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Q15465 (SHH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 168. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sonic hedgehog protein

Short name=SHH
Alternative name(s):
HHG-1
Gene names
Name:SHH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length462 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.11

Subunit structure

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. Ref.12

Subcellular location

Sonic hedgehog protein C-product: Secretedextracellular space By similarity. Note: The C-terminal peptide diffuses from the cell By similarity. Ref.13

Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor By similarity. Cell membrane. Note: The N-product either remains associated with lipid rafts at the cell surface, or forms freely diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside By similarity. Ref.13

Tissue specificity

Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues.

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. Ref.11 Ref.12 Ref.13

Post-translational modification

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.

Cholesterylation is required for N-product targeting to lipid rafts and multimerization By similarity.

N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity By similarity. Ref.6

Involvement in disease

Microphthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM:611638]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Holoprosencephaly 3 (HPE3) [MIM:142945]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28

Solitary median maxillary central incisor (SMMCI) [MIM:147250]: Rare dental anomaly characterized by the congenital absence of one maxillary central incisor.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.21

Triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]: Autosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development.
Note: The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH expression. Ref.8 Ref.10

Preaxial polydactyly 2 (PPD2) [MIM:174500]: Polydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal.
Note: The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (Ref.8).

Sequence similarities

Belongs to the hedgehog family.

Mass spectrometry

Molecular mass is 19.560 Da from positions 24 - 197. Determined by ESI. Soluble N-product, purified from insect cells. Ref.6

Molecular mass is 20.167 Da from positions 24 - 197. Determined by ESI. Membrane-bound N-product, purified from insect cells. Ref.6

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   DiseaseDisease mutation
Holoprosencephaly
Microphthalmia
   DomainSignal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionDevelopmental protein
Hydrolase
Protease
   PTMAutocatalytic cleavage
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processBergmann glial cell differentiation

Inferred from electronic annotation. Source: Ensembl

CD4-positive or CD8-positive, alpha-beta T cell lineage commitment

Inferred from direct assay PubMed 17227833. Source: BHF-UCL

T cell differentiation in thymus

Inferred from sequence or structural similarity. Source: BHF-UCL

androgen metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: Ensembl

artery development

Inferred from electronic annotation. Source: Ensembl

axon guidance

Inferred from sequence or structural similarity. Source: UniProtKB

blood coagulation

Inferred from electronic annotation. Source: Ensembl

branching involved in salivary gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

branching involved in ureteric bud morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

branching morphogenesis of an epithelial tube

Inferred from sequence or structural similarity. Source: UniProtKB

bud outgrowth involved in lung branching

Inferred from electronic annotation. Source: Ensembl

camera-type eye development

Inferred from electronic annotation. Source: Ensembl

canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from sequence or structural similarity. Source: UniProtKB

cell fate specification

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell signaling

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to lithium ion

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Inferred from sequence or structural similarity. Source: UniProtKB

determination of left/right asymmetry in lateral mesoderm

Inferred from sequence or structural similarity. Source: BHF-UCL

dorsal/ventral neural tube patterning

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral pattern formation

Inferred from sequence or structural similarity. Source: UniProtKB

ectoderm development

Inferred from electronic annotation. Source: Ensembl

embryo development

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic digit morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic foregut morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic forelimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic pattern specification

Traceable author statement PubMed 11001584. Source: BHF-UCL

embryonic skeletal system development

Inferred from electronic annotation. Source: Ensembl

endocytosis

Inferred from electronic annotation. Source: Ensembl

epithelial cell proliferation involved in salivary gland morphogenesis

Inferred from electronic annotation. Source: Ensembl

epithelial-mesenchymal signaling involved in prostate gland development

Inferred from direct assay PubMed 12221011. Source: MGI

establishment of cell polarity

Inferred from electronic annotation. Source: Ensembl

forebrain development

Inferred from sequence or structural similarity. Source: UniProtKB

formation of anatomical boundary

Inferred from electronic annotation. Source: Ensembl

hair follicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from sequence or structural similarity. Source: UniProtKB

heart looping

Inferred from sequence or structural similarity. Source: BHF-UCL

hindbrain development

Inferred from sequence or structural similarity. Source: UniProtKB

hindgut morphogenesis

Inferred from electronic annotation. Source: Ensembl

inner ear development

Inferred from electronic annotation. Source: Ensembl

intein-mediated protein splicing

Inferred from electronic annotation. Source: InterPro

intermediate filament organization

Inferred from electronic annotation. Source: Ensembl

left lung development

Inferred from electronic annotation. Source: Ensembl

limb bud formation

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from sequence or structural similarity. Source: UniProtKB

lung epithelium development

Inferred from electronic annotation. Source: Ensembl

lung lobe morphogenesis

Inferred from electronic annotation. Source: Ensembl

lung-associated mesenchyme development

Inferred from electronic annotation. Source: Ensembl

lymphoid progenitor cell differentiation

Inferred from mutant phenotype PubMed 14764698. Source: BHF-UCL

male genitalia development

Inferred from sequence or structural similarity. Source: UniProtKB

mesenchymal cell proliferation involved in lung development

Inferred from electronic annotation. Source: Ensembl

mesenchymal smoothened signaling pathway involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

metanephric mesenchymal cell proliferation involved in metanephros development

Inferred from sequence or structural similarity. Source: UniProtKB

metanephros development

Inferred from sequence or structural similarity. Source: UniProtKB

midbrain development

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular structure septum development

Inferred from electronic annotation. Source: Ensembl

myoblast differentiation

Inferred from electronic annotation. Source: Ensembl

myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of alpha-beta T cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cholesterol efflux

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of kidney smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of mesenchymal cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription elongation from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of ureter smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative thymic T cell selection

Inferred from sequence or structural similarity. Source: UniProtKB

neural crest cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

neuroblast proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron fate commitment

Inferred from sequence or structural similarity. Source: UniProtKB

odontogenesis of dentin-containing tooth

Inferred from electronic annotation. Source: Ensembl

oligodendrocyte development

Inferred from electronic annotation. Source: Ensembl

organ formation

Inferred from electronic annotation. Source: Ensembl

osteoblast development

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

pancreas development

Inferred from electronic annotation. Source: Ensembl

pattern specification process

Inferred from sequence or structural similarity. Source: UniProtKB

patterning of blood vessels

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell differentiation in thymus

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of alpha-beta T cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell division

Inferred from direct assay PubMed 11331587. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

positive regulation of hh target transcription factor activity

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of immature T cell proliferation in thymus

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of kidney smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mesenchymal cell proliferation involved in ureter development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of oligodendrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of sclerotome development

Inferred from direct assay PubMed 10654605. Source: BHF-UCL

positive regulation of skeletal muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

positive regulation of smoothened signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of striated muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10654605. Source: BHF-UCL

positive regulation of ureter smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive thymic T cell selection

Inferred from sequence or structural similarity. Source: UniProtKB

primary prostatic bud elongation

Inferred from electronic annotation. Source: Ensembl

prostate epithelial cord elongation

Inferred from electronic annotation. Source: Ensembl

prostate gland development

Inferred from sequence or structural similarity. Source: UniProtKB

protein localization to nucleus

Inferred from electronic annotation. Source: Ensembl

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mesenchymal cell proliferation involved in prostate gland development

Inferred from electronic annotation. Source: Ensembl

regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Non-traceable author statement PubMed 17507406. Source: BHF-UCL

regulation of odontogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of prostatic bud formation

