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P35247 (SFTPD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pulmonary surfactant-associated protein D

Short name=PSP-D
Short name=SP-D
Alternative name(s):
Collectin-7
Lung surfactant protein D
Gene names
Name:SFTPD
Synonyms:COLEC7, PSPD, SFTP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length375 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Contributes to the lung's defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modulates leukocyte action in immune response. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties. Ref.9

Subunit structure

Oligomeric complex of 4 set of homotrimers.

Subcellular location

Secretedextracellular spaceextracellular matrix. Secretedextracellular spacesurface film.

Tissue specificity

Expressed in lung, brain, pancreas and adipose tissue (mainly mature adipocytes). Ref.9

Post-translational modification

The N-terminus is blocked.

Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates By similarity.

S-nitrosylation at Cys-35 and Cys-40 alters the quaternary structure which results in a pro-inflammatory chemoattractive signaling activity with macrophages By similarity.

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 SFTPD family.

Contains 1 C-type lectin domain.

Contains 1 collagen-like domain.

Ontologies

Keywords
   Biological processGaseous exchange
Immunity
Innate immunity
   Cellular componentExtracellular matrix
Secreted
Surface film
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Collagen
Repeat
Signal
   LigandCalcium
Lectin
   PTMDisulfide bond
Glycoprotein
Hydroxylation
S-nitrosylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to bacterium

Traceable author statement PubMed 9751757. Source: UniProtKB

innate immune response

Traceable author statement PubMed 10485905. Source: UniProtKB

lung alveolus development

Inferred from mutant phenotype PubMed 9751757. Source: UniProtKB

macrophage chemotaxis

Traceable author statement PubMed 10485905. Source: UniProtKB

negative regulation of T cell proliferation

Traceable author statement PubMed 10485905. Source: UniProtKB

negative regulation of interleukin-2 biosynthetic process

Traceable author statement PubMed 10485905. Source: UniProtKB

positive regulation of phagocytosis

Traceable author statement PubMed 10485905. Source: UniProtKB

reactive oxygen species metabolic process

Traceable author statement PubMed 10485905. Source: UniProtKB

receptor-mediated endocytosis

Traceable author statement PubMed 10485905. Source: UniProtKB

regulation of cytokine production

Non-traceable author statement PubMed 9751757. Source: UniProtKB

respiratory gaseous exchange

Inferred from electronic annotation. Source: UniProtKB-KW

surfactant homeostasis

Inferred from mutant phenotype PubMed 9751757. Source: UniProtKB

   Cellular_componentcollagen trimer

Inferred from electronic annotation. Source: UniProtKB-KW

endocytic vesicle

Traceable author statement PubMed 10485905. Source: UniProtKB

extracellular region

Traceable author statement PubMed 9751757. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Traceable author statement PubMed 10485905. Source: UniProtKB

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncarbohydrate binding

Traceable author statement PubMed 10485905. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12884308. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 By similarity
Chain21 – 375355Pulmonary surfactant-associated protein D
PRO_0000017465

Regions

Domain46 – 222177Collagen-like
Domain260 – 375116C-type lectin
Coiled coil223 – 25230 Potential

Amino acid modifications

Modified residue351S-nitrosocysteine By similarity
Modified residue401S-nitrosocysteine By similarity
Modified residue7814-hydroxyproline By similarity
Modified residue8715-hydroxylysine By similarity
Modified residue9614-hydroxyproline By similarity
Modified residue9915-hydroxylysine By similarity
Modified residue17114-hydroxyproline By similarity
Modified residue17714-hydroxyproline By similarity
Glycosylation901N-linked (GlcNAc...) Potential
Disulfide bond281 ↔ 373
Disulfide bond351 ↔ 365

Natural variations

Natural variant311M → T. Ref.1 Ref.3 Ref.4 Ref.11
Corresponds to variant rs721917 [ dbSNP | Ensembl ].
VAR_020937
Natural variant1231L → V. Ref.4 Ref.11
Corresponds to variant rs17878336 [ dbSNP | Ensembl ].
VAR_020938
Natural variant1801T → A. Ref.1 Ref.3 Ref.4 Ref.11
Corresponds to variant rs2243639 [ dbSNP | Ensembl ].
VAR_020939
Natural variant2901S → T. Ref.4 Ref.11
Corresponds to variant rs3088308 [ dbSNP | Ensembl ].
VAR_020940
Natural variant3091E → K. Ref.4
Corresponds to variant rs4469829 [ dbSNP | Ensembl ].
VAR_020941

