Gene: SHH

Basic information

Tag Content
Uniprot ID Q15465; A4D247; Q75MC9;
Entrez ID 6469
Genbank protein ID AAB67604.1; AAA62179.1; AAQ87879.1; AAS01990.1; EAL23913.1;
Genbank nucleotide ID NM_000193.3
Ensembl protein ID ENSP00000297261
Ensembl nucleotide ID ENSG00000164690
Gene name Sonic hedgehog protein
Gene symbol SHH
Organism Homo sapiens
NCBI taxa ID 9606
Cleft type
Developmental stage
Data sources Homology search
Reference
Functional description Sonic hedgehog protein.The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).
Sequence
MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN VAEKTLGASG 60
RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ RCKDKLNALA ISVMNQWPGV 120
KLRVTEGWDE DGHHSEESLH YEGRAVDITT SDRDRSKYGM LARLAVEAGF DWVYYESKAH 180
IHCSVKAENS VAAKSGGCFP GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT 240
FLDRDDGAKK VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG 300
PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA QGTILINRVL 360
ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD SGGGDRGGGG GRVALTAPGA 420
ADAPGAGATA GIHWYSQLLY QIGTWLLDSE ALHPLGMAVK SS 462

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

  

Gene expression in different tissues (ENCODE)

  

Protein structural annotations

3D structure in PDB database


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Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologSHHA0A452FUF0Capra hircusPredictionMore>>
1:1 orthologSHH6469Q15465Homo sapiensPredictionMore>>
1:1 orthologShh20423Q62226CPOE11.5, E12.0, E12.5, E13.0, E14.0, E13.5, E14.5, E14.5-15.0, E15.0, E16.0, E15.5, E16.5Mus musculusPublicationMore>>
1:1 orthologSHH743371A0A2I3SFH2Pan troglodytesPredictionMore>>
1:1 orthologSHH100352774G1TCI1Oryctolagus cuniculusPredictionMore>>
1:1 orthologShhG3V6T0Rattus norvegicusPredictionMore>>

Other genetic variants/mutations

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Disease or phenotype associated information

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID GO Term Evidence
GO:0005113 patched bindingIBA
GO:0005113 patched bindingIDA
GO:0005509 calcium ion bindingIDA
GO:0005509 calcium ion bindingIBA
GO:0005515 protein bindingIPI
GO:0005539 glycosaminoglycan bindingIEA
GO:0008233 peptidase activityIEA
GO:0008270 zinc ion bindingIDA
GO:0016015 morphogen activityTAS
GO:0016015 morphogen activityNAS
GO:0043237 laminin-1 bindingISS

