Q8IWL1 (SFPA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pulmonary surfactant-associated protein A2
Short name=PSP-A
Short name=PSPA
Short name=SP-A
Short name=SP-A2

Alternative name(s):
35 kDa pulmonary surfactant-associated protein
Alveolar proteinosis protein
Collectin-5

Gene names

Name:	SFTPA2
Synonyms:	COLEC5, PSAP, SFTP1, SFTPA, SFTPA2B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	248 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	In presence of calcium ions, it binds to surfactant phospholipids and contributes to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration.
Subunit structure	Oligomeric complex of 6 set of homotrimers.
Subcellular location	Secreted › extracellular space › extracellular matrix. Secreted › extracellular space › surface film.
Polymorphism	At least 6 alleles of SFTPA2 are known: 1A, 1A0, 1A1, 1A2, 1A3 and 1A4. The sequence shown is that of allele 1A0.
Involvement in disease	Pulmonary fibrosis, idiopathic (IPF) [MIM:178500]: A lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. It results in acute lung injury with subsequent scarring and endstage lung disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
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	Belongs to the SFTPA family. Contains 1 C-type lectin domain. Contains 1 collagen-like domain.

Ontologies

Keywords
Biological process	Gaseous exchange
Cellular component	Extracellular matrix Secreted Surface film
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Collagen Signal
Ligand	Calcium Lectin
PTM	Acetylation Disulfide bond Glycoprotein Hydroxylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	respiratory gaseous exchange Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	collagen Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20
	Chain	21 – 248	228	Pulmonary surfactant-associated protein A2		PRO_0000017458
Regions
	Domain	28 – 100	73	Collagen-like
	Domain	132 – 248	117	C-type lectin
Amino acid modifications
	Modified residue	21	1	N-acetylglutamate; partial Ref.1
	Modified residue	30	1	4-hydroxyproline By similarity
	Modified residue	33	1	4-hydroxyproline By similarity
	Modified residue	36	1	4-hydroxyproline By similarity
	Modified residue	42	1	4-hydroxyproline By similarity
	Modified residue	54	1	4-hydroxyproline By similarity
	Modified residue	57	1	4-hydroxyproline By similarity
	Modified residue	63	1	4-hydroxyproline By similarity
	Modified residue	67	1	4-hydroxyproline By similarity
	Modified residue	70	1	4-hydroxyproline By similarity
	Glycosylation	207	1	N-linked (GlcNAc...) Probable
	Disulfide bond	26		Interchain Probable
	Disulfide bond	155 ↔ 246		Ref.7
	Disulfide bond	224 ↔ 238		Ref.7
Natural variations
	Natural variant	9	1	N → T in allele 1A, allele 1A(1), allele 1A(2) and allele 1A(4). Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.9 Corresponds to variant rs1059046 [ dbSNP | Ensembl ].		VAR_021293
	Natural variant	12	1	L → W. Ref.9		VAR_063518
	Natural variant	50	1	V → L. Ref.4 Ref.9		VAR_021294
	Natural variant	91	1	A → P in allele 1A. Ref.1 Ref.4 Ref.9 Corresponds to variant rs17886395 [ dbSNP | Ensembl ].		VAR_021295
	Natural variant	198	1	F → S in IPF; rare mutation; the mutant protein is retained in the endoplasmic reticulum and is not secreted. Ref.9		VAR_063519
	Natural variant	223	1	Q → K in allele 1A(1), allele 1A(3) and allele 1A(4). Ref.3 Ref.4 Ref.6 Ref.9 Corresponds to variant rs1965708 [ dbSNP | Ensembl ].		VAR_021296
	Natural variant	231	1	G → V in IPF; rare mutation; the mutant protein is retained in the endoplasmic reticulum and is not secreted. Ref.9		VAR_063520
Experimental info
	Sequence conflict	247	1	E → D in AAA60319. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8IWL1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 3949613C32CA0078	FASTA	248	26,182
	10 20 30 40 50 60 MWLCPLALNL ILMAASGAAC EVKDVCVGSP GIPGTPGSHG LPGRDGRDGV KGDPGPPGPM 70 80 90 100 110 120 GPPGETPCPP GNNGLPGAPG VPGERGEKGE AGERGPPGLP AHLDEELQAT LHDFRHQILQ 130 140 150 160 170 180 TRGALSLQGS IMTVGEKVFS SNGQSITFDA IQEACARAGG RIAVPRNPEE NEAIASFVKK 190 200 210 220 230 240 YNTYAYVGLT EGPSPGDFRY SDGTPVNYTN WYRGEPAGRG KEQCVEMYTD GQWNDRNCLY SRLTICEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of cDNA clones for the 35-kDa pulmonary surfactant-associated protein." Floros J., Steinbrink R., Jacobs K., Phelps D., Kriz R., Recny M., Sultzman L., Jones S., Taeusch H.W., Frank H.A., Fritsch E.F. J. Biol. Chem. 261:9029-9033(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ACETYLATION AT GLU-21, VARIANTS THR-9 AND PRO-91.
