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Protein

Sonic hedgehog protein

Gene

SHH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi89Calcium 1Combined sources1 Publication1
Metal bindingi90Calcium 1Combined sources1 Publication1
Metal bindingi90Calcium 2Combined sources1 Publication1
Metal bindingi95Calcium 1Combined sources1 Publication1
Metal bindingi125Calcium 1; via carbonyl oxygenCombined sources1 Publication1
Metal bindingi126Calcium 1Combined sources1 Publication1
Metal bindingi126Calcium 2Combined sources1 Publication1
Metal bindingi129Calcium 2Combined sources1 Publication1
Metal bindingi131Calcium 2Combined sources1 Publication1
Metal bindingi140ZincCombined sources2 Publications1
Metal bindingi147ZincCombined sources2 Publications1
Metal bindingi182ZincCombined sources2 Publications1
Sitei243Involved in cholesterol transferBy similarity1
Sitei267Involved in auto-cleavageBy similarity1
Sitei270Essential for auto-cleavageBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • glycoprotein binding Source: Ensembl
  • glycosaminoglycan binding Source: Ensembl
  • laminin-1 binding Source: UniProtKB
  • morphogen activity Source: BHF-UCL
  • patched binding Source: BHF-UCL
  • peptidase activity Source: UniProtKB-KW
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164690-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362768. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
R-HSA-5362798. Release of Hh-Np from the secreting cell.
R-HSA-5632681. Ligand-receptor interactions.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5635838. Activation of SMO.
R-HSA-5658034. HHAT G278V abrogates palmitoylation of Hh-Np.
SignaLinkiQ15465.
SIGNORiQ15465.

Protein family/group databases

MEROPSiC46.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Sonic hedgehog protein
Short name:
SHH
Alternative name(s):
HHG-1
Cleaved into the following 2 chains:
Gene namesi
Name:SHH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:10848. SHH.

Subcellular locationi

Sonic hedgehog protein C-product :
  • Secretedextracellular space By similarity

  • Note: The C-terminal peptide diffuses from the cell.By similarity
Sonic hedgehog protein N-product :
  • Cell membrane By similarity; Lipid-anchor By similarity

