SHH sonic hedgehog [ Homo sapiens (human) ]

Gene ID: 6469, updated on 12-Aug-2018

Summary

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Official Symbol: SHHprovided by HGNC
Official Full Name: sonic hedgehogprovided by HGNC
Primary source: HGNC:HGNC:10848
See related: Ensembl:ENSG00000164690 MIM:600725; Vega:OTTHUMG00000151349
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TPT; HHG1; HLP3; HPE3; SMMCI; ShhNC; TPTPS; MCOPCB5
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]
Expression: Biased expression in stomach (RPKM 3.1), urinary bladder (RPKM 2.9) and 10 other tissues See more
Orthologs: mouse all

Genomic context

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See SHH in Genome Data Viewer

Location:: 7q36.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	7	NC_000007.14 (155799984..155812273, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (155595558..155604967, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

SHH-related signaling pathway affects antineoplastic drug resistance in cultured glioma cells.
Title: Relationship between Hedgehog Signaling Pathway and Drug Resistance of Poorly Differentiated Gliomas.
SHH is expressed in cilia in the airway epithelial cells.SHH may mediate noncanonical hedgehog signaling through motile cilia to dampen respiratory defenses.
Title: Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.
High SHH expression is associated with radioresistance in esophageal adenocarcinoma.
Title: Hedgehog inhibition mediates radiation sensitivity in mouse xenograft models of human esophageal adenocarcinoma.
Identify SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts and the subsequent proliferation of smooth muscle cells and neointima formation.
Title: Sonic hedgehog-dependent activation of adventitial fibroblasts promotes neointima formation.
In conclusion, our data suggest that overexpression of the Hedgehog components SHH, GLI2 and FOXA2 might be used as markers of an aggressive hemangioma.
Title: Transcriptional activation of Hedgehog pathway components in aggressive haemangioma.
These findings showed the upexpression of sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins which imply that the reducing hypoxia or using sonic hedgehog antagonists may be helpful for this vascular disease.
Title: Increased expression of the sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins.
Shh and Gli1 expression were associated with lymph node metastasis, TNM stage and tumor recurrence, suggesting Shh and Gli1 protein could become the valuable biomarker in evaluating the lymph node metastasis in oral squamous cell carcinoma.
Title: Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway.
Epithelial-mesenchymal transition programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling.
Title: EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling.
Case Report: medullablastoma with activated SHH expression.
Title: Medulloblastoma with extensive nodularity (SHH medulloblastoma).
NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous buildup (scar tissue) and inflammation of the liver tissue. For the first time patients with holoprosencephaly, a disease caused by SHH signaling mutations, are shown to have increased liver steatosis independent of obesity.
Title: Human germline hedgehog pathway mutations predispose to fatty liver.

Submit: New GeneRIF Correction See all GeneRIFs (410)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Holoprosencephaly 3 MedGen: C1840529 OMIM: 142945 GeneReviews: Microphthalmia/Anophthalmia/Coloboma Spectrum, Holoprosencephaly Overview	Compare labs
Microphthalmia, isolated, with coloboma 5 MedGen: C1968843 OMIM: 611638 GeneReviews: Microphthalmia/Anophthalmia/Coloboma Spectrum	Compare labs
SCHIZENCEPHALY MedGen: C0266484 OMIM: 269160 GeneReviews: Not available	Compare labs
Single median maxillary incisor MedGen: C1840235 OMIM: 147250 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity Little evidence for dosage pathogenicity (Last evaluated (2012-02-23) ClinGen Genome Curation PagePubMed Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated (2012-02-23) ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Identification of a candidate gene for astigmatism. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Activation of SMO, organism-specific biosystem (from REACTOME)
Activation of SMO, organism-specific biosystemActivation of the transmembrane protein SMO in response to Hh stimulation is a major control point in the Hh signaling pathway (reviewed in Ayers and Therond, 2010; Jiang and Hui, 2008). In the absen...
Axon guidance, organism-specific biosystem (from KEGG)
Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
Axon guidance, conserved biosystem (from KEGG)
Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
Basal cell carcinoma, organism-specific biosystem (from KEGG)
Basal cell carcinoma, organism-specific biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Basal cell carcinoma, conserved biosystem (from KEGG)
Basal cell carcinoma, conserved biosystemCancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare fam...
Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
Differentiation Pathway, organism-specific biosystem (from WikiPathways)
Differentiation Pathway, organism-specific biosystemThis pathway provides an overview of the directed differentiation molecules used to induce early and derivative cell lineages from human pluripotent stem cells. The initial version of this pathway is...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Diseases of signal transduction, organism-specific biosystem (from REACTOME)
Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
Dopaminergic Neurogenesis, organism-specific biosystem (from WikiPathways)
Dopaminergic Neurogenesis, organism-specific biosystemConverted to human from mouse: http://www.wikipathways.org/index.php/Pathway:WP1498
Ectoderm Differentiation, organism-specific biosystem (from WikiPathways)
Ectoderm Differentiation, organism-specific biosystemModel depicting ectoderm specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell lin...
FOXA1 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
FOXA1 transcription factor network, organism-specific biosystem
FOXA1 transcription factor network
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
Glypican 3 network, organism-specific biosystem (from Pathway Interaction Database)
Glypican 3 network, organism-specific biosystem
Glypican 3 network
HHAT G278V abrogates palmitoylation of Hh-Np, organism-specific biosystem (from REACTOME)
HHAT G278V abrogates palmitoylation of Hh-Np, organism-specific biosystemA loss-of-function mutation in HHAT that abrogates palmitoylation of Hh ligand is associated with Syndromic 46, XY Disorder of Sex Development, which results in testis dysgenesis (Callier et al, 2014...
Heart Development, organism-specific biosystem (from WikiPathways)
Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
Hedgehog 'on' state, organism-specific biosystem (from REACTOME)
Hedgehog 'on' state, organism-specific biosystemHedgehog is a secreted morphogen that has evolutionarily conserved roles in body organization by regulating the activity of the Ci/Gli transcription factor family. In Drosophila in the absence of Hh ...
Hedgehog Signaling Pathway, organism-specific biosystem (from WikiPathways)
Hedgehog Signaling Pathway, organism-specific biosystemThe Hedgehog family of proteins are signaling proteins that are crucial for a number of physiological processes including morphogenesis during development. In adult organisms, it is also involved in ...
Hedgehog ligand biogenesis, organism-specific biosystem (from REACTOME)
Hedgehog ligand biogenesis, organism-specific biosystemMammalian genomes encode three Hedgehog ligands, Sonic Hedgehog (SHH), Indian Hedgehog (IHH) and Desert Hedgehog (DHH). These secreted morphogens can remain associated with lipid rafts on the surfac...
Hedgehog signaling, organism-specific biosystem (from KEGG)
Hedgehog signaling, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling, conserved biosystem (from KEGG)
Hedgehog signaling, conserved biosystemFunctional set; Cellular processes; Cell signaling
Hedgehog signaling events mediated by Gli proteins, organism-specific biosystem (from Pathway Interaction Database)
Hedgehog signaling events mediated by Gli proteins, organism-specific biosystem
Hedgehog signaling events mediated by Gli proteins
Hedgehog signaling pathway, organism-specific biosystem (from KEGG)
Hedgehog signaling pathway, organism-specific biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Hedgehog signaling pathway, conserved biosystem (from KEGG)
Hedgehog signaling pathway, conserved biosystemThe Hedgehog (Hh) signaling pathway has numerous roles in the control of cell proliferation, tissue patterning, stem cell maintenance and development. The primary cilium is an important center for tr...
Hh mutants abrogate ligand secretion, organism-specific biosystem (from REACTOME)
Hh mutants abrogate ligand secretion, organism-specific biosystemHh signaling is required for a number of developmental processes, and mutations that disrupt the normal processing and biogenesis of Hh ligand can result in neonatal abnormalities. SHH is one of a n...
Hh mutants that don't undergo autocatalytic processing are degraded by ERAD, organism-specific biosystem (from REACTOME)
Hh mutants that don't undergo autocatalytic processing are degraded by ERAD, organism-specific biosystemHh signaling is required for a number of developmental processes, and mutations that disrupt the normal processing and biogenesis of Hh ligand can result in neonatal abnormalities. SHH is one of a n...
Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
Ligand-receptor interactions, organism-specific biosystem (from REACTOME)
Ligand-receptor interactions, organism-specific biosystemRepression of Hh signaling in the absence of ligand depends on the transmembrane receptor protein Patched (PTCH), which inhibits Smoothened (SMO) activity by an unknown mechanism. This promotes the p...
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
Proteoglycans in cancer, organism-specific biosystem (from KEGG)
Proteoglycans in cancer, organism-specific biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Proteoglycans in cancer, conserved biosystem (from KEGG)
Proteoglycans in cancer, conserved biosystemMany proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis a...
Release of Hh-Np from the secreting cell, organism-specific biosystem (from REACTOME)
Release of Hh-Np from the secreting cell, organism-specific biosystemCholesterol and palmitoyl-modification of Hh-Np render the ligand highly hydrophobic and results in its close association with the plasma membrane of the producing cell after secretion. Hh-Np tether...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
Signaling by Hedgehog, organism-specific biosystem (from REACTOME)
Signaling by Hedgehog, organism-specific biosystemHedgehog (Hh) is a secreted morphogen that regulates developmental processes in vertebrates including limb bud formation, neural tube patterning, cell growth and differentiation (reviewed in Hui and ...
Signaling events mediated by the Hedgehog family, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by the Hedgehog family, organism-specific biosystem
Signaling events mediated by the Hedgehog family
Tgif disruption of Shh signaling, organism-specific biosystem (from WikiPathways)
Tgif disruption of Shh signaling, organism-specific biosystemMutations in the Sonic Hedgehog(SHH) gene result in HPE in humans and mice, and the Shh pathway is targeted by other mutations that cause HPE. HPE is a severe human genetic disease affecting craniofa...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71367 (e-PCR)
- UniSTS:49423

