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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 similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi89 – 891Calcium 1
Metal bindingi90 – 901Calcium 1
Metal bindingi90 – 901Calcium 2
Metal bindingi95 – 951Calcium 1
Metal bindingi125 – 1251Calcium 1; via carbonyl oxygen
Metal bindingi126 – 1261Calcium 1
Metal bindingi126 – 1261Calcium 2
Metal bindingi129 – 1291Calcium 2
Metal bindingi131 – 1311Calcium 2
Metal bindingi140 – 1401Zinc2 Publications
Metal bindingi147 – 1471Zinc2 Publications
Metal bindingi182 – 1821Zinc2 Publications
Sitei197 – 1982Cleavage; by autolysisBy similarity
Sitei243 – 2431Involved in cholesterol transferBy similarity
Sitei267 – 2671Involved in auto-cleavageBy similarity
Sitei270 – 2701Essential for auto-cleavageBy similarity

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • 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

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_263883. Hh mutants that don't undergo autocatalytic processing are degraded by ERAD.
REACT_264256. Release of Hh-Np from the secreting cell.
REACT_264605. Hedgehog ligand biogenesis.
REACT_268573. Ligand-receptor interactions.
SignaLinkiQ15465.

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
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:10848. SHH.

Subcellular locationi

Sonic hedgehog protein C-product :
Sonic hedgehog protein N-product :
  • Cell membrane By similarity; 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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → T in HPE3. 2 Publications
VAR_023804
Natural varianti17 – 171L → P in HPE3. 1 Publication
VAR_062592
Natural varianti26 – 261P → L in HPE3. 1 Publication
VAR_062593
Natural varianti27 – 271G → A in HPE3. 2 Publications
VAR_039888
Natural varianti31 – 311G → 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 Publications
Corresponds to variant rs28936675 [ dbSNP | Ensembl ].
VAR_003619
Natural varianti39 – 391L → P in HPE3. 1 Publication
VAR_062594
Natural varianti53 – 531E → K in HPE3. 1 Publication
VAR_062595
Natural varianti83 – 831D → V in HPE3. 1 Publication
VAR_062596
Natural varianti84 – 841I → F in HPE3. 1 Publication
VAR_062597
Natural varianti88 – 881D → 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 Publications
VAR_009163
Natural varianti100 – 1001Q → 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 Publications
VAR_009164
Natural varianti102 – 1021C → R in HPE3. 1 Publication
VAR_062598
Natural varianti102 – 1021C → Y in HPE3. 1 Publication
VAR_062599
Natural varianti106 – 1072Missing in HPE3. 2 Publications
VAR_023805
Natural varianti109 – 1091L → F in HPE3. 1 Publication
VAR_062600
Natural varianti110 – 1101A → D in HPE3. 2 Publications
VAR_023806
Natural varianti110 – 1101A → T in HPE3. 1 Publication
VAR_062601
Natural varianti111 – 1111I → N in HPE3. 2 Publications
VAR_039889
Natural varianti115 – 1151N → K in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures. 3 Publications
VAR_009165
Natural varianti117 – 1171W → 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 Publications
VAR_003620
Natural varianti117 – 1171W → 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 Publications
VAR_003621
Natural varianti124 – 1241V → M in HPE3. 1 Publication
VAR_062602
Natural varianti136 – 1361E → K in HPE3. 1 Publication
VAR_062603
Natural varianti140 – 1401H → P in HPE3. 2 Publications
VAR_039890
Natural varianti140 – 1401H → Q in HPE3. 3 Publications
VAR_039891
Natural varianti143 – 1431G → D in HPE3. 1 Publication
VAR_062604
Natural varianti144 – 1441R → P in HPE3. 1 Publication
VAR_062605
Natural varianti147 – 1471D → N in HPE3. 1 Publication
VAR_062606
Natural varianti150 – 1501T → K in HPE3. 1 Publication
VAR_062607
Natural varianti150 – 1501T → R in HPE3. 2 Publications
VAR_023807
Natural varianti156 – 1561S → R in HPE3. 1 Publication
VAR_062608
Natural varianti170 – 1701F → C in HPE3. 1 Publication
VAR_062609
Natural varianti171 – 1711D → H in HPE3. 1 Publication
VAR_062610
Natural varianti176 – 1783Missing in HPE3. 2 Publications
VAR_023808
Natural varianti183 – 1831C → F in HPE3. 2 Publications
VAR_039892
Natural varianti183 – 1831C → R in HPE3. 1 Publication
VAR_062611
Natural varianti183 – 1831C → Y in HPE3. 1 Publication
VAR_062612