Inferred from electronic annotation. Source: Ensembl

regulation of protein localization to nucleus

Inferred from direct assay PubMed 11331587. Source: BHF-UCL

regulation of proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

renal system development

Inferred from expression pattern PubMed 17850284. Source: UniProtKB

right lung development

Inferred from electronic annotation. Source: Ensembl

salivary gland cavitation

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway

Inferred from expression pattern PubMed 17850284. Source: UniProtKB

smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation

Inferred from electronic annotation. Source: Ensembl

somite development

Inferred from sequence or structural similarity. Source: BHF-UCL

spinal cord dorsal/ventral patterning

Inferred from electronic annotation. Source: Ensembl

spinal cord motor neuron differentiation

Inferred from electronic annotation. Source: Ensembl

stem cell development

Inferred from sequence or structural similarity. Source: UniProtKB

striated muscle tissue development

Inferred from electronic annotation. Source: Ensembl

telencephalon regionalization

Inferred from electronic annotation. Source: Ensembl

thalamus development

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from sequence or structural similarity. Source: UniProtKB

thyroid gland development

Inferred from electronic annotation. Source: Ensembl

trachea morphogenesis

Inferred from electronic annotation. Source: Ensembl

vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

ventral midline development

Traceable author statement PubMed 11001584. Source: BHF-UCL

   Cellular_componentcell surface

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay Ref.12. Source: UniProtKB

membrane raft

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from direct assay Ref.12. Source: UniProtKB

glycosaminoglycan binding

Inferred from electronic annotation. Source: Ensembl

laminin-1 binding

Inferred from sequence or structural similarity. Source: UniProtKB

morphogen activity

Non-traceable author statement PubMed 8647801. Source: BHF-UCL

patched binding

Inferred from direct assay PubMed 8906787. Source: BHF-UCL

peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

signal transducer activity

Inferred from direct assay Ref.12. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.6
Chain24 – 462439Sonic hedgehog protein
PRO_0000013208
Chain24 – 197174Sonic hedgehog protein N-product
PRO_0000013209
Chain198 – 462265Sonic hedgehog protein C-product
PRO_0000013210

Regions

Compositional bias407 – 4115Poly-Gly

Sites

Metal binding891Calcium 1
Metal binding901Calcium 1
Metal binding901Calcium 2
Metal binding951Calcium 1
Metal binding1251Calcium 1; via carbonyl oxygen
Metal binding1261Calcium 1
Metal binding1261Calcium 2
Metal binding1291Calcium 2
Metal binding1311Calcium 2
Metal binding1401Zinc
Metal binding1471Zinc
Metal binding1821Zinc
Site197 – 1982Cleavage; by autolysis By similarity
Site2431Involved in cholesterol transfer By similarity
Site2671Involved in auto-cleavage By similarity
Site2701Essential for auto-cleavage By similarity

Amino acid modifications

Lipidation241N-palmitoyl cysteine Ref.6
Lipidation1971Cholesterol glycine ester By similarity
Glycosylation2781N-linked (GlcNAc...) Ref.9

