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47  structures 7324  species 0  interactions 24271  sequences 255  architectures

Family: Rhomboid (PF01694)

Summary: Rhomboid family

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 "Rhomboid protease". More...

Rhomboid protease Edit Wikipedia article

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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.

Rhomboid family Provide feedback

This family contains integral membrane proteins that are related to Drosophila rhomboid protein P20350. Members of this family are found in bacteria and eukaryotes. Rhomboid promotes the cleavage of the membrane-anchored TGF-alpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Analysis has shown that Rhomboid-1 is an intramembrane serine protease [2] ( EC:3.4.21.105). Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite [5].

Literature references

  1. Bier E, Jan LY, Jan YN; , Genes Dev 1990;4:190-203.: rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. PUBMED:2110920 EPMC:2110920

  2. Urban S, Lee JR, Freeman M; , Cell 2001;107:173-182.: Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. PUBMED:11672525 EPMC:11672525

  3. Koonin EV, Makarova KS, Rogozin IB, Davidovic L, Letellier MC, Pellegrini L; , Genome Biol 2003;4:R19.: The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers. PUBMED:12620104 EPMC:12620104

  4. Urban S, Wolfe MS; , Proc Natl Acad Sci U S A. 2005;102:1883-1888.: Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity. PUBMED:15684070 EPMC:15684070

  5. Brossier F, Jewett TJ, Sibley LD, Urban S; , Proc Natl Acad Sci U S A. 2005;102:4146-4151.: A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. PUBMED:15753289 EPMC:15753289


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022764

This entry represents a six transmembrane helix rhomboid domain.

This domain is found in serine peptidases belonging to the MEROPS peptidase family S54 (Rhomboid, clan ST). They are integral membrane proteins related to the Drosophila melanogaster (Fruit fly) rhomboid protein SWISSPROT . Members of this family are found in archaea, bacteria and eukaryotes.

The rhomboid protease cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine. The active site is embedded within the membrane and the active site residues are on different transmembrane regions. From the tertiary structure of the Escherichia coli homologue GlpG [ PUBMED:17051161 ] it was shown that hydrolysis occurs in a fluid filled cavity within the membrane. Initially, a catalytic triad including a highly conserved asparagine had been proposed, but this residue has been shown not to be essential [ PUBMED:15616571 ]. Drosophila rhomboid cleaves the transmembrane proteins Spitz, Gurken and Keren within their transmembrane domains to release a soluble TGFalpha-like growth factor. Cleavage occurs in the Golgi, following translocation of the substrates from the endoplasmic reticulum membrane by Star, another transmembrane protein. The growth factors are then able to activate the epidermal growth factor receptor [ PUBMED:2110920 , PUBMED:11672525 ].

Few substrates of mammalian rhomboid homologues have been determined, but rhomboid-like protein 2 has been shown to cleave ephrin B3 [ PUBMED:15047175 ]. Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite. Invasion of host cells first requires their recognition and this is achieved by parasite transmembrane adhesins interacting with host cell receptors. Before the parasite can enter a host cell the adhesins must be released by cleavage. In Toxoplasma rhomboid TgROM5 cleaves the adhesins, and in Plasmodium, which lacks a TgROM5 orthologue, PfROMs 1 and 4 cleave the diverse array of malaria parasite adhesins [ PUBMED:17040128 ].

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 Rhomboid-like (CL0207), which has the following description:

This clan contains proteins from both bacteria and eukaryotes. The Rhomboid protein is an intramembrane serine protease which is involved in epidermal growth factor (EGF)-dependent signalling pathways [1]. The DER1 family is involved in degradation of misfolded ER proteins [2].

The clan contains the following 3 members:

DER1 DUF1751 Rhomboid

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 and the UniProtKB 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
(60)
Full
(24271)
Representative proteomes UniProt
(85068)
RP15
(3677)
RP35
(11349)
RP55
(22715)
RP75
(35732)
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PP/heatmap 1            

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

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

Format an alignment

  Seed
(60)
Full
(24271)
Representative proteomes UniProt
(85068)
RP15
(3677)
RP35
(11349)
RP55
(22715)
RP75
(35732)
Alignment:
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Sequence:
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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
(60)
Full
(24271)
Representative proteomes UniProt
(85068)
RP15
(3677)
RP35
(11349)
RP55
(22715)
RP75
(35732)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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: Pfam-B_1399 (release 4.1)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Sohrmann M, Bateman A
Number in seed: 60
Number in full: 24271
Average length of the domain: 148.60 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 45.17 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.6 22.6
Trusted cut-off 22.6 22.6
Noise cut-off 22.5 22.5
Model length: 150
Family (HMM) version: 24
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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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 Rhomboid domain has been found. There are 47 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0N7KDT0 View 3D Structure Click here
A0A0N7KS35 View 3D Structure Click here
A0A0P0V9G8 View 3D Structure Click here
A0A0P0VIC0 View 3D Structure Click here
A0A0R0EML8 View 3D Structure Click here
A0A0R0FAC4 View 3D Structure Click here
A0A0R0FW66 View 3D Structure Click here
A0A0R0GDG3 View 3D Structure Click here
A0A0R0J795 View 3D Structure Click here
A0A0R0J795 View 3D Structure Click here
A0A143ZYK6 View 3D Structure Click here
A0A1D6ER91 View 3D Structure Click here
A0A1D6GVC3 View 3D Structure Click here
A0A1D6K700 View 3D Structure Click here
A0A1D6KZC9 View 3D Structure Click here
A0A1D6MLH7 View 3D Structure Click here
A0A1D6MQK4 View 3D Structure Click here
A0A1D6PN10 View 3D Structure Click here
A0A1D6QPD1 View 3D Structure Click here
A0A1D8PFE0 View 3D Structure Click here
A0A1D8PJD6 View 3D Structure Click here
A0A1X7YH41 View 3D Structure Click here
A0A5K1K8S0 View 3D Structure Click here
A0A5K1K8X1 View 3D Structure Click here
A0A5K1K991 View 3D Structure Click here
A0A6V7QZA6 View 3D Structure Click here
A1Z8R8 View 3D Structure Click here
A2AGA4 View 3D Structure Click here
A4HS82 View 3D Structure Click here
A5PMS4 View 3D Structure Click here
B3H707 View 3D Structure Click here
B4F7X8 View 3D Structure Click here
B4FJ85 View 3D Structure Click here
B4FMX3 View 3D Structure Click here
B4FQY5 View 3D Structure Click here
B4FRA9 View 3D Structure Click here
B4FU25 View 3D Structure Click here
B4G1H4 View 3D Structure Click here
B6TJT4 View 3D Structure Click here
B7F9A1 View 3D Structure Click here
C6KT26 View 3D Structure Click here
C6T841 View 3D Structure Click here
C6TG18 View 3D Structure Click here
C7G025 View 3D Structure Click here
D3ZA62 View 3D Structure Click here
D3ZQG3 View 3D Structure Click here
D4AAW6 View 3D Structure Click here
E7F9C6 View 3D Structure Click here
E7FCU6 View 3D Structure Click here
E9QI41 View 3D Structure Click here
F1LWZ3 View 3D Structure Click here
F1QAX9 View 3D Structure Click here
F1QUY6 View 3D Structure Click here
F1R9M8 View 3D Structure Click here
F4I8K2 View 3D Structure Click here
F4ICF4 View 3D Structure Click here
F4JBM4 View 3D Structure Click here
F4JY73 View 3D Structure Click here
H2KML1 View 3D Structure Click here
I1JLP8 View 3D Structure Click here
I1JN41 View 3D Structure Click here
I1JQD8 View 3D Structure Click here
I1JZG9 View 3D Structure Click here
I1KUK6 View 3D Structure Click here
I1L3B4 View 3D Structure Click here
I1LDT9 View 3D Structure Click here
I1LJP1 View 3D Structure Click here
I1LQD4 View 3D Structure Click here
I1MDE7 View 3D Structure Click here
I1MQ05 View 3D Structure Click here
I1MS13 View 3D Structure Click here
I1N1Q9 View 3D Structure Click here
I1N2H7 View 3D Structure Click here
I1N6P4 View 3D Structure Click here
I1NGR1 View 3D Structure Click here
K7KM97 View 3D Structure Click here
K7KUE9 View 3D Structure Click here
K7LXT1 View 3D Structure Click here
K7M3E7 View 3D Structure Click here
K7M8T4 View 3D Structure Click here
K7MZE5 View 3D Structure Click here
K7U7I3 View 3D Structure Click here
O14364 View 3D Structure Click here
O53632 View 3D Structure Click here
O74926 View 3D Structure Click here
O75783 View 3D Structure Click here
O82756 View 3D Structure Click here
O88779 View 3D Structure Click here
P09391 View 3D Structure Click here
P20350 View 3D Structure Click here
P34356 View 3D Structure Click here
P53259 View 3D Structure Click here
P58872 View 3D Structure Click here
P58873 View 3D Structure Click here
P9WM21 View 3D Structure Click here
Q0WQX7 View 3D Structure Click here
Q10SN4 View 3D Structure Click here
Q12270 View 3D Structure Click here
Q19821 View 3D Structure Click here
Q2A943 View 3D Structure Click here
Q2FY24 View 3D Structure Click here
Q3B8P0 View 3D Structure Click here
Q499S9 View 3D Structure Click here
Q4CMB2 View 3D Structure Click here
Q4CV15 View 3D Structure Click here
Q4E348 View 3D Structure Click here
Q4V8F3 View 3D Structure Click here
Q53KX4 View 3D Structure Click here
Q53MA5 View 3D Structure Click here
Q54D88 View 3D Structure Click here
Q54NX5 View 3D Structure Click here
Q54U20 View 3D Structure Click here
Q55AV6 View 3D Structure Click here
Q58EK4 View 3D Structure Click here
Q5AH12 View 3D Structure Click here
Q5JLU6 View 3D Structure Click here
Q5XJY4 View 3D Structure Click here
Q642B3 View 3D Structure Click here
Q651M0 View 3D Structure Click here
Q67UY4 View 3D Structure Click here
Q6GMF8 View 3D Structure Click here
Q6NTF9 View 3D Structure Click here
Q6PIX5 View 3D Structure Click here
Q6PJF5 View 3D Structure Click here
Q6ZFV7 View 3D Structure Click here
Q75G53 View 3D Structure Click here
Q76NQ1 View 3D Structure Click here
Q7XRW9 View 3D Structure Click here
Q80WQ6 View 3D Structure Click here
Q84MB5 View 3D Structure Click here
Q84WG3 View 3D Structure Click here
Q869L9 View 3D Structure Click here
Q86BL6 View 3D Structure Click here
Q8BHC7 View 3D Structure Click here
Q8BP97 View 3D Structure Click here
Q8I3V7 View 3D Structure Click here
Q8I433 View 3D Structure Click here
Q8IIM2 View 3D Structure Click here
Q8ILY3 View 3D Structure Click here
Q8LB17 View 3D Structure Click here
Q8RXQ2 View 3D Structure Click here
Q8RXW0 View 3D Structure Click here
Q8TEB9 View 3D Structure Click here
Q8VC82 View 3D Structure Click here
Q8VEK2 View 3D Structure Click here
Q8VZ48 View 3D Structure Click here
Q96CC6 View 3D Structure Click here
Q9AQU7 View 3D Structure Click here
Q9CAN1 View 3D Structure Click here
Q9FFX0 View 3D Structure Click here
Q9FZ81 View 3D Structure Click here
Q9H300 View 3D Structure Click here
Q9LET3 View 3D Structure Click here
Q9LYP1 View 3D Structure Click here
Q9M1B5 View 3D Structure Click here
Q9NX52 View 3D Structure Click here
Q9P375 View 3D Structure Click here
Q9P7D8 View 3D Structure Click here
Q9SDB9 View 3D Structure Click here
Q9SSR0 View 3D Structure Click here
Q9U2S3 View 3D Structure Click here
Q9VYW6 View 3D Structure Click here
Q9W0E9 View 3D Structure Click here
Q9W0F8 View 3D Structure Click here
Q9Y3P4 View 3D Structure Click here