Experimental info

Sequence conflict221E → G in AAH22318. Ref.6
Sequence conflict591P → F AA sequence Ref.7
Sequence conflict1221P → A in AAB59450. Ref.2
Sequence conflict2401H → P AA sequence Ref.7
Sequence conflict3411E → K in AAH22318. Ref.6
Sequence conflict3691R → S in CAG46746. Ref.3

Secondary structure

......................... 375
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P35247 [UniParc].

Last modified January 11, 2011. Version 3.
Checksum: 298917699FC40F6A

FASTA37537,728
        10         20         30         40         50         60 
MLLFLLSALV LLTQPLGYLE AEMKTYSHRT MPSACTLVMC SSVESGLPGR DGRDGREGPR 

        70         80         90        100        110        120 
GEKGDPGLPG AAGQAGMPGQ AGPVGPKGDN GSVGEPGPKG DTGPSGPPGP PGVPGPAGRE 

       130        140        150        160        170        180 
GPLGKQGNIG PQGKPGPKGE AGPKGEVGAP GMQGSAGARG LAGPKGERGV PGERGVPGNT 

       190        200        210        220        230        240 
GAAGSAGAMG PQGSPGARGP PGLKGDKGIP GDKGAKGESG LPDVASLRQQ VEALQGQVQH 

       250        260        270        280        290        300 
LQAAFSQYKK VELFPNGQSV GEKIFKTAGF VKPFTEAQLL CTQAGGQLAS PRSAAENAAL 

       310        320        330        340        350        360 
QQLVVAKNEA AFLSMTDSKT EGKFTYPTGE SLVYSNWAPG EPNDDGGSED CVEIFTNGKW 

