Pathways & interactions
Spermadhesin, CUB domain superfamily (IPR035914)
Short name: Sperma_CUB_dom_sf
- CUB domain (IPR000859)
- Peptidase S1A, enteropeptidase (IPR011163)
- Neuropilin (IPR014648)
- Bone morphogenetic protein 1/tolloid-like protein (IPR015446)
- Uncharacterised conserved protein UCP027682, CUB, vWA (IPR016857)
- Peptidase S1A, matripase (IPR017051)
- Kremen (IPR017076)
- Peptidase S1A, matriptase-2 (IPR017118)
- SPAN protein/blastula protease 10 (IPR017369)
- Hatching enzyme, Uvs2 (IPR017370)
- Platelet-derived growth factor D (IPR027123)
- Neuropilin-2 (IPR027143)
- Neuropilin-1 (IPR027146)
- Neuropilin and tolloid-like protein 1 (IPR028867)
- Neuropilin and tolloid-like protein 2 (IPR028868)
- Procollagen C-endopeptidase enhancer 1 (IPR028870)
- Platelet-derived growth factor C (IPR029817)
- Complement subcomponent C1r (IPR035707)
- Complement C1s subcomponent (IPR035708)
- Mannan-binding lectin-associated serine peptidase 2 (IPR037571)
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 [PMID: 8510165, 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:188.8.131.52), 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 beta-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].
Structurally, the spermadhesins consist of a CUB domain [PMID: 8510165].