ID   SFTA1_HUMAN             Reviewed;         248 AA.
AC   Q8IWL2; A8K3T8; B7ZW50; E3VLD8; E3VLD9; E3VLE0; E3VLE1; G5E9J3; P07714;
AC   Q14DV4; Q5RIR5; Q5RIR7; Q6PIT0; Q8TC19;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2005, sequence version 2.
DT   24-JAN-2024, entry version 190.
DE   RecName: Full=Pulmonary surfactant-associated protein A1;
DE            Short=PSP-A;
DE            Short=PSPA;
DE            Short=SP-A;
DE            Short=SP-A1;
DE   AltName: Full=35 kDa pulmonary surfactant-associated protein;
DE   AltName: Full=Alveolar proteinosis protein;
DE   AltName: Full=Collectin-4;
DE   Flags: Precursor;
GN   Name=SFTPA1; Synonyms=COLEC4, PSAP, SFTP1, SFTPA, SFTPA1B;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2995821; DOI=10.1038/317361a0;
RA   White R.T., Damm D., Miller J., Spratt K., Schilling J., Hawgood S.,
RA   Benson B., Cordell B.;
RT   "Isolation and characterization of the human pulmonary surfactant
RT   apoprotein gene.";
RL   Nature 317:361-363(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-19, AND ACETYLATION.
RX   PubMed=3755136; DOI=10.1016/s0021-9258(19)84483-6;
RA   Floros J., Steinbrink R., Jacobs K., Phelps D., Kriz R., Recny M.,
RA   Sultzman L., Jones S., Taeusch H.W., Frank H.A., Fritsch E.F.;
RT   "Isolation and characterization of cDNA clones for the 35-kDa pulmonary
RT   surfactant-associated protein.";
RL   J. Biol. Chem. 261:9029-9033(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ALA-19; VAL-50 AND TRP-219.
RX   PubMed=20693318; DOI=10.1152/ajplung.00113.2010;
RA   Silveyra P., Wang G., Floros J.;
RT   "Human SP-A1 (SFTPA1) variant-specific 3' UTRs and poly(A) tail
RT   differentially affect the in vitro translation of a reporter gene.";
RL   Am. J. Physiol. 299:L523-L534(2010).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-9; ALA-19; VAL-50 AND
RP   TRP-219.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   DISULFIDE BONDS, AND SUBUNIT.
RX   PubMed=2610270; DOI=10.1152/ajplung.1989.257.6.l421;
RA   Haagsman H.P., White R.T., Schilling J., Lau K., Benson B.J., Golden J.,
RA   Hawgood S., Clements J.A.;
RT   "Studies of the structure of lung surfactant protein SP-A.";
RL   Am. J. Physiol. 257:L421-L429(1989).
RN   [10]
RP   DEFINITION OF SFTPA1 ALLELES.
RX   PubMed=9813381; DOI=10.1016/s0925-4439(98)00077-5;
RA   Floros J., Hoover R.R.;
RT   "Genetics of the hydrophilic surfactant proteins A and D.";
RL   Biochim. Biophys. Acta 1408:312-322(1998).
RN   [11]
RP   INVOLVEMENT IN RDS.
RX   PubMed=10762543; DOI=10.1086/302906;
RA   Raemet M., Haataja R., Marttila R., Floros J., Hallman M.;
RT   "Association between the surfactant protein A (SP-A) gene locus and
RT   respiratory-distress syndrome in the Finnish population.";
RL   Am. J. Hum. Genet. 66:1569-1579(2000).
RN   [12]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH M.PNEUMONIAE CARDS
RP   TOXIN.
RX   PubMed=15845487; DOI=10.1128/iai.73.5.2828-2834.2005;
RA   Kannan T.R., Provenzano D., Wright J.R., Baseman J.B.;
RT   "Identification and characterization of human surfactant protein A binding
RT   protein of Mycoplasma pneumoniae.";
RL   Infect. Immun. 73:2828-2834(2005).
RN   [13]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH M.BOVIS APA.