[2]	"Characterization of a second human pulmonary surfactant-associated protein SP-A gene." Katyal S.L., Singh G., Locker J.L. Am. J. Respir. Cell Mol. Biol. 6:446-452(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Human SP-A1 (SFTPA1) variant-specific 3' UTRs and poly(A) tail differentially affect the in vitro translation of a reporter gene." Silveyra P., Wang G., Floros J. Am. J. Physiol. 299:L523-L534(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-9 AND LYS-223.
[4]	SeattleSNPs variation discovery resource Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-9; LEU-50; PRO-91 AND LYS-223.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-9.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-9 AND LYS-223.
[7]	"Studies of the structure of lung surfactant protein SP-A." Haagsman H.P., White R.T., Schilling J., Lau K., Benson B.J., Golden J., Hawgood S., Clements J.A. Am. J. Physiol. 257:L421-L429(1989) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[8]	"Genetics of the hydrophilic surfactant proteins A and D." Floros J., Hoover R.R. Biochim. Biophys. Acta 1408:312-322(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DEFINITION OF SFTPA2 ALLELES.
[9]	"Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer." Wang Y., Kuan P.J., Xing C., Cronkhite J.T., Torres F., Rosenblatt R.L., DiMaio J.M., Kinch L.N., Grishin N.V., Garcia C.K. Am. J. Hum. Genet. 84:52-59(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-9; TRP-12; LEU-50; PRO-91 AND LYS-223, VARIANTS IPF SER-198 AND VAL-231.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	K03475 mRNA. Translation: AAA36520.1. M68519 Genomic DNA. Translation: AAA60319.1. HQ021421 mRNA. Translation: ADO27664.1. HQ021422 mRNA. Translation: ADO27665.1. HQ021423 mRNA. Translation: ADO27666.1. HQ021424 mRNA. Translation: ADO27667.1. HQ021427 mRNA. Translation: ADO27670.1. HQ021428 mRNA. Translation: ADO27671.1. HQ021429 mRNA. Translation: ADO27672.1. HQ021430 mRNA. Translation: ADO27673.1. AY206682 Genomic DNA. Translation: AAO13490.1. BX248123 Genomic DNA. Translation: CAI16061.1. BX248123 Genomic DNA. Translation: CAI16062.1. BC111571 mRNA. Translation: AAI11572.1. BC139727 mRNA. Translation: AAI39728.1. BC157866 mRNA. Translation: AAI57867.1. BC157890 mRNA. Translation: AAI57891.1.
IPI	IPI00012889. IPI00293120.
PIR	LNHUP1. B25720. I51921.
RefSeq	NP_001092138.1. NM_001098668.2.
UniGene	Hs.523084.
3D structure databases
ProteinModelPortal	Q8IWL1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000361400.
PTM databases
PhosphoSite	Q8IWL1.
Polymorphism databases
DMDM	60416439.
Proteomic databases
PaxDb	Q8IWL1.
PRIDE	Q8IWL1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372325; ENSP00000361400; ENSG00000185303. ENST00000372327; ENSP00000361402; ENSG00000185303. ENST00000417041; ENSP00000397375; ENSG00000185303.
GeneID	729238.
KEGG	hsa:729238.
UCSC	uc009xrz.3. human.
Organism-specific databases
CTD	729238.
GeneCards	GC10M081305.
HGNC	HGNC:10799. SFTPA2.
HPA	CAB002439.
MIM	178500. phenotype. 178642. gene.
neXtProt	NX_Q8IWL1.
Orphanet	2032. Idiopathic pulmonary fibrosis.
PharmGKB	PA35711.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315755.
HOVERGEN	HBG108270.
InParanoid	Q8IWL1.
KO	K10067.
OrthoDB	EOG4RFKTM.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3apathway. FOXA1 transcription factor network.
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	Q8IWL1.
Bgee	Q8IWL1.
CleanEx	HS_PSAP. HS_SFTPA2B.
Genevestigator	Q8IWL1.
GermOnline	ENSG00000122854. Homo sapiens. ENSG00000182314. Homo sapiens.
Family and domain databases
Gene3D	3.10.100.10. 1 hit.
InterPro	IPR001304. C-type_lectin. IPR016186. C-type_lectin-like. IPR018378. C-type_lectin_CS. IPR016187. C-type_lectin_fold. IPR008160. Collagen. [Graphical view]
Pfam	PF01391. Collagen. 1 hit. PF00059. Lectin_C. 1 hit. [Graphical view]
SMART	SM00034. CLECT. 1 hit. [Graphical view]
SUPFAM	SSF56436. C-type_lectin_fold. 1 hit.
PROSITE	PS00615. C_TYPE_LECTIN_1. 1 hit. PS50041. C_TYPE_LECTIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SFTPA2. human.
GenomeRNAi	729238.
NextBio	129641.
SOURCE	Search...

Entry information

Entry name

SFPA2_HUMAN

Accession

Primary (citable) accession number: Q8IWL1
Secondary accession number(s): A4QPA7 , B2RXI6, B2RXK9, C9J9I7, E3VLC6, E3VLC7, E3VLC8, E3VLC9, P07714, Q14DV3, Q5RIR8, Q5RIR9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.