Natural variations

Natural variant61R → T in HPE3. Ref.23 Ref.28
VAR_023804
Natural variant171L → P in HPE3. Ref.28
VAR_062592
Natural variant261P → L in HPE3. Ref.28
VAR_062593
Natural variant271G → A in HPE3. Ref.22 Ref.28
VAR_039888
Natural variant311G → R in HPE3; the same mutation in the mouse sequence introduces a cleavage site for a furin-like protease resulting in abnormal protein processing; cleavage at this site removes 11 amino acids from the N-terminal domain and reduces affinity of Shh for Ptch1 and signaling potency in assays using chicken embryo neural plate explants and mouse C3H10T1/2 stem cells. Ref.14 Ref.15 Ref.26 Ref.28
Corresponds to variant rs28936675 [ dbSNP | Ensembl ].
VAR_003619
Natural variant391L → P in HPE3. Ref.28
VAR_062594
Natural variant531E → K in HPE3. Ref.28
VAR_062595
Natural variant831D → V in HPE3. Ref.28
VAR_062596
Natural variant841I → F in HPE3. Ref.28
VAR_062597
Natural variant881D → V in HPE3; familial; the same mutation in the mouse sequence moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. Ref.17 Ref.26 Ref.28
VAR_009163
Natural variant1001Q → H in HPE3; sporadic; in the mouse sequence does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. Ref.16 Ref.23 Ref.26 Ref.28
VAR_009164
Natural variant1021C → R in HPE3. Ref.28
VAR_062598
Natural variant1021C → Y in HPE3. Ref.28
VAR_062599
Natural variant106 – 1072Missing in HPE3.
VAR_023805
Natural variant1091L → F in HPE3. Ref.28
VAR_062600
Natural variant1101A → D in HPE3. Ref.23 Ref.28
VAR_023806
Natural variant1101A → T in HPE3. Ref.28
VAR_062601
Natural variant1111I → F in SMMCI. Ref.18 Ref.28
VAR_017883
Natural variant1111I → N in HPE3. Ref.24 Ref.28
VAR_039889
Natural variant1151N → K in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures. Ref.17 Ref.26 Ref.28
VAR_009165
Natural variant1171W → G in HPE3; the same mutation in the mouse sequence causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; the mutation drastically reduces signaling potency in chicken embryo neural plate explant assays. Ref.14 Ref.15 Ref.26 Ref.28
VAR_003620
Natural variant1171W → R in HPE3; the same mutation in the mouse sequence causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays. Ref.14 Ref.15 Ref.26 Ref.28
VAR_003621
Natural variant1241V → M in HPE3. Ref.28
VAR_062602
Natural variant1361E → K in HPE3. Ref.28
VAR_062603
Natural variant1401H → P in HPE3. Ref.19 Ref.28
VAR_039890
Natural variant1401H → Q in HPE3. Ref.25 Ref.27 Ref.28
VAR_039891
Natural variant1431G → D in HPE3. Ref.28
VAR_062604
Natural variant1441R → P in HPE3. Ref.28
VAR_062605
Natural variant1471D → N in HPE3. Ref.28
VAR_062606
Natural variant1501T → K in HPE3. Ref.28
VAR_062607
Natural variant1501T → R in HPE3. Ref.23 Ref.28
VAR_023807
Natural variant1561S → R in HPE3. Ref.28
VAR_062608
Natural variant1701F → C in HPE3. Ref.28
VAR_062609
Natural variant1711D → H in HPE3. Ref.28
VAR_062610
Natural variant176 – 1783Missing in HPE3.
VAR_023808
Natural variant1831C → F in HPE3. Ref.19 Ref.28
VAR_039892
Natural variant1831C → R in HPE3. Ref.28
VAR_062611
Natural variant1831C → Y in HPE3. Ref.28
VAR_062612
Natural variant1841S → L in HPE3. Ref.28
VAR_062613
Natural variant1881E → Q in HPE3; familial. Ref.16 Ref.23 Ref.26 Ref.28
VAR_009166
Natural variant196 – 2005Missing in HPE3.
VAR_062614
