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Protein

Sonic hedgehog protein

Gene

Shh

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sonic hedgehog protein: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (PubMed:8824192, PubMed:7891723). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (PubMed:8824192). Both activities occur in the reticulum endoplasmic (PubMed:21357747). Once cleaved, ShhC is degraded in the endoplasmic reticulum (PubMed:21357747).1 Publication3 Publications
Sonic hedgehog protein N-product: The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (PubMed:11430830, PubMed:24863049). Involved in the patterning of the anterior-posterior axis of the developing limb bud (PubMed:15315762). Essential for axon guidance (PubMed:12679031). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (By similarity).1 PublicationBy similarity2 Publications

Miscellaneous

Mice overexpressing Shh display digit duplications in both forelimbs and hindlimbs.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi90Calcium 13 Publications1
Metal bindingi91Calcium 13 Publications1
Metal bindingi91Calcium 23 Publications1
Metal bindingi96Calcium 13 Publications1
Metal bindingi126Calcium 1; via carbonyl oxygen3 Publications1
Metal bindingi127Calcium 13 Publications1
Metal bindingi127Calcium 23 Publications1
Metal bindingi130Calcium 23 Publications1
Metal bindingi132Calcium 23 Publications1
Metal bindingi141Zinc4 Publications1
Metal bindingi148Zinc4 Publications1
Metal bindingi183Zinc4 Publications1
Sitei244Involved in cholesterol transferBy similarity1
Sitei268Involved in auto-cleavageBy similarity1
Sitei271Essential for auto-cleavageBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • glycosaminoglycan binding Source: MGI
  • laminin-1 binding Source: MGI
  • patched binding Source: Roslin
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • anatomical structure development Source: MGI
  • anatomical structure formation involved in morphogenesis Source: MGI
  • androgen metabolic process Source: MGI
  • angiogenesis Source: MGI
  • animal organ formation Source: MGI
  • anterior/posterior pattern specification Source: MGI
  • apoptotic signaling pathway Source: Roslin
  • artery development Source: MGI
  • axon guidance Source: MGI
  • Bergmann glial cell differentiation Source: MGI
  • blood coagulation Source: MGI
  • branching involved in blood vessel morphogenesis Source: MGI
  • branching involved in prostate gland morphogenesis Source: MGI
  • branching involved in salivary gland morphogenesis Source: MGI
  • branching involved in ureteric bud morphogenesis Source: MGI
  • branching morphogenesis of an epithelial tube Source: MGI
  • bud outgrowth involved in lung branching Source: MGI
  • camera-type eye development Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment Source: BHF-UCL
  • cell-cell signaling Source: MGI
  • cell development Source: MGI
  • cell fate commitment Source: MGI
  • cell fate specification Source: MGI
  • cell proliferation Source: MGI
  • cell proliferation in external granule layer Source: MGI
  • cellular response to lithium ion Source: MGI
  • central nervous system development Source: MGI
  • cerebellar granule cell precursor proliferation Source: UniProtKB
  • determination of left/right asymmetry in lateral mesoderm Source: BHF-UCL
  • determination of left/right symmetry Source: MGI
  • developmental growth Source: MGI
  • digestive tract morphogenesis Source: MGI
  • dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • dorsal/ventral neural tube patterning Source: MGI
  • dorsal/ventral pattern formation Source: MGI
  • ectoderm development Source: MGI
  • embryonic digestive tract morphogenesis Source: MGI
  • embryonic digit morphogenesis Source: Roslin
  • embryonic foregut morphogenesis Source: MGI
  • embryonic forelimb morphogenesis Source: MGI
  • embryonic hindlimb morphogenesis Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • embryonic morphogenesis Source: MGI
  • embryonic organ development Source: MGI
  • embryonic skeletal system development Source: MGI
  • endocytosis Source: MGI
  • epithelial cell proliferation involved in salivary gland morphogenesis Source: MGI
  • epithelial-mesenchymal cell signaling Source: MGI
  • epithelial-mesenchymal signaling involved in prostate gland development Source: MGI
  • epithelial tube branching involved in lung morphogenesis Source: MGI
  • establishment of cell polarity Source: MGI
  • forebrain development Source: MGI
  • forebrain regionalization Source: MGI
  • formation of anatomical boundary Source: MGI
  • hair follicle development Source: MGI
  • hair follicle morphogenesis Source: MGI
  • heart development Source: MGI
  • heart looping Source: BHF-UCL
  • hindbrain development Source: MGI
  • hindgut morphogenesis Source: MGI
  • inner ear development Source: MGI
  • intein-mediated protein splicing Source: InterPro
  • intermediate filament organization Source: MGI
  • kidney development Source: MGI
  • left lung development Source: MGI
  • limb bud formation Source: MGI
  • limb development Source: MGI
  • lung-associated mesenchyme development Source: MGI
  • lung development Source: MGI
  • lung epithelium development Source: MGI
  • lung lobe morphogenesis Source: MGI