Natural varianti184 – 1841S → L in HPE3. 1 Publication
VAR_062613
Natural varianti188 – 1881E → Q in HPE3; familial. 4 Publications
VAR_009166
Natural varianti196 – 2005Missing in HPE3. 1 Publication
VAR_062614
Natural varianti196 – 1961G → E in HPE3. 1 Publication
VAR_062615
Natural varianti197 – 1971G → V in HPE3. 1 Publication
VAR_062616
Natural varianti198 – 1981C → F in HPE3. 1 Publication
VAR_062617
Natural varianti198 – 1981C → S in HPE3. 1 Publication
VAR_062618
Natural varianti218 – 2181L → P in HPE3. 2 Publications
VAR_062619
Natural varianti222 – 2221D → N in HPE3; familial. 3 Publications
VAR_009167
Natural varianti224 – 2241V → E in HPE3. 2 Publications
VAR_009168
Natural varianti226 – 2261A → T in HPE3; familial. 2 Publications
VAR_009169
Natural varianti231 – 2311G → V in HPE3. 1 Publication
VAR_062620
Natural varianti232 – 2321R → G in HPE3. 1 Publication
VAR_062621
Natural varianti234 – 2341L → P in HPE3. 1 Publication
VAR_062622
Natural varianti236 – 2361S → N in HPE3. 1 Publication
VAR_062623
Natural varianti236 – 2361S → R in HPE3; familial. 2 Publications
VAR_009170
Natural varianti241 – 2411F → L in HPE3. 1 Publication
VAR_062624
Natural varianti241 – 2411F → V in HPE3. 1 Publication
VAR_062625
Natural varianti255 – 2551I → N in HPE3. 1 Publication
VAR_062626
Natural varianti263 – 2697Missing in HPE3; sporadic. 2 Publications
VAR_009171
Natural varianti267 – 2671T → I in HPE3. 2 Publications
VAR_039893
Natural varianti271 – 2711L → P in HPE3. 2 Publications
VAR_023809
Natural varianti275 – 2751A → E in HPE3. 1 Publication
VAR_062627
Natural varianti280 – 2801S → W in HPE3. 1 Publication
VAR_062628
Natural varianti290 – 2901G → D in HPE3; sporadic. 2 Publications
Corresponds to variant rs104894047 [ dbSNP | Ensembl ].
VAR_009172
Natural varianti296 – 2961G → A in HPE3; unknown pathological significance. 1 Publication
VAR_062629
Natural varianti310 – 3101R → C in HPE3. 1 Publication
VAR_062630
Natural varianti321 – 3211R → S in HPE3. 1 Publication
VAR_062631
Natural varianti332 – 3321V → A in HPE3 and SMMCI. 3 Publications
VAR_023810
Natural varianti346 – 3461A → V in HPE3. 1 Publication
VAR_062632
Natural varianti347 – 3471P → L in HPE3. 1 Publication
VAR_062633
Natural varianti347 – 3471P → Q in HPE3. 2 Publications
VAR_023811
Natural varianti347 – 3471P → R in HPE3. 1 Publication
VAR_062634
Natural varianti354 – 3541I → T in HPE3. 2 Publications
VAR_023812
Natural varianti362 – 3621S → L in HPE3. 1 Publication
VAR_062635
Natural varianti363 – 3631C → Y in HPE3. 2 Publications
VAR_062636
Natural varianti364 – 3641Y → C in HPE3. 1 Publication
VAR_062637
Natural varianti373 – 3731A → T in HPE3. 2 Publications
VAR_039894
Natural varianti374 – 3741H → R in HPE3. 1 Publication
VAR_062638
Natural varianti376 – 3761A → D in HPE3. 1 Publication
VAR_062639
Natural varianti377 – 3771F → S in HPE3. 1 Publication
VAR_062640
Natural varianti378 – 3803Missing in HPE3; familial. 1 Publication
VAR_009173
Natural varianti381 – 3811R → P in HPE3. 2 Publications
VAR_023813
Natural varianti382 – 3821L → P in HPE3. 1 Publication
VAR_062641
Natural varianti383 – 3831A → T in HPE3; sporadic. 2 Publications
VAR_009174
Natural varianti391 – 3911A → T in HPE3; unknown pathological significance. 1 Publication
VAR_062642
Natural varianti402 – 4098Missing in HPE3; unknown pathological significance. 1 Publication
VAR_062643
Natural varianti404 – 4085Missing in HPE3; familial.
VAR_009175
Natural varianti405 – 4095Missing in HPE3; unknown pathological significance. 1 Publication
VAR_062644
Natural varianti411 – 4111G → GG in HPE3; unknown pathological significance. 1 Publication
VAR_062645
Natural varianti416 – 4161T → A in HPE3; unknown pathological significance. 1 Publication
VAR_062646
Natural varianti424 – 4241P → A in HPE3; familial. 2 Publications
VAR_009176
Natural varianti435 – 4351Y → N in HPE3. 1 Publication
VAR_062647
Natural varianti436 – 4361S → L in HPE3; sporadic. 2 Publications
VAR_009177
Natural varianti456 – 4561G → R in HPE3; unknown pathological significance. 1 Publication
VAR_062648
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti111 – 1111I → F in SMMCI. 2 Publications
VAR_017883
Natural varianti332 – 3321V → A in HPE3 and SMMCI. 3 Publications
VAR_023810
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)

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).

