Homo sapiens Gene: SHH
Summary
InnateDB Gene IDBG-50464.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SHH
Gene Name sonic hedgehog
Synonyms HHG1; HLP3; HPE3; MCOPCB5; SMMCI; TPT; TPTPS;
Species Homo sapiens
Ensembl Gene ENSG00000164690
Encoded Proteins
sonic hedgehog
sonic hedgehog
sonic hedgehog
sonic hedgehog
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
Entrez Gene
Summary 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]
Gene Information
Type Protein coding
Genomic Location Chromosome 7:155799986-155812273
Strand Reverse strand
Band q36.3
Transcripts
ENST00000297261 ENSP00000297261
ENST00000441114 ENSP00000410546
ENST00000430104 ENSP00000396621
ENST00000435425 ENSP00000413871
ENST00000472308
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
Experimentally validated
Total 8 [view]
Protein-Protein 7 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 6 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001948 glycoprotein binding
GO:0005113 patched binding
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0005539 glycosaminoglycan binding
GO:0008233 peptidase activity
GO:0008270 zinc ion binding
GO:0016015 morphogen activity
GO:0043237 laminin-1 binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001525 angiogenesis
GO:0001569 patterning of blood vessels
GO:0001570 vasculogenesis
GO:0001656 metanephros development
GO:0001658 branching involved in ureteric bud morphogenesis
GO:0001708 cell fate specification
GO:0001755 neural crest cell migration
GO:0001822 kidney development
GO:0001942 hair follicle development
GO:0001944 vasculature development
GO:0001947 heart looping
GO:0002052 positive regulation of neuroblast proliferation
GO:0002053 positive regulation of mesenchymal cell proliferation
GO:0002076 osteoblast development
GO:0002320 lymphoid progenitor cell differentiation
GO:0003140 determination of left/right asymmetry in lateral mesoderm
GO:0006355 regulation of transcription, DNA-templated
GO:0006508 proteolysis
GO:0006897 endocytosis
GO:0006915 apoptotic process
GO:0007154 cell communication
GO:0007224 smoothened signaling pathway
GO:0007228 positive regulation of hh target transcription factor activity
GO:0007267 cell-cell signaling
GO:0007275 multicellular organismal development
GO:0007368 determination of left/right symmetry
GO:0007389 pattern specification process
GO:0007398 ectoderm development
GO:0007405 neuroblast proliferation
GO:0007411 axon guidance
GO:0007417 central nervous system development
GO:0007418 ventral midline development
GO:0007442 hindgut morphogenesis
GO:0007507 heart development
GO:0007596 blood coagulation
GO:0008209 androgen metabolic process
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0009790 embryo development
GO:0009880 embryonic pattern specification
GO:0009949 polarity specification of anterior/posterior axis
GO:0009952 anterior/posterior pattern specification
GO:0009953 dorsal/ventral pattern formation
GO:0010463 mesenchymal cell proliferation
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0014003 oligodendrocyte development
GO:0014706 striated muscle tissue development
GO:0014858 positive regulation of skeletal muscle cell proliferation
GO:0014902 myotube differentiation
GO:0016539 intein-mediated protein splicing
GO:0021513 spinal cord dorsal/ventral patterning
GO:0021522 spinal cord motor neuron differentiation
GO:0021794 thalamus development
GO:0021904 dorsal/ventral neural tube patterning
GO:0021930 cerebellar granule cell precursor proliferation
GO:0021938 smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
GO:0021940 positive regulation of cerebellar granule cell precursor proliferation
GO:0021978 telencephalon regionalization
GO:0030010 establishment of cell polarity
GO:0030162 regulation of proteolysis
GO:0030177 positive regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030326 embryonic limb morphogenesis
GO:0030336 negative regulation of cell migration
GO:0030539 male genitalia development
GO:0030850 prostate gland development
GO:0030878 thyroid gland development
GO:0030900 forebrain development
GO:0030901 midbrain development
GO:0030902 hindbrain development
GO:0031016 pancreas development
GO:0031069 hair follicle morphogenesis
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0033077 T cell differentiation in thymus
GO:0033089 positive regulation of T cell differentiation in thymus
GO:0033092 positive regulation of immature T cell proliferation in thymus
GO:0034244 negative regulation of transcription elongation from RNA polymerase II promoter
GO:0034504 protein localization to nucleus
GO:0035115 embryonic forelimb morphogenesis
GO:0035116 embryonic hindlimb morphogenesis
GO:0042127 regulation of cell proliferation
GO:0042130 negative regulation of T cell proliferation
GO:0042177 negative regulation of protein catabolic process
GO:0042307 positive regulation of protein import into nucleus
GO:0042475 odontogenesis of dentin-containing tooth
GO:0042476 odontogenesis
GO:0042481 regulation of odontogenesis
GO:0042733 embryonic digit morphogenesis
GO:0043010 camera-type eye development
GO:0043066 negative regulation of apoptotic process
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0043588 skin development
GO:0045059 positive thymic T cell selection
GO:0045060 negative thymic T cell selection
GO:0045109 intermediate filament organization
