Full text data of FCN3
FCN3
(FCNH, HAKA1)
[Confidence: low (only semi-automatic identification from reviews)]
Ficolin-3 (Collagen/fibrinogen domain-containing lectin 3 p35; Collagen/fibrinogen domain-containing protein 3; Hakata antigen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ficolin-3 (Collagen/fibrinogen domain-containing lectin 3 p35; Collagen/fibrinogen domain-containing protein 3; Hakata antigen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O75636
ID FCN3_HUMAN Reviewed; 299 AA.
AC O75636; Q6IBJ5; Q8WW86;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-MAR-2006, sequence version 2.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Ficolin-3;
DE AltName: Full=Collagen/fibrinogen domain-containing lectin 3 p35;
DE AltName: Full=Collagen/fibrinogen domain-containing protein 3;
DE AltName: Full=Hakata antigen;
DE Flags: Precursor;
GN Name=FCN3; Synonyms=FCNH, HAKA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Lung;
RX PubMed=9694814; DOI=10.1074/jbc.273.33.20721;
RA Sugimoto R., Yae Y., Akaiwa M., Kitajima S., Shibata Y., Sato H.,
RA Hirata J., Okochi K., Izuhara K., Hamasaki N.;
RT "Cloning and characterization of the Hakata antigen, a member of the
RT ficolin/opsonin p35 lectin family.";
RL J. Biol. Chem. 273:20721-20727(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=10330454;
RA Akaiwa M., Yae Y., Sugimoto R., Suzuki S.O., Iwaki T., Izuhara K.,
RA Hamasaki N.;
RT "Hakata antigen, a new member of the ficolin/opsonin p35 family, is a
RT novel human lectin secreted into bronchus/alveolus and bile.";
RL J. Histochem. Cytochem. 47:777-786(1999).
RN [9]
RP FUNCTION, AND INTERACTION WITH MASP1 AND MASP2.
RX PubMed=11907111;
RA Matsushita M., Kuraya M., Hamasaki N., Tsujimura M., Shiraki H.,
RA Fujita T.;
RT "Activation of the lectin complement pathway by H-ficolin (Hakata
RT antigen).";
RL J. Immunol. 168:3502-3506(2002).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP GLYCOSYLATION AT ASN-189.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [13]
RP INVOLVEMENT IN FCN3D.
RX PubMed=19535802; DOI=10.1056/NEJMoa0900381;
RA Munthe-Fog L., Hummelshoj T., Honore C., Madsen H.O., Permin H.,
RA Garred P.;
RT "Immunodeficiency associated with FCN3 mutation and ficolin-3
RT deficiency.";
RL N. Engl. J. Med. 360:2637-2644(2009).
RN [14]
RP 3D-STRUCTURE MODELING.
RA Mallena S.C., Yadugiri K.;
RT "In silico designed structure of ficolin precursor.";
RL Submitted (NOV-2002) to the PDB data bank.
CC -!- FUNCTION: May function in innate immunity through activation of
CC the lectin complement pathway. Calcium-dependent and GlcNAc-
CC binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as
CC mono/oligosaccharide and lipopolysaccharides from S.typhimurium
CC and S.minnesota.
CC -!- SUBUNIT: Homopolymer; disulfide-linked. May be an octadecamer
CC consisting of an elementary trimer unit. Does not interact with
CC fibronectin, elastin or zymosan. Interacts with MASP1 and MASP2.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Found in blood plasma,
CC bronchus, alveolus and bile duct.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75636-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75636-2; Sequence=VSP_001541;
CC -!- TISSUE SPECIFICITY: Liver and lung. In liver it is produced by
CC bile duct epithelial cells and hepatocytes. In lung it is produced
CC by both ciliated bronchial epithelial cells and type II alveolar
CC epithelial cells.
CC -!- PTM: The N-terminus is blocked.
CC -!- DISEASE: Ficolin 3 deficiency (FCN3D) [MIM:613860]: A disorder
CC characterized by immunodeficiency, recurrent infections, brain
CC abscesses and recurrent warts on the fingers. Affected individuals
CC have normal levels of lymphocytes, normal T-cell responses, and
CC normal antibodies, but a selective deficient antibody response to
CC pneumococcal polysaccharide vaccine. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ficolin lectin family.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fcn3/";
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DR EMBL; D88587; BAA32277.1; -; mRNA.
DR EMBL; AK075140; BAC11429.1; -; mRNA.