Natural variant1961G → E in HPE3. Ref.28
VAR_062615
Natural variant1971G → V in HPE3. Ref.28
VAR_062616
Natural variant1981C → F in HPE3. Ref.28
VAR_062617
Natural variant1981C → S in HPE3. Ref.28
VAR_062618
Natural variant2181L → P in HPE3. Ref.27 Ref.28
VAR_062619
Natural variant2221D → N in HPE3; familial. Ref.16 Ref.23 Ref.28
VAR_009167
Natural variant2241V → E in HPE3. Ref.15 Ref.28
VAR_009168
Natural variant2261A → T in HPE3; familial. Ref.15 Ref.28
VAR_009169
Natural variant2311G → V in HPE3. Ref.28
VAR_062620
Natural variant2321R → G in HPE3. Ref.28
VAR_062621
Natural variant2341L → P in HPE3. Ref.28
VAR_062622
Natural variant2361S → N in HPE3. Ref.28
VAR_062623
Natural variant2361S → R in HPE3; familial. Ref.17 Ref.28
VAR_009170
Natural variant2411F → L in HPE3. Ref.28
VAR_062624
Natural variant2411F → V in HPE3. Ref.28
VAR_062625
Natural variant2551I → N in HPE3. Ref.28
VAR_062626
Natural variant263 – 2697Missing in HPE3; sporadic.
VAR_009171
Natural variant2671T → I in HPE3. Ref.22 Ref.28
VAR_039893
Natural variant2711L → P in HPE3. Ref.23 Ref.28
VAR_023809
Natural variant2751A → E in HPE3. Ref.28
VAR_062627
Natural variant2801S → W in HPE3. Ref.28
VAR_062628
Natural variant2901G → D in HPE3; sporadic. Ref.17 Ref.28
Corresponds to variant rs104894047 [ dbSNP | Ensembl ].
VAR_009172
Natural variant2961G → A in HPE3; unknown pathological significance. Ref.28
VAR_062629
Natural variant3101R → C in HPE3. Ref.28
VAR_062630
Natural variant3211R → S in HPE3. Ref.28
VAR_062631
Natural variant3321V → A in HPE3 and SMMCI. Ref.21 Ref.23 Ref.28
VAR_023810
Natural variant3461A → V in HPE3. Ref.28
VAR_062632
Natural variant3471P → L in HPE3. Ref.28
VAR_062633
Natural variant3471P → Q in HPE3. Ref.23 Ref.28
VAR_023811
Natural variant3471P → R in HPE3. Ref.28
VAR_062634
Natural variant3541I → T in HPE3. Ref.23 Ref.28
VAR_023812
Natural variant3621S → L in HPE3. Ref.28
VAR_062635
Natural variant3631C → Y in HPE3. Ref.27 Ref.28
VAR_062636
Natural variant3641Y → C in HPE3. Ref.28
VAR_062637
Natural variant3731A → T in HPE3. Ref.22 Ref.28
VAR_039894
Natural variant3741H → R in HPE3. Ref.28
VAR_062638
Natural variant3761A → D in HPE3. Ref.28
VAR_062639
Natural variant3771F → S in HPE3. Ref.28
VAR_062640
Natural variant378 – 3803Missing in HPE3; familial.
VAR_009173
Natural variant3811R → P in HPE3. Ref.23 Ref.28
VAR_023813
Natural variant3821L → P in HPE3. Ref.28
VAR_062641
Natural variant3831A → T in HPE3; sporadic. Ref.15 Ref.28
VAR_009174
Natural variant3911A → T in HPE3; unknown pathological significance. Ref.28
VAR_062642
Natural variant401 – 4088Missing in ocular coloboma.
VAR_017884
Natural variant402 – 4098Missing in HPE3; unknown pathological significance.
VAR_062643
Natural variant404 – 4085Missing in HPE3; familial.
VAR_009175
Natural variant405 – 4095Missing in HPE3; unknown pathological significance.
VAR_062644
Natural variant4111G → GG in HPE3; unknown pathological significance. Ref.28
VAR_062645
Natural variant4161T → A in HPE3; unknown pathological significance. Ref.28
VAR_062646
Natural variant4241P → A in HPE3; familial. Ref.17 Ref.28
VAR_009176
Natural variant4351Y → N in HPE3. Ref.28
VAR_062647
Natural variant4361S → L in HPE3; sporadic. Ref.17 Ref.28
VAR_009177
Natural variant4561G → R in HPE3; unknown pathological significance. Ref.28
VAR_062648