GDB:456307 (e-PCR)
- UniSTS:157484

D7S550 (e-PCR)
- UniSTS:67923

Shh (e-PCR), detects polymorphism
- UniSTS:465494

Shh (e-PCR), detects polymorphism
- UniSTS:238169

D7S559 (e-PCR), detects polymorphism
- UniSTS:148075

RH69762 (e-PCR)
- UniSTS:9070

NoName (e-PCR)
- UniSTS:481236

Shh (e-PCR), detects polymorphism
- UniSTS:547824

Homology

Homologs of the SHH gene: The SHH gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 203 organisms have orthologs with human gene SHH
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
endopeptidase activity	TAS Traceable Author Statement more info
glycosaminoglycan binding	IEA Inferred from Electronic Annotation more info
laminin-1 binding	ISS Inferred from Sequence or Structural Similarity more info
morphogen activity	NAS Non-traceable Author Statement more info	PubMed
morphogen activity	TAS Traceable Author Statement more info	PubMed
patched binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
Bergmann glial cell differentiation	IEA Inferred from Electronic Annotation more info
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	IDA Inferred from Direct Assay more info	PubMed
T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
androgen metabolic process	ISS Inferred from Sequence or Structural Similarity more info
animal organ formation	IEA Inferred from Electronic Annotation more info
apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
artery development	IEA Inferred from Electronic Annotation more info
axon guidance	ISS Inferred from Sequence or Structural Similarity more info
blood coagulation	IEA Inferred from Electronic Annotation more info
branching involved in blood vessel morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
branching involved in salivary gland morphogenesis	IEA Inferred from Electronic Annotation more info
branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
branching morphogenesis of an epithelial tube	ISS Inferred from Sequence or Structural Similarity more info
bud outgrowth involved in lung branching	IEA Inferred from Electronic Annotation more info
camera-type eye development	IEA Inferred from Electronic Annotation more info
canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
cell development	ISS Inferred from Sequence or Structural Similarity more info
cell fate specification	ISS Inferred from Sequence or Structural Similarity more info
cell-cell signaling	ISS Inferred from Sequence or Structural Similarity more info
cellular response to lithium ion	IEA Inferred from Electronic Annotation more info
central nervous system development	ISS Inferred from Sequence or Structural Similarity more info
cerebellar granule cell precursor proliferation	ISS Inferred from Sequence or Structural Similarity more info
determination of left/right asymmetry in lateral mesoderm	ISS Inferred from Sequence or Structural Similarity more info
dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
dorsal/ventral neural tube patterning	IEA Inferred from Electronic Annotation more info
dorsal/ventral pattern formation	ISS Inferred from Sequence or Structural Similarity more info
ectoderm development	IEA Inferred from Electronic Annotation more info
embryonic digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic digit morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
embryonic foregut morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic forelimb morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic hindlimb morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic limb morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
embryonic pattern specification	TAS Traceable Author Statement more info	PubMed
embryonic skeletal system development	IEA Inferred from Electronic Annotation more info
endocytosis	IEA Inferred from Electronic Annotation more info
epithelial cell proliferation involved in salivary gland morphogenesis	IEA Inferred from Electronic Annotation more info
epithelial-mesenchymal signaling involved in prostate gland development	IDA Inferred from Direct Assay more info	PubMed
establishment of cell polarity	IEA Inferred from Electronic Annotation more info
forebrain development	ISS Inferred from Sequence or Structural Similarity more info
formation of anatomical boundary	IEA Inferred from Electronic Annotation more info
hair follicle morphogenesis	IEA Inferred from Electronic Annotation more info
heart development	ISS Inferred from Sequence or Structural Similarity more info
heart looping	ISS Inferred from Sequence or Structural Similarity more info
hindbrain development	ISS Inferred from Sequence or Structural Similarity more info
hindgut morphogenesis	IEA Inferred from Electronic Annotation more info
inner ear development	IEA Inferred from Electronic Annotation more info
intein-mediated protein splicing	IEA Inferred from Electronic Annotation more info
intermediate filament organization	IEA Inferred from Electronic Annotation more info
left lung development	IEA Inferred from Electronic Annotation more info
limb bud formation	IEA Inferred from Electronic Annotation more info
lung development	ISS Inferred from Sequence or Structural Similarity more info
lung epithelium development	IEA Inferred from Electronic Annotation more info
lung lobe morphogenesis	IEA Inferred from Electronic Annotation more info
lung-associated mesenchyme development	IEA Inferred from Electronic Annotation more info
lymphoid progenitor cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
male genitalia development	ISS Inferred from Sequence or Structural Similarity more info
mesenchymal cell proliferation involved in lung development	IEA Inferred from Electronic Annotation more info
mesenchymal smoothened signaling pathway involved in prostate gland development	IEA Inferred from Electronic Annotation more info
metanephric mesenchymal cell proliferation involved in metanephros development	ISS Inferred from Sequence or Structural Similarity more info
metanephros development	ISS Inferred from Sequence or Structural Similarity more info
midbrain development	ISS Inferred from Sequence or Structural Similarity more info
myoblast differentiation	IEA Inferred from Electronic Annotation more info
myotube differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of T cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of alpha-beta T cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cell migration	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of cholesterol efflux	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of kidney smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of mesenchymal cell apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of transcription elongation from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
negative regulation of ureter smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative thymic T cell selection	ISS Inferred from Sequence or Structural Similarity more info
neural crest cell migration	ISS Inferred from Sequence or Structural Similarity more info
neuroblast proliferation	ISS Inferred from Sequence or Structural Similarity more info
neuron fate commitment	ISS Inferred from Sequence or Structural Similarity more info
odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
oligodendrocyte development	IEA Inferred from Electronic Annotation more info
osteoblast development	IEA Inferred from Electronic Annotation more info
pancreas development	IEA Inferred from Electronic Annotation more info
pattern specification process	ISS Inferred from Sequence or Structural Similarity more info
polarity specification of anterior/posterior axis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell division	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of epithelial cell proliferation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
positive regulation of hh target transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of immature T cell proliferation in thymus	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of kidney smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of mesenchymal cell proliferation involved in ureter development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuroblast proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of protein import into nucleus	IEA Inferred from Electronic Annotation more info
positive regulation of sclerotome development	IDA Inferred from Direct Assay more info	PubMed
positive regulation of skeletal muscle cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of skeletal muscle tissue development	IEA Inferred from Electronic Annotation more info
positive regulation of smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of striated muscle cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of ureter smooth muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
positive thymic T cell selection	ISS Inferred from Sequence or Structural Similarity more info
primary prostatic bud elongation	IEA Inferred from Electronic Annotation more info
prostate epithelial cord elongation	IEA Inferred from Electronic Annotation more info
prostate gland development	ISS Inferred from Sequence or Structural Similarity more info
protein localization to nucleus	IEA Inferred from Electronic Annotation more info
regulation of cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
regulation of mesenchymal cell proliferation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry	NAS Non-traceable Author Statement more info	PubMed
regulation of odontogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of prostatic bud formation	IEA Inferred from Electronic Annotation more info
regulation of protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
regulation of proteolysis	ISS Inferred from Sequence or Structural Similarity more info
regulation of signaling receptor activity	IEA Inferred from Electronic Annotation more info
renal system development	IEP Inferred from Expression Pattern more info	PubMed
right lung development	IEA Inferred from Electronic Annotation more info
roof of mouth development	IEA Inferred from Electronic Annotation more info
salivary gland cavitation	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway	IEP Inferred from Expression Pattern more info	PubMed
smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation	IEA Inferred from Electronic Annotation more info
somite development	ISS Inferred from Sequence or Structural Similarity more info
spinal cord dorsal/ventral patterning	IEA Inferred from Electronic Annotation more info
spinal cord motor neuron differentiation	IEA Inferred from Electronic Annotation more info
stem cell development	ISS Inferred from Sequence or Structural Similarity more info
striated muscle tissue development	IEA Inferred from Electronic Annotation more info
telencephalon regionalization	IEA Inferred from Electronic Annotation more info
thalamus development	IEA Inferred from Electronic Annotation more info
thymus development	ISS Inferred from Sequence or Structural Similarity more info
thyroid gland development	IEA Inferred from Electronic Annotation more info
trachea morphogenesis	IEA Inferred from Electronic Annotation more info
tracheoesophageal septum formation	IEA Inferred from Electronic Annotation more info
vasculogenesis	ISS Inferred from Sequence or Structural Similarity more info
ventral midline development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cell surface	ISS Inferred from Sequence or Structural Similarity more info
cytosol	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular matrix	IEA Inferred from Electronic Annotation more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed
extracellular space	ISS Inferred from Sequence or Structural Similarity more info
membrane raft	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: sonic hedgehog protein