  • lung morphogenesis Source: MGI
  • lymphoid progenitor cell differentiation Source: BHF-UCL
  • male genitalia development Source: MGI
  • mesenchymal cell proliferation Source: MGI
  • mesenchymal cell proliferation involved in lung development Source: MGI
  • mesenchymal smoothened signaling pathway involved in prostate gland development Source: MGI
  • metanephric mesenchymal cell proliferation involved in metanephros development Source: UniProtKB
  • metanephros development Source: UniProtKB
  • midbrain development Source: MGI
  • myoblast differentiation Source: MGI
  • myotube differentiation Source: MGI
  • negative regulation of alpha-beta T cell differentiation Source: MGI
  • negative regulation of apoptotic process Source: Roslin
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of cell differentiation Source: MGI
  • negative regulation of cell migration Source: MGI
  • negative regulation of cholesterol efflux Source: BHF-UCL
  • negative regulation of dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of mesenchymal cell apoptotic process Source: MGI
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • negative regulation of protein catabolic process Source: MGI
  • negative regulation of T cell proliferation Source: MGI
  • negative regulation of transcription elongation from RNA polymerase II promoter Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: MGI
  • negative thymic T cell selection Source: BHF-UCL
  • neural crest cell migration Source: MGI
  • neuroblast proliferation Source: MGI
  • neuron fate commitment Source: MGI
  • odontogenesis Source: MGI
  • odontogenesis of dentin-containing tooth Source: MGI
  • oligodendrocyte development Source: MGI
  • oligodendrocyte differentiation Source: MGI
  • osteoblast development Source: MGI
  • palate development Source: MGI
  • pancreas development Source: MGI
  • pattern specification process Source: MGI
  • polarity specification of anterior/posterior axis Source: Roslin
  • positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
  • positive regulation of cell differentiation Source: MGI
  • positive regulation of cell division Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cerebellar granule cell precursor proliferation Source: MGI
  • positive regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of hh target transcription factor activity Source: MGI
  • positive regulation of immature T cell proliferation in thymus Source: BHF-UCL
  • positive regulation of kidney smooth muscle cell differentiation Source: UniProtKB
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of mesenchymal cell proliferation involved in ureter development Source: UniProtKB
  • positive regulation of neuroblast proliferation Source: MGI
  • positive regulation of oligodendrocyte differentiation Source: MGI
  • positive regulation of protein import into nucleus Source: MGI
  • positive regulation of sclerotome development Source: MGI
  • positive regulation of skeletal muscle cell proliferation Source: MGI
  • positive regulation of skeletal muscle tissue development Source: MGI
  • positive regulation of smoothened signaling pathway Source: BHF-UCL
  • positive regulation of striated muscle cell differentiation Source: MGI
  • positive regulation of T cell differentiation in thymus Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of ureter smooth muscle cell differentiation Source: UniProtKB
  • positive regulation of Wnt signaling pathway Source: MGI
  • positive thymic T cell selection Source: BHF-UCL
  • primary prostatic bud elongation Source: MGI
  • prostate epithelial cord elongation Source: MGI
  • prostate gland development Source: MGI
  • protein localization to nucleus Source: MGI
  • regulation of cell proliferation Source: MGI
  • regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of mesenchymal cell proliferation involved in prostate gland development Source: MGI
  • regulation of odontogenesis Source: BHF-UCL
  • regulation of prostatic bud formation Source: MGI
  • regulation of protein localization to nucleus Source: MGI
  • regulation of proteolysis Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • respiratory tube development Source: MGI
  • right lung development Source: MGI
  • salivary gland cavitation Source: MGI
  • signal transduction Source: MGI
  • skin development Source: MGI
  • smoothened signaling pathway Source: MGI
  • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation Source: MGI
  • somite development Source: BHF-UCL
  • spinal cord dorsal/ventral patterning Source: MGI
  • spinal cord motor neuron differentiation Source: MGI
  • stem cell development Source: BHF-UCL
  • striated muscle cell differentiation Source: MGI
  • striated muscle tissue development Source: MGI
  • T cell differentiation in thymus Source: BHF-UCL
  • telencephalon regionalization Source: MGI
  • thalamus development Source: MGI
  • thymus development Source: BHF-UCL
  • thyroid gland development Source: MGI
  • trachea development Source: MGI
  • trachea morphogenesis Source: MGI
  • tracheoesophageal septum formation Source: MGI
  • vasculature development Source: MGI
  • vasculogenesis Source: MGI
  • vasculogenesis involved in coronary vascular morphogenesis Source: DFLAT
  • ventral spinal cord interneuron specification Source: MGI

