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Gene Model: Shh

NomenclatureGenomic Location
SymbolShhChromosome2
NameSonic hedgehog proteinLinkage mapunknown
SpeciesDracomimus familiarisGenome CoordinatesChr2: 19 Mbp

Molecular Function

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.

Molecular Function Terms:

binding
   carbohydrate binding
      polysaccharide binding
         glycosaminoglycan binding
   extracellular matrix binding
      laminin binding
   ion binding
      cation binding
         metal ion binding
   protein binding
      glycoprotein binding
      laminin binding
      patched binding

catalytic activity
   hydrolase activity
      peptidase activity

molecular transducer activity
   signal transducer activity

Human Disease Association

Defects in SHH are the cause of microphthalmia isolated with coloboma type 5 (MCOPCB5) [MIM:611638]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataract and other abnormalities like cataract may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).

Defects in SHH are the cause of holoprosencephaly type 3 (HPE3) [MIM:142945]. Holoprosencephaly (HPE) [MIM:236100] is the most common structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of HPE3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described. Interestingly, up to 30% of obligate carriers of HPE3 gene in autosomal dominant pedigrees are clinically unaffected.

Defects in SHH are a cause of solitary median maxillary central incisor (SMMCI) [MIM:147250]. SMMCI is a rare dental anomaly characterized by the congenital absence of one maxillary central incisor.

Defects in SHH are the cause of triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]. TPTPS is an autosomal dominant syndrome characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development. TPTPS mutations have been mapped to the 7q36 locus in the LMBR1 gene which contains in its intron 5 a long-range cis-regulatory element of SHH expression.

Predicted Transcript
     1 GTGCCGTGGGGCGCGGGGCGGTGGTGTCGGGCTCCGGCGCTGCTGCTCCTGCTGCTCCTC
    61 TGCCCCTCCAGCCTGGCGTGCGGGCCCGGGAGGGGCTTCGGGAAGCGGCGGCACCCCAAG
   121 AAGCTCACGCCCTTGGCCTACAAGCAGTTCATCCCCAACGTGGCCGAGAAGACGCTGGGC
   181 GCCTCCGGGCGCTACGAGGGCAAGATCAGCCGCAGCTCGGAGCGCTTCAAGGAGCTCACC
   241 CCCAACTACAACCCGGACATCATCTTCAAGGATGAGGAGAACACCGGCGCGGACCGGCTC
   301 ATGACCCAGCGTTGCAAGGACAAGCTAAATGCCTTGGCCATCTCAGTGATGAACCAGTGG
   361 CCCGGGGTGAAGCTGCGTGTGACCGAGGGCTGGGACGAGGACGGGCACCACTCCGAGGAG
   421 TCCCTCCACTATGAGGGCCGTGCCGTGGACATCACCACCTCAGATCGGGACCGCAGCAAG
   481 TACGGCATGTTGGCCCGCCTTGCTGTGGAGGCTGGCTTCGACTGGGTCTACTACGAGTCC
   541 AAGGCCCACATCCACTGCTCTGTCAAGGCCGAGAATTCAGTGGCCGCTAAGTCAGGCGGC
   601 TGCTTCCCGGGCACTGCTTGGGTGAACTTGGAGCAAGGAGGCACCAAGCTGGTCAGAGAC
   661 CTCCATCCCGGCGACCGGGTGCTGGCGGCGGACCTGCAAGGCCGGCTGCTCTACAGCGAC
   721 TTCCTAACCTTCTTGGACCAGGAGGAACCTCCCGTCCGCAAGCTCTTCTATGTGATTGAG
   781 ACCCGGAGCCCCCGGACGCGCCTGTTGCTGACGGCCGCTCACCTGCTCTTTGTGGCCTCG
   841 ACACAGAACAACCATTCCCAACCCCAGCCCATTTTTGCCAGCCGGGTGCAGCCGGGACAA
   901 CGCATCTATGTGCTGGGCCACGGGGGGAGGACACTTTTGCCGGCCGCCGTGCACCGAGTG
   961 TCCCTGAAGGAAGAGGCCTCAGGGGCGTACGCCCCGCTCACTGCTCAGGGCACCATCCTC
  1021 ATCAACCAGGTGCTGGCTTCCTGTTATGCCGTCATTGAAGAGCATAGCTGGGCCCACTGG
  1081 GCGTTTGCCCCTTTCCGGGTGGCACATGCCCTCCTGGCCATGCTGTACCCCGCCGGCCTC
  1141 TCGTCCCCCGCCCTCTTTCCGGCTGCAGCACCGGCGGATGCTCCGGGCGGCGTCCATTGG
  1201 TATTCACATCTCCTCTACCATCTTGGTCTTTGGCTGTTGGATTCTGAGACGATGCATCCC
  1261 TTGGGCATGGCCAGCTGA

