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5  structures 737  species 0  interactions 954  sequences 30  architectures

Family: SUFU (PF05076)

Summary: Suppressor of fused protein (SUFU)

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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[edit]

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[edit]

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[edit]

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[edit]

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

References[edit]

  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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Suppressor of fused protein (SUFU) Provide feedback

SUFU, encoding the human orthologue of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signaling. SUFU exerts its repressor role by physically interacting with GLI proteins in both the cytoplasm and the nucleus [1]. SUFU has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway [2]. Genomic contextual analysis of bacterial SUFU versions revealed that they are immunity proteins against diverse nuclease toxins in polymorphic toxin systems [3].

Literature references

  1. Rubin JB, Rowitch DH; , Cancer Cell 2002;2:7-8.: Medulloblastoma: A problem of developmental biology. PUBMED:12150819 EPMC:12150819

  2. 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; , Nat Genet 2002;31:306-310.: Mutations in SUFU predispose to medulloblastoma. PUBMED:12068298 EPMC:12068298

  3. Zhang D, Iyer LM, Aravind L;, Nucleic Acids Res. 2011;39:4532-4552.: A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems. PUBMED:21306995 EPMC:21306995


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR020941

Sufu, encoding the human ortholog of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signalling. It is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade [PUBMED:12150819], and functions by binding these proteins and preventing their translocation to the nucleus. Sufu has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signalling pathway [PUBMED:12068298]. Homologues of Sufu have been found in bacteria, though their function is not currently known. This entry represents a domain found in Sufu and its homologues. In eukaryotic Sufu, an additional domain () is found at the C terminus of the protein. This domain binds to the C-terminal domain of the Gli/Ci transcription factors, inhibiting their activity [PUBMED:15367681].

Domain organisation

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Alignments

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(132)
Full
(954)
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(788)
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(16)
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(80)
RP35
(153)
RP55
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RP75
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  Seed
(132)
Full
(954)
Representative proteomes NCBI
(788)
Meta
(16)
RP15
(80)
RP35
(153)
RP55
(211)
RP75
(252)
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  Seed
(132)
Full
(954)
Representative proteomes NCBI
(788)
Meta
(16)
RP15
(80)
RP35
(153)
RP55
(211)
RP75
(252)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Seed source: Pfam-B_6089 (release 7.7)
Previous IDs: none
Type: Family
Author: Moxon SJ
Number in seed: 132
Number in full: 954
Average length of the domain: 163.50 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 53.36 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.3 19.3
Trusted cut-off 19.3 19.3
Noise cut-off 19.2 19.2
Model length: 169
Family (HMM) version: 8
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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 SUFU domain has been found. There are 5 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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