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0  structures 15  species 0  interactions 2070  sequences 33  architectures

Family: RIFIN (PF02009)

Summary: Rifin

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Plasmodium falciparum is the causative agent of deadly malaria disease. It encodes repetitive interspersed families of polypeptides (RIFINs), which are expressed on the surface of infected erythrocytes [1]. All RIFIN sequences contain the PEXEL motif (a pentameric sequence RxLxE/Q/D, known as the Plasmodium export element) required for correct export and surface expression or host-targeting (HT) signal which plays a central role in the export of proteins into the host cell [2]. It has been reported that PEXEL is preferably located 15–20 amino acids downstream of an N-terminal hydrophobic signal sequence [3]. The RIFIN protein family can be divided into A and B types based on the presence or absence of a 25 amino acid motif located approximately 66 amino acids downstream of the PEXEL motif [3] with A- and B-types serving different roles in distinct parasite stages [2]. The specific type B RIFIN variant (PF13_0006) is expressed on the surface of free merozoites, internally in developing gametocytes and on the surface of gametes at the point of emerging from activated, mature stage V gametocytes. While type A RIFIN are expressed on the infected erythrocyte surface, potentially contributing to the antigenic variation capacity of the parasite [2].

Literature references

  1. Goel S, Palmkvist M, Moll K, Joannin N, Lara P, Akhouri RR, Moradi N, Ojemalm K, Westman M, Angeletti D, Kjellin H, Lehtio J, Blixt O, Idestrom L, Gahmberg CG, Storry JR, Hult AK, Olsson ML, von Heijne G, Nilsson I, Wahlgren M;, Nat Med. 2015;21:314-317.: RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. PUBMED:25751816 EPMC:25751816

  2. Mwakalinga SB, Wang CW, Bengtsson DC, Turner L, Dinko B, Lusingu JP, Arnot DE, Sutherland CJ, Theander TG, Lavstsen T;, Malar J. 2012;11:429.: Expression of a type B RIFIN in Plasmodium falciparum merozoites and gametes. PUBMED:23259643 EPMC:23259643

  3. Hiss JA, Przyborski JM, Schwarte F, Lingelbach K, Schneider G;, PLoS One. 2008;3:e1560.: The Plasmodium export element revisited. PUBMED:18253504 EPMC:18253504


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006373

Malaria is still a major cause of mortality in many areas of the world. Plasmodium falciparum causes the most severe human form of the disease and is responsible for most fatalities. Severe cases of malaria can occur when the parasite invades and then proliferates within red blood cell erythrocytes. The parasite produces many variant antigenic proteins, encoded by multigene families, which are present on the surface of the infected erythrocyte and play important roles in virulence. A crucial survival mechanism for the malaria parasite is its ability to evade the immune response by switching these variant surface antigens. The high virulence of P. falciparum relative to other malarial parasites is in large part due to the fact that in this organism many of these surface antigens mediate the binding of infected erythrocytes to the vascular endothelium (cytoadherence) and non-infected erythrocytes (rosetting). This can lead to the accumulation of infected cells in the vasculature of a variety of organs, blocking the blood flow and reducing the oxygen supply. Clinical symptoms of severe infection can include fever, progressive anaemia, multi-organ dysfunction and coma. For more information see [PUBMED:10885986].

This entry represents the rifin family of variant surface antigens, encoded by the rif (short for "repetetive interspersed family") genes. This is the largest variant surface antigen family in Plasmodium falciparum, with roughly 150 genes present in the genome of this parasite [PUBMED:12368864]. Rifins have a fundamental role in the development of severe malaria [PUBMED:25751816]. They are strongly immunogenic and high levels of anti-rifin antibodies are correlated with rapid parasite clearance and asymptomatic infections [PUBMED:14573641].

All RIFIN sequences contain the PEXEL motif (a pentameric sequence RxLxE/Q/D, known as the Plasmodium export element) required for correct export and surface expression or host-targeting (HT) signal which plays a central role in the export of proteins into the host cell [PUBMED:23259643]. It has been reported that PEXEL is preferably located 15-20 amino acids downstream of an N-terminal hydrophobic signal sequence [PUBMED:18253504]. The RIFIN protein family can be divided into A and B types based on the presence or absence of a 25 amino acid motif located approximately 66 amino acids downstream of the PEXEL motif [PUBMED:18253504], with A- and B-types serving different roles in distinct parasite stages [PUBMED:23259643]. The specific type B RIFIN variant (PF13_0006) is expressed on the surface of free merozoites, internally in developing gametocytes and on the surface of gametes at the point of emerging from activated, mature stage V gametocytes. While type A RIFIN are expressed on the infected erythrocyte surface, potentially contributing to the antigenic variation capacity of the parasite [PUBMED:23259643].

Domain organisation

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Pfam Clan

This family is a member of clan VSA (CL0656), which has the following description:

Members of this clan belong to variant surface antigens (VSA). They are gene products encoded by multi-copy gene families. Four of the largest multi-copy gene families found in the genome of P. falciparum are designated as var, rif (repetitive interspersed family), stevor (subtelomeric variable open reading frame) and pfmc-2tm (P. falciparum Maurer's clefts 2 transmembrane). They code for variable proteins termed PfEMP1 (P. falciparum erythrocyte membrane protein 1), RIFIN, STEVOR and PfMC-2TM, respectively. All small VSA proteins contain a signal peptide and a PEXEL/HT motif. This characteristic as well as their large number and hypervariability support their suggested role in antigenic variation. Antigenic variation and sequestration are strategies used by the malaria parasite P. falciparum to evade antibody mediated immune recognition and splenic clearance [1].

The clan contains the following 2 members:

RIFIN Stevor

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
(254)
Full
(2070)
Representative proteomes UniProt
(3021)
NCBI
(4041)
Meta
(0)
RP15
(152)
RP35
(245)
RP55
(387)
RP75
(1756)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(254)
Full
(2070)
Representative proteomes UniProt
(3021)
NCBI
(4041)
Meta
(0)
RP15
(152)
RP35
(245)
RP55
(387)
RP75
(1756)
Alignment:
Format:
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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
(254)
Full
(2070)
Representative proteomes UniProt
(3021)
NCBI
(4041)
Meta
(0)
RP15
(152)
RP35
(245)
RP55
(387)
RP75
(1756)
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: Lawson D
Previous IDs: Rifin_STEVOR;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Lawson D, El-Gebali S
Number in seed: 254
Number in full: 2070
Average length of the domain: 262.80 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 82.86 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 32.0 32.0
Trusted cut-off 32.0 32.2
Noise cut-off 31.8 31.8
Model length: 321
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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