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SUFU

Function

Negative regulator in the hedgehog/smoothened signaling pathway (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:12068298, PubMed:12975309, PubMed:15367681, PubMed:22365972, PubMed:24217340, PubMed:24311597, PubMed:27234298, PubMed:28965847). Down-regulates GLI1-mediated transactivation of target genes (PubMed:15367681, PubMed:24217340, PubMed:24311597). Down-regulates GLI2-mediated transactivation of target genes (PubMed:24217340, PubMed:24311597). 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 (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:24217340). Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein (PubMed:10559945, PubMed:10564661, PubMed:10806483, PubMed:24217340). Negative regulator of beta-catenin signaling (By similarity). Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3 (GLI3FL) (PubMed:24311597, PubMed:28965847). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state (PubMed:24311597, PubMed:28965847). Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R (PubMed:24311597, PubMed:28965847). 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) (PubMed:24311597, PubMed:28965847). Required for normal embryonic development (By similarity). Required for the proper formation of hair follicles and the control of epidermal differentiation (By similarity).

Involvement in disease

Medulloblastoma

MDB

Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.

None

The disease is caused by variants affecting the gene represented in this entry.

Joubert syndrome 32

JBTS32

A form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS32 inheritance is autosomal recessive.

None

The disease is caused by variants affecting the gene represented in this entry.

Basal cell nevus syndrome 2

BCNS2

A form of basal cell nevus syndrome, a disease characterized by nevoid basal cell carcinomas and developmental abnormalities such as rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In addition, the patients suffer from a multitude of tumors like fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Polyubiquitinated at Lys-257 by the SCF(FBXL17) complex, leading to its subsequent degradation and allowing the release of GLI1 for proper hedgehog/smoothened signal transduction (PubMed:27234298). Ubiquitination is impaired by phosphorylation at Ser-342, Ser-346, Ser-352 and Thr-353 (PubMed:27234298).

Phosphorylation at Ser-342, Ser-346, Ser-352 and Thr-353 prevents ubiquitination by the SCF(FBXL17) complex.

Sequence Similarities

Belongs to the SUFU family.

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.

Cellular localization

Alternative names

UNQ650/PRO1280, SUFU, Suppressor of fused homolog, SUFUH

swissprot:Q9UMX1 omim:607035 entrezGene:51684

Other research areas