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28  structures 98  species 1  interaction 124  sequences 7  architectures

Family: SUFU_C (PF12470)

Summary: Suppressor of Fused Gli/Ci N terminal binding domain

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This is the Wikipedia entry entitled "Suppressor of fused Sufu protein N terminal domain". More...

Suppressor of fused Sufu protein N terminal domain Edit Wikipedia article

SUFU
PDB 1m1l EBI.jpg
N terminal domain of the human suppressor of fused (SUFU) protein
Identifiers
Symbol SUFU
Pfam PF05076
InterPro IPR020941

In molecular biology, the protein domain suppressor of fused protein (Sufu) has an important role in the cell. The Sufu is important in negatively regulating an important signalling pathway in the cell, the Hedgehog signalling pathway (HH). This particular pathway is crucial in embryonic development. There are several homologues of Sufu, found in a wide variety of organisms. This particular article focuses on the N-terminal domain of the Sufu protein.

Function

Sufu has also been found to have a crucial role in tumour suppression. To be more specific, it has a tumour-suppressor gene that predisposes, or in other words makes individuals more susceptible to medulloblastoma, because it modulates the SHH signalling pathway.[1] The N-terminal domain, which this entry refers to;contains Gli transcription factors.[2]

Conservation

The human ortholog of Drosophila suppressor of fused, has a conserved sequence, this means that particular amino acids have remained the same throughout evolution. Consequently, they have very similar roles in repressing Hedgehog signalling. It represses the Gli and Ci transcription factors of the Hedgehog pathway,[3] and functions by binding to these proteins and preventing their translocation to the nucleus. Homologues of Sufu have been found in bacteria. However their function remains to be elucidated.

Structure

Sufu is actually protein that contains two domains.[2]In eukaryotic Sufu, an additional domain is found at the C terminus of the protein. This protein domain also binds to the C-terminal domain of the Gli/Ci transcription factors, inhibiting their activity.[4]

Genes

Human gene that encodes SUFU, also named SUFU, is found to be localized on chromosome 10q24–25, and contains 12 exons.[3]

References

  1. ^ Taylor MD, Liu L, Raffel C, Hui CC, Mainprize TG, Zhang X, Agatep R, Chiappa S, Gao L, Lowrance A, Hao A, Goldstein AM, Stavrou T, Scherer SW, Dura WT, Wainwright B, Squire JA, Rutka JT, Hogg D (July 2002). "Mutations in SUFU predispose to medulloblastoma". Nat. Genet. 31 (3): 306–10. doi:10.1038/ng916. PMID 12068298. 
  2. ^ a b Das D, Finn RD, Abdubek P, Astakhova T, Axelrod HL, Bakolitsa C, et al. (2010). "The crystal structure of a bacterial Sufu-like protein defines a novel group of bacterial proteins that are similar to the N-terminal domain of human Sufu.". Protein Sci 19 (11): 2131–40. doi:10.1002/pro.497. PMC 3005784. PMID 20836087. 
  3. ^ a b Rubin JB, Rowitch DH (July 2002). "Medulloblastoma: a problem of developmental biology". Cancer Cell 2 (1): 7–8. doi:10.1016/S1535-6108(02)00090-9. PMID 12150819. 
  4. ^ Merchant M, Vajdos FF, Ultsch M, Maun HR, Wendt U, Cannon J, Desmarais W, Lazarus RA, de Vos AM, de Sauvage FJ (October 2004). "Suppressor of fused regulates Gli activity through a dual binding mechanism". Mol. Cell. Biol. 24 (19): 8627–41. doi:10.1128/MCB.24.19.8627-8641.2004. PMC 516763. PMID 15367681. 

This article incorporates text from the public domain Pfam and InterPro IPR020941

External links

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Suppressor of Fused Gli/Ci N terminal binding domain Provide feedback

This domain family is found in eukaryotes, and is typically between 192 and 219 amino acids in length. The family is found in association with PF05076. There is a conserved HGRHFT sequence motif. This family is the C terminal domain of the Suppressor of Fused protein (Su(fu)). Su(fu) is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade. It functions by binding these proteins and preventing their translocation to the nucleus. The C terminal domain is only found in eukaryotic Su(fu) proteins; it is not present in bacterial homologues. The C terminal domain binds to the N terminal of Gli/Ci while the N terminal of Su(fu) binds to the C terminal of Gli/Ci. This dual binding mechanism is likely an evolutionary advancement in this signalling cascade which is not present in bacterial homologues.

Literature references

  1. Merchant M, Vajdos FF, Ultsch M, Maun HR, Wendt U, Cannon J, Desmarais W, Lazarus RA, de Vos AM, de Sauvage FJ;, Mol Cell Biol. 2004;24:8627-8641.: Suppressor of fused regulates Gli activity through a dual binding mechanism. PUBMED:15367681 EPMC:15367681


This tab holds annotation information from the InterPro database.

InterPro entry IPR024314

This entry represents a domain found in the C-terminal of eukaryotic suppressor of fused (Sufu) proteins; it is not present in bacterial homologues.

Sufu is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade. It functions by binding to these proteins and preventing their translocation to the nucleus. The Sufu C-terminal domain binds to the N-terminal of Gli/Ci, while the N-terminal of Sufu binds to the C-terminal of Gli/Ci. This dual binding mechanism is likely to be an evolutionary advancement in this signalling cascade, which is not present in bacterial homologues [PUBMED:15367681].

Gene Ontology

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Domain organisation

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Alignments

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(216)
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(425)
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RP35
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RP55
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RP75
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  Seed
(16)
Full
(124)
Representative proteomes UniProt
(216)
NCBI
(425)
Meta
(0)
RP15
(36)
RP35
(57)
RP55
(85)
RP75
(109)
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  Seed
(16)
Full
(124)
Representative proteomes UniProt
(216)
NCBI
(425)
Meta
(0)
RP15
(36)
RP35
(57)
RP55
(85)
RP75
(109)
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.

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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.

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Curation and family details

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Curation View help on the curation process

Seed source: Manual
Previous IDs: none
Type: Family
Author: Gavin OL
Number in seed: 16
Number in full: 124
Average length of the domain: 183.50 aa
Average identity of full alignment: 50 %
Average coverage of the sequence by the domain: 38.91 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 30.9 29.3
Noise cut-off 22.4 21.9
Model length: 211
Family (HMM) version: 5
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Species distribution

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Interactions

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SUFU

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 SUFU_C domain has been found. There are 28 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 seqence.

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