Reviewed, UniProtKB/Swiss-Prot P11686 (PSPC_HUMAN)

Names and origin

Protein names

Recommended name:
    Pulmonary surfactant-associated protein C
      Short name=SP-C
Alternative name(s):
    SP5
    Pulmonary surfactant-associated proteolipid SPL(Val)

Gene names

Name:	SFTPC
Synonyms:	SFTP2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	197 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (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.
Involvement in 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. A rare disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course, due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress. Ref.15 Ref.16 Ref.18 Ref.19 Ref.21 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. Ref.17
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).
Sequence similarities	Contains 1 BRICHOS domain.

Ontologies

Keywords
Biological process	Gaseous exchange
Cellular component	Secreted Surface film
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	respiratory gaseous exchange Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11686-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P11686-2)

Also known as: C1;

The sequence of this isoform differs from the canonical sequence as follows:
     146-151: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 23	23			PRO_0000033477
	Chain	24 – 58	35	Pulmonary surfactant-associated protein C		PRO_0000033478
	Propeptide	59 – 197	139			PRO_0000033479
Regions
	Domain	94 – 197	104	BRICHOS
Amino acid modifications
	Modified residue	16	1	Phosphotyrosine Ref.14
	Lipidation	28	1	S-palmitoyl cysteine Ref.13
	Lipidation	29	1	S-palmitoyl cysteine Ref.13
Natural variations
	Alternative sequence	146 – 151	6	Missing in isoform 2.		VSP_006311
	Natural variant	66	1	E → K in SMDP2; targeted abnormally to early endosomes and likely to result in a toxic gain of function. Ref.21		VAR_036855
	Natural variant	73	1	I → T in SMDP2; abnormal trafficking and accumulation of aberrantly processed proSPC within alveoli. Ref.16 Ref.18 Ref.19		VAR_026753
	Natural variant	116	1	A → D in SMDP2. Ref.20		VAR_026754
	Natural variant	138	1	N → T Influences susceptibility to RDS in premature infants. dbSNP rs4715. Ref.17 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10		VAR_007453
	Natural variant	167	1	R → Q in SMDP2. dbSNP rs34957318. Ref.16		VAR_026755
	Natural variant	186	1	N → S Influences susceptibility to RDS in premature infants. dbSNP rs1124. Ref.17 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10		VAR_016175
	Natural variant	188	1	L → Q in SMDP2. Ref.15		VAR_026756
Experimental info
	Sequence conflict	14	1	P → PPCQ in AAB60332. Ref.4
	Sequence conflict	45	1	L → S in AAB60332. Ref.4
	Sequence conflict	65 – 67	3	TEM → FPQ in AAB60332. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: C26A21E33C60AA78	FASTA	197	21,053
	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
	Isoform 2 (C1). Checksum: 4C45300448DE03FA	FASTA	191	20,361
	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 VHNFQAKPAV PTSKLGQAEG RDAGSAPSGG DPAFLGMAVN 190 TLCGEVPLYY I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences." 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. Proc. Natl. Acad. Sci. U.S.A. 84:7915-7919(1987) [PubMed: 3479771] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)." Glasser S.W., Korfhagen T.R., Weaver T.E., Clark J.C., Pilot-Matias T., Meuth J., Fox J.L., Whitsett J.A. J. Biol. Chem. 263:9-12(1988) [PubMed: 3335510] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 26-42.
[3]	"Two SP-C genes encoding human pulmonary surfactant proteolipid." Glasser S.W., Korfhagen T.R., Perme C.M., Pilot-Matias T.J., Kister S.E., Whitsett J.A. J. Biol. Chem. 263:10326-10331(1988) [PubMed: 2839484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, VARIANT THR-138.
[4]	"Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species." Hatzis D., Deiter G., deMello D.E., Floros J. Exp. Lung Res. 20:57-72(1994) [PubMed: 8181452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS THR-138 AND SER-186.
[5]	Frerking I., Stevens P., Pison U., Witt H. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS THR-138 AND SER-186.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS THR-138 AND SER-186. Tissue: Lung.
[7]	"A computer system platform used to predict novel genes." Yu Z., Zheng Z., Tang T., Fu Y. Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[8]	SeattleSNPs variation discovery resource Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-138 AND SER-186.
[9]	"DNA sequence and analysis of human chromosome 8." 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. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS THR-138 AND SER-186.
[10]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS THR-138 AND SER-186.
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[12]	"Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms." Johansson J., Joernvall H., Eklund A., Christensen N., Robertson B., Curstedt T. FEBS Lett. 232:61-64(1988) [PubMed: 3366248] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-58.
[13]	"Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups." Curstedt T., Johansson J., Persson P., Eklund A., Robertson B., Loewenadler B., Joernvall H. Proc. Natl. Acad. Sci. U.S.A. 87:2985-2989(1990) [PubMed: 2326260] [Abstract] Cited for: PALMITOYLATION AT CYS-28 AND CYS-29.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." 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. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-16, MASS SPECTROMETRY.
[15]	"Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred." 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. Am. J. Respir. Crit. Care Med. 165:1322-1328(2002) [PubMed: 11991887] [Abstract] Cited for: VARIANT SMDP2 GLN-188.
[16]	"Mutation of SFTPC in infantile pulmonary alveolar proteinosis with or without fibrosing lung disease." Tredano M., Griese M., Brasch F., Schumacher S., de Blic J., Marque S., Houdayer C., Elion J., Couderc R., Bahuau M. Am. J. Med. Genet. A 126:18-26(2004) [PubMed: 15039969] [Abstract] Cited for: VARIANTS SMDP2 THR-73 AND GLN-167.
[17]	"Surfactant protein C gene variation in the Finnish population -association with perinatal respiratory disease." Lahti M., Marttila R., Hallman M. Eur. J. Hum. Genet. 12:312-320(2004) [PubMed: 14735158] [Abstract] Cited for: VARIANTS THR-138 AND SER-186, INVOLVEMENT IN RDS.
[18]	"Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene." Brasch F., Griese M., Tredano M., Johnen G., Ochs M., Rieger C., Mulugeta S., Mueller K.M., Bahuau M., Beers M.F. Eur. Respir. J. 24:30-39(2004) [PubMed: 15293602] [Abstract] Cited for: VARIANT SMDP2 THR-73, CHARACTERIZATION OF VARIANT SMDP2 THR-73.
[19]	"Variable phenotype associated with SP-C gene mutations: fatal case with the I73T mutation." Percopo S., Cameron H.S., Nogee L.M., Pettinato G., Montella S., Santamaria F. Eur. Respir. J. 24:1072-1073(2004) [PubMed: 15572558] [Abstract] Cited for: VARIANT SMDP2 THR-73.
[20]	"Hydroxychloroquine and surfactant protein C deficiency." Rosen D.M., Waltz D.A. N. Engl. J. Med. 352:207-208(2005) [PubMed: 15647591] [Abstract] Cited for: VARIANT SURFACTANT PROTEIN C DEFICIENCY ASP-116.
[21]	"Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene." Stevens P.A., Pettenazzo A., Brasch F., Mulugeta S., Baritussio A., Ochs M., Morrison L., Russo S.J., Beers M.F. Pediatr. Res. 57:89-98(2005) [PubMed: 15557112] [Abstract] Cited for: VARIANT SMDP2 LYS-66, CHARACTERIZATION OF VARIANT SMDP2 LYS-66.
+	Additional computationally mapped references.