RX   PubMed=17158455; DOI=10.1074/jbc.m610183200;
RA   Ragas A., Roussel L., Puzo G., Riviere M.;
RT   "The Mycobacterium tuberculosis cell-surface glycoprotein Apa as a
RT   potential adhesin to colonize target cells via the innate immune system
RT   pulmonary C-type lectin surfactant protein A.";
RL   J. Biol. Chem. 282:5133-5142(2007).
RN   [14]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=21203928; DOI=10.1007/s13238-010-0101-3;
RA   Carroll M.V., Sim R.B., Bigi F., Jaekel A., Antrobus R., Mitchell D.A.;
RT   "Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG.";
RL   Protein Cell 1:859-870(2010).
RN   [15]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH S.AUREUS EPA.
RX   PubMed=21123169; DOI=10.1074/jbc.m110.125567;
RA   Sever-Chroneos Z., Krupa A., Davis J., Hasan M., Yang C.H., Szeliga J.,
RA   Herrmann M., Hussain M., Geisbrecht B.V., Kobzik L., Chroneos Z.C.;
RT   "Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus
RT   involves binding of SP-A to the staphylococcal adhesin eap and the
RT   macrophage receptors SP-A receptor 210 and scavenger receptor class A.";
RL   J. Biol. Chem. 286:4854-4870(2011).
RN   [16]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH M.PNEUMONIAE CARDS
RP   TOXIN.
RX   PubMed=25139904; DOI=10.1128/mbio.01497-14;
RA   Somarajan S.R., Al-Asadi F., Ramasamy K., Pandranki L., Baseman J.B.,
RA   Kannan T.R.;
RT   "Annexin A2 mediates Mycoplasma pneumoniae community-acquired respiratory
RT   distress syndrome toxin binding to eukaryotic cells.";
RL   MBio 5:0-0(2014).
RN   [17]
RP   VARIANT TRP-219, AND ASSOCIATION WITH IDIOPATHIC PULMONARY FIBROSIS.
RX   PubMed=13680361; DOI=10.1007/s00439-003-1015-4;
RA   Selman M., Lin H.-M., Montano M., Jenkins A.L., Estrada A., Lin Z.,
RA   Wang G., DiAngelo S.L., Guo X., Umstead T.M., Lang C.M., Pardo A.,
RA   Phelps D.S., Floros J.;
RT   "Surfactant protein A and B genetic variants predispose to idiopathic
RT   pulmonary fibrosis.";
RL   Hum. Genet. 113:542-550(2003).
RN   [18]
RP   VARIANTS LEU-5; THR-9; ALA-19; VAL-50 AND TRP-219.
RX   PubMed=19100526; DOI=10.1016/j.ajhg.2008.11.010;
RA   Wang Y., Kuan P.J., Xing C., Cronkhite J.T., Torres F., Rosenblatt R.L.,
RA   DiMaio J.M., Kinch L.N., Grishin N.V., Garcia C.K.;
RT   "Genetic defects in surfactant protein A2 are associated with pulmonary
RT   fibrosis and lung cancer.";
RL   Am. J. Hum. Genet. 84:52-59(2009).
RN   [19]
RP   VARIANT ILD1 ARG-211, CHARACTERIZATION OF VARIANT ILD1 ARG-211, VARIANT
RP   TRP-219, CHARACTERIZATION OF VARIANT TRP-219, INVOLVEMENT IN ILD1, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=26792177; DOI=10.1093/hmg/ddw014;
RA   Nathan N., Giraud V., Picard C., Nunes H., Dastot-Le Moal F., Copin B.,
RA   Galeron L., De Ligniville A., Kuziner N., Reynaud-Gaubert M., Valeyre D.,
RA   Couderc L.J., Chinet T., Borie R., Crestani B., Simansour M., Nau V.,
RA   Tissier S., Duquesnoy P., Mansour-Hendili L., Legendre M.,
RA   Kannengiesser C., Coulomb-L'Hermine A., Gouya L., Amselem S., Clement A.;
RT   "Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and
RT   lung cancer.";
RL   Hum. Mol. Genet. 25:1457-1467(2016).