  • 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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, isolated, with coloboma, 5 (MCOPCB5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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).
See also OMIM:611638
Holoprosencephaly 3 (HPE3)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:142945
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0238046R → T in HPE3. 2 Publications1
Natural variantiVAR_06259217L → P in HPE3. 1 Publication1
Natural variantiVAR_06259326P → L in HPE3. 1 Publication1
Natural variantiVAR_03988827G → A in HPE3. 2 Publications1
Natural variantiVAR_00361931G → 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. 4 PublicationsCorresponds to variant rs28936675dbSNPEnsembl.1
Natural variantiVAR_06259439L → P in HPE3. 1 Publication1
Natural variantiVAR_06259553E → K in HPE3. 1 Publication1
Natural variantiVAR_06259683D → V in HPE3. 1 Publication1
Natural variantiVAR_06259784I → F in HPE3. 1 Publication1
Natural variantiVAR_00916388D → 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. 3 PublicationsCorresponds to variant rs104894050dbSNPEnsembl.1
Natural variantiVAR_009164100Q → 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. 4 PublicationsCorresponds to variant rs587778792dbSNPEnsembl.1
Natural variantiVAR_062598102C → R in HPE3. 1 Publication1
Natural variantiVAR_062599102C → Y in HPE3. 1 Publication1
Natural variantiVAR_023805106 – 107Missing in HPE3. 2 Publications2
Natural variantiVAR_062600109L → F in HPE3. 1 Publication1
Natural variantiVAR_023806110A → D in HPE3. 2 Publications1
Natural variantiVAR_062601110A → T in HPE3. 1 Publication1
Natural variantiVAR_039889111I → N in HPE3. 2 Publications1
Natural variantiVAR_009165115N → K in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures. 3 PublicationsCorresponds to variant rs267607047dbSNPEnsembl.1
Natural variantiVAR_003620117W → 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. 4 PublicationsCorresponds to variant rs104894040dbSNPEnsembl.1
Natural variantiVAR_003621117W → 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. 4 PublicationsCorresponds to variant rs104894040dbSNPEnsembl.1
Natural variantiVAR_062602124V → M in HPE3. 1 Publication1
Natural variantiVAR_062603136E → K in HPE3. 1 Publication1
Natural variantiVAR_039890140H → P in HPE3. 2 Publications1
Natural variantiVAR_039891140H → Q in HPE3. 3 Publications1
Natural variantiVAR_062604143G → D in HPE3. 1 Publication1
Natural variantiVAR_062605144R → P in HPE3. 1 Publication1
Natural variantiVAR_062606147D → N in HPE3. 1 Publication1
Natural variantiVAR_062607150T → K in HPE3. 1 Publication1
Natural variantiVAR_023807150T → R in HPE3. 2 Publications1
Natural variantiVAR_062608156S → R in HPE3. 1 Publication1
Natural variantiVAR_062609170F → C in HPE3. 1 Publication1
Natural variantiVAR_062610171D → H in HPE3. 1 Publication1
Natural variantiVAR_023808176 – 178Missing in HPE3. 2 Publications3
Natural variantiVAR_039892183C → F in HPE3. 2 Publications1
Natural variantiVAR_062611183C → R in HPE3. 1 Publication1
Natural variantiVAR_062612183C → Y in HPE3. 1 Publication1
Natural variantiVAR_062613184S → L in HPE3. 1 Publication1
Natural variantiVAR_009166188E → Q in HPE3; familial. 4 PublicationsCorresponds to variant rs587778799dbSNPEnsembl.1
Natural variantiVAR_062614196 – 200Missing in HPE3. 1 Publication5
Natural variantiVAR_062615196G → E in HPE3. 1 PublicationCorresponds to variant rs752650571dbSNPEnsembl.1
Natural variantiVAR_062616197G → V in HPE3. 1 Publication1
Natural variantiVAR_062617198C → F in HPE3. 1 Publication1
Natural variantiVAR_062618198C → S in HPE3. 1 Publication1
Natural variantiVAR_062619218L → P in HPE3. 2 Publications1
Natural variantiVAR_009167222D → N in HPE3; familial. 3 PublicationsCorresponds to variant rs587778805dbSNPEnsembl.1
Natural variantiVAR_009168224V → E in HPE3. 2 PublicationsCorresponds to variant rs104894042dbSNPEnsembl.1
Natural variantiVAR_009169226A → T in HPE3; familial. 2 PublicationsCorresponds to variant rs104894043dbSNPEnsembl.1
Natural variantiVAR_062620231G → V in HPE3. 1 Publication1
Natural variantiVAR_062621232R → G in HPE3. 1 Publication1
Natural variantiVAR_062622234L → P in HPE3. 1 Publication1
Natural variantiVAR_062623236S → N in HPE3. 1 Publication1
Natural variantiVAR_009170236S → R in HPE3; familial. 2 PublicationsCorresponds to variant rs587778806dbSNPEnsembl.1
Natural variantiVAR_062624241F → L in HPE3. 1 Publication1
Natural variantiVAR_062625241F → V in HPE3. 1 Publication1
Natural variantiVAR_062626255I → N in HPE3. 1 Publication1
Natural variantiVAR_009171263 – 269Missing in HPE3; sporadic. 2 Publications7
Natural variantiVAR_039893267T → I in HPE3. 2 Publications1
Natural variantiVAR_023809271L → P in HPE3. 2 Publications1
Natural variantiVAR_062627275A → E in HPE3. 1 PublicationCorresponds to variant rs556192490dbSNPEnsembl.1
Natural variantiVAR_062628280S → W in HPE3. 1 Publication1
Natural variantiVAR_009172290G → D in HPE3; sporadic. 2 PublicationsCorresponds to variant rs104894047dbSNPEnsembl.1
Natural variantiVAR_062629296G → A in HPE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_062630310R → C in HPE3. 1 Publication1
Natural variantiVAR_062631321R → S in HPE3. 1 Publication1
Natural variantiVAR_023810332V → A in HPE3 and SMMCI. 3 PublicationsCorresponds to variant rs104894052dbSNPEnsembl.1
Natural variantiVAR_062632346A → V in HPE3. 1 Publication1
Natural variantiVAR_062633347P → L in HPE3. 1 Publication1
Natural variantiVAR_023811347P → Q in HPE3. 2 Publications1
Natural variantiVAR_062634347P → R in HPE3. 1 Publication1
Natural variantiVAR_023812354I → T in HPE3. 2 Publications1
Natural variantiVAR_062635362S → L in HPE3. 1 Publication1
Natural variantiVAR_062636363C → Y in HPE3. 2 Publications1
Natural variantiVAR_062637364Y → C in HPE3. 1 Publication1
Natural variantiVAR_039894373A → T in HPE3. 2 Publications1
Natural variantiVAR_062638374H → R in HPE3. 1 Publication1
Natural variantiVAR_062639376A → D in HPE3. 1 Publication1
Natural variantiVAR_062640377F → S in HPE3. 1 Publication1
Natural variantiVAR_009173378 – 380Missing in HPE3; familial. 1 Publication3
Natural variantiVAR_023813381R → P in HPE3. 2 Publications1
Natural variantiVAR_062641382L → P in HPE3. 1 Publication1
Natural variantiVAR_009174383A → T in HPE3; sporadic. 2 PublicationsCorresponds to variant rs137853341dbSNPEnsembl.1
Natural variantiVAR_062642391A → T in HPE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_062643402 – 409Missing in HPE3; unknown pathological significance. 1 Publication8
Natural variantiVAR_009175404 – 408Missing in HPE3; familial. 5
Natural variantiVAR_062644405 – 409Missing in HPE3; unknown pathological significance. 1 Publication5
Natural variantiVAR_062645411G → GG in HPE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_062646416T → A in HPE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_009176424P → A in HPE3; familial. 2 PublicationsCorresponds to variant rs104894048dbSNPEnsembl.1
Natural variantiVAR_062647435Y → N in HPE3. 1 Publication1
Natural variantiVAR_009177436S → L in HPE3; sporadic. 2 Publications1
Natural variantiVAR_062648456G → R in HPE3; unknown pathological significance. 1 Publication1
Solitary median maxillary central incisor (SMMCI)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare dental anomaly characterized by the congenital absence of one maxillary central incisor.
See also OMIM:147250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017883111I → F in SMMCI. 2 PublicationsCorresponds to variant rs104894049dbSNPEnsembl.1
Natural variantiVAR_023810332V → A in HPE3 and SMMCI. 3 PublicationsCorresponds to variant rs104894052dbSNPEnsembl.1
Triphalangeal thumb-polysyndactyly syndrome (TPTPS)2 Publications
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.
Disease descriptionAutosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development.
See also OMIM:174500
Preaxial polydactyly 2 (PPD2)1 Publication
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 (PubMed:12837695).1 Publication
Disease descriptionPolydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal.
See also OMIM:174500
Hypoplasia or aplasia of tibia with polydactyly (THYP)2 Publications
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.2 Publications
Disease descriptionAn autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly.
See also OMIM:188740
Laurin-Sandrow syndrome (LSS)1 Publication
The gene represented in this entry is involved in disease pathogenesis. Abnormal SHH limb expression with pathological consequences is caused by duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5 (PubMed:24456159).
Disease descriptionA rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. Some patients do not have nasal abnormalities (segmental Laurin-Sandrow syndrome).
See also OMIM:135750

