67734.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AK315742; BAG38097.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ884411; ABI63378.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY337315; AAP88034.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AC105206; -; NOT_ANNOTATED_CDS; Genomic_DNA.	[EMBL / GenBank / DDBJ]
CH471080; EAW63707.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC005913; AAH05913.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00006707; -.
IPI00218499; -.

A28801; LNHUC.

NP_003009.2; -.

3D structure databases

ModBase

P11686.

PTM databases

PhosphoSite

P11686; -.

Organism-specific databases

GC08P022072; -.

HIX0007365; -.

HGNC:10802; SFTPC.

CAB009313; -.

178620; gene. [NCBI / EBI]
267450; phenotype. [NCBI / EBI]
610913; phenotype. [NCBI / EBI]

Orphanet

70587; Acute respiratory distress syndrome, Infant.
91359; Chronic pneumonitis of infancy.
747; Pulmonary alveolar proteinosis.
2032; Pulmonary fibrosis, idiopathic.
100049; Pulmonary surfactant protein anomalies.
79127; Respiratory bronchiolitis - interstitial lung disease.

PharmGKB

PA35714; -.

Gene expression databases

P11686; -.

P11686; -.

HS_SFTPC; -.

ENSG00000168484; Homo sapiens.

Ontologies

GO:0005615;	Cellular component: extracellular space (inferred from electronic annotation from UniProtKB-SubCell).
GO:0050828;	Biological process: regulation of liquid surface tension (inferred from electronic annotation from UniProtKB-KW).
GO:0007585;	Biological process: respiratory gaseous exchange (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR007084; BRICHOS.
IPR001729; Pulm_surfact_AP.
IPR018051; SP-C_palmitoylation.
IPR015091; Surfactant_protein_propep.
Graphical view of domain structure.

Pfam

PF04089; BRICHOS; 1.
PF08999; SP_C-Propep; 1.
Pfam graphical view of domain structure.

ProDom

PD009591; Pulm_surf_ChM1; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00019; SF_P; 1.
SMART graphical view of domain structure.

PROSITE

PS50869; BRICHOS; 1.
PS00341; SURFACT_PALMYTOYL; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

P11686; -.

Genome annotation databases

Ensembl

ENSG00000168484; Homo sapiens. [Contig view]

GeneID

6440; -.

KEGG

hsa:6440; -.

Phylogenomic databases

HOGENOM

P11686; -.

HOVERGEN

P11686; -.

Other

25027; -.

SFTPC; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Direct protein sequencing; Disease mutation; Gaseous exchange; Lipoprotein; Palmitate; Phosphoprotein; Polymorphism; Secreted; Surface film.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`PROPEP`	`1 23`	`23`		`PRO_0000033477`
`CHAIN`	`24 58`	`35`	`Pulmonary surfactant-associated protein C.`	`PRO_0000033478`
`PROPEP`	`59 197`	`139`		`PRO_0000033479`
`DOMAIN`	`94 197`	`104`	`BRICHOS.`
`MOD_RES`	`16 16`		`Phosphotyrosine.`
`LIPID`	`28 28`		`S-palmitoyl cysteine.`
`LIPID`	`29 29`		`S-palmitoyl cysteine.`
`VAR_SEQ`	`146 151`		`Missing (in isoform 2).`	`VSP_006311`
`VARIANT`	`66 66`	`1`	`E -> K (in SMDP2; targeted abnormally to early endosomes and likely to result in a toxic gain of function).`	`VAR_036855`
`VARIANT`	`73 73`	`1`	`I -> T (in SMDP2; abnormal trafficking and accumulation of aberrantly processed proSPC within alveoli).`	`VAR_026753`
`VARIANT`	`116 116`	`1`	`A -> D (in SMDP2).`	`VAR_026754`
`VARIANT`	`138 138`	`1`	`N -> T (influences susceptibility to RDS in premature infants; dbSNP:rs4715 [NCBI]).`	`VAR_007453`
`VARIANT`	`167 167`	`1`	`R -> Q (in SMDP2; dbSNP:rs34957318 [NCBI]).`	`VAR_026755`
`VARIANT`	`186 186`	`1`	`N -> S (influences susceptibility to RDS in premature infants; dbSNP:rs1124 [NCBI]).`	`VAR_016175`
`VARIANT`	`188 188`	`1`	`L -> Q (in SMDP2).`	`VAR_026756`
`CONFLICT`	`14 14`		`P -> PPCQ (in Ref. 4; AAB60332).`
`CONFLICT`	`45 45`		`L -> S (in Ref. 4; AAB60332).`
`CONFLICT`	`65 67`		`TEM -> FPQ (in Ref. 4; AAB60332).`

Sequence information

Length: 197 AA [This is the length of the unprocessed precursor]

Molecular weight: 21053 Da [This is the MW of the unprocessed precursor]

CRC64: C26A21E33C60AA78 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MDVGSKEVLM ESPPDYSAAP RGRFGIPCCP VHLKRLLIVV VVVVLIVVVI VGALLMGLHM 

        70         80         90        100        110        120 
SQKHTEMVLE MSIGAPEAQQ RLALSEHLVT TATFSIGSTG LVVYDYQQLL IAYKPAPGTC 

       130        140        150        160        170        180 
CYIMKIAPES IPSLEALNRK VHNFQMECSL QAKPAVPTSK LGQAEGRDAG SAPSGGDPAF 

       190 
LGMAVNTLCG EVPLYYI

P11686 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools