CUB domain

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CUB domain
Identifiers
Symbol CUB
Pfam PF00431
InterPro IPR000859
PROSITE PDOC00758
SCOP 1sfp
SUPERFAMILY 1sfp
CDD cd00041

CUB domain is an evolutionarily conserved protein domain.

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.[1][2] 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.[3] Many CUB-containing proteins are peptidases belonging to MEROPS peptidase families M12A (astacin) and S1A (chymotrypsin).

Examples[edit]

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.
  • C. 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.[4]

Human genes encoding proteins containing this domain include:

References[edit]

  1. ^ Bork P, Beckmann G (May 1993). "The CUB domain. A widespread module in developmentally regulated proteins". J. Mol. Biol. 231 (2): 539–45. doi:10.1006/jmbi.1993.1305. PMID 8510165. 
  2. ^ Bork P (April 1991). "Complement components C1r/C1s, bone morphogenic protein 1 and Xenopus laevis developmentally regulated protein UVS.2 share common repeats". FEBS Lett. 282 (1): 9–12. doi:10.1016/0014-5793(91)80433-4. PMID 2026272. 
  3. ^ Perry SE, Robinson P, Melcher A, Quirke P, Bühring HJ, Cook GP, Blair GE (March 2007). "Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells". FEBS Lett. 581 (6): 1137–42. doi:10.1016/j.febslet.2007.02.025. PMID 17335815. 
  4. ^ Blanc G, Font B, Eichenberger D, Moreau C, Ricard-Blum S, Hulmes DJ, Moali C (June 2007). "Insights into how CUB domains can exert specific functions while sharing a common fold: conserved and specific features of the CUB1 domain contribute to the molecular basis of procollagen C-proteinase enhancer-1 activity". J. Biol. Chem. 282 (23): 16924–33. doi:10.1074/jbc.M701610200. PMID 17446170. 

This article incorporates text from the public domain Pfam and InterPro IPR000858