RN   [20]
RP   VARIANT ILD1 MET-178, AND INVOLVEMENT IN ILD1.
RX   PubMed=30854216; DOI=10.1038/s41439-019-0044-z;
RA   Doubkova M., Stano Kozubik K., Radova L., Pesova M., Trizuljak J., Pal K.,
RA   Svobodova K., Reblova K., Svozilova H., Vrzalova Z., Pospisilova S.,
RA   Doubek M.;
RT   "A novel germline mutation of the SFTPA1 gene in familial interstitial
RT   pneumonia.";
RL   Hum. Genome Var. 6:12-12(2019).
RN   [21]
RP   VARIANT ILD1 HIS-208.
RX   PubMed=31601679; DOI=10.1084/jem.20182351;
RA   Takezaki A., Tsukumo S.I., Setoguchi Y., Ledford J.G., Goto H.,
RA   Hosomichi K., Uehara H., Nishioka Y., Yasutomo K.;
RT   "A homozygous SFTPA1 mutation drives necroptosis of type II alveolar
RT   epithelial cells in patients with idiopathic pulmonary fibrosis.";
RL   J. Exp. Med. 216:2724-2735(2019).
RN   [22]
RP   VARIANTS ILD1 MET-178 AND MET-225, CHARACTERIZATION OF VARIANTS ILD1
RP   MET-178; ARG-211 AND MET-225, AND SUBCELLULAR LOCATION.
RX   PubMed=32855221; DOI=10.1183/13993003.02806-2020;
RA   Legendre M., Butt A., Borie R., Debray M.P., Bouvry D., Filhol-Blin E.,
RA   Desroziers T., Nau V., Copin B., Dastot-Le Moal F., Hery M., Duquesnoy P.,
RA   Allou N., Bergeron A., Bermudez J., Cazes A., Chene A.L., Cottin V.,
RA   Crestani B., Dalphin J.C., Dombret C., Doray B., Dupin C., Giraud V.,
RA   Gondouin A., Gouya L., Israel-Biet D., Kannengiesser C., Le Borgne A.,
RA   Leroy S., Longchampt E., Lorillon G., Nunes H., Picard C.,
RA   Reynaud-Gaubert M., Traclet J., de Vuyst P., Coulomb L'Hermine A.,
RA   Clement A., Amselem S., Nathan N.;
RT   "Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2
RT   mutations in interstitial lung diseases and lung cancer.";
RL   Eur. Respir. J. 56:0-0(2020).
CC   -!- FUNCTION: In presence of calcium ions, it binds to surfactant
CC       phospholipids and contributes to lower the surface tension at the air-
CC       liquid interface in the alveoli of the mammalian lung and is essential
CC       for normal respiration. Enhances the expression of MYO18A/SP-R210 on
CC       alveolar macrophages (By similarity). {ECO:0000250|UniProtKB:P35242}.
CC   -!- FUNCTION: (Microbial infection) Recognition of M.tuberculosis by
CC       dendritic cells may occur partially via this molecule (PubMed:17158455,
CC       PubMed:21203928). Can recognize, bind, and opsonize pathogens to
CC       enhance their elimination by alveolar macrophages (PubMed:21123169).
CC       {ECO:0000269|PubMed:17158455, ECO:0000269|PubMed:21123169,
CC       ECO:0000269|PubMed:21203928}.
CC   -!- FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, serves
CC       as one receptor for this pathogen (PubMed:15845487, PubMed:25139904).
CC       When SFTPA1 is down-regulated by siRNA, less toxin binds to human cells
CC       and less vacuolization (a symptom of M.pneumoniae infection) is seen
CC       (PubMed:25139904). {ECO:0000269|PubMed:15845487,
CC       ECO:0000269|PubMed:25139904}.
CC   -!- SUBUNIT: Oligomeric complex of 6 set of homotrimers.
CC       {ECO:0000269|PubMed:2610270}.
CC   -!- SUBUNIT: (Microbial infection) Binds M.bovis cell surface protein Apa
CC       via its glycosylated sites; probably also recognizes other bacterial
CC       moieties. {ECO:0000269|PubMed:17158455}.
