CUB domain
IPR000859
Definition
The CUB domain (for complement C1r/C1s, Uegf, Bmp1) is a structural motif of approximately 110 residues found almost exclusively in extracellular and plasma membrane-associated proteins, many of which are developmentally regulated [[cite:PMID:8510165], [cite:PMID:2026272]]. These proteins are involved in a diverse range of functions, including complement activation, developmental patterning, tissue repair, axon guidance and angiogenesis, cell signalling, fertilisation, haemostasis, inflammation, neurotransmission, receptor-mediated endocytosis, and tumour suppression PMID:17335815. Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin). Proteins containing a CUB domain include: Mammalian complement subcomponents C1s/C1r, which form the calcium-dependent complex C1, the first component of the classical pathway of the complement system. Cricetidae sp. (Hamster) serine protease Casp, which degrades type I and IV collagen and fibronectin in the presence of calcium. Mammalian complement-activating component of Ra-reactive factor (RARF), a protease that cleaves the C4 component of complement. Vertebrate enteropeptidase ([ec:3.4.21.9]), a type II membrane protein of the intestinal brush border, which activates trypsinogen. Vertebrate bone morphogenic protein 1 (BMP-1), a protein which induces cartilage and bone formation and expresses metalloendopeptidase activity. Sea urchin blastula proteins BP10 and SpAN. Caenorhabditis elegans hypothetical proteins F42A10.8 and R151.5. Neuropilin (A5 antigen), a calcium-independent cell adhesion molecule that functions during the formation of certain neuronal circuits. Fibropellins I and III from Strongylocentrotus purpuratus (Purple sea urchin). Mammalian hyaluronate-binding protein TSG-6 (or PS4), a serum and growth factor induced protein. Mammalian spermadhesins. Xenopus laevis embryonic protein UVS.2, which is expressed during dorsoanterior development. Several of the above proteins consist of a catalytic domain together with several CUB domains interspersed by calcium-binding EGF domains. Some CUB domains appear to be involved in oligomerisation and/or recognition of substrates and binding partners. For example, in the complement proteases, the CUB domains mediate dimerisation and binding to collagen-like regions of target proteins (e.g. C1q for C1r/C1s). The structure of CUB domains consists of a β-sandwich with a jelly-roll fold. Almost all CUB domains contain four conserved cysteines that probably form two disulphide bridges (C1-C2, C3-C4). The CUB1 domains of C1s and Map19 have calcium-binding sites PMID:17446170.
51 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
Loading the interactive Seroatlas explorer...