Keywordsi

Molecular functionDevelopmental protein, Hydrolase, Protease
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5358346. Hedgehog ligand biogenesis.
R-MMU-5362798. Release of Hh-Np from the secreting cell.
R-MMU-5632681. Ligand-receptor interactions.
R-MMU-5635838. Activation of SMO.

Protein family/group databases

MEROPSiC46.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Sonic hedgehog protein
Short name:
SHH
Alternative name(s):
HHG-1
Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains1 Publication
Short name:
ShhNC1 Publication
Cleaved into the following chain:
Alternative name(s):
Shh N-terminal processed signaling domains1 Publication
Short name:
ShhNp1 Publication
Sonic hedgehog protein 19 kDa product
Gene namesi
Name:ShhImported
Synonyms:Hhg1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:98297. Shh.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25C → S: Strongly reduces effects of in vivo overexpression; impairs multimer formation; does not affect subcellular location to lipid rafts. Homozygous mice are characterized by a smaller size and holoprosencephaly at E10.5, and shortening of limbs at E13.5. They die soon after birth. 3 Publications1
Mutagenesisi32G → R: 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. 1 Publication1
Mutagenesisi89D → V: Moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence. 1 Publication1
Mutagenesisi101Q → H: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication1
Mutagenesisi116N → K: Shows no change in activities at different temperatures. 1 Publication1
Mutagenesisi118W → G: 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. 1 Publication1
Mutagenesisi118W → R: 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. 1 Publication1
Mutagenesisi189E → Q: Does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5387.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24By similarityAdd BLAST24
ChainiPRO_000001321125 – 437Sonic hedgehog proteinAdd BLAST413
ChainiPRO_000001321225 – 198Sonic hedgehog protein N-productAdd BLAST174

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi25N-palmitoyl cysteine2 Publications1
Lipidationi198Cholesterol glycine ester1 Publication1
Glycosylationi279N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Sonic hedgehog protein: The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (PubMed:7891723, PubMed:7736596, PubMed:8824192). 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 (ShhN)(PubMed:7891723, PubMed:7736596, PubMed:8824192). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (PubMed:24522195, PubMed:8824192). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (PubMed:21357747).2 Publications4 Publications
Sonic hedgehog protein N-product: N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (PubMed:11486055, PubMed:15075292). It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (PubMed:24522195).3 Publications
Sonic hedgehog protein N-product: The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding)(PubMed:24522195). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate (PubMed:23118222). The cleavage is enhanced by SCUBE2.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei198 – 199Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiQ62226.
PaxDbiQ62226.
PRIDEiQ62226.