Web resources

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	J03553 mRNA. Translation: AAA36631.1. J03517 mRNA. Translation: AAA36634.1. J03890 Genomic DNA. Translation: AAC32022.1. J03890 Genomic DNA. Translation: AAC32023.1. U02948 Genomic DNA. Translation: AAB60332.1. AY357924 Genomic DNA. Translation: AAQ67734.1. AK315742 mRNA. Translation: BAG38097.1. DQ884411 mRNA. Translation: ABI63378.1. AY337315 Genomic DNA. Translation: AAP88034.1. AC105206 Genomic DNA. No translation available. CH471080 Genomic DNA. Translation: EAW63707.1. BC005913 mRNA. Translation: AAH05913.1.
IPI	IPI00006707. IPI00218499.
PIR	LNHUC. A28801.
RefSeq	NP_003009.2.
UniGene	Hs.1074
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P11686.
PTM databases
PhosphoSite	P11686.
Proteomic databases
PRIDE	P11686.
Genome annotation databases
Ensembl	ENST00000318561; ENSP00000316152; ENSG00000168484; Homo sapiens. [Genome view] ENST00000437090; ENSP00000407931; ENSG00000168484; Homo sapiens. [Genome view] ENST00000455550; ENSP00000416065; ENSG00000168484; Homo sapiens. [Genome view]
GeneID	6440.
KEGG	hsa:6440.
UCSC	uc003xaw.2. human. uc003xax.2. human.
Organism-specific databases
CTD	6440.
GeneCards	GC08P022072.
H-InvDB	HIX0007365.
HGNC	HGNC:10802. SFTPC.
HPA	CAB009313. HPA010928. HPA011644.
MIM	178620. gene. 267450. phenotype. 610913. phenotype.
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.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P11686.
HOVERGEN	P11686.
Gene expression databases
ArrayExpress	P11686.
Bgee	P11686.
CleanEx	HS_SFTPC.
Genevestigator	P11686.
GermOnline	ENSG00000168484. Homo sapiens.
Family and domain databases
InterPro	IPR007084. BRICHOS. IPR001729. Pulm_surfact_AP. IPR018051. SP-C_palmitoylation_site. IPR015091. Surfactant_protein_propep. [Graphical view]
Pfam	PF04089. BRICHOS. 1 hit. PF08999. SP_C-Propep. 1 hit. [Graphical view]
ProDom	PD009591. Pulm_surf_ChM1. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00019. SF_P. 1 hit. [Graphical view]
PROSITE	PS50869. BRICHOS. 1 hit. PS00341. SURFACT_PALMYTOYL. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	25027.
SOURCE	Search...

Entry information

Entry name

PSPC_HUMAN

Accession

Primary (citable) accession number: P11686
Secondary accession number(s): A6XNE4 , B2RE00, P11687, Q12793, Q7Z5D0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	April 1, 1990
Last modified:	October 13, 2009
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.