Experimental info

Mutagenesis241C → S: Abolishes palmitoylation. Ref.6

Secondary structure

............................... 462
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15465 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: DD687AFA582A4749

FASTA46249,607
        10         20         30         40         50         60 
MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN VAEKTLGASG 

        70         80         90        100        110        120 
RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ RCKDKLNALA ISVMNQWPGV 

       130        140        150        160        170        180 
KLRVTEGWDE DGHHSEESLH YEGRAVDITT SDRDRSKYGM LARLAVEAGF DWVYYESKAH 

       190        200        210        220        230        240 
IHCSVKAENS VAAKSGGCFP GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT 

       250        260        270        280        290        300 
FLDRDDGAKK VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG 

       310        320        330        340        350        360 
PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA QGTILINRVL 

       370        380        390        400        410        420 
ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD SGGGDRGGGG GRVALTAPGA 

       430        440        450        460 
ADAPGAGATA GIHWYSQLLY QIGTWLLDSE ALHPLGMAVK SS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog."
Marigo V., Roberts D.J., Lee S.M.K., Tsukurov O., Levi T., Gastier J.M., Epstein D.J., Gilbert D.J., Copeland N.G., Seidman C.E., Jenkins N.A., Seidman J.G., McMahon A.P., Tabin C.
Genomics 28:44-51(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal lung.
[2]"Expression of Sonic hedgehog and its receptor Patched/Smoothened in human cancer cell lines and embryonic organs."
Tate G., Kishimoto K., Mitsuya T.
J. Biochem. Mol. Biol. Biophys. 4:27-34(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]NIEHS SNPs program
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Identification of a palmitic acid-modified form of human Sonic hedgehog."
Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P., Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R., Wang E.A., Galdes A.
J. Biol. Chem. 273:14037-14045(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-32, PALMITOYLATION AT CYS-24, CHOLESTERYLATION, MUTAGENESIS OF CYS-24, MASS SPECTROMETRY.
[7]"Products, genetic linkage and limb patterning activity of a murine hedgehog gene."
Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.
Development 120:3339-3353(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-167.
[8]"A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly."
Lettice L.A., Heaney S.J.H., Purdie L.A., Li L., de Beer P., Oostra B.A., Goode D., Elgar G., Hill R.E., de Graaff E.
Hum. Mol. Genet. 12:1725-1735(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN TPTPS.
[9]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278.
Tissue: Plasma.
[10]"Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer."
Sun M., Ma F., Zeng X., Liu Q., Zhao X.-L., Wu F.-X., Wu G.-P., Zhang Z.-F., Gu B., Zhao Y.-F., Tian S.-H., Lin B., Kong X.-Y., Zhang X.-L., Yang W., Lo W.H.-Y., Zhang X.
J. Med. Genet. 45:589-595(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN TPTPS.
[11]"Mapping sonic hedgehog-receptor interactions by steric interference."
Pepinsky R.B., Rayhorn P., Day E.S., Dergay A., Williams K.P., Galdes A., Taylor F.R., Boriack-Sjodin P.A., Garber E.A.
J. Biol. Chem. 275:10995-11001(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-197 IN COMPLEX WITH ZINC IONS, FUNCTION, DOMAIN.
[12]"The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling."
Bosanac I., Maun H.R., Scales S.J., Wen X., Lingel A., Bazan J.F., de Sauvage F.J., Hymowitz S.G., Lazarus R.A.
Nat. Struct. Mol. Biol. 16:691-697(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 29-197 IN COMPLEX WITH HHIP; ZINC AND CALCIUM IONS, DOMAIN, INTERACTION WITH HHIP.
[13]"Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site."
Maun H.R., Wen X., Lingel A., de Sauvage F.J., Lazarus R.A., Scales S.J., Hymowitz S.G.
J. Biol. Chem. 285:26570-26580(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 29-197 IN COMPLEX WITH MONOCLONAL ANTIBODY; ZINC AND CALCIUM IONS, SUBCELLULAR LOCATION, DOMAIN.
[14]"Mutations in the human Sonic hedgehog gene cause holoprosencephaly."
Roessler E., Belloni E., Gaudenz K., Jay P., Berta P., Scherer S.W., Tsui L.-C., Muenke M.
Nat. Genet. 14:357-360(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 ARG-31; GLY-117 AND ARG-117.
[15]"Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly."
Roessler E., Belloni E., Gaudenz K., Vargas F., Scherer S.W., Tsui L.-C., Muenke M.
Hum. Mol. Genet. 6:1847-1853(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 ARG-31; GLY-117; ARG-117; GLU-224; THR-226 AND THR-383.
[16]"Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly."
Odent S., Atti-Bitach T., Blayau M., Mathieu M., Aug J., Delezo de A.L., Gall J.Y., Le Marec B., Munnich A., David V., Vekemans M.
