Q8IWL2 (SFTA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pulmonary surfactant-associated protein A1
Short name=PSP-A
Short name=PSPA
Short name=SP-A
Short name=SP-A1

Alternative name(s):
35 kDa pulmonary surfactant-associated protein
Alveolar proteinosis protein
Collectin-4

Gene names

Name:	SFTPA1
Synonyms:	COLEC4, PSAP, SFTP1, SFTPA, SFTPA1B

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 5 allelic variants of SFTPA1 are known: 6A, 6A2, 6A3, 6A4 and 6A5. The sequence shown is that of allele 6A3.
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: Disease susceptibility is associated with variations affecting the gene represented in this entry. Respiratory distress syndrome in premature infants (RDS) [MIM:267450]: A lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called 'hyaline membranes'. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. The association between SFTPA1 alleles and respiratory distress syndrome in premature infants is dependent on a variation Ile to Thr at position 131 in SFTPB. Ref.11
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.
Sequence caution	The sequence CAI16065.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Gaseous exchange
Cellular component	Extracellular matrix Secreted Surface film
Coding sequence diversity	Polymorphism
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 lipid transporter activity Traceable author statement Ref.1. Source: ProtInc
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 A1		PRO_0000017457
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.2
	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.9
	Disulfide bond	224 ↔ 238		Ref.9
Natural variations
	Natural variant	5	1	P → L. Ref.13		VAR_063517
	Natural variant	9	1	N → T. Ref.5 Ref.13 Corresponds to variant rs1059046 [ dbSNP | Ensembl ].		VAR_004184
	Natural variant	19	1	V → A in allele 6A and allele 6A(5). Ref.2 Ref.3 Ref.5 Ref.13 Corresponds to variant rs1059047 [ dbSNP | Ensembl ].		VAR_021292
	Natural variant	50	1	L → V in allele 6A(2). Ref.3 Ref.5 Ref.13 Corresponds to variant rs1136450 [ dbSNP | Ensembl ].		VAR_012231
	Natural variant	219	1	R → W Associated with susceptibility to idiopathic pulmonary fibrosis in smokers; allele 6A(4) and allele 6A(5). Ref.3 Ref.5 Ref.12 Ref.13 Corresponds to variant rs4253527 [ dbSNP | Ensembl ].		VAR_012232
	Natural variant	223	1	Q → K. Corresponds to variant rs1965708 [ dbSNP | Ensembl ].		VAR_012233
Experimental info
	Sequence conflict	45	1	D → H in AAA36510. Ref.1
	Sequence conflict	54	1	P → L in AAA36510. Ref.1
	Sequence conflict	100	1	P → R in AAA36510. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8IWL2 [UniParc]. Last modified March 1, 2005. Version 2. Checksum: AFFFCF38B87BE081	FASTA	248	26,242
	10 20 30 40 50 60 MWLCPLALNL ILMAASGAVC EVKDVCVGSP GIPGTPGSHG LPGRDGRDGL KGDPGPPGPM 70 80 90 100 110 120 GPPGEMPCPP GNDGLPGAPG IPGECGEKGE PGERGPPGLP 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 the human pulmonary surfactant apoprotein gene." White R.T., Damm D., Miller J., Spratt K., Schilling J., Hawgood S., Benson B., Cordell B. Nature 317:361-363(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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], VARIANT ALA-19, ACETYLATION AT GLU-21.
[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 ALA-19; VAL-50 AND TRP-219.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	SeattleSNPs variation discovery resource Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-9; ALA-19; VAL-50 AND TRP-219.
[6]	"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].
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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].
[9]	"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.
[10]	"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 SFTPA1 ALLELES.
[11]	"Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population." Raemet M., Haataja R., Marttila R., Floros J., Hallman M. Am. J. Hum. Genet. 66:1569-1579(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RDS.
[12]	"Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis." Selman M., Lin H.-M., Montano M., Jenkins A.L., Estrada A., Lin Z., Wang G., DiAngelo S.L., Guo X., Umstead T.M., Lang C.M., Pardo A., Phelps D.S., Floros J. Hum. Genet. 113:542-550(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-219, ASSOCIATION WITH IDIOPATHIC PULMONARY FIBROSIS.
[13]	"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 LEU-5; THR-9; ALA-19; VAL-50 AND TRP-219.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Functional Glycomics Gateway - Glycan Binding

