Gene/Proteome Database (LMPD)

LMPD ID
LMP002984
Gene ID
6469
Species
Homo sapiens (Human)
Gene Name
sonic hedgehog
Gene Symbol
SHH
Synonyms
HHG1; HLP3; HPE3; MCOPCB5; SMMCI; TPT; TPTPS
Alternate Names
sonic hedgehog protein; sonic hedgehog homolog
Chromosome
7
Map Location
7q36
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]
Orthologs
View orthologs and multiple alignments for SHH

Proteins

sonic hedgehog protein preproprotein
Refseq ID NP_000184
Protein GI 4506939
UniProt ID Q15465
mRNA ID NM_000193
Length 462
RefSeq Status REVIEWED
MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS
sig_peptide: 1..23 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2401 peptide sequence: MLLLARCLLLVLVSSLLVCSGLA mat_peptide: 24..462 product: Sonic hedgehog protein experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q15465.1) calculated_mol_wt: 47224 peptide sequence: CGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS mat_peptide: 24..197 product: sonic hedgehog protein N-terminal peptide calculated_mol_wt: 19560 peptide sequence: CGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGG mat_peptide: 198..462 product: sonic hedgehog protein C-terminal peptide calculated_mol_wt: 27682 peptide sequence: CFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS

Gene Information

Entrez Gene ID
6469
Gene Name
sonic hedgehog
Gene Symbol
SHH
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0009986 ISS:UniProtKB C cell surface
GO:0031012 IEA:Ensembl C extracellular matrix
GO:0005615 IDA:UniProtKB C extracellular space
GO:0045121 ISS:UniProtKB C membrane raft
GO:0005634 IEA:Ensembl C nucleus
GO:0005886 IEA:UniProtKB-KW C plasma membrane
GO:0005509 IDA:UniProtKB F calcium ion binding
GO:0005539 IEA:Ensembl F glycosaminoglycan binding
GO:0043237 ISS:UniProtKB F laminin-1 binding
GO:0016015 NAS:BHF-UCL F morphogen activity
GO:0005113 IDA:BHF-UCL F patched binding
GO:0008233 IEA:UniProtKB-KW F peptidase activity
GO:0008270 IDA:UniProtKB F zinc ion binding
GO:0060020 IEA:Ensembl P Bergmann glial cell differentiation
GO:0043369 IDA:BHF-UCL P CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0033077 ISS:BHF-UCL P T cell differentiation in thymus
GO:0008209 ISS:UniProtKB P androgen metabolic process
GO:0097190 ISS:UniProt P apoptotic signaling pathway
GO:0060840 IEA:Ensembl P artery development
GO:0007411 ISS:UniProtKB P axon guidance
GO:0007596 IEA:Ensembl P blood coagulation
GO:0060445 IEA:Ensembl P branching involved in salivary gland morphogenesis
GO:0001658 ISS:UniProtKB P branching involved in ureteric bud morphogenesis
GO:0048754 ISS:UniProtKB P branching morphogenesis of an epithelial tube
GO:0060447 IEA:Ensembl P bud outgrowth involved in lung branching
GO:0043010 IEA:Ensembl P camera-type eye development
GO:0060070 IEA:Ensembl P canonical Wnt signaling pathway
GO:0048468 ISS:UniProtKB P cell development
GO:0001708 ISS:UniProtKB P cell fate specification
GO:0007267 ISS:UniProtKB P cell-cell signaling
GO:0071285 IEA:Ensembl P cellular response to lithium ion
GO:0007417 ISS:UniProtKB P central nervous system development
GO:0021930 ISS:UniProtKB P cerebellar granule cell precursor proliferation
GO:0003140 ISS:BHF-UCL P determination of left/right asymmetry in lateral mesoderm
GO:0021904 IEA:Ensembl P dorsal/ventral neural tube patterning
GO:0009953 ISS:UniProtKB P dorsal/ventral pattern formation
GO:0007398 IEA:Ensembl P ectoderm development
GO:0009790 ISS:UniProtKB P embryo development
GO:0048557 IEA:Ensembl P embryonic digestive tract morphogenesis
GO:0042733 ISS:UniProtKB P embryonic digit morphogenesis
GO:0048617 IEA:Ensembl P embryonic foregut morphogenesis
