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SHH sonic hedgehog signaling molecule [ Homo sapiens (human) ]

Gene ID: 6469, updated on 24-Nov-2020

Summary

Official Symbol
SHHprovided by HGNC
Official Full Name
sonic hedgehog signaling moleculeprovided by HGNC
Primary source
HGNC:HGNC:10848
See related
Ensembl:ENSG00000164690 MIM:600725
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

Genomic context

See SHH in Genome Data Viewer
Location:
7q36.3
Exon count:
8
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (155799980..155812463, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (155595558..155604967, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100506302 Neighboring gene RNA binding motif protein 33 Neighboring gene VISTA enhancer hs1268 Neighboring gene uncharacterized LOC389602 Neighboring gene uncharacterized LOC105375597

Genomic regions, transcripts, and products

Expression

  • 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists.
GeneReviews: Not available
Holoprosencephaly 3 Compare labs
Identification of a candidate gene for astigmatism.
GeneReviews: Not available
Microphthalmia, isolated, with coloboma 5 Compare labs
SCHIZENCEPHALY
MedGen: C0266484 OMIM: 269160 GeneReviews: Not available
Compare labs
Solitary median maxillary central incisor syndrome
MedGen: C1840235 OMIM: 147250 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2020-06-24)

ClinGen Genome Curation PagePubMed
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2020-06-24)

ClinGen Genome Curation PagePubMed

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
calcium ion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
calcium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
patched binding IDA
Inferred from Direct Assay
more info
PubMed 
peptidase activity IEA
Inferred from Electronic Annotation
more info
 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 collecting duct development IEP
Inferred from Expression Pattern
more info
PubMed 
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
 
oligodendrocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 population proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell population 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 autoprocessing IEA
Inferred from Electronic Annotation
more info
 
protein localization to nucleus IEA
Inferred from Electronic Annotation
more info
 
regulation of cell population proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of gene expression IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
 
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
 
smooth muscle tissue development IEP
Inferred from Expression Pattern
more info
PubMed 
smoothened signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
smoothened signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
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
 
collagen-containing extracellular matrix HDA PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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

Preferred Names
sonic hedgehog protein
Names
shh unprocessed N-terminal signaling and C-terminal autoprocessing domains
sonic hedgehog homolog

NCBI Reference Sequences (RefSeq)

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

  1. NG_007504.2 RefSeqGene

    Range
    4811..17294
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000193.4NP_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, ENST00000297261.7
    Conserved Domains (3) summary
    cd00081
    Location:198363
    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:187448
    Hint; Hint module
    pfam01085
    Location:39184
    HH_signal; Hedgehog amino-terminal signalling domain
  2. NM_001310462.2NP_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)
    AC078834, AI192528, AY927452, AY927455
    Related
    ENSP00000396621.1, ENST00000430104.5
    Conserved Domains (1) summary
    pfam01085
    Location:1297
    HH_signal; Hedgehog amino-terminal signalling domain

RNA

  1. NR_132318.2 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
  2. NR_132319.2 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

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    155799980..155812463 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    See identical proteins and their annotated locations for XP_011514781.1

    Conserved Domains (3) summary
    cd00081
    Location:111276
    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:100361
    Hint; Hint module
    pfam01085
    Location:1297
    HH_signal; Hedgehog amino-terminal signalling domain
  2. XM_011516480.2XP_011514782.1  sonic hedgehog protein isoform X1

    See identical proteins and their annotated locations for XP_011514782.1

    Conserved Domains (3) summary
    cd00081
    Location:111276
    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:100361
    Hint; Hint module
    pfam01085
    Location:1297
    HH_signal; Hedgehog amino-terminal signalling domain
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