Pulmonary surfactant protein SP-A1

Cross-references

Sequence databases
EMBL GenBank DDBJ	M30838 Genomic DNA. Translation: AAA36510.1. M13686 mRNA. Translation: AAA60211.1. HQ021433 mRNA. Translation: ADO27676.1. HQ021434 mRNA. Translation: ADO27677.1. HQ021435 mRNA. Translation: ADO27678.1. HQ021436 mRNA. Translation: ADO27679.1. HQ021437 mRNA. Translation: ADO27680.1. HQ021438 mRNA. Translation: ADO27681.1. HQ021439 mRNA. Translation: ADO27682.1. HQ021440 mRNA. Translation: ADO27683.1. HQ021441 mRNA. Translation: ADO27684.1. HQ021442 mRNA. Translation: ADO27685.1. AK290703 mRNA. Translation: BAF83392.1. AY198391 Genomic DNA. Translation: AAO13486.1. BX248123 Genomic DNA. Translation: CAI16065.1. Sequence problems. BX248123 Genomic DNA. Translation: CAI16066.1. BX248123 Genomic DNA. Translation: CAI16067.1. CH471083 Genomic DNA. Translation: EAW54651.1. CH471083 Genomic DNA. Translation: EAW54658.1. BC029913 mRNA. Translation: AAH29913.1. BC111570 mRNA. Translation: AAI11571.1. BC171875 mRNA. Translation: AAI71875.1.
IPI	IPI00012889. IPI00941049.
PIR	LNHUPS. A24622. LNHUP6. A25720.
RefSeq	NP_001087239.2. NM_001093770.2. NP_001158116.1. NM_001164644.1. NP_001158119.1. NM_001164647.1. NP_005402.3. NM_005411.4.
UniGene	Hs.535295. Hs.725773.
3D structure databases
ProteinModelPortal	Q8IWL2.
ModBase	Search...
PTM databases
PhosphoSite	Q8IWL2.
Polymorphism databases
DMDM	60416440.
Proteomic databases
PaxDb	Q8IWL2.
PRIDE	Q8IWL2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000394569; ENSP00000378070; ENSG00000122852. ENST00000398636; ENSP00000381633; ENSG00000122852. ENST00000428376; ENSP00000411102; ENSG00000122852. ENST00000429958; ENSP00000395527; ENSG00000122852. ENST00000439264; ENSP00000401649; ENSG00000122852.
GeneID	653509.
KEGG	hsa:653509.
UCSC	uc001kap.3. human.
Organism-specific databases
CTD	653509.
GeneCards	GC10P081372.
HGNC	HGNC:10798. SFTPA1.
HPA	CAB016793.
MIM	178500. phenotype. 178630. gene. 267450. phenotype.
neXtProt	NX_Q8IWL2.
Orphanet	2032. Idiopathic pulmonary fibrosis.
PharmGKB	PA35710.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315755.
HOVERGEN	HBG108270.
InParanoid	Q8IWL2.
KO	K10067.
PhylomeDB	Q8IWL2.
Enzyme and pathway databases
Pathway_Interaction_DB	hnf3apathway. FOXA1 transcription factor network.
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	Q8IWL2.
Bgee	Q8IWL2.
CleanEx	HS_PSAP. HS_SFTPA1B.
Genevestigator	Q8IWL2.
GermOnline	ENSG00000122852. Homo sapiens. ENSG00000185303. 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
GenomeRNAi	653509.
NextBio	123347.
SOURCE	Search...

Entry information

Entry name

SFTA1_HUMAN

Accession

Primary (citable) accession number: Q8IWL2
Secondary accession number(s): A8K3T8 , B7ZW50, E3VLD8, E3VLD9, E3VLE0, E3VLE1, P07714, Q14DV4, Q5RIR5, Q5RIR7, Q6PIT0, Q8TC19

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	March 1, 2005
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 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.