GO:0035115 IEA:Ensembl P embryonic forelimb morphogenesis
GO:0035116 IEA:Ensembl P embryonic hindlimb morphogenesis
GO:0030326 ISS:UniProtKB P embryonic limb morphogenesis
GO:0009880 TAS:BHF-UCL P embryonic pattern specification
GO:0048706 IEA:Ensembl P embryonic skeletal system development
GO:0006897 IEA:Ensembl P endocytosis
GO:0060664 IEA:Ensembl P epithelial cell proliferation involved in salivary gland morphogenesis
GO:0060738 IDA:MGI P epithelial-mesenchymal signaling involved in prostate gland development
GO:0030010 IEA:Ensembl P establishment of cell polarity
GO:0030900 ISS:UniProtKB P forebrain development
GO:0048859 IEA:Ensembl P formation of anatomical boundary
GO:0031069 IEA:Ensembl P hair follicle morphogenesis
GO:0007507 ISS:UniProtKB P heart development
GO:0001947 ISS:BHF-UCL P heart looping
GO:0030902 ISS:UniProtKB P hindbrain development
GO:0007442 IEA:Ensembl P hindgut morphogenesis
GO:0048839 IEA:Ensembl P inner ear development
GO:0016539 IEA:InterPro P intein-mediated protein splicing
GO:0045109 IEA:Ensembl P intermediate filament organization
GO:0060459 IEA:Ensembl P left lung development
GO:0060174 IEA:Ensembl P limb bud formation
GO:0030324 ISS:UniProtKB P lung development
GO:0060428 IEA:Ensembl P lung epithelium development
GO:0060463 IEA:Ensembl P lung lobe morphogenesis
GO:0060484 IEA:Ensembl P lung-associated mesenchyme development
GO:0002320 IMP:BHF-UCL P lymphoid progenitor cell differentiation
GO:0030539 ISS:UniProtKB P male genitalia development
GO:0060916 IEA:Ensembl P mesenchymal cell proliferation involved in lung development
GO:0060783 IEA:Ensembl P mesenchymal smoothened signaling pathway involved in prostate gland development
GO:0072136 ISS:UniProtKB P metanephric mesenchymal cell proliferation involved in metanephros development
GO:0001656 ISS:UniProtKB P metanephros development
GO:0030901 ISS:UniProtKB P midbrain development
GO:0080125 IEA:Ensembl P multicellular structure septum development
GO:0045445 IEA:Ensembl P myoblast differentiation
GO:0014902 IEA:Ensembl P myotube differentiation
GO:0042130 IEA:Ensembl P negative regulation of T cell proliferation
GO:0046639 IEA:Ensembl P negative regulation of alpha-beta T cell differentiation
GO:0043066 ISS:UniProt P negative regulation of apoptotic process
GO:0090090 IEA:Ensembl P negative regulation of canonical Wnt signaling pathway
GO:0045596 ISS:UniProtKB P negative regulation of cell differentiation
GO:0030336 ISS:UniProtKB P negative regulation of cell migration
GO:0090370 ISS:BHF-UCL P negative regulation of cholesterol efflux
GO:2000357 ISS:UniProtKB P negative regulation of kidney smooth muscle cell differentiation
GO:2001054 IEA:Ensembl P negative regulation of mesenchymal cell apoptotic process
GO:0032435 IEA:Ensembl P negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034244 IEA:Ensembl P negative regulation of transcription elongation from RNA polymerase II promoter
GO:0000122 ISS:BHF-UCL P negative regulation of transcription from RNA polymerase II promoter
GO:2000062 ISS:UniProtKB P negative regulation of ureter smooth muscle cell differentiation
GO:0045060 ISS:UniProtKB P negative thymic T cell selection
GO:0001755 ISS:UniProtKB P neural crest cell migration
GO:0007405 ISS:UniProtKB P neuroblast proliferation
GO:0048663 ISS:UniProtKB P neuron fate commitment
GO:0042475 IEA:Ensembl P odontogenesis of dentin-containing tooth
GO:0014003 IEA:Ensembl P oligodendrocyte development
GO:0048645 IEA:Ensembl P organ formation
GO:0002076 IEA:Ensembl P osteoblast development
GO:0060021 IEA:Ensembl P palate development
GO:0031016 IEA:Ensembl P pancreas development
