O75636 (FCN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ficolin-3

Alternative name(s):
Collagen/fibrinogen domain-containing lectin 3 p35
Collagen/fibrinogen domain-containing protein 3
Hakata antigen

Gene names

Name:	FCN3
Synonyms:	FCNH, HAKA1

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	299 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	May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide and lipopolysaccharides from S.typhimurium and S.minnesota. Ref.9
Subunit structure	Homopolymer; disulfide-linked. May be an octadecamer consisting of an elementary trimer unit. Does not interact with fibronectin, elastin or zymosan. Interacts with MASP1 and MASP2. Ref.9
Subcellular location	Secreted. Note: Found in blood plasma, bronchus, alveolus and bile duct.
Tissue specificity	Liver and lung. In liver it is produced by bile duct epithelial cells and hepatocytes. In lung it is produced by both ciliated bronchial epithelial cells and type II alveolar epithelial cells. Ref.8
Post-translational modification	The N-terminus is blocked.
Involvement in disease	Defects in FCN3 are the cause of ficolin 3 deficiency (FCN3D) [MIM:613860]. FCN3D is a disorder characterized by immunodeficiency, recurrent infections, brain abscesses and recurrent warts on the fingers. Affected individuals have normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine. Ref.12
Sequence similarities	Belongs to the ficolin lectin family. Contains 1 collagen-like domain. Contains 1 fibrinogen C-terminal domain.

Ontologies

Keywords
Biological process	Complement activation lectin pathway Immunity Innate immunity
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Collagen Repeat Signal
Ligand	Lectin
PTM	Disulfide bond Glycoprotein Hydroxylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	complement activation, lectin pathway Inferred from direct assay Ref.9. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	collagen Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Inferred from electronic annotation. Source: InterPro
Molecular function	receptor binding Inferred from electronic annotation. Source: InterPro sugar binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O75636-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O75636-2)

The sequence of this isoform differs from the canonical sequence as follows:
     79-89: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.7

Chain

24 – 299

276

Ficolin-3

PRO_0000009142

Regions

Domain

48 – 80

33

Collagen-like

Domain

84 – 299

216

Fibrinogen C-terminal

Amino acid modifications

Modified residue

50

1

Hydroxyproline

Modified residue

53

1

Hydroxyproline

Modified residue

59

1

Hydroxyproline

Modified residue

65

1

Hydroxyproline

Modified residue

68

1

Hydroxyproline

Modified residue

77

1

Hydroxyproline

Glycosylation

189

1

N-linked (GlcNAc...) Ref.10 Ref.11

Natural variations

Alternative sequence

79 – 89

11

Missing in isoform 2.

VSP_001541

Experimental info

Sequence conflict

271

1

E → D in BAA32277. Ref.1

Sequence conflict

271

1

E → D in AAH20731. Ref.6

Secondary structure

1

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299

Helix Strand Turn

Details...

Helix

93 – 98

6

Beta strand

103 – 110

8

Beta strand

116 – 122

7

Helix

125 – 127

3

Beta strand

130 – 139

10

Helix

147 – 152

6

Beta strand

154 – 156

3

Helix

165 – 172

8

Beta strand

173 – 175

3

Beta strand

178 – 184

7

Beta strand

190 – 196

7

Beta strand

198 – 200

3

Helix

203 – 205

3

Beta strand

209 – 211

3

Helix

224 – 226

3

Beta strand

239 – 243

5

Helix

245 – 249

5

Beta strand

256 – 258

3

Beta strand

269 – 271

3

Turn

282 – 285

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 5CB8A7D3668FA364	FASTA	299	32,903
	10 20 30 40 50 60 MDLLWILPSL WLLLLGGPAC LKTQEHPSCP GPRELEASKV VLLPSCPGAP GSPGEKGAPG 70 80 90 100 110 120 PQGPPGPPGK MGPKGEPGDP VNLLRCQEGP RNCRELLSQG ATLSGWYHLC LPEGRALPVF 130 140 150 160 170 180 CDMDTEGGGW LVFQRRQDGS VDFFRSWSSY RAGFGNQESE FWLGNENLHQ LTLQGNWELR 190 200 210 220 230 240 VELEDFNGNR TFAHYATFRL LGEVDHYQLA LGKFSEGTAG DSLSLHSGRP FTTYDADHDS 250 260 270 280 290 SNSNCAVIVH GAWWYASCYR SNLNGRYAVS EAAAHKYGID WASGRGVGHP YRRVRMMLR
	Isoform 2 [UniParc]. Checksum: 5027676AFCA39752	FASTA	288	31,678
	10 20 30 40 50 60 MDLLWILPSL WLLLLGGPAC LKTQEHPSCP GPRELEASKV VLLPSCPGAP GSPGEKGAPG 70 80 90 100 110 120 PQGPPGPPGK MGPKGEPGPR NCRELLSQGA TLSGWYHLCL PEGRALPVFC DMDTEGGGWL 130 140 150 160 170 180 VFQRRQDGSV DFFRSWSSYR AGFGNQESEF WLGNENLHQL TLQGNWELRV ELEDFNGNRT 190 200 210 220 230 240 FAHYATFRLL GEVDHYQLAL GKFSEGTAGD SLSLHSGRPF TTYDADHDSS NSNCAVIVHG 250 260 270 280 AWWYASCYRS NLNGRYAVSE AAAHKYGIDW ASGRGVGHPY RRVRMMLR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the Hakata antigen, a member of the ficolin/opsonin p35 lectin family." Sugimoto R., Yae Y., Akaiwa M., Kitajima S., Shibata Y., Sato H., Hirata J., Okochi K., Izuhara K., Hamasaki N. J. Biol. Chem. 273:20721-20727(1998) [PubMed: 9694814] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Lung.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	SeattleSNPs variation discovery resource Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [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] (ISOFORM 2). Tissue: Lung.
[7]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-38.
[8]	"Hakata antigen, a new member of the ficolin/opsonin p35 family, is a novel human lectin secreted into bronchus/alveolus and bile." Akaiwa M., Yae Y., Sugimoto R., Suzuki S.O., Iwaki T., Izuhara K., Hamasaki N. J. Histochem. Cytochem. 47:777-786(1999) [PubMed: 10330454] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Activation of the lectin complement pathway by H-ficolin (Hakata antigen)." Matsushita M., Kuraya M., Hamasaki N., Tsujimura M., Shiraki H., Fujita T. J. Immunol. 168:3502-3506(2002) [PubMed: 11907111] [Abstract] Cited for: FUNCTION, INTERACTION WITH MASP1 AND MASP2.
[10]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, MASS SPECTROMETRY. Tissue: Plasma.
[11]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency." Munthe-Fog L., Hummelshoj T., Honore C., Madsen H.O., Permin H., Garred P. N. Engl. J. Med. 360:2637-2644(2009) [PubMed: 19535802] [Abstract] Cited for: INVOLVEMENT IN FCN3D.
[13]	"In silico designed structure of ficolin precursor." Mallena S.C., Yadugiri K. Submitted (NOV-2002) to the PDB data bank Cited for: 3D-STRUCTURE MODELING.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D88587 mRNA. Translation: BAA32277.1.
AK075140 mRNA. Translation: BAC11429.1.
CR456808 mRNA. Translation: CAG33089.1.
AY756173 Genomic DNA. Translation: AAU85296.1.
AL663123 Genomic DNA. Translation: CAI14774.1.
BC020731 mRNA. Translation: AAH20731.1.

IPI

IPI00293925.
IPI00419744.

RefSeq

NP_003656.2. NM_003665.2.
NP_775628.1. NM_173452.1.

UniGene

Hs.333383.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LA5	model	-	A	1-299	[»]
2J5Z	X-ray	1.73	A/B/C	81-299	[»]
2J60	X-ray	1.80	A/B/C	81-299	[»]
2J64	X-ray	2.20	A/B/C	89-299	[»]

ProteinModelPortal

O75636.

SMR

O75636. Positions 45-70, 86-299.

ModBase

Search...

Protein-protein interaction databases

STRING

O75636.

Proteomic databases

PeptideAtlas

O75636.

PRIDE

O75636.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000270879; ENSP00000270879; ENSG00000142748.

GeneID

8547.

KEGG

hsa:8547.

UCSC

uc001boa.1. human.

Organism-specific databases

CTD

8547.

GeneCards

GC01M027695.

H-InvDB

HIX0199981.

HGNC

HGNC:3625. FCN3.

HPA

CAB025945.

MIM

604973. gene.
613860. phenotype.

neXtProt

NX_O75636.

PharmGKB

PA28071.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14986.

GeneTree

ENSGT00560000076728.

HOGENOM

HBG715866.

HOVERGEN

HBG001644.

InParanoid

O75636.

OMA

NCAVIVH.

OrthoDB

EOG4229KB.

PhylomeDB

O75636.

Gene expression databases

ArrayExpress

O75636.

Bgee

O75636.

CleanEx

HS_FCN3.

Genevestigator

O75636.

GermOnline

ENSG00000142748. Homo sapiens.

Family and domain databases

InterPro

IPR008160. Collagen.
IPR002181. Fibrinogen_a/b/g_C.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR020837. Fibrinogen_CS.
[Graphical view]

Gene3D

G3DSA:3.90.215.10. Fibrinogen_a/b/g_C_1. 1 hit.
G3DSA:4.10.530.10. Fibrinogen_a/b/g_C_2. 1 hit.

KO

K10104.

Pfam

PF01391. Collagen. 1 hit.
PF00147. Fibrinogen_C. 1 hit.
[Graphical view]

SMART

SM00186. FBG. 1 hit.
[Graphical view]

SUPFAM

SSF56496. Fibrinogen_a/b/g_C. 1 hit.

PROSITE

PS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32022.

SOURCE

Search...

Entry information

Entry name

FCN3_HUMAN

Accession

Primary (citable) accession number: O75636
Secondary accession number(s): Q6IBJ5, Q8WW86

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	March 7, 2006
Last modified:	January 25, 2012
This is version 127 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.