CC   -!- SUBUNIT: (Microbial infection) Binds to the S.aureus extracellular
CC       adherence protein, Eap, thereby enhancing phagocytosis and killing of
CC       S.aureus by alveolar macrophages. {ECO:0000269|PubMed:21123169}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with M.pneumoniae CARDS toxin;
CC       CARDS probably uses this protein as a receptor.
CC       {ECO:0000269|PubMed:15845487, ECO:0000269|PubMed:25139904}.
CC   -!- INTERACTION:
CC       Q8IWL2; Q9UGM3: DMBT1; NbExp=2; IntAct=EBI-11316418, EBI-1044970;
CC       Q8IWL2; P75409: cards; Xeno; NbExp=2; IntAct=EBI-11316418, EBI-2259548;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26792177,
CC       ECO:0000269|PubMed:32855221}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000305}. Secreted, extracellular space,
CC       surface film {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8IWL2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IWL2-2; Sequence=VSP_046802;
CC   -!- PTM: N-acetylated. {ECO:0000269|PubMed:3755136}.
CC   -!- POLYMORPHISM: At least 5 allelic variants of SFTPA1 are known: 6A,
CC       6A(2), 6A(3), 6A(4) and 6A(5). The sequence shown is that of allele
CC       6A(3).
CC   -!- DISEASE: Interstitial lung disease 1 (ILD1) [MIM:619611]: A form of
CC       interstitial lung disease, a heterogeneous group of diseases affecting
CC       the distal part of the lung and characterized by a progressive
CC       remodeling of the alveolar interstitium. The disease spectrum ranges
CC       from idiopathic interstitial pneumonia or pneumonitis to idiopathic
CC       pulmonary fibrosis, that is associated with an increased risk of
CC       developing lung cancer. Clinical features of interstitial lung disease
CC       include dyspnea, clubbing of the fingers, and restrictive lung
CC       capacity. ILD1 inheritance can be autosomal dominant with incomplete
CC       penetrance, and autosomal recessive. {ECO:0000269|PubMed:26792177,
CC       ECO:0000269|PubMed:30854216, ECO:0000269|PubMed:31601679,
CC       ECO:0000269|PubMed:32855221}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Respiratory distress syndrome in premature infants (RDS)
CC       [MIM:267450]: A lung disease affecting usually premature newborn
CC       infants. It is characterized by deficient gas exchange, diffuse
CC       atelectasis, high-permeability lung edema and fibrin-rich alveolar
CC       deposits called 'hyaline membranes'. {ECO:0000269|PubMed:10762543}.
CC       Note=Disease susceptibility may be associated with variants affecting
CC       the gene represented in this entry. The association between SFTPA1
CC       alleles and respiratory distress syndrome in premature infants is
CC       dependent on a variation Ile to Thr at position 131 in SFTPB.
CC   -!- MISCELLANEOUS: Pulmonary surfactant consists of 90% lipid and 10%
CC       protein. There are 4 surfactant-associated proteins: 2 collagenous,
CC       carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small
CC       hydrophobic proteins (SP-B and SP-C).
CC   -!- SIMILARITY: Belongs to the SFTPA family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/sftpa1/";
CC   -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC       Note=Pulmonary surfactant protein SP-A1;
CC       URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_232";
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DR   EMBL; M30838; AAA36510.1; -; Genomic_DNA.
DR   EMBL; M13686; AAA60211.1; -; mRNA.
DR   EMBL; HQ021433; ADO27676.1; -; mRNA.
DR   EMBL; HQ021434; ADO27677.1; -; mRNA.
DR   EMBL; HQ021435; ADO27678.1; -; mRNA.
DR   EMBL; HQ021436; ADO27679.1; -; mRNA.
DR   EMBL; HQ021437; ADO27680.1; -; mRNA.
DR   EMBL; HQ021438; ADO27681.1; -; mRNA.
DR   EMBL; HQ021439; ADO27682.1; -; mRNA.
DR   EMBL; HQ021440; ADO27683.1; -; mRNA.
