SHH Antibody – Mouse Monoclonal

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]

SHH: Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. 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. Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues. Belongs to the hedgehog family.

Protein type: Cell cycle regulation; Cell development/differentiation; Motility/polarity/chemotaxis; Oncoprotein

Chromosomal Location of Human Ortholog: 7q36.3

Cellular Component: cell surface; cytosol; endoplasmic reticulum lumen; extracellular region; extracellular space; lipid raft; plasma membrane

Molecular Function: calcium ion binding; laminin-1 binding; morphogen activity; patched binding; protein binding; zinc ion binding

Biological Process: activation of hh target transcription factor; androgen metabolic process; axon guidance; branching morphogenesis of a tube; CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; cell development; cell fate specification; cell-cell signaling; central nervous system development; dorsal/ventral pattern formation; embryonic development; embryonic digit morphogenesis; embryonic limb morphogenesis; embryonic pattern specification; forebrain development; granule cell precursor proliferation; heart development; heart looping; hindbrain development; lung development; lymphoid progenitor cell differentiation; male genitalia development; metanephros development; midbrain development; negative regulation of apoptosis; negative regulation of cell differentiation; negative regulation of cell migration; negative regulation of transcription from RNA polymerase II promoter; negative thymic T cell selection; neural crest cell migration; neuroblast proliferation; neuron fate commitment; pattern specification process; patterning of blood vessels; polarity specification of anterior/posterior axis; positive regulation of alpha-beta T cell differentiation; positive regulation of cell division; positive regulation of cell proliferation; positive regulation of immature T cell proliferation in the thymus; positive regulation of smoothened signaling pathway; positive regulation of T cell differentiation in the thymus; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; positive thymic T cell selection; prostate gland development; regulation of cell proliferation; regulation of odontogenesis; regulation of proteolysis; smoothened signaling pathway; stem cell development; T cell differentiation in the thymus; thymus development; ureteric bud branching; vasculogenesis; ventral midline development

Disease: Holoprosencephaly 3; Microphthalmia, Isolated, With Coloboma 5; Schizencephaly; Solitary Median Maxillary Central Incisor