GO:Biological Process

GO ID GO Term Evidence
GO:0000122 negative regulation of transcription by RNA polymerase IIISS
GO:0001569 branching involved in blood vessel morphogenesisISS
GO:0001570 vasculogenesisISS
GO:0001656 metanephros developmentISS
GO:0001658 branching involved in ureteric bud morphogenesisISS
GO:0001708 cell fate specificationISS
GO:0001708 cell fate specificationIBA
GO:0001755 neural crest cell migrationISS
GO:0001947 heart loopingISS
GO:0002052 positive regulation of neuroblast proliferationIEA
GO:0002076 osteoblast developmentIEA
GO:0002320 lymphoid progenitor cell differentiationIMP
GO:0003140 determination of left/right asymmetry in lateral mesodermISS
GO:0006897 endocytosisIEA
GO:0007224 smoothened signaling pathwayISS
GO:0007224 smoothened signaling pathwayIEP
GO:0007224 smoothened signaling pathwayIBA
GO:0007228 positive regulation of hh target transcription factor activityISS
GO:0007267 cell-cell signalingISS
GO:0007389 pattern specification processISS
GO:0007398 ectoderm developmentIEA
GO:0007405 neuroblast proliferationISS
GO:0007411 axon guidanceISS
GO:0007417 central nervous system developmentISS
GO:0007418 ventral midline developmentTAS
GO:0007442 hindgut morphogenesisIEA
GO:0007507 heart developmentISS
GO:0007596 blood coagulationIEA
GO:0008209 androgen metabolic processISS
GO:0008284 positive regulation of cell population proliferationISS
GO:0008284 positive regulation of cell population proliferationIDA
GO:0009880 embryonic pattern specificationTAS
GO:0009949 polarity specification of anterior/posterior axisISS
GO:0009953 dorsal/ventral pattern formationISS
GO:0010468 regulation of gene expressionIBA
GO:0014003 oligodendrocyte developmentIEA
GO:0014706 striated muscle tissue developmentIEA
GO:0014858 positive regulation of skeletal muscle cell proliferationIEA
GO:0014902 myotube differentiationIEA
GO:0016539 intein-mediated protein splicingIEA
GO:0021513 spinal cord dorsal/ventral patterningIEA
GO:0021522 spinal cord motor neuron differentiationIEA
GO:0021794 thalamus developmentIEA
GO:0021904 dorsal/ventral neural tube patterningIEA
GO:0021930 cerebellar granule cell precursor proliferationISS
GO:0021938 smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferationIEA
GO:0021978 telencephalon regionalizationIEA
GO:0030010 establishment of cell polarityIEA
GO:0030162 regulation of proteolysisISS
GO:0030177 positive regulation of Wnt signaling pathwayIEA
GO:0030324 lung developmentISS
GO:0030326 embryonic limb morphogenesisISS
GO:0030336 negative regulation of cell migrationISS
GO:0030539 male genitalia developmentISS
GO:0030850 prostate gland developmentISS
GO:0030878 thyroid gland developmentIEA
GO:0030900 forebrain developmentISS
GO:0030901 midbrain developmentISS
GO:0030902 hindbrain developmentISS
GO:0031016 pancreas developmentIEA
GO:0031069 hair follicle morphogenesisIEA
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic processIEA
GO:0033077 T cell differentiation in thymusISS
GO:0033089 positive regulation of T cell differentiation in thymusISS
GO:0033092 positive regulation of immature T cell proliferation in thymusISS
GO:0034244 negative regulation of transcription elongation from RNA polymerase II promoterIEA
GO:0034504 protein localization to nucleusIEA
GO:0035115 embryonic forelimb morphogenesisIEA
GO:0035116 embryonic hindlimb morphogenesisIEA
GO:0042127 regulation of cell population proliferationISS
GO:0042130 negative regulation of T cell proliferationIEA
GO:0042307 positive regulation of protein import into nucleusIEA
GO:0042475 odontogenesis of dentin-containing toothIEA
GO:0042481 regulation of odontogenesisISS
GO:0042733 embryonic digit morphogenesisISS
GO:0043010 camera-type eye developmentIEA
GO:0043066 negative regulation of apoptotic processISS
GO:0043369 CD4-positive or CD8-positive, alpha-beta T cell lineage commitmentIDA
GO:0045059 positive thymic T cell selectionISS
GO:0045060 negative thymic T cell selectionISS
GO:0045109 intermediate filament organizationIEA
GO:0045445 myoblast differentiationIEA
GO:0045596 negative regulation of cell differentiationISS
GO:0045880 positive regulation of smoothened signaling pathwayISS
GO:0045880 positive regulation of smoothened signaling pathwayIDA
GO:0045893 positive regulation of transcription, DNA-templatedIDA
GO:0045944 positive regulation of transcription by RNA polymerase IIISS
GO:0046638 positive regulation of alpha-beta T cell differentiationISS
GO:0046639 negative regulation of alpha-beta T cell differentiationIEA
GO:0048468 cell developmentISS
GO:0048538 thymus developmentISS
GO:0048557 embryonic digestive tract morphogenesisIEA
GO:0048617 embryonic foregut morphogenesisIEA
GO:0048643 positive regulation of skeletal muscle tissue developmentIEA
GO:0048645 animal organ formationIEA
GO:0048663 neuron fate commitmentISS
GO:0048706 embryonic skeletal system developmentIEA
GO:0048709 oligodendrocyte differentiationIBA
GO:0048714 positive regulation of oligodendrocyte differentiationIEA
GO:0048745 smooth muscle tissue developmentIEP
GO:0048754 branching morphogenesis of an epithelial tubeISS
GO:0048839 inner ear developmentIEA
GO:0048859 formation of anatomical boundaryIEA
GO:0048864 stem cell developmentISS
GO:0051155 positive regulation of striated muscle cell differentiationIEA
GO:0051781 positive regulation of cell divisionIDA
GO:0060020 Bergmann glial cell differentiationIEA
GO:0060021 roof of mouth developmentIEA
GO:0060070 canonical Wnt signaling pathwayIEA
GO:0060174 limb bud formationIEA
GO:0060428 lung epithelium developmentIEA
GO:0060439 trachea morphogenesisIEA
GO:0060445 branching involved in salivary gland morphogenesisIEA
GO:0060447 bud outgrowth involved in lung branchingIEA
GO:0060458 right lung developmentIEA
GO:0060459 left lung developmentIEA
GO:0060463 lung lobe morphogenesisIEA
GO:0060484 lung-associated mesenchyme developmentIEA
GO:0060516 primary prostatic bud elongationIEA
GO:0060523 prostate epithelial cord elongationIEA
GO:0060662 salivary gland cavitationIEA
GO:0060664 epithelial cell proliferation involved in salivary gland morphogenesisIEA
GO:0060685 regulation of prostatic bud formationIEA
GO:0060738 epithelial-mesenchymal signaling involved in prostate gland developmentIDA
GO:0060769 positive regulation of epithelial cell proliferation involved in prostate gland developmentIEA
GO:0060782 regulation of mesenchymal cell proliferation involved in prostate gland developmentIEA
GO:0060783 mesenchymal smoothened signaling pathway involved in prostate gland developmentIEA
GO:0060840 artery developmentIEA
GO:0060916 mesenchymal cell proliferation involved in lung developmentIEA
GO:0061053 somite developmentISS
GO:0061189 positive regulation of sclerotome developmentIDA
GO:0071285 cellular response to lithium ionIEA
GO:0071542 dopaminergic neuron differentiationTAS
GO:0072136 metanephric mesenchymal cell proliferation involved in metanephros developmentISS
GO:0072205 metanephric collecting duct developmentIEP
GO:0090090 negative regulation of canonical Wnt signaling pathwayIEA
GO:0090370 negative regulation of cholesterol effluxISS
GO:0097190 apoptotic signaling pathwayISS
GO:1900175 regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetryNAS
GO:1900180 regulation of protein localization to nucleusIDA
GO:1904339 negative regulation of dopaminergic neuron differentiationIEA
GO:1905327 tracheoesophageal septum formationIEA
GO:2000062 negative regulation of ureter smooth muscle cell differentiationISS
GO:2000063 positive regulation of ureter smooth muscle cell differentiationISS
GO:2000357 negative regulation of kidney smooth muscle cell differentiationISS
GO:2000358 positive regulation of kidney smooth muscle cell differentiationISS
GO:2000729 positive regulation of mesenchymal cell proliferation involved in ureter developmentISS
GO:2001054 negative regulation of mesenchymal cell apoptotic processIEA