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24C → S: Abolishes palmitoylation. 1 Publication1

Keywords - Diseasei

Disease mutation, Holoprosencephaly, Microphthalmia

Organism-specific databases

DisGeNETi6469.
MalaCardsiSHH.
MIMi135750. phenotype.
142945. phenotype.
147250. phenotype.
174500. phenotype.
188740. phenotype.
611638. phenotype.
OpenTargetsiENSG00000164690.
Orphaneti93925. 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.
PharmGKBiPA35752.

Chemistry databases

ChEMBLiCHEMBL5602.

Polymorphism and mutation databases

BioMutaiSHH.
DMDMi6094283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000001320824 – 462Sonic hedgehog proteinAdd BLAST439
ChainiPRO_000001320924 – 197Sonic hedgehog protein N-productAdd BLAST174
ChainiPRO_0000013210198 – 462Sonic hedgehog protein C-productAdd BLAST265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi24N-palmitoyl cysteine1 Publication1
Lipidationi197Cholesterol glycine esterBy similarity1
Glycosylationi278N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei197 – 198Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ15465.
PeptideAtlasiQ15465.
PRIDEiQ15465.

PTM databases

iPTMnetiQ15465.
PhosphoSitePlusiQ15465.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000164690.
CleanExiHS_SHH.
ExpressionAtlasiQ15465. baseline and differential.
GenevisibleiQ15465. HS.

Organism-specific databases

HPAiCAB018966.

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HHIPQ96QV110EBI-11666886,EBI-6598521
PTCH1Q136352EBI-11666886,EBI-8775406

GO - Molecular functioni

  • laminin-1 binding Source: UniProtKB
  • patched binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112365. 8 interactors.
DIPiDIP-61763N.
IntActiQ15465. 2 interactors.
STRINGi9606.ENSP00000297261.

Chemistry databases

BindingDBiQ15465.

