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38  structures 276  species 2  interactions 3204  sequences 175  architectures

Family: Fz (PF01392)

Summary: Fz domain

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Fz domain Provide feedback

Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups [1,2,3,4]. The domain contains 10 conserved cysteines.

Literature references

  1. Xu YK, Nusse R; , Curr Biol 1998;8:405-406.: The Frizzled CRD domain is conserved in diverse proteins including several receptor tyrosine kinases. PUBMED:9637908 EPMC:9637908

  2. Masiakowski P, Yancopoulos GD; , Curr Biol 1998;8:407-407.: The Wnt receptor CRD domain is also found in MuSK and related orphan receptor tyrosine kinases. PUBMED:9637909 EPMC:9637909

  3. Saldanha J, Singh J, Mahadevan D , Protein Sci 1998;7:1632-1635.: Identification of a Frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases. PUBMED:9684897 EPMC:9684897

  4. Rehn M, Pihlajaniemi T, Hofmann K, Bucher P; , Trends Biochem Sci 1998;23:415-417.: The frizzled motif: in how many different protein families does it occur?. PUBMED:9852758 EPMC:9852758


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR020067

The frizzled (fz) domain is an extracellular domain of about 120 amino acids.It was first identified in the alpha-1 chain of type XVIII collagen and in members of the Frizzled family of seven transmembrane (7TM) proteins which act as receptors for secreted Wingless (Wg)/Wnt glycoproteins [PUBMED:7876242]. In addition to these proteins, one or two copies of the fz domain are also found [PUBMED:9637908, PUBMED:9637909, PUBMED:10082384, PUBMED:9852758, PUBMED:10329693] in:

  • The frizbee (Frzb) family; secreted frizzled-like proteins.
  • Smoothened; another 7TM receptor involved in hedgehog signaling.
  • Carboxpeptidase Z (CPZ).
  • Transmembrane serine protease corin.
  • Two receptor tyrosine kinases (RTKs) subfamilies, the Ror family and the muscle-specific kinase (MuSK) family.

As the fz domain contains 10 cysteines which are largely conserved, it has also been called cysteine-rich domain (CRD) [PUBMED:7876242]. The fz domain also contains several other highly conserved residues, for example, a basic amino acid follows C6, and a conserved proline residues lies four residues C-terminal to C9 [PUBMED:9852758]. The crystal structure of a fz domain shows that it is predominantly alpha-helical with all cysteines forming disulphide bonds. In addition to helical regions, two short beta-strands at the N terminus form a minimal beta-sheet with the second beta sheet passing through a knot created by disulphide bonds [PUBMED:11452312].

Several fz domains have been shown to be both necessary and sufficient for Wg/Wnt ligand binding, strongly suggesting that the fz domain is a Wg/Wnt interacting domain [PUBMED:8717036, PUBMED:9326585].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

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Pfam Clan

This family is a member of clan Fz (CL0644), which has the following description:

This superfamily includes diverse cysteine rich domains identified as being homologous [1].

The clan contains the following 4 members:

Folate_rec Fz Glypican NPC1_N

Alignments

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...

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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.

  Seed
(349)
Full
(3204)
Representative proteomes UniProt
(5044)
NCBI
(9221)
Meta
(0)
RP15
(876)
RP35
(1452)
RP55
(2387)
RP75
(2985)
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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

  Seed
(349)
Full
(3204)
Representative proteomes UniProt
(5044)
NCBI
(9221)
Meta
(0)
RP15
(876)
RP35
(1452)
RP55
(2387)
RP75
(2985)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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.

  Seed
(349)
Full
(3204)
Representative proteomes UniProt
(5044)
NCBI
(9221)
Meta
(0)
RP15
(876)
RP35
(1452)
RP55
(2387)
RP75
(2985)
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...

Trees

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: Bateman A
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 349
Number in full: 3204
Average length of the domain: 107.50 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 19.15 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.8 26.8
Trusted cut-off 26.8 26.8
Noise cut-off 26.7 26.7
Model length: 111
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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

Selections

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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...

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Interactions

There are 2 interactions for this family. More...

Fz wnt

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fz domain has been found. There are 38 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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