GO:Cellular Component

GO ID GO Term Evidence
GO:0005576 extracellular regionTAS
GO:0005615 extracellular spaceISS
GO:0005615 extracellular spaceIDA
GO:0005615 extracellular spaceIBA
GO:0005788 endoplasmic reticulum lumenTAS
GO:0005829 cytosolTAS
GO:0005886 plasma membraneTAS
GO:0009986 cell surfaceISS
GO:0045121 membrane raftISS
GO:0062023 collagen-containing extracellular matrixHDA

Reactome Pathway

Reactome ID Reactome Term Evidence
R-HSA-162582 Signal TransductionIEA
R-HSA-162582 Signal TransductionTAS
R-HSA-1643685 DiseaseTAS
R-HSA-372790 Signaling by GPCRIEA
R-HSA-373080 Class B/2 (Secretin family receptors)IEA
R-HSA-500792 GPCR ligand bindingIEA
R-HSA-5358346 Hedgehog ligand biogenesisIEA
R-HSA-5358346 Hedgehog ligand biogenesisTAS
R-HSA-5358351 Signaling by HedgehogIEA
R-HSA-5358351 Signaling by HedgehogTAS
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERADTAS
R-HSA-5362798 Release of Hh-Np from the secreting cellIEA
R-HSA-5362798 Release of Hh-Np from the secreting cellTAS
R-HSA-5387390 Hh mutants abrogate ligand secretionTAS
R-HSA-5632681 Ligand-receptor interactionsTAS
R-HSA-5632681 Ligand-receptor interactionsIEA
R-HSA-5632684 Hedgehog 'on' stateIEA
R-HSA-5632684 Hedgehog 'on' stateTAS
R-HSA-5635838 Activation of SMOTAS
R-HSA-5658034 HHAT G278V abrogates palmitoylation of Hh-NpTAS
R-HSA-5663202 Diseases of signal transductionTAS

Drugs and compounds information

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Functional annotations

Keywords

Keyword ID Keyword Term
KW-0002 3D-structure
KW-0068 Autocatalytic cleavage
KW-0106 Calcium
KW-1003 Cell membrane
KW-0217 Developmental protein
KW-0903 Direct protein sequencing
KW-0225 Disease mutation
KW-0325 Glycoprotein
KW-0370 Holoprosencephaly
KW-0378 Hydrolase
KW-0449 Lipoprotein
KW-0472 Membrane
KW-0479 Metal-binding
KW-1013 Microphthalmia
KW-0564 Palmitate
KW-0645 Protease
KW-1185 Reference proteome
KW-0732 Signal
KW-0862 Zinc

Interpro

InterPro ID InterPro Term
IPR001657 Hedgehog
IPR001767 Hedgehog_Hint
IPR009045 Hedgehog_sig/DD-Pept_Zn-bd_sf
IPR000320 Hedgehog_signalling_dom
IPR003586 Hint_dom_C
IPR003587 Hint_dom_N
IPR036844 Hint_dom_sf
IPR006141 Intein_N

PROSITE

PROSITE ID PROSITE Term
PS50817 INTEIN_N_TER

Pfam

Pfam ID Pfam Term
PF01085 HH_signal
PF01079 Hint

Protein-protein interaction

Protein-miRNA interaction