DR EMBL; CR456808; CAG33089.1; -; mRNA.
DR EMBL; AY756173; AAU85296.1; -; Genomic_DNA.
DR EMBL; FO393419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020731; AAH20731.1; -; mRNA.
DR RefSeq; NP_003656.2; NM_003665.2.
DR RefSeq; NP_775628.1; NM_173452.1.
DR UniGene; Hs.333383; -.
DR PDB; 1LA5; Model; -; A=1-299.
DR PDB; 2J5Z; X-ray; 1.73 A; A/B/C=81-299.
DR PDB; 2J60; X-ray; 1.80 A; A/B/C=81-299.
DR PDB; 2J64; X-ray; 2.20 A; A/B/C=89-299.
DR PDBsum; 1LA5; -.
DR PDBsum; 2J5Z; -.
DR PDBsum; 2J60; -.
DR PDBsum; 2J64; -.
DR ProteinModelPortal; O75636; -.
DR SMR; O75636; 86-299.
DR STRING; 9606.ENSP00000270879; -.
DR PaxDb; O75636; -.
DR PeptideAtlas; O75636; -.
DR PRIDE; O75636; -.
DR DNASU; 8547; -.
DR Ensembl; ENST00000270879; ENSP00000270879; ENSG00000142748.
DR Ensembl; ENST00000354982; ENSP00000347077; ENSG00000142748.
DR GeneID; 8547; -.
DR KEGG; hsa:8547; -.
DR UCSC; uc001boa.3; human.
DR CTD; 8547; -.
DR GeneCards; GC01M027695; -.
DR HGNC; HGNC:3625; FCN3.
DR HPA; CAB025945; -.
DR MIM; 604973; gene.
DR MIM; 613860; phenotype.
DR neXtProt; NX_O75636; -.
DR Orphanet; 331190; Immunodeficiency due to ficolin3 deficiency.
DR PharmGKB; PA28071; -.
DR eggNOG; NOG331678; -.
DR HOGENOM; HOG000037127; -.
DR HOVERGEN; HBG001644; -.
DR InParanoid; O75636; -.
DR KO; K10104; -.
DR OMA; SSYKAGF; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; O75636; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; O75636; -.
DR GeneWiki; FCN3; -.
DR GenomeRNAi; 8547; -.
DR NextBio; 32022; -.
DR PRO; PR:O75636; -.
DR ArrayExpress; O75636; -.
DR Bgee; O75636; -.
DR CleanEx; HS_FCN3; -.
DR Genevestigator; O75636; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0001867; P:complement activation, lectin pathway; IDA:UniProtKB.
DR Gene3D; 3.90.215.10; -; 1.
DR Gene3D; 4.10.530.10; -; 1.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR014715; Fibrinogen_a/b/g_C_2.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF01391; Collagen; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Collagen;
KW Complement activation lectin pathway; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydroxylation; Immunity; Innate immunity; Lectin; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1 23
FT CHAIN 24 299 Ficolin-3.
FT /FTId=PRO_0000009142.
FT DOMAIN 48 80 Collagen-like.
FT DOMAIN 84 299 Fibrinogen C-terminal.
FT MOD_RES 50 50 Hydroxyproline.
FT MOD_RES 53 53 Hydroxyproline.
FT MOD_RES 59 59 Hydroxyproline.
FT MOD_RES 65 65 Hydroxyproline.
FT MOD_RES 68 68 Hydroxyproline.
FT MOD_RES 77 77 Hydroxyproline.
FT CARBOHYD 189 189 N-linked (GlcNAc...) (complex).
FT VAR_SEQ 79 89 Missing (in isoform 2).
FT /FTId=VSP_001541.
FT CONFLICT 271 271 E -> D (in Ref. 1; BAA32277 and 6;
FT AAH20731).