GO:0007389 ISS:UniProtKB P pattern specification process
GO:0001569 ISS:UniProtKB P patterning of blood vessels
GO:0009949 ISS:UniProt P polarity specification of anterior/posterior axis
GO:0033089 ISS:UniProtKB P positive regulation of T cell differentiation in thymus
GO:0030177 IEA:Ensembl P positive regulation of Wnt signaling pathway
GO:0046638 ISS:UniProtKB P positive regulation of alpha-beta T cell differentiation
GO:0051781 IDA:BHF-UCL P positive regulation of cell division
GO:0008284 ISS:UniProtKB P positive regulation of cell proliferation
GO:0060769 IEA:Ensembl P positive regulation of epithelial cell proliferation involved in prostate gland development
GO:0007228 ISS:BHF-UCL P positive regulation of hh target transcription factor activity
GO:0033092 ISS:BHF-UCL P positive regulation of immature T cell proliferation in thymus
GO:2000358 ISS:UniProtKB P positive regulation of kidney smooth muscle cell differentiation
GO:2000729 ISS:UniProtKB P positive regulation of mesenchymal cell proliferation involved in ureter development
GO:0002052 IEA:Ensembl P positive regulation of neuroblast proliferation
GO:0048714 IEA:Ensembl P positive regulation of oligodendrocyte differentiation
GO:0042307 IEA:Ensembl P positive regulation of protein import into nucleus
GO:0061189 IDA:BHF-UCL P positive regulation of sclerotome development
GO:0014858 IEA:Ensembl P positive regulation of skeletal muscle cell proliferation
GO:0048643 IEA:Ensembl P positive regulation of skeletal muscle tissue development
GO:0045880 IDA:UniProtKB P positive regulation of smoothened signaling pathway
GO:0051155 IEA:Ensembl P positive regulation of striated muscle cell differentiation
GO:0045944 ISS:BHF-UCL P positive regulation of transcription from RNA polymerase II promoter
GO:0045893 IDA:BHF-UCL P positive regulation of transcription, DNA-templated
GO:2000063 ISS:UniProtKB P positive regulation of ureter smooth muscle cell differentiation
GO:0045059 ISS:UniProtKB P positive thymic T cell selection
GO:0060516 IEA:Ensembl P primary prostatic bud elongation
GO:0060523 IEA:Ensembl P prostate epithelial cord elongation
GO:0030850 ISS:UniProtKB P prostate gland development
GO:0034504 IEA:Ensembl P protein localization to nucleus
GO:0042127 ISS:UniProtKB P regulation of cell proliferation
GO:0060782 IEA:Ensembl P regulation of mesenchymal cell proliferation involved in prostate gland development
GO:1900175 NAS:BHF-UCL P regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
GO:0042481 ISS:BHF-UCL P regulation of odontogenesis
GO:0060685 IEA:Ensembl P regulation of prostatic bud formation
GO:1900180 IDA:BHF-UCL P regulation of protein localization to nucleus
GO:0030162 ISS:UniProtKB P regulation of proteolysis
GO:0072001 IEP:UniProtKB P renal system development
GO:0060458 IEA:Ensembl P right lung development
GO:0060662 IEA:Ensembl P salivary gland cavitation
GO:0007224 IEP:UniProtKB P smoothened signaling pathway
GO:0021938 IEA:Ensembl P smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
GO:0061053 ISS:BHF-UCL P somite development
GO:0021513 IEA:Ensembl P spinal cord dorsal/ventral patterning
GO:0021522 IEA:Ensembl P spinal cord motor neuron differentiation
GO:0048864 ISS:UniProtKB P stem cell development
GO:0014706 IEA:Ensembl P striated muscle tissue development
GO:0021978 IEA:Ensembl P telencephalon regionalization
GO:0021794 IEA:Ensembl P thalamus development
GO:0048538 ISS:UniProtKB P thymus development
GO:0030878 IEA:Ensembl P thyroid gland development
GO:0060439 IEA:Ensembl P trachea morphogenesis
GO:0001570 ISS:UniProtKB P vasculogenesis
GO:0007418 TAS:BHF-UCL P ventral midline development

KEGG Pathway Links

KEGG Pathway ID Description
hsa05217 Basal cell carcinoma
hsa04340 Hedgehog signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR001657 Hedgehog protein
IPR001767 Hedgehog protein, Hint domain
IPR009045 Hedgehog signalling/DD-peptidase zinc-binding domain
IPR000320 Hedgehog, N-terminal signalling domain
IPR028992 Hedgehog/Intein (Hint) domain
IPR003586 Hint domain C-terminal
IPR003587 Hint domain N-terminal
IPR006141 Intein splice site

UniProt Annotations

Entry Information

Gene Name
sonic hedgehog
Protein Entry
SHH_HUMAN
UniProt ID
Q15465
Species
Human

Comments

Comment Type Description
Disease Holoprosencephaly 3 (HPE3) [MIM
Disease Microphthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM
Disease Preaxial polydactyly 2 (PPD2) [MIM
Disease Solitary median maxillary central incisor (SMMCI) [MIM
Disease Triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM
Domain The sonic hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain. {ECO
Function 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. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO (By similarity).
Mass Spectrometry Mass=19.560; Method=Electrospray; Range=24-197; Note=Soluble N-product, purified from insect cells.; Evidence= ;
Mass Spectrometry Mass=20.167; Method=Electrospray; Range=24-197; Note=Membrane-bound N-product, purified from insect cells.; Evidence= ;
Ptm Cholesterylation is required for N-product targeting to lipid rafts and multimerization.
Ptm N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity.
Ptm The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N- terminal fragment (N-product). The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity.
Similarity Belongs to the hedgehog family.
Subcellular Location Sonic hedgehog protein C-product: Secreted, extracellular space . Note=The C-terminal peptide diffuses from the cell.
Subcellular Location Sonic hedgehog protein N-product: Cell membrane {ECO
Subunit Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer. Interacts with BOC and CDON (By similarity). Interacts with HHIP. {ECO
Tissue Specificity Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues.
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/SHHID378.html";
Web Resource Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/shh/";

Identical and Related Proteins

Unique RefSeq proteins for LMP002984 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4506939 RefSeq NP_000184 462 sonic hedgehog protein preproprotein

Identical Sequences to LMP002984 proteins

Reference Database Accession Length Protein Name
GI:4506939 GenBank ADL91049.1 462 Sequence 60 from patent US 7709454
GI:4506939 GenBank ADR89537.1 462 Sequence 2 from patent US 7741298
GI:4506939 GenBank AED17250.1 462 Sequence 565 from patent US 7879544
GI:4506939 GenBank AED59010.1 462 Sequence 13 from patent US 7901686
GI:4506939 GenBank AFQ78538.1 462 Sequence 4 from patent US 8241846
GI:4506939 GenBank AGM78063.1 462 Sequence 39 from patent US 8426200

Related Sequences to LMP002984 proteins

Reference Database Accession Length Protein Name
GI:4506939 GenBank AAR45513.1 475 Sequence 13 from patent US 6607913
GI:4506939 GenBank AAR47117.1 475 Sequence 13 from patent US 6610656
GI:4506939 GenBank AAR56216.1 475 Sequence 15 from patent US 6616926
GI:4506939 GenBank AAR65002.1 475 Sequence 13 from patent US 6630148
GI:4506939 GenBank AAR71001.1 475 Sequence 15 from patent US 6639051
GI:4506939 GenBank AAS22630.1 475 Sequence 13 from patent US 6664075