DR   EMBL; HQ021441; ADO27684.1; -; mRNA.
DR   EMBL; HQ021442; ADO27685.1; -; mRNA.
DR   EMBL; AK290703; BAF83392.1; -; mRNA.
DR   EMBL; AY198391; AAO13486.1; -; Genomic_DNA.
DR   EMBL; BX248123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471083; EAW54657.1; -; Genomic_DNA.
DR   EMBL; CH471083; EAW54651.1; -; Genomic_DNA.
DR   EMBL; CH471083; EAW54658.1; -; Genomic_DNA.
DR   EMBL; BC029913; AAH29913.1; -; mRNA.
DR   EMBL; BC111570; AAI11571.1; -; mRNA.
DR   EMBL; BC171875; AAI71875.1; -; mRNA.
DR   CCDS; CCDS44444.2; -. [Q8IWL2-2]
DR   CCDS; CCDS44445.1; -. [Q8IWL2-1]
DR   PIR; A24622; LNHUPS.
DR   PIR; A25720; LNHUP6.
DR   RefSeq; NP_001087239.2; NM_001093770.2. [Q8IWL2-2]
DR   RefSeq; NP_001158116.1; NM_001164644.1. [Q8IWL2-1]
DR   RefSeq; NP_001158119.1; NM_001164647.1. [Q8IWL2-1]
DR   RefSeq; NP_005402.3; NM_005411.4. [Q8IWL2-1]
DR   RefSeq; XP_005270119.1; XM_005270062.4. [Q8IWL2-1]
DR   RefSeq; XP_006718016.1; XM_006717953.2. [Q8IWL2-2]
DR   AlphaFoldDB; Q8IWL2; -.
DR   SMR; Q8IWL2; -.
DR   BioGRID; 575839; 4.
DR   IntAct; Q8IWL2; 2.
DR   STRING; 9606.ENSP00000397082; -.
DR   BindingDB; Q8IWL2; -.
DR   DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR   GlyCosmos; Q8IWL2; 1 site, No reported glycans.
DR   GlyGen; Q8IWL2; 1 site.
DR   iPTMnet; Q8IWL2; -.
DR   PhosphoSitePlus; Q8IWL2; -.
DR   BioMuta; SFTPA1; -.
DR   DMDM; 60416440; -.
DR   CPTAC; CPTAC-1214; -.
DR   MassIVE; Q8IWL2; -.
DR   PaxDb; 9606-ENSP00000397082; -.
DR   PeptideAtlas; Q8IWL2; -.
DR   ProteomicsDB; 33955; -.
DR   ProteomicsDB; 70869; -. [Q8IWL2-1]
DR   ABCD; Q8IWL2; 8 sequenced antibodies.
DR   Antibodypedia; 45521; 429 antibodies from 35 providers.
DR   DNASU; 653509; -.
DR   Ensembl; ENST00000398636.8; ENSP00000381633.3; ENSG00000122852.15. [Q8IWL2-1]
DR   Ensembl; ENST00000419470.6; ENSP00000397082.2; ENSG00000122852.15. [Q8IWL2-2]
DR   Ensembl; ENST00000428376.6; ENSP00000411102.2; ENSG00000122852.15. [Q8IWL2-1]
DR   GeneID; 653509; -.
DR   KEGG; hsa:653509; -.
DR   MANE-Select; ENST00000398636.8; ENSP00000381633.3; NM_005411.5; NP_005402.3.
DR   UCSC; uc001kap.4; human. [Q8IWL2-1]
DR   AGR; HGNC:10798; -.
DR   CTD; 653509; -.
DR   DisGeNET; 653509; -.
DR   GeneCards; SFTPA1; -.
DR   HGNC; HGNC:10798; SFTPA1.
DR   HPA; ENSG00000122852; Tissue enriched (lung).
DR   MalaCards; SFTPA1; -.
DR   MIM; 178630; gene.
DR   MIM; 267450; phenotype.
DR   MIM; 619611; phenotype.
DR   neXtProt; NX_Q8IWL2; -.
