Aliases for SHH Gene
External Ids for SHH Gene
Previous Symbols for SHH Gene
This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq, Jul 2008]
GeneCards Summary for SHH Gene
SHH (Sonic Hedgehog) is a Protein Coding gene. Diseases associated with SHH include microphthalmia with coloboma 5 and single median maxillary central incisor. Among its related pathways are Signaling by GPCR and Pathways in cancer. GO annotations related to this gene include calcium ion binding and peptidase activity. An important paralog of this gene is IHH.
UniProtKB/Swiss-Prot for SHH Gene
Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO (By similarity).
The hedgehog (Hh) signaling pathway is crucial in the development of all known animals. In the embryo, it regulates morphogenesis of a variety of tissues and organs, in the adult, it controls stem cell proliferation. There are three human Hh proteins; Sonic hedgehog (Shh), Desert hedgehog (Dhh) and Indian hedgehog (Ihh). Each is expressed at different times of development and in specific cell types and they are tightly controlled by highly complex, yet divergent transcriptional enhancers. Hh protein release and diffusion is controlled by various proteins including Skinny hedgehog (Sit), Dispatched (Disp), Tout-velu (Ttv) and Hedgehog-interacting protein (Hip). Hh proteins bind to the twelve transmembrane domain protein, Patched (Ptc). In the absence of Hh proteins, Ptc catalytically inhibits Smo. Hh-Ptc binding results in loss of Ptc activity and activation of Smo, which transduces the Hh signal to the cytoplasm. This leads to the activation of the Ci/GLI family of transcription factors, through complex interactions of Costal2 (Cos2), Fused (Fu) and Suppressor of fu [Su(fu)]. Furthermore, PKA, CK1, GSK-3 and Slimb modulate this signal transduction pathway. Abberant activation of the Hh pathway has been linked to multiple types of human cancer, particularly basal cell carcinoma. Disruption of Hh signaling during embryonic development, either through congenital mutation or maternal teratogen consumption, can lead to severe developmental disorders such as holoprosencephaly.