P35247 (SFTPD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	375 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	Contributes to the lung's defense against inhaled microorganisms. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties.
Subunit structure	Oligomeric complex of 4 set of homotrimers.
Subcellular location	Secreted › extracellular space › extracellular matrix. Secreted › extracellular space › surface film.
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.
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 process	Gaseous exchange
Cellular component	Extracellular matrix Secreted Surface film
Coding sequence diversity	Polymorphism
Domain	Coiled coil Collagen Repeat Signal
Ligand	Calcium Lectin
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell junction assembly Traceable author statement. Source: Reactome innate immune response Traceable author statement. Source: UniProtKB lung alveolus development Inferred from mutant phenotype. Source: UniProtKB macrophage chemotaxis Traceable author statement. Source: UniProtKB negative regulation of T cell proliferation Traceable author statement. Source: UniProtKB negative regulation of interleukin-2 biosynthetic process Traceable author statement. Source: UniProtKB positive regulation of phagocytosis Traceable author statement. Source: UniProtKB reactive oxygen species metabolic process Traceable author statement. Source: UniProtKB receptor-mediated endocytosis Traceable author statement. Source: UniProtKB respiratory gaseous exchange Inferred from electronic annotation. Source: UniProtKB-KW surfactant homeostasis Inferred from mutant phenotype. Source: UniProtKB
Cellular component	collagen Inferred from electronic annotation. Source: UniProtKB-KW endocytic vesicle Traceable author statement. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Traceable author statement. Source: UniProtKB
Molecular function	bacterial cell surface binding Traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB sugar binding Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

By similarity

Chain

21 – 375

355

Pulmonary surfactant-associated protein D

PRO_0000017465

Regions

Domain

46 – 222

177

Collagen-like

Domain

260 – 375

116

C-type lectin

Coiled coil

223 – 252

30

Potential

Amino acid modifications

Modified residue

78

1

4-hydroxyproline By similarity

Modified residue

87

1

5-hydroxylysine By similarity

Modified residue

96

1

4-hydroxyproline By similarity

Modified residue

99

1

5-hydroxylysine By similarity

Modified residue

171

1

4-hydroxyproline By similarity

Modified residue

177

1

4-hydroxyproline By similarity

Glycosylation

90

1

N-linked (GlcNAc...) Potential

Disulfide bond

281 ↔ 373

Disulfide bond

351 ↔ 365

Natural variations

Natural variant

31

1

M → T. Ref.1 Ref.3 Ref.4 Ref.10
Corresponds to variant rs721917 [ dbSNP | Ensembl ].

VAR_020937

Natural variant

123

1

L → V. Ref.4 Ref.10

VAR_020938

Natural variant

180

1

T → A. Ref.1 Ref.3 Ref.4 Ref.10
Corresponds to variant rs2243639 [ dbSNP | Ensembl ].

VAR_020939

Natural variant

290

1

S → T. Ref.4 Ref.10
Corresponds to variant rs3088308 [ dbSNP | Ensembl ].

VAR_020940

Natural variant

309

1

E → K. Ref.4
Corresponds to variant rs4469829 [ dbSNP | Ensembl ].

VAR_020941

Experimental info

Sequence conflict

22

1

E → G in AAH22318. Ref.6

Sequence conflict

59

1

P → F AA sequence Ref.7

Sequence conflict

122

1

P → A in AAB59450. Ref.2

Sequence conflict

240

1

H → P AA sequence Ref.7

Sequence conflict

341

1

E → K in AAH22318. Ref.6

Sequence conflict

369

1

R → S in CAG46746. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

375

Helix Strand Turn

Details...

Helix

226 – 253

28

Turn

254 – 256

3

Beta strand

257 – 260

4

Beta strand

263 – 273

11

Helix

274 – 283

10

Beta strand

286 – 288

3

Helix

294 – 307

14

Beta strand

318 – 320

3

Helix

345 – 347

3

Beta strand

351 – 354

4

Beta strand

360 – 363

4

Beta strand

367 – 375

9

Sequences

	Sequence		Length	Mass (Da)
	P35247 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 298917699FC40F6A	FASTA	375	37,728
	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

References

	« Hide 'large scale' referencesShow '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: 1339284] [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: 8428971] [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. , 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: 15164054] [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: 15489334] [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: 8424457] [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: 1898081] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-375, PARTIAL PROTEIN SEQUENCE. Tissue: Lung.
[9]	"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: 10368295] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[10]	"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: 19100526] [Abstract] Cited for: VARIANTS THR-31; VAL-123; ALA-180 AND THR-290.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Functional Glycomics Gateway - Glycan Binding

Pulmonary surfactant protein SP-D

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.

