Hedgehog Homolog, Sonic (SHH)

HHG1; HLP3; HPE3; SMMCI; SHHN; SHH-N

SPN	V010
HGNC	10848
MGI	98297
PubMed	8269519
RGD	3673
UniProt	Q15465
Wiki	SHH

Sonic hedgehog (Shh) is a member of a small family of secreted proteins that are essential for development in both vertebrates and invertebrates. In mammals, there are three related hedgehog genes (sonic; desert; Indian) which share approximately 60 % amino acid (aa) identity. Human Shh is synthesized as a 437 aa precursor that contains a 24 aa signal sequence and a 413 aa mature region.

The mature region is autocatalytically processed into a nonglycosylated, 20 kDa, 174 aa N-terminal fragment (Shh-N), and a catalytic-processing, glycosylated, 34 kDa, 239 aa C-terminal fragment.The 20 kDa Shh-N fragment is the core of the active hedgehog molecule. It begins with a Cys and ends with a Gly, and both amino acids are sites of lipid modification.

Reference

"Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog."
Genomics 28:44-51(1995) [PubMed] [Europe PMC] [Abstract]

"Expression of Sonic hedgehog and its receptor Patched/Smoothened in human cancer cell lines and embryonic organs."
J. Biochem. Mol. Biol. Biophys. 4:27-34(2000)

"The DNA sequence of human chromosome 7."
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 7: DNA sequence and biology."
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]

"Identification of a palmitic acid-modified form of human Sonic hedgehog."
J. Biol. Chem. 273:14037-14045(1998) [PubMed] [Europe PMC] [Abstract]

"Products, genetic linkage and limb patterning activity of a murine hedgehog gene."
Development 120:3339-3353(1994) [PubMed] [Europe PMC] [Abstract]

"A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly."
Hum. Mol. Genet. 12:1725-1735(2003) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]

"Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer."
J. Med. Genet. 45:589-595(2008) [PubMed] [Europe PMC] [Abstract]

"A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb."
Hum. Mutat. 31:81-89(2010) [PubMed] [Europe PMC] [Abstract]

"Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome."
Clin. Genet. 86:318-325(2014) [PubMed] [Europe PMC] [Abstract]

"ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly and triphalangeal first fingers."
J. Hum. Genet. 59:467-470(2014) [PubMed] [Europe PMC] [Abstract]

"Mapping sonic hedgehog-receptor interactions by steric interference."
J. Biol. Chem. 275:10995-11001(2000) [PubMed] [Europe PMC] [Abstract]

"The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling."
Nat. Struct. Mol. Biol. 16:691-697(2009) [PubMed] [Europe PMC] [Abstract]

"Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site."
J. Biol. Chem. 285:26570-26580(2010) [PubMed] [Europe PMC] [Abstract]

"Mutations in the human Sonic hedgehog gene cause holoprosencephaly."
Nat. Genet. 14:357-360(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly."
Hum. Mol. Genet. 6:1847-1853(1997) [PubMed] [Europe PMC] [Abstract]

"Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly."
Hum. Mol. Genet. 8:1683-1689(1999) [PubMed] [Europe PMC] [Abstract]

"The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly."
Hum. Mol. Genet. 8:2479-2488(1999) [PubMed] [Europe PMC] [Abstract]

"SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature."
Am. J. Med. Genet. 102:1-10(2001) [PubMed] [Europe PMC] [Abstract]

"Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly."
Hum. Genet. 109:1-6(2001) [PubMed] [Europe PMC] [Abstract]

"Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia."
Am. J. Med. Genet. A 116:215-221(2003) [PubMed] [Europe PMC] [Abstract]

"Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog."
Am. J. Med. Genet. A 127:93-95(2004) [PubMed] [Europe PMC] [Abstract]

"Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation."
Eur. J. Pediatr. 163:347-352(2004) [PubMed] [Europe PMC] [Abstract]

"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations."
Hum. Mutat. 24:43-51(2004) [PubMed] [Europe PMC] [Abstract]

"SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor."
Am. J. Med. Genet. A 136:345-345(2005) [PubMed] [Europe PMC] [Abstract]

"Single median maxillary central incisor, hypophyseal tumor, and SHH mutation."
Am. J. Med. Genet. A 136:346-347(2005) [PubMed] [Europe PMC] [Abstract]

"Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly."
Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005) [PubMed] [Europe PMC] [Abstract]

"Holoprosencephaly-like phenotype: clinical and genetic perspectives."
Am. J. Med. Genet. A 140:2587-2593(2006) [PubMed] [Europe PMC] [Abstract]

"The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis."
Hum. Mutat. 30:E921-E935(2009) [PubMed] [Europe PMC] [Abstract]