CUB domain
Encyclopedia
CUB domain is an evolutionary conserved protein domain
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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. 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. Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin).
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.
Human genes encoding proteins containing this domain include:
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
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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. 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. Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin).
Examples
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 enteropeptidaseEnteropeptidaseEnteropeptidase is an enzyme produced by cells of the duodenum and involved in human digestion. It is secreted from intestinal glands following the entry of ingested food passing from the stomach...
, a type II membrane protein of the intestinal brush border, which activates trypsinogen. - Vertebrate bone morphogenic protein 1 (BMP-1Bone morphogenetic protein 1Bone morphogenetic protein 1, also known as BMP1, is a protein which in humans is encoded by the BMP1 gene. There are seven isoforms of the protein created by alternate splicing.-Function:...
), a protein which induces cartilage and bone formation and expresses metalloendopeptidase activity. - Sea urchin blastula proteins BP10 and SpAN.
- C. elegansCaenorhabditis elegansCaenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
hypothetical proteins F42A10.8 and R151.5. - NeuropilinNeuropilinNeuropilin is a protein receptor active in neurons.There are two forms of Neuropilins, NRP-1 and NRP-2. They are transmembrane glycoproteins, and predominantly co-receptors for another class of proteins known as semaphorins...
(A5 antigen), a calcium-independent cell adhesion molecule that functions during the formation of certain neuronal circuits. - Fibropellins I and III from Strongylocentrotus purpuratusStrongylocentrotus purpuratusThe purple sea urchin, Strongylocentrotus purpuratus, lives along the eastern edge of the Pacific Ocean extending from Ensenada, Mexico to British Columbia, Canada. This sea urchin species is deep purple in color and lives in lower intertidal and nearshore subtidal communities...
(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
EGF-like domain
EGF-like domain is an evolutionary conserved protein domain, of about thirty to forty amino-acid residues long, which was found in a large number of mostly animal proteins. All these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted...
. 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.
Human genes encoding proteins containing this domain include:
- ATRNATRNAttractin is a protein that in humans is encoded by the ATRN gene.Attractin is a Group XI C-type lectin.-Further reading:...
, ATRNL1, BMP1Bone morphogenetic protein 1Bone morphogenetic protein 1, also known as BMP1, is a protein which in humans is encoded by the BMP1 gene. There are seven isoforms of the protein created by alternate splicing.-Function:...
, - C1RC1R (gene)Complement C1r subcomponent is a protein that in humans is encoded by the C1R gene.-Further reading:...
, C1RL, C1SC1SComplement C1s subcomponent is a protein that in humans is encoded by the C1S gene.-Interactions:C1S has been shown to interact with C1R.-Further reading:...
, CDCP2, CSMD1CSMD1CUB and sushi domain-containing protein 1 is a protein that in humans is encoded by the CSMD1 gene.. It is a potential tumour suppressor, the deletion of which may result in head and neck carcinomas behaving more aggressively.-Further reading:...
, CSMD2CSMD2CUB and sushi domain-containing protein 2 is a protein that in humans is encoded by the CSMD2 gene.-Further reading:...
, CSMD3, CUBN, CUZD1CUZD1CUB and zona pellucida-like domain-containing protein 1 is a protein that in humans is encoded by the CUZD1 gene.-Further reading:...
, - DCBLD1, DCBLD2DCBLD2Discoidin, CUB and LCCL domain-containing protein 2 is a protein that in humans is encoded by the DCBLD2 gene.-Further reading:...
, DMBT1DMBT1Deleted in malignant brain tumors 1 protein is a protein that in humans is encoded by the DMBT1 gene.-Interactions:DMBT1 has been shown to interact with Surfactant protein D.-Further reading:...
, DREG, - GPR126GPR126Probable G-protein coupled receptor 126 is a protein that in humans is encoded by the GPR126 gene. It is involved in the process of myelination.-Further reading:...
, - KREMEN1KREMEN1Kremen protein 1 is a protein that in humans is encoded by the KREMEN1 gene.-Further reading:...
, KREMEN2, - LRP10LRP10Low-density lipoprotein receptor-related protein 10 is a protein that in humans is encoded by the LRP10 gene....
, LRP12, LRP3LRP3Low density lipoprotein receptor-related protein 3 is a protein that in humans is encoded by the LRP3 gene....
, - MASP1, MASP2, MFRPMFRPMembrane frizzled-related protein is a protein that in humans is encoded by the MFRP gene.-Further reading:...
, - NETO1, NETO2, NRP1Neuropilin 1Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene.. This is one of two human neuropilins.-Interactions:Neuropilin 1 has been shown to interact with Vascular endothelial growth factor A.-Further reading:...
, NRP2NRP2Neuropilin-2 is a protein that in humans is encoded by the NRP2 gene.-Further reading:...
, - OVCH1, OVCH2,
- PCOLCEPCOLCEProcollagen C-endopeptidase enhancer 1 is an enzyme that in humans is encoded by the PCOLCE gene.-Further reading:...
, PCOLCE2PCOLCE2Procollagen C-endopeptidase enhancer 2 is an enzyme that in humans is encoded by the PCOLCE2 gene.-Further reading:...
, PDGFCPDGFCPlatelet-derived growth factor C, also known as PDGF-C, is a 345-amino acid protein that in humans is encoded by the PDGFC gene. Platelet-derived growth factors are important in connective tissue growth, survival and function, and consist of disulphide-linked dimers involving two polypeptide...
, PDGFDPDGFDPlatelet-derived growth factor D is a protein that in humans is encoded by the PDGFD gene.-Further reading:...
, PRSS7, - RAMP,
- SCUBE1, SCUBE2, SCUBE3, SEZ6SEZ6Seizure protein 6 homolog is a protein that in humans is encoded by the SEZ6 gene.-Further reading:...
, SEZ6LSEZ6LSeizure 6-like protein is a protein that in humans is encoded by the SEZ6L gene.-Further reading:...
, SEZ6L2, ST14ST14Suppression of tumorigenicity 14 , also known as ST14, is a human gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.-Further reading:...
, - TLL1TLL1Tolloid-like protein 1 is a protein that in humans is encoded by the TLL1 gene.-Further reading:...
, TLL2TLL2Tolloid-like protein 2 is a protein that in humans is encoded by the TLL2 gene.-Further reading:...
, TMPRSS7, TNFAIP6 - psk-2PAPSS2Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 is an enzyme that in humans is encoded by the PAPSS2 gene.-Further reading:...