Hum. Mol. Genet. 8:1683-1689(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 HIS-100; GLN-188 AND ASN-222.
[17]"The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly."
Nanni L., Ming J.E., Bocian M., Steinhaus K., Bianchi D.W., Die-Smulders C., Giannotti A., Imaizumi K., Jones K.L., Campo M.D., Martin R.A., Meinecke P., Pierpont M.E.M., Robin N.H., Young I.D., Roessler E., Muenke M.
Hum. Mol. Genet. 8:2479-2488(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 VAL-88; LYS-115; ARG-236; 263-ARG--ALA-269 DEL; ASP-290; ALA-424 AND LEU-436.
[18]"SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature."
Nanni L., Ming J.E., Du Y., Hall R.K., Aldred M., Bankier A., Muenke M.
Am. J. Med. Genet. 102:1-10(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SMMCI PHE-111.
[19]"Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly."
Orioli I.M., Castilla E.E., Ming J.E., Nazer J., Burle de Aguiar M.J., Llerena J.C., Muenke M.
Hum. Genet. 109:1-6(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 PRO-140 AND PHE-183.
[20]"Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia."
Schimmenti L.A., de la Cruz J., Lewis R.A., Karkera J.D., Manligas G.S., Roessler E., Muenke M.
Am. J. Med. Genet. A 116:215-221(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MCOPCB5 401-SER--GLY-408 DEL.
[21]"Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog."
Garavelli L., Zanacca C., Caselli G., Banchini G., Dubourg C., David V., Odent S., Gurrieri F., Neri G.
Am. J. Med. Genet. A 127:93-95(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SMMCI ALA-332.
[22]"Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation."
Hehr U., Gross C., Diebold U., Wahl D., Beudt U., Heidemann P., Hehr A., Mueller D.
Eur. J. Pediatr. 163:347-352(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 ALA-27; ILE-267 AND THR-373.
[23]"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations."
Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F., Durou M.-R., Odent S., David V.
Hum. Mutat. 24:43-51(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 THR-6; HIS-100; 106-LEU-ASN-107 DEL; ASP-110; ARG-150; 176-GLU--LYS-178 DEL; GLN-188; ASN-222; PRO-271; ALA-332; GLN-347; THR-354 AND PRO-381.
[24]"SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor."
El-Jaick K.B., Brunoni D., Castilla E.E., Moreira M.A., Orioli I.M.
Am. J. Med. Genet. A 136:345-345(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPE3 ASN-111.
[25]"Single median maxillary central incisor, hypophyseal tumor, and SHH mutation."
Ribeiro L.A., Richieri-Costa A.
Am. J. Med. Genet. A 136:346-347(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HPE3 GLN-140.
[26]"Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly."
Maity T., Fuse N., Beachy P.A.
Proc. Natl. Acad. Sci. U.S.A. 102:17026-17031(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS HPE3 ARG-31; VAL-88; HIS-100; LYS-115; ARG-117; GLY-117 AND GLN-188.
[27]"Holoprosencephaly-like phenotype: clinical and genetic perspectives."
Richieri-Costa A., Ribeiro L.A.
Am. J. Med. Genet. A 140:2587-2593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 GLN-140; PRO-218 AND TYR-363.
[28]"The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis."
Roessler E., El-Jaick K.B., Dubourg C., Velez J.I., Solomon B.D., Pineda-Alvarez D.E., Lacbawan F., Zhou N., Ouspenskaia M., Paulussen A., Smeets H.J., Hehr U., Bendavid C., Bale S., Odent S., David V., Muenke M.
Hum. Mutat. 30:E921-E935(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPE3 THR-6; PRO-17; LEU-26; ALA-27; ARG-31; PRO-39; LYS-53; VAL-83; PHE-84; VAL-88; HIS-100; ARG-102; TYR-102; 106-LEU-ASN-107 DEL; PHE-109; THR-110; ASP-110; PHE-111; ASN-111; LYS-115; GLY-117; ARG-117; MET-124; LYS-136; PRO-140; GLN-140; ASP-143; PRO-144; ASN-147; ARG-150; LYS-150; ARG-156; CYS-170; HIS-171; 176-GLU--LYS-178 DEL; ARG-183; PHE-183; TYR-183; LEU-184; GLN-188; GLU-196; 196-GLY--PRO-200 DEL; VAL-197; SER-198; PHE-198; PRO-218; ASN-222; GLU-224; THR-226; VAL-231; GLY-232; PRO-234; ARG-236; ASN-236; VAL-241; LEU-241; ASN-255; 263-ARG--ALA-269 DEL; ILE-267; PRO-271; GLU-275; TRP-280; ASP-290; ALA-296; CYS-310; SER-321; ALA-332; VAL-346; ARG-347; GLN-347; LEU-347; THR-354; LEU-362; TYR-363; CYS-364; THR-373; ARG-374; ASP-376; SER-377; 378-ALA--PHE-380 DEL; PRO-381; PRO-382; THR-383; THR-391; 402-GLY--GLY-409 DEL; 405-ASP--GLY-409 DEL; GLY-411 INS; ALA-416; ALA-424; ASN-435; LEU-436 AND ARG-456.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L38518 mRNA. Translation: AAA62179.1.
AY422195 Genomic DNA. Translation: AAQ87879.1.
AC002484 Genomic DNA. Translation: AAB67604.1.
AC078834 Genomic DNA. Translation: AAS01990.1.
CH236954 Genomic DNA. Translation: EAL23913.1.
RefSeqNP_000184.1. NM_000193.2.
UniGeneHs.164537.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3HO5X-ray3.01H29-197[»]
3M1NX-ray1.85A/B25-197[»]
3MXWX-ray1.83A29-197[»]
ProteinModelPortalQ15465.
SMRQ15465. Positions 25-190, 198-365.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112365. 5 interactions.
STRING9606.ENSP00000297261.