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241C → S: Abolishes palmitoylation. 1 Publication

Keywords - Diseasei

Disease mutation, Holoprosencephaly, Microphthalmia

Organism-specific databases

MIMi135750. phenotype.
142945. phenotype.
147250. phenotype.
174500. phenotype.
188740. phenotype.
611638. phenotype.
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.

Polymorphism and mutation databases

BioMutaiSHH.
DMDMi6094283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 462439Sonic hedgehog proteinPRO_0000013208Add
BLAST
Chaini24 – 197174Sonic hedgehog protein N-productPRO_0000013209Add
BLAST
Chaini198 – 462265Sonic hedgehog protein C-productPRO_0000013210Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi24 – 241N-palmitoyl cysteine1 Publication
Lipidationi197 – 1971Cholesterol glycine esterBy similarity
Glycosylationi278 – 2781N-linked (GlcNAc...)1 Publication

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

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ15465.
PRIDEiQ15465.

PTM databases

PhosphoSiteiQ15465.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ15465.
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

Protein-protein interaction databases

BioGridi112365. 5 interactions.
STRINGi9606.ENSP00000297261.

Structurei

Secondary structure

1
462
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 323Combined sources
Beta strandi47 – 515Combined sources
Turni56 – 594Combined sources
Helixi72 – 754Combined sources
Beta strandi84 – 863Combined sources
Beta strandi91 – 933Combined sources
Helixi94 – 963Combined sources
Helixi100 – 11617Combined sources
Beta strandi122 – 1287Combined sources
Helixi139 – 1424Combined sources
Beta strandi145 – 1506Combined sources
Helixi155 – 1573Combined sources
Helixi158 – 16710Combined sources
Beta strandi171 – 1777Combined sources
Beta strandi180 – 1845Combined sources
Helixi188 – 1903Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3HO5X-ray3.01H29-197[»]
3M1NX-ray1.85A/B23-197[»]
3MXWX-ray1.83A29-197[»]
ProteinModelPortaliQ15465.
SMRiQ15465. Positions 25-190, 198-365.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15465.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi407 – 4115Poly-Gly

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

eggNOGiNOG250647.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ15465.
KOiK11988.
OMAiHSWAHRA.
OrthoDBiEOG779NZ5.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61R → T in HPE3. 2 Publications
VAR_023804
Natural varianti17 – 171L → P in HPE3. 1 Publication
VAR_062592
Natural varianti26 – 261P → L in HPE3. 1 Publication
VAR_062593
Natural varianti27 – 271G → A in HPE3. 2 Publications
VAR_039888
Natural varianti31 – 311G → 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 Publications
Corresponds to variant rs28936675 [ dbSNP | Ensembl ].
VAR_003619
Natural varianti39 – 391L → P in HPE3. 1 Publication
VAR_062594
Natural varianti53 – 531E → K in HPE3. 1 Publication
VAR_062595
Natural varianti83 – 831D → V in HPE3. 1 Publication
VAR_062596
Natural varianti84 – 841I → F in HPE3. 1 Publication
VAR_062597
Natural varianti88 – 881D → 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 Publications
VAR_009163
Natural varianti100 – 1001Q → 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 Publications
VAR_009164
Natural varianti102 – 1021C → R in HPE3. 1 Publication
VAR_062598
Natural varianti102 – 1021C → Y in HPE3. 1 Publication
VAR_062599
Natural varianti106 – 1072Missing in HPE3. 2 Publications
VAR_023805
Natural varianti109 – 1091L → F in HPE3. 1 Publication
VAR_062600
Natural varianti110 – 1101A → D in HPE3. 2 Publications
VAR_023806
Natural varianti110 – 1101A → T in HPE3. 1 Publication
VAR_062601
Natural varianti111 – 1111I → F in SMMCI. 2 Publications
VAR_017883
Natural varianti111 – 1111I → N in HPE3. 2 Publications
VAR_039889
Natural varianti115 – 1151N → K in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures. 3 Publications
VAR_009165
Natural varianti117 – 1171W → 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 Publications
VAR_003620
Natural varianti117 – 1171W → 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 Publications
VAR_003621
Natural varianti124 – 1241V → M in HPE3. 1 Publication
VAR_062602
Natural varianti136 – 1361E → K in HPE3. 1 Publication
VAR_062603
Natural varianti140 – 1401H → P in HPE3. 2 Publications
VAR_039890
Natural varianti140 – 1401H → Q in HPE3. 3 Publications
VAR_039891
Natural varianti143 – 1431G → D in HPE3. 1 Publication
VAR_062604
Natural varianti144 – 1441R → P in HPE3. 1 Publication
VAR_062605
Natural varianti147 – 1471D → N in HPE3. 1 Publication
VAR_062606
Natural varianti150 – 1501T → K in HPE3. 1 Publication
VAR_062607
Natural varianti150 – 1501T → R in HPE3. 2 Publications
VAR_023807
Natural varianti156 – 1561S → R in HPE3. 1 Publication
VAR_062608
Natural varianti170 – 1701F → C in HPE3. 1 Publication
VAR_062609
Natural varianti171 – 1711D → H in HPE3. 1 Publication
VAR_062610
Natural varianti176 – 1783Missing in HPE3. 2 Publications