Human Gene SUFU (uc001kvy.2) Description and Page Index
Description: Homo sapiens suppressor of fused homolog (Drosophila) (SUFU), transcript variant 1, mRNA. RefSeq Summary (NM_016169): The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]. Transcript (Including UTRs) Position: hg19 chr10:104,263,719-104,393,214 Size: 129,496 Total Exon Count: 12 Strand: + Coding Region Position: hg19 chr10:104,263,910-104,389,912 Size: 126,003 Coding Exon Count: 12
ID:SUFU_HUMAN DESCRIPTION: RecName: Full=Suppressor of fused homolog; Short=SUFUH; 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). SUBUNIT: May form homodimers. Part of a DNA-bound corepressor complex containing SAP18, GLI1 and SIN3. Part of a complex containing CTNNB1. Binds BTRC, GLI2, GLI3, SAP18 and STK36. Binds both free and DNA-bound GLI1. Interacts with KIF7. Interacts with GLI3FL and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with GLI3FL is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A (By similarity). Interacts with ULK3; inactivating the protein kinase activity of ULK3. INTERACTION: P08151:GLI1; NbExp=4; IntAct=EBI-740621, EBI-308084; Q7Z412:PEX26; NbExp=2; IntAct=EBI-740595, EBI-752057; Q96D15:RCN3; NbExp=2; IntAct=EBI-740595, EBI-746283; Q9NRP7:STK36; NbExp=2; IntAct=EBI-740595, EBI-863797; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. 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. DISEASE: Defects in SUFU are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Defects in SUFU play a role in predisposition to desmoplastic MDB. These tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. SIMILARITY: Belongs to the SUFU family.
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): SUFU CDC HuGE Published Literature: SUFU
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UMX1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
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:0003281 ventricular septum development GO:0006355 regulation of transcription, DNA-templated GO:0006508 proteolysis GO:0007165 signal transduction GO:0007275 multicellular organism 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:0035904 aorta development GO:0042308 negative regulation of protein 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:0060976 coronary vasculature development 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