The domain within your query sequence starts at position 556 and ends at position 667; the E-value for the CUB domain shown below is 5.1e-38.

CGGVISSLSGSFTSPRYPENYPTDIQCVWEIHVEKNFRIELMIPNLNLEDILGCPYDSIE
IFDGPRIASLSMGKFCAPSAVVFFSSSDILTVVFRSDYMTTNTGFYAFFNAI

CUB

Domain first found in C1r, C1s, uEGF, and bone morphogenetic protein.

• SMART accession number: SM00042
• Description: This domain is found mostly among developmentally-regulated proteins. Spermadhesins contain only this domain.
• Interpro abstract (IPR000859):

  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 [ (PUBMED:8510165) (PUBMED: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 [ (PUBMED: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 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 [ (PUBMED:17446170) ].

There are 84744 CUB domains in 33329 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Bork P, Beckmann G
• The CUB domain. A widespread module in developmentally regulated proteins.
• J Mol Biol. 1993; 231: 539-45

Sequence analysis has revealed the presence of 31 copies of an extracellular domain, here called CUB, in 16 functionally diverse proteins such as the dorso-ventral patterning protein tolloid, bone morphogenetic protein 1, a family of spermadhesins, complement subcomponents Cls/Clr and the neuronal recognition molecule A5. Most of them are known to be involved in developmental processes. Our analysis of this new family includes the identification of seven previously undescribed members, the characterization of conserved features and a topology prediction of this approximately 110 residue spanning domain, which suggests an antiparallel beta-barrel similar to those in immunoglobulins.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
26.05	map04610	Complement and coagulation cascades
10.92	map04810	Regulation of actin cytoskeleton
10.92	map04060	Cytokine-cytokine receptor interaction
10.92	map04540	Gap junction
10.92	map04510	Focal adhesion
10.92	map05215	Prostate cancer
10.92	map05218	Melanoma
8.40	map04360	Axon guidance

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with CUB domain which could be assigned to a KEGG orthologous group, and not all proteins containing CUB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of CUB domains in PDB

PDB code	Title
1nt0	Crystal structure of the CUB1-EGF-CUB2 region of MASP2
1nzi	Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s
1sfp	CRYSTAL STRUCTURE OF ACIDIC SEMINAL FLUID PROTEIN (ASFP) AT 1.9 A RESOLUTION: A BOVINE POLYPEPTIDE FROM THE SPERMADHESIN FAMILY
1spp	THE CRYSTAL STRUCTURES OF TWO MEMBERS OF THE SPERMADHESIN FAMILY REVEAL THE FOLDING OF THE CUB DOMAIN
1szb	Crystal structure of the human MBL-associated protein 19 (MAp19)
2qqk	Neuropilin-2 a1a2b1b2 Domains in Complex with a Semaphorin-Blocking Fab
2qql	Neuropilin-2 a1a2b1b2 Domains in Complex with a Semaphorin-Blocking Fab
2qqm	Crystal Structure of the a2b1b2 Domains from Human Neuropilin-1
2qqo	Crystal Structure of the a2b1b2 Domains from Human Neuropilin-2
2wno	X-ray Structure of CUB_C domain from TSG-6
3dem	CUB1-EGF-CUB2 domain of HUMAN MASP-1/3
3kq4	Structure of Intrinsic Factor-Cobalamin bound to its receptor Cubilin
3pob	Crystal structure of MASP-1 CUB2 domain in complex with the collagen-like domain of MBL
3poe	Crystal structure of the MASP-1 CUB2 domain bound to Ca2+
3pof	Crystal structure of MASP-1 CUB2 domain bound to Ca2+
3pog	Crystal structure of the MASP-1 CUB2 domain bound to Ca2+
3poi	Crystal structure of MASP-1 CUB2 domain bound to Methylamine
3poj	Crystal structure of MASP-1 CUB2 domain bound to Ethylamine
4aqb	MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44
4gz9	Mouse Neuropilin-1, extracellular domains 1-4 (a1a2b1b2)
4gza	Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1
4lmf	C1s CUB1-EGF-CUB2
4lor	C1s CUB1-EGF-CUB2 in complex with a collagen-like peptide from C1q
4los	C1s CUB2-CCP1
4lot	C1s CUB2-CCP1-CCP2
5fws	5FWS
5fwt	5FWT
5fwu	5FWU
5fwv	5FWV
5fww	5FWW

Links (links to other resources describing this domain)

• PFAM: CUB
• INTERPRO: IPR000859
• PROSITE: CUB_DOMAIN