Recent molecule_pages items

H-Ficolin

Fri, 31 Jan 2014 00:00:00 +0000

H-ficolin is a serum lectin synthesized (as a ~34 kDa polypeptide) predominantly by the liver and lung tissues and is one of the soluble pattern recognition receptors of the innate immune system. It is structurally similar to L- and M- ficolins, but is different in its tissue expression and binding affinities to pathogenic ligands. Ficolins have an amino (N)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a fibrinogen-like domain in the carboxy (C)-terminus. Three identical polypeptides form a structural (triple helical) subunit, with the help of the collagen-like domain. Further oligomerization of this subunit results in different sized H-ficolin molecules in circulation. The polypeptides in the structural subunit are cross-linked by disulphide bonds in the N-terminal region and the fibrinogen-like...

Complement C2

Fri, 31 Jan 2014 00:00:00 +0000

Complement C2 is a single chain serum glycoprotein (110 kDa), which serves as the catalytic subunit of C3 and C5 convertases in the classical and lectin pathways. During complement activation, C2 is cleaved by classical (C1s) or lectin (MBL-associated serine protease-2; MASP-2) proteases into two fragments: C2b and C2a. C2a, a serine protease, in complex with C4b fragment of complement factor C4, generates the C3 (C4b2a) or C5 (C4b2a3b) convertase. C3 convertase is very short-lived and cleaves complement C3 into C3a and C3b fragments (selective cleavage of Arg-|-Ser bond in C3 alpha-chain). C3 convertase requires the presence of magnesium and decays over time at physiologic...

MASP-3

Fri, 31 Jan 2014 00:00:00 +0000

MASP-3 (mannose/mannan binding lectin (MBL) associated serine protease-3) is ~82 kDa protein generated through alternative splicing of the MASP1 gene. This gene also generates MASP-1 and MAp44 proteins. MASP-3 is bound to multimeric forms of pathogen receptors, such as MBL and the three ficolins. MASP-3 has two CUB, a calcium-binding EGF-like, a trypsin-like serine protease and two complement control protein (CCP) domains. The serine protease domain however, is not known to be active and does not act on substrates of either MASP-1 or MASP-2. Instead, it competes with MASP-1 and MASP-2 to bind to MBL and therefore plays a regulatory role in the lectin pathway of complement...

Integrin beta-2

Fri, 31 Jan 2014 00:00:00 +0000

Integrins are heterodimeric transmembrane (TM) glycoproteins containing one each of α and β subunit, which are held together by non-covalent forces. Integrin β2 (CD18) is the β subunit for four heterodimers: αDβ2, αXβ2, αMβ2 and αLβ2. Integrin β2 family plays an essential role in leukocyte recruitment and activation during inflammation. Structurally, while most part of the αβ dimer is extracellular, both the subunits traverse the plasma membrane and terminate as short cytoplasmic domains. Each heterodimeric integrin exists on the cell surface mainly in an inactive (bent) form until they receive stimulating signals from other receptors (via inside-out signaling), and the end result of integrin activation is a shift in integrin conformation from a bent to an extended one. The binding of cytoplasmic proteins to α- and/or β-subunit carboxy-terminal tails is an essential part of the activation process, as these interactions stabilize the extended integrin conformation and...

MASP-2

Fri, 31 Jan 2014 00:00:00 +0000

MASP-2 (mannose/mannan binding lectin (MBL) associated serine protease-2) is a serum protein predominantly synthesized by the liver as a ~75kDa protein and is one of the key molecules of the innate immune system. It is mainly bound to multimeric protein complexes, such as MBL, the three ficolins (M-ficolin, L-ficolin and H-ficolin) and collectin kidney 1 (CL-K1, alias CL-11). These complexes serve as pathogen receptors, which are further bound to MASP-1, a serine protease. Binding of these complexes to their appropriate...

MASP-1

Fri, 31 Jan 2014 00:00:00 +0000

MASP-1 (mannose/mannan binding lectin associated serine protease-1) is a serum protein (~79kDa poylpeptide) predominantly synthesized by the liver. It is an important player in the innate immune system and is mainly bound to multimeric pathogen recognition receptors such as mannose/mannan-binding lectin (MBL) and the three ficolins (M-ficolin, L-ficolin and H-ficolin). MASP-1 has two CUB, a calcium-binding EGF-like, a trypsin-like serine protease and two complement control protein (CCP) domains. The serine protease domain is auto-activated upon binding of these receptors to their appropriate pathogenic ligands, generally carbohydrate domains or acetylated sugar residues. MASP-1...

MAp44

Fri, 31 Jan 2014 00:00:00 +0000

MAp44 is a ~44 kDa alternate splice product of MASP1 and is mainly expressed in the heart. Mannose/mannan binding lectin (MBL) associated serine proteases, MASP-1 and MASP-3 are other products of MASP1. Similar to MASP-1 (isoform 1 of MASP1, which represents the longest transcript), MAp44 has a C1r/C1s/Uegf/bmp1 (CUB) domain, calcium-binding EGF-like domain and complement control protein (CCP) domains. However, it lacks the serine protease domain of MASP-1 and therefore cannot perform MASP-1's functions. MAp44 binds to multimeric pathogen receptors such asMBL and the three ficolins, and is believed to play a regulatory role in the lectin pathway of complement activation.

A peer reviewed journal with structured data

Mon, 17 Jun 2013 00:00:00 +0000

The Molecule Pages from UCSD Signaling Gateway have been regularly published online since one decade and are now printed biannually. As a researcher involved in biomathematical and biomechanical modeling and simulation, I found these pages very informative, either when dealing with biological processes happening at the nano- and microscopic scales, or incorporating these events in a meso- and macroscopic scale modeling to enhance reductionist models when necessary. UCSD Molecule Pages indeed yield information that enables interdisciplinary research and I have cited the Molecule Pages over 130 times in my recent book ‘Intracellular Signaling Mediators in the Circulatory and Ventilatory Systems’ (Springer New York, 2013).

p38 beta MAP kinase

Mon, 10 Jun 2013 00:00:00 +0000

In mammals, there are four p38 protein kinases: p38α, p38β, p38γ and p38δ. p38β was identified in 1996 as a closely related protein kinase of p38α, sharing 74% sequence identity and the Thr-Gly-Tyr dual phosphorylation motif characteristic of all p38 MAPKs. p38β is widely distributed in cells and tissues, but less so than p38α; p38β is particularly abundant in endothelial cells. p38β is activated in vivo by dual phosphorylation at Thr180 and Tyr182 by the MAP2K, MKK3 and MKK6 in response to a multitude of stimuli including environmental stressors, cytokines and growth factors. p38β can be dephosphorylated on both its Thr and Tyr residues by Dual-Specificity Phosphatases. p38β, like p38α, is targeted by a class of pyridinyl imidazole drugs that do not target the other two p38 MAPKs. These compounds were invaluable in discovering functions regulated by p38α and p38β. However, they do not permit to distinguish functions mediated by p38β from those regulated by p38α. This...

L-Ficolin

Mon, 10 Jun 2013 00:00:00 +0000

L-ficolin is a serum lectin synthesized (as a ~37 kDa polypeptide) predominantly by the liver, and is one of the key molecules of the innate immune system. It has an amino (N)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a fibrinogen-like domain in the carboxy (C)-terminus. Three identical polypeptides form a structural (triple helical) subunit, with the help of the collagen-like domain. Further oligomerization of this subunit results in different sized L-ficolin molecules (from dimers to tetramers) in circulation. However, the tetrameric form (composed of 12 polypeptides) is the most prevalent structure. The polypeptides in the structural subunit are cross-linked by disulphide bonds in the N-terminal region. The fibrinogen-like domain forms a globular structure. The overall structure of oligomeric L-ficolin closely resembles mannose-binding lectin (MBL). Similar to MBL, L-ficolin also acts as a pattern recognition receptor. It primarily...

Mannose/mannan-binding lectin

Mon, 10 Jun 2013 00:00:00 +0000

Mannose/mannan-binding lectin (MBL) is a serum lectin synthesized (as a ~32 kDa peptide) by the liver and is one of the key molecules of the innate immune system. Each peptide has an N (amino)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a carbohydrate recognition domain (CRD) in the C (carboxy)-terminus. Three identical peptides form a structural subunit, similar to a collagenous triple helix, which is the basic building block of all circulating molecular forms of MBL. Further oligomerization of these structural subunits by disulphide bonds in the N-terminal region results in MBL molecules of different sizes (from dimers to hexamers), but the hexameric form is probably the most common. MBL-associated serine proteases (MASPs) bind to MBL multimeric forms to stabilize the molecule. MBL is a pattern-recognition receptor and the CRDs of MBL serve to bind to a wide range of pathogens such as bacteria, viruses and protozoa, by recognizing carbohydrate...

Tsh receptor

Mon, 10 Jun 2013 00:00:00 +0000

The TSH receptor is a member of the G protein-coupled receptor(GPCR)family. It is one of the glycoprotein hormone receptors, which also includes the FSH and LH/CG receptors. The TSH receptor mediates the action of the pituitary-derived glycoprotein, TSH (thyroid stimulating hormone, thyrotropin or thyrotrophin). TSH binds to the TSH receptor which is located on thyroid follicular cells (but is also expressed in extrathyroidal sites). Glycosylation of the TSH receptor occurs, as does cleavage of the receptor from an intact to an extracellular form (α subunit), which may be shed after deletion of a short region (aa 316-366) near the C terminal of the extracellular domain, thus leaving a transmembrane form (β subunit). The α subunit is responsible for ligand/autoantibody binding, facilitated by glycosylation and possibly by the extracellular loops of the 7 transmembrane segments. The intracellular loops of the β subunit interact with G proteins when the receptor is activated....

Leukocyte surface antigen CD47

Mon, 10 Jun 2013 00:00:00 +0000

CD47, also known as integrin-associated protein (IAP), ovarian cancer antigen OA3, Rh-related antigen and MER6, is a widely expressed transmembrane receptor belonging to the immunoglobulin superfamily. CD47 is the counter-receptor for two members of the signal-regulatory protein (SHPS/SIRP) family and a high-affinity receptor for the secreted protein thrombospondin-1. Interactions with SIRP receptors play roles in self recognition and regulation of innate immune responses. Over-expression of CD47 on some cancers is a negative prognostic factor and protects against innate immune surveillance. Engagement of CD47 on vascular cells by thrombospondin-1 regulates calcium, cAMP, and nitric oxide/cGMP signaling pathways that control blood pressure, tissue perfusion, and angiogenesis. Moreover, CD47 signaling in various cell types regulates pathways that can trigger cell death, limit stem cell self-renewal, regulate mitochondrial homeostasis and other differentiation pathways, and activate...

Cdc7l1