GO:0045165 cell fate commitment
GO:0045445 myoblast differentiation
GO:0045596 negative regulation of cell differentiation
GO:0045597 positive regulation of cell differentiation
GO:0045880 positive regulation of smoothened signaling pathway
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046638 positive regulation of alpha-beta T cell differentiation
GO:0046639 negative regulation of alpha-beta T cell differentiation
GO:0048468 cell development
GO:0048538 thymus development
GO:0048546 digestive tract morphogenesis
GO:0048557 embryonic digestive tract morphogenesis
GO:0048568 embryonic organ development
GO:0048589 developmental growth
GO:0048598 embryonic morphogenesis
GO:0048617 embryonic foregut morphogenesis
GO:0048643 positive regulation of skeletal muscle tissue development
GO:0048645 organ formation
GO:0048646 anatomical structure formation involved in morphogenesis
GO:0048663 neuron fate commitment
GO:0048706 embryonic skeletal system development
GO:0048709 oligodendrocyte differentiation
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0048754 branching morphogenesis of an epithelial tube
GO:0048839 inner ear development
GO:0048856 anatomical structure development
GO:0048859 formation of anatomical boundary
GO:0048864 stem cell development
GO:0051146 striated muscle cell differentiation
GO:0051155 positive regulation of striated muscle cell differentiation
GO:0051781 positive regulation of cell division
GO:0060020 Bergmann glial cell differentiation
GO:0060021 palate development
GO:0060070 canonical Wnt signaling pathway
GO:0060173 limb development
GO:0060174 limb bud formation
GO:0060425 lung morphogenesis
GO:0060428 lung epithelium development
GO:0060438 trachea development
GO:0060439 trachea morphogenesis
GO:0060441 epithelial tube branching involved in lung morphogenesis
GO:0060442 branching involved in prostate gland morphogenesis
GO:0060445 branching involved in salivary gland morphogenesis
GO:0060447 bud outgrowth involved in lung branching
GO:0060458 right lung development
GO:0060459 left lung development
GO:0060463 lung lobe morphogenesis
GO:0060484 lung-associated mesenchyme development
GO:0060516 primary prostatic bud elongation
GO:0060523 prostate epithelial cord elongation
GO:0060662 salivary gland cavitation
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060684 epithelial-mesenchymal cell signaling
GO:0060685 regulation of prostatic bud formation
GO:0060738 epithelial-mesenchymal signaling involved in prostate gland development
GO:0060768 regulation of epithelial cell proliferation involved in prostate gland development
GO:0060769 positive regulation of epithelial cell proliferation involved in prostate gland development
GO:0060782 regulation of mesenchymal cell proliferation involved in prostate gland development
GO:0060783 mesenchymal smoothened signaling pathway involved in prostate gland development
GO:0060840 artery development
GO:0060916 mesenchymal cell proliferation involved in lung development
GO:0061053 somite development
GO:0061189 positive regulation of sclerotome development
GO:0071285 cellular response to lithium ion
GO:0072001 renal system development
GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros development
GO:0080125 multicellular structure septum development
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0090370 negative regulation of cholesterol efflux
GO:0097190 apoptotic signaling pathway
GO:1900175 regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:1900180 regulation of protein localization to nucleus
GO:2000062 negative regulation of ureter smooth muscle cell differentiation
GO:2000063 positive regulation of ureter smooth muscle cell differentiation
GO:2000357 negative regulation of kidney smooth muscle cell differentiation
GO:2000358 positive regulation of kidney smooth muscle cell differentiation
GO:2000729 positive regulation of mesenchymal cell proliferation involved in ureter development
GO:2001054 negative regulation of mesenchymal cell apoptotic process
Cellular Component
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0031012 extracellular matrix
GO:0045121 membrane raft
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Not yet available
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Pathways
NETPATH
Hedgehog pathway
REACTOME
Processing-defective Hh variants abrogate ligand secretion pathway
Signaling by Hedgehog pathway
Release of Hh-Np from the secreting cell pathway
Signaling by GPCR pathway
Signal Transduction pathway
Hh ligand biogenesis disease pathway
Hedgehog ligand biogenesis pathway
GPCR ligand binding pathway
Class B/2 (Secretin family receptors) pathway
Disease pathway
KEGG
Hedgehog signaling pathway pathway
Pathways in cancer pathway
Basal cell carcinoma pathway
INOH
GPCR signaling pathway
Hedgehog signaling pathway pathway
PID BIOCARTA
Sonic hedgehog receptor ptc1 regulates cell cycle [Biocarta view]
PID NCI
Glypican 3 network
Signaling events mediated by the Hedgehog family
Hedgehog signaling events mediated by Gli proteins
Validated transcriptional targets of TAp63 isoforms
FOXA1 transcription factor network
Cross-References
SwissProt
TrEMBL C9JC48
UniProt Splice Variant
Entrez Gene 6469
UniGene Hs.164537 Hs.606487 Hs.609372 Hs.619304 Hs.731051 Hs.738995
RefSeq NM_000193
HUGO HGNC:10848
OMIM 600725
CCDS CCDS5942
HPRD 02838
IMGT
EMBL AC078834
GenPept
RNA Seq Atlas 6469