Predicted Protein Product
VPWGAGRWCRAPALLLLLLLCPSSLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLG
ASGRYEGKISRSSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQW
PGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYES
KAHIHCSVKAENSVAAKSGGCFPGTAWVNLEQGGTKLVRDLHPGDRVLAADLQGRLLYSD
FLTFLDQEEPPVRKLFYVIETRSPRTRLLLTAAHLLFVASTQNNHSQPQPIFASRVQPGQ
RIYVLGHGGRTLLPAAVHRVSLKEEASGAYAPLTAQGTILINQVLASCYAVIEEHSWAHW
AFAPFRVAHALLAMLYPAGLSSPALFPAAAPADAPGGVHWYSHLLYHLGLWLLDSETMHP
LGMAS
Protein Alignment to Mouse
sp|Q62226|SHH_MOUSE Sonic hedgehog protein OS=Mus musculus GN=Shh PE=1 SV=2
      MGI:98297 Shh sonic hedgehog (Chr 5)
        Length = 437

 Score = 1518 (539.4 bits), Expect = 2.0e-156, P = 2.0e-156
 Identities = 304/409 (74%), Positives = 325/409 (79%)

Query:    28 GPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRSSERFKELTPNYNPDI 87
             GPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKI+R+SERFKELTPNYNPDI
Sbjct:    26 GPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKITRNSERFKELTPNYNPDI 85

Query:    88 IFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGR 147
             IFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGR
Sbjct:    86 IFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGR 145

Query:   148 AVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGTAW 207
             AVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPG+A 
Sbjct:   146 AVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSAT 205

Query:   208 VNLEQGGTKLVRDLHPGDRVLAADLQGRLLYSDFLTFLDQEEPPVRKLFYVIETRSPXXX 267
             V+LEQGGTKLV+DL PGDRVLAAD QGRLLYSDFLTFLD++E   +K+FYVIET  P   
Sbjct:   206 VHLEQGGTKLVKDLRPGDRVLAADDQGRLLYSDFLTFLDRDEG-AKKVFYVIETLEPRER 264

Query:   268 XXXXXXXXXFVASTQNNHSQPQP--IFASRVQPGQRIYVLGH--GGRTLLPAAVHRVSLK 323
                      FVA   ++   P P  +FASRV+PGQR+YV+    G R LLPAAVH V+L+
Sbjct:   265 LLLTAAHLLFVAPHNDSGPTPGPSALFASRVRPGQRVYVVAERGGDRRLLPAAVHSVTLR 324

Query:   324 EEASGAYAPLTAQGTILINQVLASCYAVIEEHSWAHWAFAPFRVAHALLAMLYXXXXX-- 381
             EE +GAYAPLTA GTILIN+VLASCYAVIEEHSWAH AFAPFR+AHALLA L        
Sbjct:   325 EEEAGAYAPLTAHGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDGG 384

Query:   382 ------XXXXXXXXXXXXXXXGVXXXXXXXXXXXXXXXDSETMHPLGMA 424
                                  G+               DSETMHPLGMA
Sbjct:   385 GGGSIPAAQSATEARGAEPTAGIHWYSQLLYHIGTWLLDSETMHPLGMA 433