DR   OpenTargets; ENSG00000122852; -.
DR   Orphanet; 2032; Idiopathic pulmonary fibrosis.
DR   PharmGKB; PA35710; -.
DR   VEuPathDB; HostDB:ENSG00000122852; -.
DR   eggNOG; KOG4297; Eukaryota.
DR   GeneTree; ENSGT00940000156653; -.
DR   HOGENOM; CLU_049894_3_0_1; -.
DR   InParanoid; Q8IWL2; -.
DR   OMA; NDRSCLQ; -.
DR   OrthoDB; 4641030at2759; -.
DR   PhylomeDB; Q8IWL2; -.
DR   TreeFam; TF330481; -.
DR   PathwayCommons; Q8IWL2; -.
DR   Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR   Reactome; R-HSA-168179; Toll Like Receptor TLR1:TLR2 Cascade.
DR   Reactome; R-HSA-391160; Signal regulatory protein family interactions.
DR   Reactome; R-HSA-5683826; Surfactant metabolism.
DR   Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR   Reactome; R-HSA-5688849; Defective CSF2RB causes SMDP5.
DR   Reactome; R-HSA-5688890; Defective CSF2RA causes SMDP4.
DR   SignaLink; Q8IWL2; -.
DR   BioGRID-ORCS; 653509; 14 hits in 1052 CRISPR screens.
DR   GeneWiki; Pulmonary_surfactant-associated_protein_A1; -.
DR   GenomeRNAi; 653509; -.
DR   Pharos; Q8IWL2; Tbio.
DR   PRO; PR:Q8IWL2; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q8IWL2; Protein.
DR   Bgee; ENSG00000122852; Expressed in right lung and 79 other cell types or tissues.
DR   ExpressionAtlas; Q8IWL2; baseline and differential.
DR   GO; GO:0045334; C:clathrin-coated endocytic vesicle; TAS:Reactome.
DR   GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0042599; C:lamellar body; TAS:Reactome.
DR   GO; GO:0005771; C:multivesicular body; IBA:GO_Central.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR   GO; GO:0005319; F:lipid transporter activity; TAS:ProtInc.
DR   GO; GO:0008228; P:opsonization; IMP:UniProtKB.
DR   GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:UniProtKB-KW.
DR   CDD; cd03591; CLECT_collectin_like; 1.
DR   Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 1.
DR   InterPro; IPR001304; C-type_lectin-like.
DR   InterPro; IPR016186; C-type_lectin-like/link_sf.
DR   InterPro; IPR018378; C-type_lectin_CS.
DR   InterPro; IPR033990; Collectin_CTLD.
DR   InterPro; IPR016187; CTDL_fold.
DR   PANTHER; PTHR22801:SF53; 27 KDA PRIMARY MESENCHYME-SPECIFIC SPICULE PROTEIN; 1.
DR   PANTHER; PTHR22801; LITHOSTATHINE; 1.
DR   Pfam; PF00059; Lectin_C; 1.
DR   SMART; SM00034; CLECT; 1.
DR   SUPFAM; SSF56436; C-type lectin-like; 1.
DR   SUPFAM; SSF57944; Triple coiled coil domain of C-type lectins; 1.
DR   PROSITE; PS00615; C_TYPE_LECTIN_1; 1.
DR   PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
DR   Genevisible; Q8IWL2; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Calcium; Collagen; Disease variant;
KW   Disulfide bond; Extracellular matrix; Gaseous exchange; Glycoprotein;
KW   Hydroxylation; Lectin; Reference proteome; Secreted; Signal; Surface film.
