Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 6  species 0  interactions 269  sequences 8  architectures

Family: CUB_2 (PF02408)

Summary: CUB-like domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "CUB domain". More...

CUB domain Edit Wikipedia article

CUB domain
Symbol CUB
Pfam PF00431
InterPro IPR000859
SCOP 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).


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, 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.

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:


  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. 
  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. 
  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. PMID 8612739. 
  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. 
  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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

CUB-like domain Provide feedback

This is a family of hypothetical C. elegans proteins. The aligned region has no known function nor do any of the proteins which possess it. However, this domain is related to the CUB domain.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003366

This domain is found in a family of hypothetical Caenorhabditis elegans proteins. The aligned region has no known function nor do any of the proteins which possess it. However, this domain is related to the CUB domain (INTERPRO). The aligned region is approximately 130 amino acids long and contains two conserved cysteine residues.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan CUB (CL0164), which has the following description:

This clan contains the CUB domain [1,2].

The clan contains the following 2 members:



We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View  View   
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1716 (release 5.4)
Previous IDs: DUF141;
Type: Domain
Author: Bashton M, Bateman A
Number in seed: 24
Number in full: 269
Average length of the domain: 113.70 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 26.11 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 120
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.