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0  structures 210  species 0  interactions 273  sequences 7  architectures

Family: C9orf72-like (PF15019)

Summary: C9orf72-like protein family

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C9orf72-like protein family Provide feedback

The precise function of this family is unknown but members have been found to be localised in the cytoplasm of brain tissue. Defects in the gene, C9orf72, are the cause of frontotemporal dementia and/or amyotrophic lateral sclerosis (FTDALS) which is an autosomal dominant neurodegenerative disorder. The disorder is caused by a large expansion of a GGGGCC hexa-nucleotide within the first C9orf72 intron located between the first and the second non-coding exons. The expansion leads to the loss of transcription of one of the two transcripts encoding isoform 1 and to the formation of nuclear RNA foci [1]. This domain family is found in eukaryotes, and is typically between 230 and 250 amino acids in length. There is a single completely conserved residue F that may be functionally important.

Literature references

  1. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R;, Neuron. 2011;72:245-256.: Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. PUBMED:21944778 EPMC:21944778


This tab holds annotation information from the InterPro database.

InterPro entry IPR027819

The entry includes guanine nucleotide exchange C9orf72 protein, a component of the C9orf72-SMCR8 complex, which has guanine nucleotide exchange factor activity [PUBMED:28195531] and regulates autophagy [PUBMED:27193190]. The C9orf72 protein is proposed to be a catalytic component for the exchange of GDP to GTP and promoting autophagosome maturation by converting inactive GDP-bound RAB8A and RAB39B into their active forms [PUBMED:27103069]. Defects in the C9orf72 gene are the cause of frontotemporal dementia and/or amyotrophic lateral sclerosis (FTDALS) which is an autosomal dominant neurodegenerative disorder. The disorder is caused by a large expansion of a GGGGCC hexa-nucleotide within the first C9orf72 intron located between the first and the second non-coding exons. The expansion leads to the loss of transcription of one of the two transcripts encoding isoform 1 and to the formation of nuclear RNA foci [PUBMED:21944778]. This family is found in eukaryotes.

C9orf72 contains the DENN domain, which forms a heart-shaped structure (PDB 3TW8), with the N-terminal residues forming one and the C-terminal residues forming the second one. The tripartite DENN (after differentially expressed in neoplastic versus normal cells) domain is found in several proteins that share common structural features and have been shown to be guanine nucleotide exchange factors (GEFs) for Rab GTPases, which are regulators of practically all membrane trafficking events in eukaryotes [PUBMED:22065758].

Gene Ontology

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Domain organisation

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Alignments

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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
(22)
Full
(273)
Representative proteomes UniProt
(381)
NCBI
(556)
Meta
(0)
RP15
(96)
RP35
(150)
RP55
(224)
RP75
(253)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(22)
Full
(273)
Representative proteomes UniProt
(381)
NCBI
(556)
Meta
(0)
RP15
(96)
RP35
(150)
RP55
(224)
RP75
(253)
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
(22)
Full
(273)
Representative proteomes UniProt
(381)
NCBI
(556)
Meta
(0)
RP15
(96)
RP35
(150)
RP55
(224)
RP75
(253)
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: Jackhmmer:Q96LT7
Previous IDs: FTDALS;
Type: Family
Sequence Ontology: SO:0100021
Author: Coggill P , Hetherington K
Number in seed: 22
Number in full: 273
Average length of the domain: 232.50 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 45.40 %

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 27.0 27.0
Trusted cut-off 27.7 27.1
Noise cut-off 24.6 26.1
Model length: 245
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

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