InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SUFU

Summary

InnateDB Protein

IDBP-88121.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SUFU

Protein Name

suppressor of fused homolog (Drosophila)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000358918

InnateDB Gene

IDBG-88119 (SUFU)

Protein Structure

UniProt Annotation

Function

Negative regulator in the hedgehog signaling pathway. Down-regulates GLI1-mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome. Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full length form of GLI3 (GLI3FL). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU- GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Required for the proper formation of hair follicles and the control of epidermal differentiation (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm. Nucleus.

Disease Associations

Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous in adult tissues. Detected in osteoblasts of the perichondrium in the developing limb of 12-week old embryos. Isoform 1 is detected in fetal brain, lung, kidney and testis. Isoform 2 is detected in fetal testis, and at much lower levels in fetal brain, lung and kidney. {ECO:0000269PubMed:10559945, ECO:0000269PubMed:10564661}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 30 experimentally validated interaction(s) in this database.
They are also associated with 20 interaction(s) predicted by orthology.

Experimentally validated
Total	30 [view]
Protein-Protein	27 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	20 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003714	transcription corepressor activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008134	transcription factor binding
GO:0019901	protein kinase binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001501	skeletal system development
GO:0001843	neural tube closure
GO:0001947	heart looping
GO:0006355	regulation of transcription, DNA-templated
GO:0006508	proteolysis
GO:0007165	signal transduction
GO:0007275	multicellular organismal development
GO:0007368	determination of left/right symmetry
GO:0021513	spinal cord dorsal/ventral patterning
GO:0021775	smoothened signaling pathway involved in ventral spinal cord interneuron specification
GO:0021776	smoothened signaling pathway involved in spinal cord motor neuron cell fate specification
GO:0042992	negative regulation of transcription factor import into nucleus
GO:0042994	cytoplasmic sequestering of transcription factor
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043588	skin development
GO:0045668	negative regulation of osteoblast differentiation
GO:0045879	negative regulation of smoothened signaling pathway
GO:1901621	negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process