Names: shh unprocessed N-terminal signaling and C-terminal autoprocessing domains; sonic hedgehog homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007504.2 RefSeqGene

Range

5001..15034

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000193.3 → NP_000184.1 sonic hedgehog protein isoform 1 preproprotein

See identical proteins and their annotated locations for NP_000184.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC078834, BX109787, BX452210, BY797055, L38518

Consensus CDS

CCDS5942.1

UniProtKB/Swiss-Prot

Q15465

Related

ENSP00000297261.2, OTTHUMP00000199886, ENST00000297261.6, OTTHUMT00000322327

Conserved Domains (3) summary

cd00081
Location:198 → 363

Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...

pfam01079
Location:187 → 448

Hint; Hint module

pfam01085
Location:39 → 184

HH_signal; Hedgehog amino-terminal signalling domain
NM_001310462.1 → NP_001297391.1 sonic hedgehog protein isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' and 3' UTRs and has multiple coding region differences, compared to variant 1. It encodes isoform 2 which has a shorter and distinct N-terminus and a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AI192528, AY927452, AY927455

Related

ENSP00000396621.1, OTTHUMP00000199887, ENST00000430104.5, OTTHUMT00000322329

Conserved Domains (1) summary

pfam01085
Location:12 → 97

HH_signal; Hedgehog amino-terminal signalling domain

RNA

NR_132318.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC078834, AI192528, AY927453, AY927454, L38518

Related

ENST00000441114.5, OTTHUMT00000322331
NR_132319.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC078834, AI192528, AY927453

Related

ENST00000435425.1, OTTHUMT00000322330

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p12 Primary Assembly

Range

155799984..155812273 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011516479.2 → XP_011514781.1 sonic hedgehog protein isoform X1

See identical proteins and their annotated locations for XP_011514781.1

Conserved Domains (3) summary

cd00081
Location:111 → 276

Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...

pfam01079
Location:100 → 361

Hint; Hint module

pfam01085
Location:12 → 97

HH_signal; Hedgehog amino-terminal signalling domain
XM_011516480.2 → XP_011514782.1 sonic hedgehog protein isoform X1

See identical proteins and their annotated locations for XP_011514782.1

Conserved Domains (3) summary

cd00081
Location:111 → 276

Hint; Hedgehog/Intein domain, found in Hedgehog proteins as well as proteins which contain inteins and undergo protein splicing (e.g. DnaB, RIR1-2, GyrA and Pol). In protein splicing an intervening polypeptide sequence - the intein - is excised from a protein, ...

pfam01079
Location:100 → 361

Hint; Hint module

pfam01085
Location:12 → 97

HH_signal; Hedgehog amino-terminal signalling domain