Structurei

Secondary structure

1462
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 32Combined sources3
Beta strandi47 – 51Combined sources5
Turni56 – 59Combined sources4
Helixi72 – 75Combined sources4
Beta strandi84 – 86Combined sources3
Beta strandi91 – 93Combined sources3
Helixi94 – 96Combined sources3
Helixi100 – 116Combined sources17
Beta strandi122 – 128Combined sources7
Helixi139 – 142Combined sources4
Beta strandi145 – 150Combined sources6
Helixi155 – 157Combined sources3
Helixi158 – 167Combined sources10
Beta strandi171 – 177Combined sources7
Beta strandi180 – 184Combined sources5
Helixi188 – 190Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3HO5X-ray3.01H29-197[»]
3M1NX-ray1.85A/B23-197[»]
3MXWX-ray1.83A29-197[»]
ProteinModelPortaliQ15465.
SMRiQ15465.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15465.

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi407 – 411Poly-Gly5

Domaini

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.3 Publications

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ15465.
KOiK11988.
OMAiEHSWAHR.
OrthoDBiEOG091G0N90.
PhylomeDBiQ15465.
TreeFamiTF106458.

Family and domain databases

Gene3Di2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProiIPR001657. Hedgehog.
IPR028992. Hedgehog/Intein_dom.
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_N.
[Graphical view]
PfamiPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
PRINTSiPR00632. SONICHHOG.
SMARTiSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMiSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEiPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15465-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN
60 70 80 90 100
VAEKTLGASG RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ
110 120 130 140 150
RCKDKLNALA ISVMNQWPGV KLRVTEGWDE DGHHSEESLH YEGRAVDITT
160 170 180 190 200
SDRDRSKYGM LARLAVEAGF DWVYYESKAH IHCSVKAENS VAAKSGGCFP
210 220 230 240 250
GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT FLDRDDGAKK
260 270 280 290 300
VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG
310 320 330 340 350
PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA
360 370 380 390 400
QGTILINRVL ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD
410 420 430 440 450
SGGGDRGGGG GRVALTAPGA ADAPGAGATA GIHWYSQLLY QIGTWLLDSE
460
ALHPLGMAVK SS
Length:462
Mass (Da):49,607
Last modified:November 1, 1996 - v1
Checksum:iDD687AFA582A4749
GO

Mass spectrometryi

Molecular mass is 19.560 Da from positions 24 - 197. Determined by ESI. Soluble N-product, purified from insect cells.1 Publication
Molecular mass is 20.167 Da from positions 24 - 197. Determined by ESI. Membrane-bound N-product, purified from insect cells.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0238046R → T in HPE3. 2 Publications1
Natural variantiVAR_06259217L → P in HPE3. 1 Publication1
Natural variantiVAR_06259326P → L in HPE3. 1 Publication1
Natural variantiVAR_03988827G → A in HPE3. 2 Publications1
Natural variantiVAR_00361931G → 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. 4 PublicationsCorresponds to variant rs28936675dbSNPEnsembl.1
Natural variantiVAR_06259439L → P in HPE3. 1 Publication1
Natural variantiVAR_06259553E → K in HPE3. 1 Publication1
Natural variantiVAR_06259683D → V in HPE3. 1 Publication1
Natural variantiVAR_06259784I → F in HPE3. 1 Publication1
Natural variantiVAR_00916388D → 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. 3 PublicationsCorresponds to variant rs104894050dbSNPEnsembl.1
Natural variantiVAR_009164100Q → 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. 4 PublicationsCorresponds to variant rs587778792dbSNPEnsembl.1
Natural variantiVAR_062598102C → R in HPE3. 1 Publication1
Natural variantiVAR_062599102C → Y in HPE3. 1 Publication1
Natural variantiVAR_023805106 – 107Missing in HPE3. 2 Publications2
Natural variantiVAR_062600109L → F in HPE3. 1 Publication1
Natural variantiVAR_023806110A → D in HPE3. 2 Publications1
Natural variantiVAR_062601110A → T in HPE3. 1 Publication1
Natural variantiVAR_017883111I → F in SMMCI. 2 PublicationsCorresponds to variant rs104894049dbSNPEnsembl.1
Natural variantiVAR_039889111I → N in HPE3. 2 Publications1
Natural variantiVAR_009165115N → K in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures. 3 PublicationsCorresponds to variant rs267607047dbSNPEnsembl.1
Natural variantiVAR_003620117W → 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. 4 PublicationsCorresponds to variant rs104894040dbSNPEnsembl.1
Natural variantiVAR_003621117W → 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. 4 PublicationsCorresponds to variant rs104894040dbSNPEnsembl.1
Natural variantiVAR_062602124V → M in HPE3. 1 Publication1
Natural variantiVAR_062603136E → K in HPE3. 1 Publication1
Natural variantiVAR_039890140H → P in HPE3. 2 Publications1
Natural variantiVAR_039891140H → Q