CUB domain

Last updated
CUB domain
Identifiers
SymbolCUB
Pfam PF00431
InterPro IPR000859
PROSITE PDOC00758
SCOP2 1sfp / SCOPe / SUPFAM
CDD cd00041
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1nzi A:18-127 1nt0 A:28-134 1szb B:28-134 1spp B:30-128 1sfp :30-127

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

Proteins containing a CUB domain include:

Several of the above proteins consist of a catalytic domain together with several CUB domains interspersed by calcium-binding EGF domains.

Spermadhesin is a subdivision of the CUB domain family and forms a major component of the mammalian seminal fluid. Spermadhesins are 110-133 amino acid polypeptides. [4] The binding activity of spermadhesins, e.g. heparin and carbohydrate binding, enables their central role in promoting attachment of the spermatozoa to carbohydrate groups on the glycoproteins found on the surface of oocytes. [5] The spermadhesins from pigs, bulls and stallions show 40-98% similarity in their amino acid sequences and all possess a disulphide bond between adjacent cysteine residues. The porcine spermadhesin polypeptides are coded by five closely linked genes. Bovine spermadhesin relies on a significantly lower number of genes with only two being associated with expression of this protein in bovine seminal fluid. Redundant genetic coding for spermadhesins have been observed in chimpanzees, dogs, and humans. [6] The region correlating to spermadhesin genes in rat and mice DNA is void of any spermadhesin code. These variations in expression and genetic coding of spermadhesins are seen to result from evolutionary adjustments in genes as a consequence of mutations and deletions in genetic material.

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. [7]

Human genes encoding proteins containing this domain include:

Related Research Articles

<span class="mw-page-title-main">Perforin-1</span> Mammalian protein found in Homo sapiens

Perforin-1 is a protein that in humans is encoded by the PRF1 gene and the Prf1 gene in mice.

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">Morphogen</span> Biological substance that guides development by non-uniform distribution

A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a morphogen is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.

<span class="mw-page-title-main">Bone morphogenetic protein 1</span> Mammalian protein found in Homo sapiens

Bone 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.

Chordin is a protein with a prominent role in dorsal–ventral patterning during early embryonic development. In humans it is encoded for by the CHRD gene.

<span class="mw-page-title-main">Complement component 1r</span> Protein-coding gene in the species Homo sapiens

Complement C1r subcomponent is a protein involved in the complement system of the innate immune system. In humans, C1r is encoded by the C1R gene.

<span class="mw-page-title-main">Complement component 1s</span> Protein-coding gene in the species Homo sapiens

Complement component 1s is a protein involved in the complement system. C1s is part of the C1 complex. In humans, it is encoded by the C1S gene.

<span class="mw-page-title-main">MASP1 (protein)</span> Protein-coding gene in the species Homo sapiens

Mannan-binding lectin serine protease 1 also known as mannose-associated serine protease 1 (MASP-1) is an enzyme that in humans is encoded by the MASP1 gene.

<span class="mw-page-title-main">Mannan-binding lectin</span> Mammalian protein found in Homo sapiens

Mannose-binding lectin (MBL), also called mannan-binding lectin or mannan-binding protein (MBP), is a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway.

<span class="mw-page-title-main">FKBP1A</span> Protein and coding gene in humans

Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins (FKBPs).

<span class="mw-page-title-main">LRP1</span> Mammalian protein found in Homo sapiens

Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene. LRP1 is also a key signalling protein and, thus, involved in various biological processes, such as lipoprotein metabolism and cell motility, and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer.

<span class="mw-page-title-main">EGF-like domain</span> Protein domain named after the epidermal growth factor protein

The EGF-like domain is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. An exception to this is the prostaglandin-endoperoxide synthase. The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds. The structures of 4-disulfide EGF-domains have been solved from the laminin and integrin proteins. The main structure of EGF-like domains is a two-stranded β-sheet followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets. EGF-like domains frequently occur in numerous tandem copies in proteins: these repeats typically fold together to form a single, linear solenoid domain block as a functional unit.

<span class="mw-page-title-main">PCOLCE</span> Protein-coding gene in the species Homo sapiens

Procollagen C-endopeptidase enhancer 1 is an enzyme that in humans is encoded by the PCOLCE gene.

<span class="mw-page-title-main">CSMD1</span> Protein-coding gene in the species Homo sapiens

CSMD1 CUB and Sushi multiple domains 1 is a protein that in humans is encoded by the CSMD1 gene.

