The CUB domain [1,2,E1] is an extracellular domain of approximately 110
residues which is found in functionally diverse, mostly developmentally
regulated proteins. Almost all CUB domains contain four conserved cysteines
which probably form two disulfide bridges (C1-C2, C3-C4). The structure of the
CUB domain has been predicted to be a β-barrel similar to that of
Proteins that have been found to contain the CUB domain are listed below.
Mammalian complement subcomponents C1s/C1r. C1q, C1s and C1r form the
calcium-dependent complex C1, which is the first component of the classical
pathway of the complement system. Both proteins contain two CUB domains,
an EGF-like domain, two CCP domains and a trypsin family serine protease
domain (see <PDOC00124>).
Hamster serine protease Casp. Casp is a heterodimer of a regulatory and a
catalytic chain which degrades type I and IV collagen and fibronectin in
the presence of calcium. It shows the same modular architecture than C1s
Mammalian complement-activating component of Ra-reactive factor (RARF).
This protein, also known as P100, is a protease that cleaves the C4
component of complement. It shows the same modular architecture than C1s
Vertebrate enteropeptidase (EC 188.8.131.52), a type II membrane protein of
the intestinal brush border, which activates trypsinogen. It consists at
least of a catalytic light chain and a multidomain heavy chain which has
2 LDL receptor-like domains, a MAM domain (see <PDOC00604>), a SRCR domain
(see <PDOC00348>) and a CUB domain.
Vertebrate bone morphogenic protein 1 (BMP-1), a protein which induces
cartilage and bone formation and which expresses metalloendopeptidase
activity. The Drosophila homolog of BMP-1 is the dorsal-ventral patterning
protein Tolloid, which is required for normal dorsal development. In purple
sea urchin a homolog protein is called SuBMP. All these molecules possess a
zinc-metalloprotease domain (see <PDOC00129>) and a varying number of CUB
(up to 5 in mouse BMP-1 and Tolloid) and EGF-like domains.
Sea urchins blastula proteins BP10 and SpAN. Both proteins consist of
2 CUB domains, an EGF-like domain and a zinc-metalloprotease domain.
Caenorhabditis elegans hypothetical proteins F42A10.8 and R151.5. Both
proteins consist of a CUB domain, a EGF-like domain and a zinc-
Neuropilin (A5 antigen), a calcium-independent cell adhesion molecule that
function during the formation of certain neuronal circuits. The sequence
contains 2 CUB domains, 2 FA58C domains (see <PDOC00988>) and a MAM domain
Fibropellins I and III from sea urchin. These proteins form the apical
lamina, a component of the extracellular matrix. These two proteins contain
a CUB domain, followed by a variable number of EGF-like domains and a C-
terminal avidin-like domain (see <PDOC00499>).
Mammalian hyaluronate-binding protein TSG-6 (or PS4), a serum and growth
factor induced protein possibly involved in cell-cell and cell-matrix
interactions during inflammation and tumorgenesis. TSG-6 contains a 'link'
domain followed by a CUB domain.
Mammalian spermadhesins (see <PDOC00758>) which consist of a CUB domain.
Xenopus embryonic protein UVS.2, which is expressed during dorsoanterior
development. It contains 2 CUB domains.
For the sensitive detection of CUB domains, we have developed a profile which
spans the whole domain.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to
or see: prosite_license.html.