Full text data of FCN1
FCN1
(FCNM)
[Confidence: low (only semi-automatic identification from reviews)]
Ficolin-1 (Collagen/fibrinogen domain-containing protein 1; Ficolin-A; Ficolin-alpha; M-ficolin; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ficolin-1 (Collagen/fibrinogen domain-containing protein 1; Ficolin-A; Ficolin-alpha; M-ficolin; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O00602
ID FCN1_HUMAN Reviewed; 326 AA.
AC O00602; Q5VYV5; Q92596;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Ficolin-1;
DE AltName: Full=Collagen/fibrinogen domain-containing protein 1;
DE AltName: Full=Ficolin-A;
DE AltName: Full=Ficolin-alpha;
DE AltName: Full=M-ficolin;
DE Flags: Precursor;
GN Name=FCN1; Synonyms=FCNM;
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].
RC TISSUE=Uterus;
RX PubMed=8573080;
RA Lu J., Tay P.N., Kon O.L., Reid K.B.;
RT "Human ficolin: cDNA cloning, demonstration of peripheral blood
RT leucocytes as the major site of synthesis and assignment of the gene
RT to chromosome 9.";
RL Biochem. J. 313:473-478(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-326.
RC TISSUE=Uterus;
RX PubMed=8947836;
RA Harumiya S., Takeda K., Sugiura T., Fukumoto Y., Tachikawa H.,
RA Miyazono K., Fujimoto D., Ichijo H.;
RT "Characterization of ficolins as novel elastin-binding proteins and
RT molecular cloning of human ficolin-1.";
RL J. Biochem. 120:745-751(1996).
RN [7]
RP PROTEIN SEQUENCE OF 30-44.
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, AND SUBCELLULAR LOCATION.
RX PubMed=20400674; DOI=10.1189/jlb.1209802;
RA Honore C., Rorvig S., Hummelshoj T., Skjoedt M.O., Borregaard N.,
RA Garred P.;
RT "Tethering of Ficolin-1 to cell surfaces through recognition of sialic
RT acid by the fibrinogen-like domain.";
RL J. Leukoc. Biol. 88:145-158(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 115-326, SUBUNIT, DISULFIDE
RP BONDS, CALCIUM-BINDING SITES, AND PH-DEPENDENCY.
RX PubMed=17148457; DOI=10.1074/jbc.M608627200;
RA Tanio M., Kondo S., Sugio S., Kohno T.;
RT "Trivalent recognition unit of innate immunity system: crystal
RT structure of trimeric human M-ficolin fibrinogen-like domain.";
RL J. Biol. Chem. 282:3889-3895(2007).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 109-326 IN COMPLEX WITH
RP CARBOHYDRATE, DISULFIDE BONDS, CALCIUM-BINDING SITES, AND
RP PH-DEPENDENCY.
RX PubMed=17897951; DOI=10.1074/jbc.M705741200;
RA Garlatti V., Martin L., Gout E., Reiser J.B., Fujita T., Arlaud G.J.,
RA Thielens N.M., Gaboriaud C.;
RT "Structural basis for innate immune sensing by M-ficolin and its
RT control by a pH-dependent conformational switch.";
RL J. Biol. Chem. 282:35814-35820(2007).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.21 ANGSTROMS) OF 110-326, DISULFIDE BONDS,
RP FUNCTION, SUBUNIT, SUBSTRATE SPECIFICITY, CALCIUM-BINDING SITES, AND
RP MUTAGENESIS OF GLY-250; ALA-285 AND TYR-300.
RX PubMed=20032467; DOI=10.1074/jbc.M109.065854;
RA Gout E., Garlatti V., Smith D.F., Lacroix M., Dumestre-Perard C.,
RA Lunardi T., Martin L., Cesbron J.Y., Arlaud G.J., Gaboriaud C.,
RA Thielens N.M.;
RT "Carbohydrate recognition properties of human ficolins: glycan array
RT screening reveals the sialic acid binding specificity of M-ficolin.";
RL J. Biol. Chem. 285:6612-6622(2010).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-175.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Complement-activating lectin and pattern recognition
CC receptor. Binds GlcNAc. Binds preferentially to 9-O-acetylated 2-
CC 6-linked sialic acid derivatives and to various glycans containing
CC sialic acid engaged in a 2-3 linkage.
CC -!- SUBUNIT: Homotrimer. Interacts with elastin.
CC -!- INTERACTION:
CC Q2TS39:CRP-1 (xeno); NbExp=3; IntAct=EBI-5282479, EBI-7468648;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Found on the monocyte and
CC granulocyte surface.
CC -!- TISSUE SPECIFICITY: Peripheral blood leukocytes, monocytes and
CC granulocytes. Also detected in spleen, lung, and thymus, may be
CC due to the presence of tissue macrophages or trapped blood in
CC these tissues. Not detected on lymphocytes.
CC -!- DOMAIN: The Fibrinogen C-terminal domain mediates calcium-
CC dependent binding to carbohydrates and tethering to the cell
CC surface in monocytes and granulocytes. The domain undergoes a
CC conformational switch at pH under 6.2, and looses its
CC carbohydrate-binding ability.
CC -!- SIMILARITY: Belongs to the ficolin lectin family.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA12120.1; Type=Erroneous initiation;
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DR EMBL; S80990; AAB50706.1; -; mRNA.
DR EMBL; AK314867; BAG37382.1; -; mRNA.
DR EMBL; AL353611; CAH73911.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88137.1; -; Genomic_DNA.
DR EMBL; BC020635; AAH20635.1; -; mRNA.
DR EMBL; D83920; BAA12120.1; ALT_INIT; mRNA.
DR PIR; S61517; S61517.
DR RefSeq; NP_001994.2; NM_002003.3.
DR UniGene; Hs.440898; -.
DR PDB; 2D39; X-ray; 1.90 A; A/B/C=115-326.
DR PDB; 2JHH; X-ray; 1.70 A; C/F=109-326.
DR PDB; 2JHI; X-ray; 1.80 A; F=109-326.
DR PDB; 2JHK; X-ray; 1.75 A; F=109-326.
DR PDB; 2JHL; X-ray; 1.75 A; F=109-326.
DR PDB; 2JHM; X-ray; 1.52 A; F=109-326.
DR PDB; 2WNP; X-ray; 1.21 A; F=110-326.
DR PDBsum; 2D39; -.
DR PDBsum; 2JHH; -.
DR PDBsum; 2JHI; -.
DR PDBsum; 2JHK; -.
DR PDBsum; 2JHL; -.
DR PDBsum; 2JHM; -.
DR PDBsum; 2WNP; -.
DR ProteinModelPortal; O00602; -.
DR SMR; O00602; 48-73, 82-107, 110-326.
DR IntAct; O00602; 1.
DR MINT; MINT-5223276; -.
DR STRING; 9606.ENSP00000360871; -.
DR PaxDb; O00602; -.
DR PeptideAtlas; O00602; -.
DR PRIDE; O00602; -.
DR DNASU; 2219; -.
DR Ensembl; ENST00000371806; ENSP00000360871; ENSG00000085265.
DR GeneID; 2219; -.
DR KEGG; hsa:2219; -.
DR UCSC; uc004cfi.3; human.
DR CTD; 2219; -.
DR GeneCards; GC09M137801; -.
DR HGNC; HGNC:3623; FCN1.
DR HPA; CAB016760; -.
DR HPA; HPA000685; -.
DR HPA; HPA001295; -.
DR MIM; 601252; gene.
DR neXtProt; NX_O00602; -.
DR PharmGKB; PA28069; -.
DR eggNOG; NOG249945; -.
DR HOGENOM; HOG000037127; -.
DR HOVERGEN; HBG001644; -.
DR KO; K10104; -.
DR OMA; NFFSTKD; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; O00602; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; O00602; -.
DR GeneWiki; FCN1; -.
DR GenomeRNAi; 2219; -.
DR NextBio; 9001; -.
DR PRO; PR:O00602; -.
DR ArrayExpress; O00602; -.
DR Bgee; O00602; -.
DR CleanEx; HS_FCN1; -.
DR Genevestigator; O00602; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0003823; F:antigen binding; TAS:ProtInc.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0001867; P:complement activation, lectin pathway; TAS:Reactome.
DR GO; GO:0008228; P:opsonization; TAS:ProtInc.
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; Calcium; Collagen; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Innate immunity; Lectin; Metal-binding; Polymorphism;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 29
FT CHAIN 30 326 Ficolin-1.
FT /FTId=PRO_0000009136.
FT DOMAIN 55 93 Collagen-like.
FT DOMAIN 109 326 Fibrinogen C-terminal.
FT REGION 115 154 A domain; contributes to trimerization.
FT REGION 155 243 B domain; contributes to trimerization.
FT REGION 282 284 Carbohydrate-binding.
FT REGION 317 326 P domain.
FT METAL 262 262 Calcium.
FT METAL 264 264 Calcium.
FT METAL 266 266 Calcium; via carbonyl oxygen.
FT METAL 268 268 Calcium; via carbonyl oxygen.
FT SITE 300 300 Mediates specificity for sialic acids.
FT SITE 312 312 Mediates specificity for sialic acids.
FT CARBOHYD 305 305 N-linked (GlcNAc...) (Potential).
FT DISULFID 111 139
FT DISULFID 118 146
FT DISULFID 270 283
FT VARIANT 93 93 R -> Q (in dbSNP:rs56345770).
FT /FTId=VAR_061172.
FT VARIANT 126 126 Y -> H (in dbSNP:rs17549179).
FT /FTId=VAR_024450.
FT VARIANT 175 175 Y -> C (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036341.
FT MUTAGEN 250 250 G->F: Inhibits binding to the 9-O-
FT acetylated sialic acid derivatives.
FT MUTAGEN 285 285 A->V: Inhibits binding to the 9-O-
FT acetylated sialic acid derivatives.
FT MUTAGEN 300 300 Y->F: Abolishes interaction with all
FT sialic acid-containing glycans.
FT CONFLICT 133 133 T -> N (in Ref. 1; AAB50706).
FT CONFLICT 287 287 N -> S (in Ref. 1; AAB50706).
FT TURN 111 113
FT HELIX 118 123
FT STRAND 130 135
FT STRAND 141 147
FT HELIX 150 152
FT STRAND 155 164
FT HELIX 172 177
FT STRAND 179 181
FT HELIX 190 198
FT STRAND 202 209
FT STRAND 215 221
FT STRAND 223 225
FT HELIX 228 230
FT STRAND 234 236
FT STRAND 239 241
FT HELIX 249 251
FT STRAND 264 268
FT HELIX 270 273
FT STRAND 281 283
FT STRAND 285 287
FT STRAND 298 301
FT STRAND 303 306
FT TURN 307 309
FT STRAND 312 315
FT STRAND 317 325
SQ SEQUENCE 326 AA; 35078 MW; 184D24B371B251AB CRC64;
MELSGATMAR GLAVLLVLFL HIKNLPAQAA DTCPEVKVVG LEGSDKLTIL RGCPGLPGAP
GPKGEAGVIG ERGERGLPGA PGKAGPVGPK GDRGEKGMRG EKGDAGQSQS CATGPRNCKD
LLDRGYFLSG WHTIYLPDCR PLTVLCDMDT DGGGWTVFQR RMDGSVDFYR DWAAYKQGFG
SQLGEFWLGN DNIHALTAQG SSELRVDLVD FEGNHQFAKY KSFKVADEAE KYKLVLGAFV
GGSAGNSLTG HNNNFFSTKD QDNDVSSSNC AEKFQGAWWY ADCHASNLNG LYLMGPHESY
ANGINWSAAK GYKYSYKVSE MKVRPA
//
ID FCN1_HUMAN Reviewed; 326 AA.
AC O00602; Q5VYV5; Q92596;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Ficolin-1;
DE AltName: Full=Collagen/fibrinogen domain-containing protein 1;
DE AltName: Full=Ficolin-A;
DE AltName: Full=Ficolin-alpha;
DE AltName: Full=M-ficolin;
DE Flags: Precursor;
GN Name=FCN1; Synonyms=FCNM;
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].
RC TISSUE=Uterus;
RX PubMed=8573080;
RA Lu J., Tay P.N., Kon O.L., Reid K.B.;
RT "Human ficolin: cDNA cloning, demonstration of peripheral blood
RT leucocytes as the major site of synthesis and assignment of the gene
RT to chromosome 9.";
RL Biochem. J. 313:473-478(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-326.
RC TISSUE=Uterus;
RX PubMed=8947836;
RA Harumiya S., Takeda K., Sugiura T., Fukumoto Y., Tachikawa H.,
RA Miyazono K., Fujimoto D., Ichijo H.;
RT "Characterization of ficolins as novel elastin-binding proteins and
RT molecular cloning of human ficolin-1.";
RL J. Biochem. 120:745-751(1996).
RN [7]
RP PROTEIN SEQUENCE OF 30-44.
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, AND SUBCELLULAR LOCATION.
RX PubMed=20400674; DOI=10.1189/jlb.1209802;
RA Honore C., Rorvig S., Hummelshoj T., Skjoedt M.O., Borregaard N.,
RA Garred P.;
RT "Tethering of Ficolin-1 to cell surfaces through recognition of sialic
RT acid by the fibrinogen-like domain.";
RL J. Leukoc. Biol. 88:145-158(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 115-326, SUBUNIT, DISULFIDE
RP BONDS, CALCIUM-BINDING SITES, AND PH-DEPENDENCY.
RX PubMed=17148457; DOI=10.1074/jbc.M608627200;
RA Tanio M., Kondo S., Sugio S., Kohno T.;
RT "Trivalent recognition unit of innate immunity system: crystal
RT structure of trimeric human M-ficolin fibrinogen-like domain.";
RL J. Biol. Chem. 282:3889-3895(2007).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 109-326 IN COMPLEX WITH
RP CARBOHYDRATE, DISULFIDE BONDS, CALCIUM-BINDING SITES, AND
RP PH-DEPENDENCY.
RX PubMed=17897951; DOI=10.1074/jbc.M705741200;
RA Garlatti V., Martin L., Gout E., Reiser J.B., Fujita T., Arlaud G.J.,
RA Thielens N.M., Gaboriaud C.;
RT "Structural basis for innate immune sensing by M-ficolin and its
RT control by a pH-dependent conformational switch.";
RL J. Biol. Chem. 282:35814-35820(2007).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.21 ANGSTROMS) OF 110-326, DISULFIDE BONDS,
RP FUNCTION, SUBUNIT, SUBSTRATE SPECIFICITY, CALCIUM-BINDING SITES, AND
RP MUTAGENESIS OF GLY-250; ALA-285 AND TYR-300.
RX PubMed=20032467; DOI=10.1074/jbc.M109.065854;
RA Gout E., Garlatti V., Smith D.F., Lacroix M., Dumestre-Perard C.,
RA Lunardi T., Martin L., Cesbron J.Y., Arlaud G.J., Gaboriaud C.,
RA Thielens N.M.;
RT "Carbohydrate recognition properties of human ficolins: glycan array
RT screening reveals the sialic acid binding specificity of M-ficolin.";
RL J. Biol. Chem. 285:6612-6622(2010).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] CYS-175.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Complement-activating lectin and pattern recognition
CC receptor. Binds GlcNAc. Binds preferentially to 9-O-acetylated 2-
CC 6-linked sialic acid derivatives and to various glycans containing
CC sialic acid engaged in a 2-3 linkage.
CC -!- SUBUNIT: Homotrimer. Interacts with elastin.
CC -!- INTERACTION:
CC Q2TS39:CRP-1 (xeno); NbExp=3; IntAct=EBI-5282479, EBI-7468648;
CC -!- SUBCELLULAR LOCATION: Secreted. Note=Found on the monocyte and
CC granulocyte surface.
CC -!- TISSUE SPECIFICITY: Peripheral blood leukocytes, monocytes and
CC granulocytes. Also detected in spleen, lung, and thymus, may be
CC due to the presence of tissue macrophages or trapped blood in
CC these tissues. Not detected on lymphocytes.
CC -!- DOMAIN: The Fibrinogen C-terminal domain mediates calcium-
CC dependent binding to carbohydrates and tethering to the cell
CC surface in monocytes and granulocytes. The domain undergoes a
CC conformational switch at pH under 6.2, and looses its
CC carbohydrate-binding ability.
CC -!- SIMILARITY: Belongs to the ficolin lectin family.
CC -!- SIMILARITY: Contains 1 collagen-like domain.
CC -!- SIMILARITY: Contains 1 fibrinogen C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA12120.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; S80990; AAB50706.1; -; mRNA.
DR EMBL; AK314867; BAG37382.1; -; mRNA.
DR EMBL; AL353611; CAH73911.1; -; Genomic_DNA.
DR EMBL; CH471090; EAW88137.1; -; Genomic_DNA.
DR EMBL; BC020635; AAH20635.1; -; mRNA.
DR EMBL; D83920; BAA12120.1; ALT_INIT; mRNA.
DR PIR; S61517; S61517.
DR RefSeq; NP_001994.2; NM_002003.3.
DR UniGene; Hs.440898; -.
DR PDB; 2D39; X-ray; 1.90 A; A/B/C=115-326.
DR PDB; 2JHH; X-ray; 1.70 A; C/F=109-326.
DR PDB; 2JHI; X-ray; 1.80 A; F=109-326.
DR PDB; 2JHK; X-ray; 1.75 A; F=109-326.
DR PDB; 2JHL; X-ray; 1.75 A; F=109-326.
DR PDB; 2JHM; X-ray; 1.52 A; F=109-326.
DR PDB; 2WNP; X-ray; 1.21 A; F=110-326.
DR PDBsum; 2D39; -.
DR PDBsum; 2JHH; -.
DR PDBsum; 2JHI; -.
DR PDBsum; 2JHK; -.
DR PDBsum; 2JHL; -.
DR PDBsum; 2JHM; -.
DR PDBsum; 2WNP; -.
DR ProteinModelPortal; O00602; -.
DR SMR; O00602; 48-73, 82-107, 110-326.
DR IntAct; O00602; 1.
DR MINT; MINT-5223276; -.
DR STRING; 9606.ENSP00000360871; -.
DR PaxDb; O00602; -.
DR PeptideAtlas; O00602; -.
DR PRIDE; O00602; -.
DR DNASU; 2219; -.
DR Ensembl; ENST00000371806; ENSP00000360871; ENSG00000085265.
DR GeneID; 2219; -.
DR KEGG; hsa:2219; -.
DR UCSC; uc004cfi.3; human.
DR CTD; 2219; -.
DR GeneCards; GC09M137801; -.
DR HGNC; HGNC:3623; FCN1.
DR HPA; CAB016760; -.
DR HPA; HPA000685; -.
DR HPA; HPA001295; -.
DR MIM; 601252; gene.
DR neXtProt; NX_O00602; -.
DR PharmGKB; PA28069; -.
DR eggNOG; NOG249945; -.
DR HOGENOM; HOG000037127; -.
DR HOVERGEN; HBG001644; -.
DR KO; K10104; -.
DR OMA; NFFSTKD; -.
DR OrthoDB; EOG7X9G60; -.
DR PhylomeDB; O00602; -.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; O00602; -.
DR GeneWiki; FCN1; -.
DR GenomeRNAi; 2219; -.
DR NextBio; 9001; -.
DR PRO; PR:O00602; -.
DR ArrayExpress; O00602; -.
DR Bgee; O00602; -.
DR CleanEx; HS_FCN1; -.
DR Genevestigator; O00602; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0003823; F:antigen binding; TAS:ProtInc.
DR GO; GO:0005509; F:calcium ion binding; TAS:ProtInc.
DR GO; GO:0030246; F:carbohydrate binding; TAS:ProtInc.
DR GO; GO:0001867; P:complement activation, lectin pathway; TAS:Reactome.
DR GO; GO:0008228; P:opsonization; TAS:ProtInc.
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; Calcium; Collagen; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Innate immunity; Lectin; Metal-binding; Polymorphism;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1 29
FT CHAIN 30 326 Ficolin-1.
FT /FTId=PRO_0000009136.
FT DOMAIN 55 93 Collagen-like.
FT DOMAIN 109 326 Fibrinogen C-terminal.
FT REGION 115 154 A domain; contributes to trimerization.
FT REGION 155 243 B domain; contributes to trimerization.
FT REGION 282 284 Carbohydrate-binding.
FT REGION 317 326 P domain.
FT METAL 262 262 Calcium.
FT METAL 264 264 Calcium.
FT METAL 266 266 Calcium; via carbonyl oxygen.
FT METAL 268 268 Calcium; via carbonyl oxygen.
FT SITE 300 300 Mediates specificity for sialic acids.
FT SITE 312 312 Mediates specificity for sialic acids.
FT CARBOHYD 305 305 N-linked (GlcNAc...) (Potential).
FT DISULFID 111 139
FT DISULFID 118 146
FT DISULFID 270 283
FT VARIANT 93 93 R -> Q (in dbSNP:rs56345770).
FT /FTId=VAR_061172.
FT VARIANT 126 126 Y -> H (in dbSNP:rs17549179).
FT /FTId=VAR_024450.
FT VARIANT 175 175 Y -> C (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036341.
FT MUTAGEN 250 250 G->F: Inhibits binding to the 9-O-
FT acetylated sialic acid derivatives.
FT MUTAGEN 285 285 A->V: Inhibits binding to the 9-O-
FT acetylated sialic acid derivatives.
FT MUTAGEN 300 300 Y->F: Abolishes interaction with all
FT sialic acid-containing glycans.
FT CONFLICT 133 133 T -> N (in Ref. 1; AAB50706).
FT CONFLICT 287 287 N -> S (in Ref. 1; AAB50706).
FT TURN 111 113
FT HELIX 118 123
FT STRAND 130 135
FT STRAND 141 147
FT HELIX 150 152
FT STRAND 155 164
FT HELIX 172 177
FT STRAND 179 181
FT HELIX 190 198
FT STRAND 202 209
FT STRAND 215 221
FT STRAND 223 225
FT HELIX 228 230
FT STRAND 234 236
FT STRAND 239 241
FT HELIX 249 251
FT STRAND 264 268
FT HELIX 270 273
FT STRAND 281 283
FT STRAND 285 287
FT STRAND 298 301
FT STRAND 303 306
FT TURN 307 309
FT STRAND 312 315
FT STRAND 317 325
SQ SEQUENCE 326 AA; 35078 MW; 184D24B371B251AB CRC64;
MELSGATMAR GLAVLLVLFL HIKNLPAQAA DTCPEVKVVG LEGSDKLTIL RGCPGLPGAP
GPKGEAGVIG ERGERGLPGA PGKAGPVGPK GDRGEKGMRG EKGDAGQSQS CATGPRNCKD
LLDRGYFLSG WHTIYLPDCR PLTVLCDMDT DGGGWTVFQR RMDGSVDFYR DWAAYKQGFG
SQLGEFWLGN DNIHALTAQG SSELRVDLVD FEGNHQFAKY KSFKVADEAE KYKLVLGAFV
GGSAGNSLTG HNNNFFSTKD QDNDVSSSNC AEKFQGAWWY ADCHASNLNG LYLMGPHESY
ANGINWSAAK GYKYSYKVSE MKVRPA
//
MIM
601252
*RECORD*
*FIELD* NO
601252
*FIELD* TI
*601252 FICOLIN 1; FCN1
;;COLLAGEN/FIBRINOGEN DOMAIN-CONTAINING LECTIN 1 P35-LIKE;;
read moreFICOLIN B, MOUSE, HOMOLOG OF; FCNB
*FIELD* TX
DESCRIPTION
Ficolin-1 (FCN1) is a recognition molecule in the lectin pathway. The
ficolins bind surface structures of various classes of microorganisms
and of various acetylated compounds and are involved in sequestration
and removal of dying host cells. FCN1, FCN2 (601624), and FCN3 (604973)
have homologous sequences and share certain structural elements,
including an N-terminal domain that contains cysteine residues, a
collagen-like domain with typical Gly-Xaa-Yaa repeats, and a
fibrinogen-like domain. The collagen-like stalk domains interact with
cellular receptors (summary by Munthe-Fog et al., 2009).
CLONING
Ichijo et al. (1991) and Ichijo et al. (1993) cloned cDNA for a putative
receptor for transforming growth factor beta-1 (190180) from the
membrane fraction of pig uterus. Two highly homologous sequences, named
ficolin-alpha and ficolin-beta by them, were shown to contain
collagen-like sequences and to have a similar overall domain
organization to that of C1q (120550).
To clone the cDNA for human ficolin, Lu et al. (1996) synthesized 2
degenerate oligonucleotide primers. The cDNA-derived amino acid sequence
of human ficolin showed approximately 75% identity with, and a similar
domain organization to, the 2 pig ficolin sequences, which are
characterized by the presence of a leader peptide, a short N-terminal
segment followed by a collagen-like region, and a C-terminal
fibrinogen-like domain. Gly-Xaa-Yaa repeating sequences are
characteristic of collagen triple helices but they are also found in a
number of other proteins, such as the complement protein C1q and the
group of C-type lectins known as collectins (see, e.g., 154545). Lu et
al. (1996) showed that blood leukocytes are probably the major site of
human ficolin-1 synthesis. Much weaker signals of the same mRNA size
were detected in spleen, lung, and thymus and may be due to the presence
of tissue macrophages or trapped blood in these tissues.
MAPPING
By analysis of somatic cell hybrids, Lu et al. (1996) mapped the
ficolin-1 gene to chromosome 9.
Endo et al. (1996) isolated a gene they called the P35-related gene,
which had identical exon sequences to ficolin as reported by Lu et al.
(1996). The P35-related gene and another gene, a lectin they called P35
(FCN2; 601624) that was previously reported by Matsushita et al. (1996),
were mapped to chromosome 9q34 by fluorescence in situ hybridization.
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.
ANIMAL MODEL
Endo et al. (2012) noted that ficolins and mannose-binding lectin (MBL,
or MBL2; 154545) are complexed with MBL-associated serine proteases
(MASPs; see 600521). MBL is important in both autoimmune and infectious
diseases. Endo et al. (2012) found that Fcna -/- mice and Fcna -/- Fcnb
-/- mice lacked complement activation in sera due to the absence of
complexes of Fcna and MASPs. Transnasal challenge of mice with a
Streptococcus pneumoniae strain recognized by ficolins, but not by Mbl,
resulted in reduced mouse survival and higher bacterial loads in Fcna
-/-, Fcnb -/-, and Fcna -/- Fcnb -/- mice. Reconstitution of the
Fcna-mediated lectin pathway with an Fcna-encoding plasmid prior to
infection improved survival of Fcna -/- mice, but not Fcna -/- Fcnb -/-
mice, indicating that both Fcna and Fcnb are essential in defense
against S. pneumoniae. Endo et al. (2012) proposed that ficolins have a
crucial role in defense against pneumococcal infection through the
lectin complement pathway.
*FIELD* RF
1. Endo, Y.; Sato, Y.; Matsushita, M.; Fujita, T.: Cloning and characterization
of the human lectin P35 gene and its related gene. Genomics 36:
515-521, 1996.
2. 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.
3. Ichijo, H.; Hellman, U.; Wernstedt, C.; Gonez, L. J.; Claesson-Welsh,
L.; Heldin, C.-H.; Miyazono, K.: Molecular cloning and characterization
of ficolin, a multimeric protein with fibrinogen- and collagen-like
domains. J. Biol. Chem. 268: 14505-14513, 1993.
4. Ichijo, H.; Ronnstrand, L.; Miyagawa, K.; Ohashi, H.; Heldin, C.-H.;
Miyazono, K.: Purification of transforming growth factor-beta 1 binding
proteins from porcine uterus membranes. J. Biol. Chem. 266: 22459-22464,
1991.
5. Lu, J.; Tay, P. N.; Kon, O. L.; Reid, K. B. M.: Human ficolin:
cDNA cloning, demonstration of peripheral blood leucocytes as the
major site of synthesis and assignment of the gene to chromosome 9. Biochem.
J. 313: 473-478, 1996.
6. Matsushita, M.; Endo, Y.; Taira, S.; Sato, Y.; Fujita, T.; Ichikawa,
N.; Nakata, M.; Mizuochi, T.: A novel human serum lectin with collagen-
and fibrinogen-like domains that functions as an opsonin. J. Biol.
Chem. 271: 2448-2454, 1996.
7. 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* CN
Matthew B. Gross - updated: 06/20/2013
Paul J. Converse - updated: 6/20/2013
Moyra Smith - updated: 1/11/1997
*FIELD* CD
Victor A. McKusick: 5/9/1996
*FIELD* ED
mgross: 06/20/2013
mgross: 6/20/2013
carol: 7/18/2011
jamie: 1/15/1997
mark: 1/11/1997
jamie: 1/8/1997
mark: 8/11/1996
mark: 5/9/1996
*RECORD*
*FIELD* NO
601252
*FIELD* TI
*601252 FICOLIN 1; FCN1
;;COLLAGEN/FIBRINOGEN DOMAIN-CONTAINING LECTIN 1 P35-LIKE;;
read moreFICOLIN B, MOUSE, HOMOLOG OF; FCNB
*FIELD* TX
DESCRIPTION
Ficolin-1 (FCN1) is a recognition molecule in the lectin pathway. The
ficolins bind surface structures of various classes of microorganisms
and of various acetylated compounds and are involved in sequestration
and removal of dying host cells. FCN1, FCN2 (601624), and FCN3 (604973)
have homologous sequences and share certain structural elements,
including an N-terminal domain that contains cysteine residues, a
collagen-like domain with typical Gly-Xaa-Yaa repeats, and a
fibrinogen-like domain. The collagen-like stalk domains interact with
cellular receptors (summary by Munthe-Fog et al., 2009).
CLONING
Ichijo et al. (1991) and Ichijo et al. (1993) cloned cDNA for a putative
receptor for transforming growth factor beta-1 (190180) from the
membrane fraction of pig uterus. Two highly homologous sequences, named
ficolin-alpha and ficolin-beta by them, were shown to contain
collagen-like sequences and to have a similar overall domain
organization to that of C1q (120550).
To clone the cDNA for human ficolin, Lu et al. (1996) synthesized 2
degenerate oligonucleotide primers. The cDNA-derived amino acid sequence
of human ficolin showed approximately 75% identity with, and a similar
domain organization to, the 2 pig ficolin sequences, which are
characterized by the presence of a leader peptide, a short N-terminal
segment followed by a collagen-like region, and a C-terminal
fibrinogen-like domain. Gly-Xaa-Yaa repeating sequences are
characteristic of collagen triple helices but they are also found in a
number of other proteins, such as the complement protein C1q and the
group of C-type lectins known as collectins (see, e.g., 154545). Lu et
al. (1996) showed that blood leukocytes are probably the major site of
human ficolin-1 synthesis. Much weaker signals of the same mRNA size
were detected in spleen, lung, and thymus and may be due to the presence
of tissue macrophages or trapped blood in these tissues.
MAPPING
By analysis of somatic cell hybrids, Lu et al. (1996) mapped the
ficolin-1 gene to chromosome 9.
Endo et al. (1996) isolated a gene they called the P35-related gene,
which had identical exon sequences to ficolin as reported by Lu et al.
(1996). The P35-related gene and another gene, a lectin they called P35
(FCN2; 601624) that was previously reported by Matsushita et al. (1996),
were mapped to chromosome 9q34 by fluorescence in situ hybridization.
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.
ANIMAL MODEL
Endo et al. (2012) noted that ficolins and mannose-binding lectin (MBL,
or MBL2; 154545) are complexed with MBL-associated serine proteases
(MASPs; see 600521). MBL is important in both autoimmune and infectious
diseases. Endo et al. (2012) found that Fcna -/- mice and Fcna -/- Fcnb
-/- mice lacked complement activation in sera due to the absence of
complexes of Fcna and MASPs. Transnasal challenge of mice with a
Streptococcus pneumoniae strain recognized by ficolins, but not by Mbl,
resulted in reduced mouse survival and higher bacterial loads in Fcna
-/-, Fcnb -/-, and Fcna -/- Fcnb -/- mice. Reconstitution of the
Fcna-mediated lectin pathway with an Fcna-encoding plasmid prior to
infection improved survival of Fcna -/- mice, but not Fcna -/- Fcnb -/-
mice, indicating that both Fcna and Fcnb are essential in defense
against S. pneumoniae. Endo et al. (2012) proposed that ficolins have a
crucial role in defense against pneumococcal infection through the
lectin complement pathway.
*FIELD* RF
1. Endo, Y.; Sato, Y.; Matsushita, M.; Fujita, T.: Cloning and characterization
of the human lectin P35 gene and its related gene. Genomics 36:
515-521, 1996.
2. 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.
3. Ichijo, H.; Hellman, U.; Wernstedt, C.; Gonez, L. J.; Claesson-Welsh,
L.; Heldin, C.-H.; Miyazono, K.: Molecular cloning and characterization
of ficolin, a multimeric protein with fibrinogen- and collagen-like
domains. J. Biol. Chem. 268: 14505-14513, 1993.
4. Ichijo, H.; Ronnstrand, L.; Miyagawa, K.; Ohashi, H.; Heldin, C.-H.;
Miyazono, K.: Purification of transforming growth factor-beta 1 binding
proteins from porcine uterus membranes. J. Biol. Chem. 266: 22459-22464,
1991.
5. Lu, J.; Tay, P. N.; Kon, O. L.; Reid, K. B. M.: Human ficolin:
cDNA cloning, demonstration of peripheral blood leucocytes as the
major site of synthesis and assignment of the gene to chromosome 9. Biochem.
J. 313: 473-478, 1996.
6. Matsushita, M.; Endo, Y.; Taira, S.; Sato, Y.; Fujita, T.; Ichikawa,
N.; Nakata, M.; Mizuochi, T.: A novel human serum lectin with collagen-
and fibrinogen-like domains that functions as an opsonin. J. Biol.
Chem. 271: 2448-2454, 1996.
7. 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* CN
Matthew B. Gross - updated: 06/20/2013
Paul J. Converse - updated: 6/20/2013
Moyra Smith - updated: 1/11/1997
*FIELD* CD
Victor A. McKusick: 5/9/1996
*FIELD* ED
mgross: 06/20/2013
mgross: 6/20/2013
carol: 7/18/2011
jamie: 1/15/1997
mark: 1/11/1997
jamie: 1/8/1997
mark: 8/11/1996
mark: 5/9/1996