IPI

IPI00291878.

PIR

A45225.

RefSeq

NP_003010.4. NM_003019.4.

UniGene

Hs.253495.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B08	X-ray	2.30	A/B/C	224-375	[»]
1M7L	NMR	-	A/B/C	220-257	[»]
1PW9	X-ray	1.60	A/B/C	201-375	[»]
1PWB	X-ray	1.40	A/B/C	201-375	[»]
2GGU	X-ray	1.90	A/B/C	223-375	[»]
2GGX	X-ray	1.90	A/B/C	223-375	[»]
2ORJ	X-ray	1.80	A/B/C	223-375	[»]
2ORK	X-ray	1.89	A/B/C	223-375	[»]
2OS9	X-ray	1.70	A/B/C	223-375	[»]
2RIA	X-ray	1.80	A/B/C	223-375	[»]
2RIB	X-ray	1.80	A/B/C	223-375	[»]
2RIC	X-ray	1.80	A/B/C	223-375	[»]
2RID	X-ray	1.80	A/B/C	223-375	[»]
2RIE	X-ray	1.60	A/B/C	223-375	[»]
3DBZ	X-ray	1.80	A/B/C	223-375	[»]
3G81	X-ray	1.80	A/B/C	223-375	[»]
3G83	X-ray	1.90	A/B/C	223-375	[»]
3G84	X-ray	2.30	A/B/C	223-375	[»]
3IKN	X-ray	1.60	A/B/C	201-375	[»]
3IKP	X-ray	1.75	A/B/C	201-375	[»]
3IKQ	X-ray	2.25	A/B/C	201-375	[»]
3IKR	X-ray	1.65	A/B/C	201-375	[»]

ProteinModelPortal

P35247.

SMR

P35247. Positions 41-108, 187-222, 224-375.

ModBase

Search...

Protein-protein interaction databases

STRING

P35247.

Polymorphism databases

DMDM

62903499.

Proteomic databases

PRIDE

P35247.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372292; ENSP00000361366; ENSG00000133661.

GeneID

6441.

KEGG

hsa:6441.

UCSC

uc001kbh.1. human.

Organism-specific databases

CTD

6441.

GeneCards

GC10M081687.

HGNC

HGNC:10803. SFTPD.

HPA

CAB004578.

MIM

178635. gene.

neXtProt

NX_P35247.

PharmGKB

PA35715.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15821.

GeneTree

ENSGT00550000074259.

HOVERGEN

HBG108270.

InParanoid

P35247.

OrthoDB

EOG4Q84ZB.

PhylomeDB

P35247.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.

Reactome

REACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpress

P35247.

Bgee

P35247.

CleanEx

HS_SFTPD.

Genevestigator

P35247.

GermOnline

ENSG00000133661. Homo sapiens.

Family and domain databases

InterPro

IPR001304. C-type_lectin.
IPR016186. C-type_lectin-like.
IPR018378. C-type_lectin_CS.
IPR016187. C-type_lectin_fold.
IPR008160. Collagen.
IPR023350. Lung_SPD-like_multimerisation.
IPR015097. Surfac_D-trimer.
[Graphical view]

Gene3D

G3DSA:3.10.100.10. C-type_lectin-like. 1 hit.
G3DSA:1.20.5.360. G3DSA:1.20.5.360. 1 hit.

KO

K10068.

Pfam

PF01391. Collagen. 2 hits.
PF00059. Lectin_C. 1 hit.
PF09006. Surfac_D-trimer. 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

NextBio

25031.

SOURCE

Search...

Entry information

Entry name

SFTPD_HUMAN

Accession

Primary (citable) accession number: P35247
Secondary accession number(s): Q5T0M3 , Q6FH08, Q86YK9, Q8TCD8, Q9UCJ2, Q9UCJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	January 11, 2011
Last modified:	January 25, 2012
This is version 133 of the entry and version 3 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.