FT   SIGNAL          1..20
FT   CHAIN           21..248
FT                   /note="Pulmonary surfactant-associated protein A1"
FT                   /id="PRO_0000017457"
FT   DOMAIN          28..100
FT                   /note="Collagen-like"
FT   DOMAIN          132..248
FT                   /note="C-type lectin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT   REGION          31..101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        55..76
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         30
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         33
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         36
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         42
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         54
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         57
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         63
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         67
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         70
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        207
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305"
FT   DISULFID        26
FT                   /note="Interchain"
FT                   /evidence="ECO:0000305|PubMed:2610270"
FT   DISULFID        155..246
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT                   ECO:0000269|PubMed:2610270"
FT   DISULFID        224..238
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00040,
FT                   ECO:0000269|PubMed:2610270"
FT   VAR_SEQ         1
FT                   /note="M -> MRPCQVPGAATGPRAM (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046802"
FT   VARIANT         5
FT                   /note="P -> L (in dbSNP:rs72659389)"
FT                   /evidence="ECO:0000269|PubMed:19100526"
FT                   /id="VAR_063517"
FT   VARIANT         9
FT                   /note="N -> T (in dbSNP:rs139899873)"
FT                   /evidence="ECO:0000269|PubMed:19100526, ECO:0000269|Ref.5"
FT                   /id="VAR_004184"
FT   VARIANT         19
FT                   /note="V -> A (in allele 6A and allele 6A(5);
FT                   dbSNP:rs1059047)"
FT                   /evidence="ECO:0000269|PubMed:19100526,
FT                   ECO:0000269|PubMed:20693318, ECO:0000269|PubMed:3755136,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_021292"
FT   VARIANT         50
FT                   /note="L -> V (in allele 6A(2); dbSNP:rs1136450)"
FT                   /evidence="ECO:0000269|PubMed:19100526,
FT                   ECO:0000269|PubMed:20693318, ECO:0000269|Ref.5"
FT                   /id="VAR_012231"
FT   VARIANT         178
FT                   /note="V -> M (in ILD1; impaired secretion)"
FT                   /evidence="ECO:0000269|PubMed:30854216,
FT                   ECO:0000269|PubMed:32855221"
FT                   /id="VAR_086118"
FT   VARIANT         208
FT                   /note="Y -> H (in ILD1)"
FT                   /evidence="ECO:0000269|PubMed:31601679"
FT                   /id="VAR_086119"
FT   VARIANT         211
FT                   /note="W -> R (in ILD1; impaired secretion)"
FT                   /evidence="ECO:0000269|PubMed:26792177,
FT                   ECO:0000269|PubMed:32855221"
FT                   /id="VAR_086120"
FT   VARIANT         219
FT                   /note="R -> W (probable risk factor for idiopathic
FT                   pulmonary fibrosis in smokers; allele 6A(4) and allele
FT                   6A(5); does not affect secretion; dbSNP:rs4253527)"
FT                   /evidence="ECO:0000269|PubMed:13680361,
FT                   ECO:0000269|PubMed:19100526, ECO:0000269|PubMed:20693318,
FT                   ECO:0000269|PubMed:26792177, ECO:0000269|Ref.5"
FT                   /id="VAR_012232"
FT   VARIANT         223
FT                   /note="Q -> K (in dbSNP:rs1965708)"
FT                   /id="VAR_012233"
FT   VARIANT         225
FT                   /note="V -> M (in ILD1; uncertain significance; impaired
FT                   secretion)"
FT                   /evidence="ECO:0000269|PubMed:32855221"
FT                   /id="VAR_086121"
FT   CONFLICT        45
FT                   /note="D -> H (in Ref. 1; AAA36510)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        54
FT                   /note="P -> L (in Ref. 1; AAA36510)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        100
FT                   /note="P -> R (in Ref. 1; AAA36510)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   248 AA;  26242 MW;  AFFFCF38B87BE081 CRC64;
     MWLCPLALNL ILMAASGAVC EVKDVCVGSP GIPGTPGSHG LPGRDGRDGL KGDPGPPGPM
     GPPGEMPCPP GNDGLPGAPG IPGECGEKGE PGERGPPGLP AHLDEELQAT LHDFRHQILQ
     TRGALSLQGS IMTVGEKVFS SNGQSITFDA IQEACARAGG RIAVPRNPEE NEAIASFVKK
     YNTYAYVGLT EGPSPGDFRY SDGTPVNYTN WYRGEPAGRG KEQCVEMYTD GQWNDRNCLY
     SRLTICEF
//