Chemistry

BindingDBQ15465.
ChEMBLCHEMBL5602.

Protein family/group databases

MEROPSC46.002.

PTM databases

PhosphoSiteQ15465.

Polymorphism databases

DMDM6094283.

Proteomic databases

PaxDbQ15465.
PRIDEQ15465.

Protocols and materials databases

DNASU6469.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297261; ENSP00000297261; ENSG00000164690.
GeneID6469.
KEGGhsa:6469.
UCSCuc003wmj.1. human.

Organism-specific databases

CTD6469.
GeneCardsGC07M155592.
HGNCHGNC:10848. SHH.
HPACAB018966.
MIM142945. phenotype.
147250. phenotype.
174500. phenotype.
600725. gene.
611638. phenotype.
neXtProtNX_Q15465.
Orphanet93925. Alobar holoprosencephaly.
98938. Colobomatous microphthalmia.
3332. Hypoplastic tibiae - postaxial polydactyly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
194. Ocular coloboma.
295150. Polydactyly of a triphalangeal thumb, bilateral.
295148. Polydactyly of a triphalangeal thumb, unilateral.
295071. Radial hemimelia, bilateral.
295069. Radial hemimelia, unilateral.
799. Schizencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
2286. Solitary median maxillary central incisor syndrome.
93405. Syndactyly type 4.
2950. Triphalangeal thumb - polysyndactyly syndrome.
PharmGKBPA35752.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250647.
HOGENOMHOG000233428.
HOVERGENHBG005480.
InParanoidQ15465.
KOK11988.
OMASWAHRAF.
OrthoDBEOG779NZ5.
PhylomeDBQ15465.
TreeFamTF106458.

Enzyme and pathway databases

SignaLinkQ15465.

Gene expression databases

ArrayExpressQ15465.
BgeeQ15465.
CleanExHS_SHH.
GenevestigatorQ15465.

Family and domain databases

Gene3D3.30.1380.10. 1 hit.
InterProIPR001657. Hedgehog.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
IPR000320. Hedgehog_signalling_dom.
IPR001767. Hint_dom.
IPR003586. Hint_dom_C.
IPR003587. Hint_dom_N.
IPR006141. Intein_splice_site.
[Graphical view]
PfamPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFPIRSF009400. Peptidase_C46. 1 hit.
PRINTSPR00632. SONICHHOG.
SMARTSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMSSF55166. SSF55166. 1 hit.
PROSITEPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15465.
GeneWikiSonic_hedgehog.
GenomeRNAi6469.
NextBio25129.
PROQ15465.
SOURCESearch...

Entry information

Entry nameSHH_HUMAN
AccessionPrimary (citable) accession number: Q15465
Secondary accession number(s): A4D247, Q75MC9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 168 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM