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2  structures 682  species 0  interactions 2401  sequences 51  architectures

Family: FragX_IP (PF05994)

Summary: Cytoplasmic Fragile-X interacting family

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Cytoplasmic Fragile-X interacting family Provide feedback

This entry includes Cytoplasmic fragile X mental retardation interacting proteins 1/2 (CYFIP1/2) from humans and their homologues, such as Sra-1 (specifically Rac1-associated protein 1) from Drosophila and PIROGI from Arabidopsis. CYFIP1/2 interact with FMRP (fragile X mental retardation protein) which is responsible for pathologic manifestations in the Fragile X Syndrome. CYFIP1 interacts with the small GTPase Rac1 [1,2]. CYFIP1 represses cap-dependent translation of mRNA by interacting with the initiation factor eIF4E [3]. CYFIP1 and CYFIP2 are part of the Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (WAVE) complex that regulates actin polymerization at synapses [4]. Drosophila Sra-1 interacts with the Kette and Wasp. It is required for neuronal and bristle development in Drosophila [5]. PIROGI is part of a WAVE complex that activates the ARP2/3 complex and is Involved in regulation of actin organisation [6].

Literature references

  1. Schenck A, Bardoni B, Moro A, Bagni C, Mandel JL; , Proc Natl Acad Sci U S A 2001;98:8844-8849.: A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P. PUBMED:11438699 EPMC:11438699

  2. Nebel RA, Zhao D, Pedrosa E, Kirschen J, Lachman HM, Zheng D, Abrahams BS;, PLoS One. 2016;11:e0148039.: Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PUBMED:26824476 EPMC:26824476

  3. Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C;, Cell. 2008;134:1042-1054.: The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. PUBMED:18805096 EPMC:18805096

  4. Tiwari SS, Mizuno K, Ghosh A, Aziz W, Troakes C, Daoud J, Golash V, Noble W, Hortobagyi T, Giese KP;, Brain. 2016;139:2751-2765.: Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss. PUBMED:27524794 EPMC:27524794

  5. Bogdan S, Grewe O, Strunk M, Mertens A, Klambt C;, Development. 2004;131:3981-3989.: Sra-1 interacts with Kette and Wasp and is required for neuronal and bristle development in Drosophila. PUBMED:15269173 EPMC:15269173

  6. Basu D, El-Assal Sel-D, Le J, Mallery EL, Szymanski DB;, Development. 2004;131:4345-4355.: Interchangeable functions of Arabidopsis PIROGI and the human WAVE complex subunit SRA1 during leaf epidermal development. PUBMED:15294869 EPMC:15294869


This tab holds annotation information from the InterPro database.

InterPro entry IPR008081

This entry includes cytoplasmic fragile X mental retardation protein interacting proteins from humans and their homologues, such as Sra-1 (specifically Rac1-associated protein 1) from Drosophila and PIROGI from Arabidopsis.

In humans, there are two members, CYFIP1 and CYFIP2. They both interact with FMRP (fragile X mental retardation protein), which is responsible for pathologic manifestations in the Fragile X Syndrome. CYFIP1 interacts with the small GTPase Rac1 [ PUBMED:26824476 , PUBMED:11438699 ]. CYFIP1 represses cap-dependent translation of mRNA by interacting with the initiation factor eIF4E [ PUBMED:18805096 ]. CYFIP1 and CYFIP2 are part of the Wiskott-Aldrich syndrome protein-family verprolin-homologous protein (WAVE) complex that regulates actin polymerization at synapses [ PUBMED:27524794 ].

Drosophila Sra-1 interacts with the Kette and Wasp. It is required for neuronal and bristle development in Drosophila [ PUBMED:15269173 ].

PIROGI is part of a WAVE complex that activates the ARP2/3 complex and is Involved in regulation of actin organization [ PUBMED:15294869 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan Nckap1_CYFIP1-2 (CL0715), which has the following description:

This clan includes components of the WASH and WAVE complexes which are structurally similar and regulate actin cytoskeletal dynamics through the control of Arp2-3 complex-mediated actin assembly [1,2,3]. WAVE is found in all eukaryotic kingdoms and plays a crucial role in many cellular processes including adhesion, migration, division and fusion [1]. In animals, WAVE proteins are important for a wide range of processes such as embryogenesis, neuron morphogenesis and plasticity, immune cell activation and chemotaxis, and cancer invasion and metastasis [1]. WASH, conserved from simple eukaryotes to human, localizes to early endosomal subdomains and regulates endocytic vesicle scission in an Arp2-3-dependent manner [3]. Including in this clan are Cytoplasmic FMR1-interacting proteins CYFIP1 and CYFIP2, Nck-associated protein 1 (Nckap1) from WAVE complex and WASH complex subunit 7 (KIAA1033).

The clan contains the following 3 members:

FragX_IP Nckap1 WASH-4_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 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
(26)
Full
(2401)
Representative proteomes UniProt
(3684)
RP15
(452)
RP35
(942)
RP55
(1846)
RP75
(2463)
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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
(26)
Full
(2401)
Representative proteomes UniProt
(3684)
RP15
(452)
RP35
(942)
RP55
(1846)
RP75
(2463)
Alignment:
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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
(26)
Full
(2401)
Representative proteomes UniProt
(3684)
RP15
(452)
RP35
(942)
RP55
(1846)
RP75
(2463)
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_8072 (release 9.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD
Number in seed: 26
Number in full: 2401
Average length of the domain: 583.40 aa
Average identity of full alignment: 52 %
Average coverage of the sequence by the domain: 66.26 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.3 23.3
Trusted cut-off 23.5 23.8
Noise cut-off 22.7 23.2
Model length: 842
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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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 FragX_IP domain has been found. There are 2 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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