       370 
NDRACGEKRL VVCEF 

« Hide

References

« Hide 'large scale' references
[1]"Purification, characterization and cDNA cloning of human lung surfactant protein D."
Lu J., Willis A.C., Reid K.B.M.
Biochem. J. 284:795-802(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 214-243, VARIANTS THR-31 AND ALA-180.
Tissue: Amniotic fluid and Lung.
[2]"Genomic organization of human surfactant protein D (SP-D). SP-D is encoded on chromosome 10q22.2-23.1."
Crouch E., Rust K., Veile R., Donis-Keller H., Grosso L.
J. Biol. Chem. 268:2976-2983(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-31 AND ALA-180.
[4]SeattleSNPs variation discovery resource
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-31; VAL-123; ALA-180; THR-290 AND LYS-309.
[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. expand/collapse author list , 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].
[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].
Tissue: Lung.
[7]"Accumulation of surfactant protein D in human pulmonary alveolar proteinosis."
Crouch E., Persson A., Chang D.
Am. J. Pathol. 142:241-248(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 46-72 AND 223-260.
[8]"Human surfactant protein D: SP-D contains a C-type lectin carbohydrate recognition domain."
Rust K., Grosso L., Zhang V., Chang D., Persson A., Longmore W., Cai G.-Z., Crouch E.
Arch. Biochem. Biophys. 290:116-126(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-375, PARTIAL PROTEIN SEQUENCE.
Tissue: Lung.
[9]"The lung innate immune gene surfactant protein-D is expressed in adipose tissue and linked to obesity status."
Ortega F.J., Pueyo N., Moreno-Navarrete J.M., Sabater M., Rodriguez-Hermosa J.I., Ricart W., Tinahones F.J., Fernandez-Real J.M.
Int. J. Obes. Relat. Metab. Disord. 37:1532-1538(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[10]"Crystal structure of the trimeric alpha-helical coiled-coil and the three lectin domains of human lung surfactant protein D."
Hakansson K., Lim N.K., Hoppe H.-J., Reid K.B.M.
Structure 7:255-264(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[11]"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-31; VAL-123; ALA-180 AND THR-290.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X65018 mRNA. Translation: CAA46152.1.
L05485, L05483, L05484 Genomic DNA. Translation: AAB59450.1.
CR541948 mRNA. Translation: CAG46746.1.
AY216721 Genomic DNA. Translation: AAO22991.1.
AL512662 Genomic DNA. Translation: CAI14436.1.
BC022318 mRNA. Translation: AAH22318.1.
CCDSCCDS7362.1.
PIRA45225.
RefSeqNP_003010.4. NM_003019.4.
UniGeneHs.253495.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1B08X-ray2.30A/B/C218-375[»]
1M7LNMR-A/B/C220-257[»]
1PW9X-ray1.60A/B/C199-375[»]
1PWBX-ray1.40A/B/C199-375[»]
2GGUX-ray1.90A/B/C223-375[»]
2GGXX-ray1.90A/B/C223-375[»]
2ORJX-ray1.80A/B/C223-375[»]
2ORKX-ray1.89A/B/C223-375[»]
2OS9X-ray1.70A/B/C223-375[»]
2RIAX-ray1.80A/B/C223-375[»]
2RIBX-ray1.80A/B/C223-375[»]
2RICX-ray1.80A/B/C223-375[»]
2RIDX-ray1.80A/B/C223-375[»]
2RIEX-ray1.60A/B/C223-375[»]
3DBZX-ray1.80A/B/C223-375[»]
3G81X-ray1.80A/B/C223-375[»]
3G83X-ray1.90A/B/C223-375[»]
3G84X-ray2.30A/B/C223-375[»]
3IKNX-ray1.60A/B/C199-375[»]
3IKPX-ray1.75A/B/C199-375[»]
3IKQX-ray2.25A/B/C199-375[»]
3IKRX-ray1.65A/B/C199-375[»]
4E52X-ray1.70A/B/C201-375[»]
4M17X-ray2.10A/B/C/D/E/F/G/H/I/J/K/L229-375[»]
4M18X-ray3.20A/B/C/D/E/F/G/H/I/J/K/L229-375[»]
ProteinModelPortalP35247.
SMRP35247. Positions 224-375.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112339. 3 interactions.
STRING9606.ENSP00000361366.

Chemistry

ChEMBLCHEMBL2176857.

Polymorphism databases

DMDM317373510.

Proteomic databases

PaxDbP35247.
PRIDEP35247.

Protocols and materials databases

DNASU6441.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372292; ENSP00000361366; ENSG00000133661.
GeneID6441.
KEGGhsa:6441.
UCSCuc001kbh.3. human.

Organism-specific databases

CTD6441.
GeneCardsGC10M081687.
H-InvDBHIX0008974.
HGNCHGNC:10803. SFTPD.
HPACAB004578.
HPA044582.
MIM178635. gene.
neXtProtNX_P35247.
PharmGKBPA35715.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG267163.
HOVERGENHBG108270.
InParanoidP35247.
KOK10068.
OMAEMKTYSQ.
OrthoDBEOG7HXCVB.
PhylomeDBP35247.
TreeFamTF330481.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpressP35247.
BgeeP35247.
CleanExHS_SFTPD.
GenevestigatorP35247.

Family and domain databases

Gene3D1.20.5.360. 1 hit.
3.10.100.10. 1 hit.
InterProIPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR015097. Surfac_D-trimer.
[Graphical view]
PfamPF01391. Collagen. 2 hits.
PF00059. Lectin_C. 1 hit.
PF09006. Surfac_D-trimer. 1 hit.
[Graphical view]
SMARTSM00034. CLECT. 1 hit.
[Graphical view]
SUPFAMSSF56436. SSF56436. 1 hit.
PROSITEPS00615. C_TYPE_LECTIN_1. 1 hit.
PS50041. C_TYPE_LECTIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP35247.
GeneWikiSurfactant_protein_D.
GenomeRNAi6441.
NextBio25031.
PROP35247.
SOURCESearch...

Entry information

Entry nameSFTPD_HUMAN
AccessionPrimary (citable) accession number: P35247
Secondary accession number(s): Q5T0M3 expand/collapse secondary AC list , Q6FH08, Q86YK9, Q8TCD8, Q9UCJ2, Q9UCJ3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 157 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM