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Lectin pathway of complement activation

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-166662

PubChem

R-HSA-166662

Description

Activation of the lectin pathway (LP) is initiated by Mannose-binding lectin (MBL), the hetero-complex CL-LK formed from COLEC11 (Collectin liver 1, CL-L1) and COLEC10 (Collectin kidney 1, CL-K1), and the ficolins (FCN1, FCN2, FCN3). All are Ca-dependent (C-type) lectins that initiate the complement cascade after binding to specific carbohydrate patterns on the target cell surface. All form trimers and larger oligomers (Jensen et al. 2005, Dommett et al. 2006, Garlatti et al. 2010). MBL and ficolins circulate in plasma as complexes with homodimers of MBL-associated serine proteases (MASP) (Fujita et al. 2004, Hajela et al. 2002). MASP1, MASP2 and MASP3 have all been reported to mediate complement activation. Upon binding of human lectin to the target surface, the complex of lectin:MASP undergoes conformational changes that result in MASP cleavage and activation (Matsushita M et al. 2000, Fujita et al. 2004). Active MASP2 cleaves C4 to generate C4a and C4b. C4b binds to the target cell surface via its thioester bond, then binds circulating C2 (Law and Dodds 1997). Bound C2 is cleaved by MASP2 to yield the C3 convertase C4b:C2a. The active form of MASP1 was reported to cleave C2 in a manner similar to MASP2 (Matsushita et al. 2000, Chen & Wallis 2004). MASP1 can cleave proenzyme MASP2, leading to complement activation (Heja et al. 2012). MASP1 can also cleave fibrinogen to yield fibrinopeptide B, and activates factor XIII. MASP1 may have a role in removal of 'dead C3', i.e. C3(H2O) (Hajela et al. 2002). In addition to MASP1 to 3, two alternatively-slpiced forms of MASP1 (MAp44) and MASP2 (sMAP) have been implicated in complement cascade signaling (Takahashi et al. 1999, Degn et al. 2010). The functions of MASP3, sMAP and MAp44 in the lectin pathway remain to be clarified.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 9** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O00602	Ficolin-1	FCN1 FCNM	view
O75636	Ficolin-3	FCN3 FCNH HAKA1 UNQ172 hCG_19629	view
P0DTC2	Spike glycoprotein	2 S	view
P0DTC3	ORF3a protein	3a	view
P0DTC5	Membrane protein	M	view
P11226	Mannose-binding protein C	COLEC1 MBL MBL2	view
P48740	Mannan-binding lectin serine protease 1	CRARF CRARF1 MASP1 PRSS5	view
Q15485	Ficolin-2	FCN2 FCNL	view
Q9Y6Z7	Collectin-10	CLL1 COLEC10 UNQ366/PRO702	view

Displaying **all 7** entries
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_000384	O00602	Ficolin-1	view
GL_000393	O75636	Ficolin-3	view
GL_002010	Q15485	Ficolin-2	view
GL_002337	P0DTC2	Spike glycoprotein	view
GL_002341	P11226	Mannose-binding protein C	view
GL_002404	Q9BWP8	Collectin-11	view
GL_004621	Q9Y6Z7	Collectin-10	view

Displaying **all 2** entries
GlyTouCan ID	KEGG GLYCAN	ChEBI	Pathway Viewer
G49108TO	G10624 G12573	28009	view
G57321FI	G00023	40356	view

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