FT HELIX 93 98
FT STRAND 103 110
FT STRAND 116 122
FT HELIX 125 127
FT STRAND 130 139
FT HELIX 147 152
FT STRAND 154 156
FT HELIX 165 172
FT STRAND 173 175
FT STRAND 178 184
FT STRAND 190 196
FT STRAND 198 200
FT HELIX 203 205
FT STRAND 209 211
FT STRAND 214 216
FT HELIX 224 226
FT STRAND 239 243
FT HELIX 245 249
FT STRAND 256 258
FT STRAND 269 271
FT TURN 282 285
FT STRAND 292 299
SQ SEQUENCE 299 AA; 32903 MW; 5CB8A7D3668FA364 CRC64;
MDLLWILPSL WLLLLGGPAC LKTQEHPSCP GPRELEASKV VLLPSCPGAP GSPGEKGAPG
PQGPPGPPGK MGPKGEPGDP VNLLRCQEGP RNCRELLSQG ATLSGWYHLC LPEGRALPVF
CDMDTEGGGW LVFQRRQDGS VDFFRSWSSY RAGFGNQESE FWLGNENLHQ LTLQGNWELR
VELEDFNGNR TFAHYATFRL LGEVDHYQLA LGKFSEGTAG DSLSLHSGRP FTTYDADHDS
SNSNCAVIVH GAWWYASCYR SNLNGRYAVS EAAAHKYGID WASGRGVGHP YRRVRMMLR
//
ID FCN3_HUMAN Reviewed; 299 AA.
AC O75636; Q6IBJ5; Q8WW86;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-MAR-2006, sequence version 2.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Ficolin-3;
DE AltName: Full=Collagen/fibrinogen domain-containing lectin 3 p35;
DE AltName: Full=Collagen/fibrinogen domain-containing protein 3;
DE AltName: Full=Hakata antigen;
DE Flags: Precursor;
GN Name=FCN3; Synonyms=FCNH, HAKA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Lung;
RX PubMed=9694814; DOI=10.1074/jbc.273.33.20721;
RA Sugimoto R., Yae Y., Akaiwa M., Kitajima S., Shibata Y., Sato H.,
RA Hirata J., Okochi K., Izuhara K., Hamasaki N.;
RT "Cloning and characterization of the Hakata antigen, a member of the
RT ficolin/opsonin p35 lectin family.";
RL J. Biol. Chem. 273:20721-20727(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 24-38.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=10330454;
RA Akaiwa M., Yae Y., Sugimoto R., Suzuki S.O., Iwaki T., Izuhara K.,
RA Hamasaki N.;
RT "Hakata antigen, a new member of the ficolin/opsonin p35 family, is a
RT novel human lectin secreted into bronchus/alveolus and bile.";
RL J. Histochem. Cytochem. 47:777-786(1999).
RN [9]
RP FUNCTION, AND INTERACTION WITH MASP1 AND MASP2.
RX PubMed=11907111;
RA Matsushita M., Kuraya M., Hamasaki N., Tsujimura M., Shiraki H.,
RA Fujita T.;
RT "Activation of the lectin complement pathway by H-ficolin (Hakata
RT antigen).";
RL J. Immunol. 168:3502-3506(2002).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-189, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP GLYCOSYLATION AT ASN-189.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [13]
RP INVOLVEMENT IN FCN3D.
RX PubMed=19535802; DOI=10.1056/NEJMoa0900381;
RA Munthe-Fog L., Hummelshoj T., Honore C., Madsen H.O., Permin H.,
RA Garred P.;
RT "Immunodeficiency associated with FCN3 mutation and ficolin-3
RT deficiency.";
RL N. Engl. J. Med. 360:2637-2644(2009).
RN [14]
RP 3D-STRUCTURE MODELING.
RA Mallena S.C., Yadugiri K.;
RT "In silico designed structure of ficolin precursor.";
RL Submitted (NOV-2002) to the PDB data bank.
CC -!- FUNCTION: May function in innate immunity through activation of
CC the lectin complement pathway. Calcium-dependent and GlcNAc-
CC binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as
CC mono/oligosaccharide and lipopolysaccharides from S.typhimurium
CC and S.minnesota.
CC -!- SUBUNIT: Homopolymer; disulfide-linked. May be an octadecamer
CC consisting of an elementary trimer unit. Does not interact with
CC fibronectin, elastin or zymosan. Interacts with MASP1 and MASP2.
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Found in blood plasma,
CC bronchus, alveolus and bile duct.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75636-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75636-2; Sequence=VSP_001541;
CC -!- TISSUE SPECIFICITY: Liver and lung. In liver it is produced by
CC bile duct epithelial cells and hepatocytes. In lung it is produced
CC by both ciliated bronchial epithelial cells and type II alveolar
CC epithelial cells.
CC -!- PTM: The N-terminus is blocked.
CC -!- DISEASE: Ficolin 3 deficiency (FCN3D) [MIM:613860]: A disorder
CC characterized by immunodeficiency, recurrent infections, brain
CC abscesses and recurrent warts on the fingers. Affected individuals
CC have normal levels of lymphocytes, normal T-cell responses, and
CC normal antibodies, but a selective deficient antibody response to
CC pneumococcal polysaccharide vaccine. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ficolin lectin family.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fcn3/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D88587; BAA32277.1; -; mRNA.
DR EMBL; AK075140; BAC11429.1; -; mRNA.
DR EMBL; CR456808; CAG33089.1; -; mRNA.
DR EMBL; AY756173; AAU85296.1; -; Genomic_DNA.
DR EMBL; FO393419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020731; AAH20731.1; -; mRNA.
DR RefSeq; NP_003656.2; NM_003665.2.
DR RefSeq; NP_775628.1; NM_173452.1.
DR UniGene; Hs.333383; -.
DR PDB; 1LA5; Model; -; A=1-299.
DR PDB; 2J5Z; X-ray; 1.73 A; A/B/C=81-299.
DR PDB; 2J60; X-ray; 1.80 A; A/B/C=81-299.
DR PDB; 2J64; X-ray; 2.20 A; A/B/C=89-299.
DR PDBsum; 1LA5; -.
DR PDBsum; 2J5Z; -.
DR PDBsum; 2J60; -.
DR PDBsum; 2J64; -.
DR ProteinModelPortal; O75636; -.
DR SMR; O75636; 86-299.
DR STRING; 9606.ENSP00000270879; -.
DR PaxDb; O75636; -.
DR PeptideAtlas; O75636; -.
DR PRIDE; O75636; -.
DR DNASU; 8547; -.
DR Ensembl; ENST00000270879; ENSP00000270879; ENSG00000142748.
DR Ensembl; ENST00000354982; ENSP00000347077; ENSG00000142748.
DR GeneID; 8547; -.
DR KEGG; hsa:8547; -.
DR UCSC; uc001boa.3; human.
DR CTD; 8547; -.
DR GeneCards; GC01M027695; -.
DR HGNC; HGNC:3625; FCN3.
DR HPA; CAB025945; -.
DR MIM; 604973; gene.
DR MIM; 613860; phenotype.
DR neXtProt; NX_O75636; -.
DR Orphanet; 331190; Immunodeficiency due to ficolin3 deficiency.
DR PharmGKB; PA28071; -.
DR eggNOG; NOG331678; -.
DR HOGENOM; HOG000037127; -.
DR HOVERGEN; HBG001644; -.
DR InParanoid; O75636; -.
DR KO; K10104; -.
DR OMA; SSYKAGF; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; O75636; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; O75636; -.
DR GeneWiki; FCN3; -.
DR GenomeRNAi; 8547; -.
DR NextBio; 32022; -.
DR PRO; PR:O75636; -.
DR ArrayExpress; O75636; -.
DR Bgee; O75636; -.
DR CleanEx; HS_FCN3; -.
DR Genevestigator; O75636; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0001867; P:complement activation, lectin pathway; IDA:UniProtKB.
DR Gene3D; 3.90.215.10; -; 1.
DR Gene3D; 4.10.530.10; -; 1.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR014715; Fibrinogen_a/b/g_C_2.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF01391; Collagen; 1.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Collagen;
KW Complement activation lectin pathway; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydroxylation; Immunity; Innate immunity; Lectin; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1 23
FT CHAIN 24 299 Ficolin-3.
FT /FTId=PRO_0000009142.
FT DOMAIN 48 80 Collagen-like.
FT DOMAIN 84 299 Fibrinogen C-terminal.
FT MOD_RES 50 50 Hydroxyproline.
FT MOD_RES 53 53 Hydroxyproline.
FT MOD_RES 59 59 Hydroxyproline.
FT MOD_RES 65 65 Hydroxyproline.
FT MOD_RES 68 68 Hydroxyproline.
FT MOD_RES 77 77 Hydroxyproline.
FT CARBOHYD 189 189 N-linked (GlcNAc...) (complex).
FT VAR_SEQ 79 89 Missing (in isoform 2).
FT /FTId=VSP_001541.
FT CONFLICT 271 271 E -> D (in Ref. 1; BAA32277 and 6;
FT AAH20731).
FT HELIX 93 98
FT STRAND 103 110
FT STRAND 116 122
FT HELIX 125 127
FT STRAND 130 139
FT HELIX 147 152
FT STRAND 154 156
FT HELIX 165 172
FT STRAND 173 175
FT STRAND 178 184
FT STRAND 190 196
FT STRAND 198 200
FT HELIX 203 205
FT STRAND 209 211
FT STRAND 214 216
FT HELIX 224 226
FT STRAND 239 243
FT HELIX 245 249
FT STRAND 256 258
FT STRAND 269 271
FT TURN 282 285
FT STRAND 292 299
SQ SEQUENCE 299 AA; 32903 MW; 5CB8A7D3668FA364 CRC64;
MDLLWILPSL WLLLLGGPAC LKTQEHPSCP GPRELEASKV VLLPSCPGAP GSPGEKGAPG
PQGPPGPPGK MGPKGEPGDP VNLLRCQEGP RNCRELLSQG ATLSGWYHLC LPEGRALPVF
CDMDTEGGGW LVFQRRQDGS VDFFRSWSSY RAGFGNQESE FWLGNENLHQ LTLQGNWELR
VELEDFNGNR TFAHYATFRL LGEVDHYQLA LGKFSEGTAG DSLSLHSGRP FTTYDADHDS
SNSNCAVIVH GAWWYASCYR SNLNGRYAVS EAAAHKYGID WASGRGVGHP YRRVRMMLR
//
MIM
604973
*RECORD*
*FIELD* NO
604973
*FIELD* TI
*604973 FICOLIN 3; FCN3
;;HAKATA ANTIGEN; HAKA1;;
COLLAGEN/FIBRINOGEN DOMAIN-CONTAINING LECTIN 3 P35
read more*FIELD* TX
DESCRIPTION
Ficolin-3, also known as the Hakata antigen, is a recognition molecule
in the lectin pathway of the complement system. It is the predominant
lectin-pathway recognition molecule in plasma (summary by Munthe-Fog et
al., 2009).
CLONING
Based on micropeptide sequence analysis and the use of PCR to screen a
lung cDNA library, Sugimoto et al. (1998) obtained a cDNA encoding the
Hakata antigen, which was later designated ficolin-3 (FCN3). Sequence
analysis predicted that the deduced 299-amino acid protein contains a
24-amino acid signal sequence, 1 potential N-glycosylation site, a
collagen-like domain, and a fibrinogen-like domain. The Hakata antigen
shows 48% sequence homology with the FCN1 (601252) and FCN2 (601624)
proteins. Western blot analysis demonstrated that the Hakata antigen is
expressed as a 35-kD protein that reacts with systemic lupus
erythematosus (SLE; 125270) sera. Electron microscopy showed that the
Hakata antigen resembles FCN1, having globular domains on the ends of
thin rods.
MAPPING
Gross (2013) mapped the FCN3 gene to chromosome 1p36.11 based on an
alignment of the FCN3 sequence (GenBank GENBANK AY756173) with the
genomic sequence (GRCh37).
GENE FUNCTION
Unlike FCN1 and FCN2, Hakata antigen does not bind fibronectin (FN1;
135600), elastin (ELN; 130160), or zymosan. Like FCN1, the lectin
activity of the Hakata antigen is calcium independent (Sugimoto et al.,
1998).
The Hakata antigen is a thermolabile beta-2-macroglycoprotein found in
all human serum. Antibody to this antigen is found 14 times more
frequently in the serum of patients with systemic lupus erythematosus
(SLE; 152700) than in patients with other autoimmune diseases (Inaba et
al., 1990).
MOLECULAR GENETICS
In a patient with immunodeficiency and recurrent infections associated
with complete ficolin-3 deficiency (613860), Munthe-Fog et al. (2009)
found homozygosity for a truncating variant in the FCN3 gene
(604973.0001; dbSNP rs28357092). He had normal levels of lymphocytes,
normal T-cell responses, and normal antibodies, but a selective
deficient antibody response to pneumococcal polysaccharide vaccine.
Laboratory studies showed impaired complement deposition when acetylated
bovine serum albumin was used, indicating a defect in complement
activation. The allele frequency of the variant was 0.01 among a total
of 1,282 patients with various immunodeficiencies; all were heterozygous
for the variant except the index patient. Munthe-Fog et al. (2009)
concluded that homozygosity for this variant in the FCN3 gene results in
a recessive complement deficiency syndrome.
EVOLUTION
Endo et al. (2012) noted that human FCN1 is the ortholog of mouse Fcnb.
Human FCN2 is closely related to mouse Fcna, but the genes appear to
have evolved independently in each murine and primate lineage. The human
FCN3 gene is a pseudogene in mouse.
*FIELD* AV
.0001
IMMUNODEFICIENCY DUE TO FICOLIN 3 DEFICIENCY
FCN3, 1-BP DEL, 1637C (dbSNP rs28357092)
In a man with immunodeficiency and recurrent infections since childhood,
associated with ficolin-3 deficiency (613860), Munthe-Fog et al. (2009)
identified homozygosity for a 1-bp deletion (1637delC; dbSNP rs28357092)
in exon 5 of the FCN3 gene, resulting in a frameshift and premature
termination. Other features included brain abscesses and recurrent warts
on the fingers. He had normal levels of lymphocytes, normal T-cell
responses, and normal antibodies, but a selective deficient antibody
response to pneumococcal polysaccharide vaccine. Laboratory studies
showed impaired complement deposition when acetylated bovine serum
albumin was used, indicating a defect in complement activation. The
patient was born of Macedonian and Albanian parents, each of whom was
unaffected and heterozygous for the variant. The allele frequency of the
variant was 0.01 among a total of 1,282 patients with various
immunodeficiencies; all were heterozygous for the variant except the
index patient.
*FIELD* RF
1. Endo, Y.; Takahashi, M.; Iwaki, D.; Ishida, Y.; Nakazawa, N.; Kodama,
T.; Matsuzaka, T.; Kanno, K.; Liu, Y.; Tsuchiya, K.; Kawamura, I.;
Ikawa, M.; Waguri, S.; Wada, I.; Matsushita, M.; Schwaeble, W. J.;
Fujita, T.: Mice deficient in ficolin, a lectin component pathway
recognition molecule, are susceptible to Streptococcus pneumoniae
infection. J. Immun. 189: 5860-5866, 2012.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 6/20/2013.
3. Inaba, S.; Okochi, K.; Yae, Y.; Niklasson, F.; de Verder, C.-H.
: Serological studies of an SLE-associated antigen-antibody system
discovered as a precipitation reaction in agarose gel: the Hakata
antigen-antibody system. Fukuoka Igaku Zasshi 81: 284-291, 1990.
4. Munthe-Fog, L.; Hummelshoj, T.; Honore, C.; Madsen, H. O.; Permin,
H.; Garred, P.: Immunodeficiency associated with FCN3 mutation and
ficolin-3 deficiency. New Eng. J. Med. 360: 2637-2644, 2009.
5. Sugimoto, R.; Yae, Y.; Akaiwa, M.; Kitajima, S.; Shibata, Y.; Sato,
H.; Hirata, J.; Okochi, K.; Izuhara, K.; Hamasaki, N.: Cloning and
characterization of the Hakata antigen, a member of the ficolin/opsonin
p35 lectin family. J. Biol. Chem. 273: 20721-20727, 1998.
*FIELD* CN
Matthew B. Gross - updated: 6/20/2013
Cassandra L. Kniffin - updated: 7/8/2009
*FIELD* CD
Paul J. Converse: 5/17/2000
*FIELD* ED
carol: 09/16/2013
mgross: 6/20/2013
carol: 4/4/2011
carol: 7/9/2009
ckniffin: 7/8/2009
carol: 8/4/2000
carol: 5/17/2000
*RECORD*
*FIELD* NO
604973
*FIELD* TI
*604973 FICOLIN 3; FCN3
;;HAKATA ANTIGEN; HAKA1;;
COLLAGEN/FIBRINOGEN DOMAIN-CONTAINING LECTIN 3 P35
read more*FIELD* TX
DESCRIPTION
Ficolin-3, also known as the Hakata antigen, is a recognition molecule
in the lectin pathway of the complement system. It is the predominant
lectin-pathway recognition molecule in plasma (summary by Munthe-Fog et
al., 2009).
CLONING
Based on micropeptide sequence analysis and the use of PCR to screen a
lung cDNA library, Sugimoto et al. (1998) obtained a cDNA encoding the
Hakata antigen, which was later designated ficolin-3 (FCN3). Sequence
analysis predicted that the deduced 299-amino acid protein contains a
24-amino acid signal sequence, 1 potential N-glycosylation site, a
collagen-like domain, and a fibrinogen-like domain. The Hakata antigen
shows 48% sequence homology with the FCN1 (601252) and FCN2 (601624)
proteins. Western blot analysis demonstrated that the Hakata antigen is
expressed as a 35-kD protein that reacts with systemic lupus
erythematosus (SLE; 125270) sera. Electron microscopy showed that the
Hakata antigen resembles FCN1, having globular domains on the ends of
thin rods.
MAPPING
Gross (2013) mapped the FCN3 gene to chromosome 1p36.11 based on an
alignment of the FCN3 sequence (GenBank GENBANK AY756173) with the
genomic sequence (GRCh37).
GENE FUNCTION
Unlike FCN1 and FCN2, Hakata antigen does not bind fibronectin (FN1;
135600), elastin (ELN; 130160), or zymosan. Like FCN1, the lectin
activity of the Hakata antigen is calcium independent (Sugimoto et al.,
1998).
The Hakata antigen is a thermolabile beta-2-macroglycoprotein found in
all human serum. Antibody to this antigen is found 14 times more
frequently in the serum of patients with systemic lupus erythematosus
(SLE; 152700) than in patients with other autoimmune diseases (Inaba et
al., 1990).
MOLECULAR GENETICS
In a patient with immunodeficiency and recurrent infections associated
with complete ficolin-3 deficiency (613860), Munthe-Fog et al. (2009)
found homozygosity for a truncating variant in the FCN3 gene
(604973.0001; dbSNP rs28357092). He had normal levels of lymphocytes,
normal T-cell responses, and normal antibodies, but a selective
deficient antibody response to pneumococcal polysaccharide vaccine.
Laboratory studies showed impaired complement deposition when acetylated
bovine serum albumin was used, indicating a defect in complement
activation. The allele frequency of the variant was 0.01 among a total
of 1,282 patients with various immunodeficiencies; all were heterozygous
for the variant except the index patient. Munthe-Fog et al. (2009)
concluded that homozygosity for this variant in the FCN3 gene results in
a recessive complement deficiency syndrome.
EVOLUTION
Endo et al. (2012) noted that human FCN1 is the ortholog of mouse Fcnb.
Human FCN2 is closely related to mouse Fcna, but the genes appear to
have evolved independently in each murine and primate lineage. The human
FCN3 gene is a pseudogene in mouse.
*FIELD* AV
.0001
IMMUNODEFICIENCY DUE TO FICOLIN 3 DEFICIENCY
FCN3, 1-BP DEL, 1637C (dbSNP rs28357092)
In a man with immunodeficiency and recurrent infections since childhood,
associated with ficolin-3 deficiency (613860), Munthe-Fog et al. (2009)
identified homozygosity for a 1-bp deletion (1637delC; dbSNP rs28357092)
in exon 5 of the FCN3 gene, resulting in a frameshift and premature
termination. Other features included brain abscesses and recurrent warts
on the fingers. He had normal levels of lymphocytes, normal T-cell
responses, and normal antibodies, but a selective deficient antibody
response to pneumococcal polysaccharide vaccine. Laboratory studies
showed impaired complement deposition when acetylated bovine serum
albumin was used, indicating a defect in complement activation. The
patient was born of Macedonian and Albanian parents, each of whom was
unaffected and heterozygous for the variant. The allele frequency of the
variant was 0.01 among a total of 1,282 patients with various
immunodeficiencies; all were heterozygous for the variant except the
index patient.
*FIELD* RF
1. Endo, Y.; Takahashi, M.; Iwaki, D.; Ishida, Y.; Nakazawa, N.; Kodama,
T.; Matsuzaka, T.; Kanno, K.; Liu, Y.; Tsuchiya, K.; Kawamura, I.;
Ikawa, M.; Waguri, S.; Wada, I.; Matsushita, M.; Schwaeble, W. J.;
Fujita, T.: Mice deficient in ficolin, a lectin component pathway
recognition molecule, are susceptible to Streptococcus pneumoniae
infection. J. Immun. 189: 5860-5866, 2012.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 6/20/2013.
3. Inaba, S.; Okochi, K.; Yae, Y.; Niklasson, F.; de Verder, C.-H.
: Serological studies of an SLE-associated antigen-antibody system
discovered as a precipitation reaction in agarose gel: the Hakata
antigen-antibody system. Fukuoka Igaku Zasshi 81: 284-291, 1990.
4. Munthe-Fog, L.; Hummelshoj, T.; Honore, C.; Madsen, H. O.; Permin,
H.; Garred, P.: Immunodeficiency associated with FCN3 mutation and
ficolin-3 deficiency. New Eng. J. Med. 360: 2637-2644, 2009.
5. Sugimoto, R.; Yae, Y.; Akaiwa, M.; Kitajima, S.; Shibata, Y.; Sato,
H.; Hirata, J.; Okochi, K.; Izuhara, K.; Hamasaki, N.: Cloning and
characterization of the Hakata antigen, a member of the ficolin/opsonin
p35 lectin family. J. Biol. Chem. 273: 20721-20727, 1998.
*FIELD* CN
Matthew B. Gross - updated: 6/20/2013
Cassandra L. Kniffin - updated: 7/8/2009
*FIELD* CD
Paul J. Converse: 5/17/2000
*FIELD* ED
carol: 09/16/2013
mgross: 6/20/2013
carol: 4/4/2011
carol: 7/9/2009
ckniffin: 7/8/2009
carol: 8/4/2000
carol: 5/17/2000
MIM
613860
*RECORD*
*FIELD* NO
613860
*FIELD* TI
#613860 IMMUNODEFICIENCY DUE TO FICOLIN 3 DEFICIENCY
;;FICOLIN 3 DEFICIENCY;;
FCN3 DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
immunodeficiency due to ficolin-3 deficiency can be caused by homozygous
mutation in the FCN3 gene (604973) on chromosome 1p36.
CLINICAL FEATURES
Munthe-Fog et al. (2009) reported a patient with immunodeficiency and
recurrent infections since childhood who had a complete ficolin-3
deficiency. Other features included brain abscesses and recurrent warts
on the fingers. He had normal levels of lymphocytes, normal T-cell
responses, and normal antibodies, but a selective deficient antibody
response to pneumococcal polysaccharide vaccine. Laboratory studies
showed impaired complement deposition when acetylated bovine serum
albumin was used, indicating a defect in complement activation.
MOLECULAR GENETICS
In a man with immunodeficiency and recurrent infections associated with
ficolin-3 deficiency, Munthe-Fog et al. (2009) identified homozygosity
for a 1-bp deletion (1637delC; 604973.0001) in exon 5 of the FCN3 gene.
The patient was born of Macedonian and Albanian parents, each of whom
was unaffected and heterozygous for the variant. The allele frequency of
the variant was 0.01 among a total of 1,282 patients with various
immunodeficiencies; all were heterozygous for the variant except the
index patient.
*FIELD* RF
1. Munthe-Fog, L.; Hummelshoj, T.; Honore, C.; Madsen, H. O.; Permin,
H.; Garred, P.: Immunodeficiency associated with FCN3 mutation and
ficolin-3 deficiency. New Eng. J. Med. 360: 2637-2644, 2009.
*FIELD* CD
Cassandra L. Kniffin: 4/4/2011
*FIELD* ED
carol: 11/28/2011
carol: 4/4/2011
*RECORD*
*FIELD* NO
613860
*FIELD* TI
#613860 IMMUNODEFICIENCY DUE TO FICOLIN 3 DEFICIENCY
;;FICOLIN 3 DEFICIENCY;;
FCN3 DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
immunodeficiency due to ficolin-3 deficiency can be caused by homozygous
mutation in the FCN3 gene (604973) on chromosome 1p36.
CLINICAL FEATURES
Munthe-Fog et al. (2009) reported a patient with immunodeficiency and
recurrent infections since childhood who had a complete ficolin-3
deficiency. Other features included brain abscesses and recurrent warts
on the fingers. He had normal levels of lymphocytes, normal T-cell
responses, and normal antibodies, but a selective deficient antibody
response to pneumococcal polysaccharide vaccine. Laboratory studies
showed impaired complement deposition when acetylated bovine serum
albumin was used, indicating a defect in complement activation.
MOLECULAR GENETICS
In a man with immunodeficiency and recurrent infections associated with
ficolin-3 deficiency, Munthe-Fog et al. (2009) identified homozygosity
for a 1-bp deletion (1637delC; 604973.0001) in exon 5 of the FCN3 gene.
The patient was born of Macedonian and Albanian parents, each of whom
was unaffected and heterozygous for the variant. The allele frequency of
the variant was 0.01 among a total of 1,282 patients with various
immunodeficiencies; all were heterozygous for the variant except the
index patient.
*FIELD* RF
1. Munthe-Fog, L.; Hummelshoj, T.; Honore, C.; Madsen, H. O.; Permin,
H.; Garred, P.: Immunodeficiency associated with FCN3 mutation and
ficolin-3 deficiency. New Eng. J. Med. 360: 2637-2644, 2009.
*FIELD* CD
Cassandra L. Kniffin: 4/4/2011
*FIELD* ED
carol: 11/28/2011
carol: 4/4/2011