<span class="mw-page-title-main">CDCP1</span> Protein-coding gene in the species Homo sapiens

CUB domain-containing protein 1 (CDCP1) is a protein that in humans is encoded by the CDCP1 gene. CDCP1 has also been designated as CD318 and Trask. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

<span class="mw-page-title-main">TLL1</span> Protein-coding gene in the species Homo sapiens

Tolloid-like protein 1 is a protein that in humans is encoded by the TLL1 gene.

Sushi domain is an evolutionarily conserved protein domain. It is also known as Complement control protein (CCP) modules or short consensus repeats (SCR). The name derives from the visual similarity of the domain to nigiri sushi when the primary structure is drawn showing the loops created by the disulfide bonds.

<span class="mw-page-title-main">Astacin</span>

Astacins are a family of multidomain metalloendopeptidases which are either secreted or membrane-anchored. These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A. The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH.

<span class="mw-page-title-main">LCCL domain</span>

In molecular biology, the LCCL domain is a protein domain which has been named after several well-characterised proteins that were found to contain it, namely Limulus clotting factor C, Cochlin (Coch-5b2) and Lgl1 (CRISPLD2). It is an about 100 amino acids domain whose C-terminal part contains a highly conserved histidine in a conserved motif YxxxSxxCxAAVHxGVI. The LCCL module is thought to be an autonomously folding domain that has been used for the construction of various modular proteins through exon-shuffling. It has been found in various metazoan proteins in association with complement B-type domains, C-type lectin domains, von Willebrand type A domains, CUB domains, discoidin lectin domains or CAP domains. It has been proposed that the LCCL domain could be involved in lipopolysaccharide (LPS) binding. LCCL exhibits a novel fold.

SNED1 is an extracellular matrix (ECM) protein expressed at low levels in a wide range of tissues. The gene encoding SNED1 is located in the human chromosome 2 at locus q37.3. The corresponding mRNA isolated from the spleen and is 6834bp in length, and the corresponding protein is 1413 amino-acid long. The mouse ortholog of SNED1 was cloned in 2004 from the embryonic kidney by Leimester et al. SNED1 present domains characteristic of ECM proteins, including an amino-terminal NIDO domain, several calcium binding EGF-like domains (EGF_CA), a Sushi domain also known as complement control protein (CCP) domain, and three type III fibronectin (FN3) domains in the carboxy-terminal region.

References

  1. Bork P, Beckmann G (May 1993). "The CUB domain. A widespread module in developmentally regulated proteins". Journal of Molecular Biology. 231 (2): 539–45. doi:10.1006/jmbi.1993.1305. PMID   8510165.
  2. Bork P (Apr 1991). "Complement components C1r/C1s, bone morphogenic protein 1 and Xenopus laevis developmentally regulated protein UVS.2 share common repeats". FEBS Letters. 282 (1): 9–12. doi: 10.1016/0014-5793(91)80433-4 . PMID   2026272. S2CID   33375087.
  3. Perry SE, Robinson P, Melcher A, Quirke P, Bühring HJ, Cook GP, Blair GE (Mar 2007). "Expression of the CUB domain containing protein 1 (CDCP1) gene in colorectal tumour cells". FEBS Letters. 581 (6): 1137–42. doi: 10.1016/j.febslet.2007.02.025 . PMID   17335815. S2CID   30701692.
  4. Romero A, Varela PF, Sanz L, Töpfer-Petersen E, Calvete JJ (Mar 1996). "Crystallization and preliminary X-ray diffraction analysis of boar seminal plasma spermadhesin PSP-I/PSP-II, a heterodimer of two CUB domains". FEBS Letters. 382 (1–2): 15–7. doi: 10.1016/0014-5793(96)00133-0 . hdl: 10261/246550 . PMID   8612739. S2CID   37515421.
  5. Töpfer-Petersen E, Romero A, Varela PF, Ekhlasi-Hundrieser M, Dostàlovà Z, Sanz L, Calvete JJ (1998). "Spermadhesins: a new protein family. Facts, hypotheses and perspectives". Andrologia. 30 (4–5): 217–24. doi: 10.1111/j.1439-0272.1998.tb01163.x . PMID   9739418. S2CID   24941844.
  6. Haase B, Schlötterer C, Hundrieser ME, Kuiper H, Distl O, Töpfer-Petersen E, Leeb T., Evolution of the spermadhesin gene family, Gene. (2005) 352, P-20-29
  7. Blanc G, Font B, Eichenberger D, Moreau C, Ricard-Blum S, Hulmes DJ, Moali C (Jun 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". The Journal of Biological Chemistry. 282 (23): 16924–33. doi: 10.1074/jbc.M701610200 . PMID   17446170.
This article incorporates text from the public domain Pfam and InterPro: IPR000858