PTM databases

iPTMnetiQ62226.
PhosphoSitePlusiQ62226.
SwissPalmiQ62226.

Expressioni

Tissue specificityi

Expressed in a number of embryonic tissues including the notochord, ventral neural tube, floor plate, lung bud, zone of polarizing activity and posterior distal mesenchyme of limbs. In the adult, expressed in lung and neural retina.

Developmental stagei

First detectable during gastrulation.

Inductioni

By retinoic acid.

Gene expression databases

BgeeiENSMUSG00000002633.
CleanExiMM_SHH.
GenevisibleiQ62226. MM.

Interactioni

Subunit structurei

Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (PubMed:18081866). ShhNp is active as a multimer (PubMed:24522195). Interacts with BOC and CDON (PubMed:18794898). Interacts with HHIP (By similarity). Interacts with DISP1 via its cholesterol anchor (PubMed:22902404, PubMed:22677548). Interacts with SCUBE2 (PubMed:24522195, PubMed:22677548).By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • laminin-1 binding Source: MGI
  • patched binding Source: Roslin

Protein-protein interaction databases

BioGridi203220. 10 interactors.
DIPiDIP-48537N.
IntActiQ62226. 6 interactors.
STRINGi10090.ENSMUSP00000002708.

Chemistry databases

BindingDBiQ62226.

Structurei

Secondary structure

1437
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi48 – 52Combined sources5
Turni57 – 60Combined sources4
Beta strandi69 – 71Combined sources3
Helixi72 – 76Combined sources5
Beta strandi85 – 87Combined sources3
Beta strandi92 – 94Combined sources3
Helixi95 – 97Combined sources3
Helixi101 – 117Combined sources17
Beta strandi123 – 127Combined sources5
Beta strandi131 – 135Combined sources5
Helixi140 – 143Combined sources4
Beta strandi146 – 151Combined sources6
Helixi156 – 158Combined sources3
Helixi159 – 168Combined sources10
Beta strandi172 – 178Combined sources7
Beta strandi181 – 185Combined sources5
Helixi189 – 192Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VHHX-ray1.70A34-195[»]
2WFXX-ray3.20A40-191[»]
2WG4X-ray3.15A40-191[»]
3D1MX-ray1.70A/B26-189[»]
3N1RX-ray2.13A40-195[»]
4C4MX-ray1.74A40-195[»]
4C4NX-ray2.36A/B40-195[»]
ProteinModelPortaliQ62226.
SMRiQ62226.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62226.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi33 – 39Cardin-Weintraub1 Publication7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi383 – 387Poly-Gly5

Domaini

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
Sonic hedgehog protein N-product: The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195).2 Publications

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiQ62226.
KOiK11988.
OMAiEHSWAHR.
OrthoDBiEOG091G0N90.
PhylomeDBiQ62226.
TreeFamiTF106458.

Family and domain databases

Gene3Di3.30.1380.10. 1 hit.
InterProiView protein in InterPro
IPR001657. Hedgehog.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_sf.
IPR000320. Hedgehog_signalling_dom.
IPR001767. Hint_dom.
IPR003586. Hint_dom_C.
IPR003587. Hint_dom_N.
IPR036844. Hint_dom_sf.
IPR006141. Intein_N.
PfamiView protein in Pfam
PF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
PRINTSiPR00632. SONICHHOG.
SMARTiView protein in SMART
SM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
SUPFAMiSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEiView protein in PROSITE
PS50817. INTEIN_N_TER. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q62226-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLLLLARCFL VILASSLLVC PGLACGPGRG FGKRRHPKKL TPLAYKQFIP
60 70 80 90 100
NVAEKTLGAS GRYEGKITRN SERFKELTPN YNPDIIFKDE ENTGADRLMT
110 120 130 140 150
QRCKDKLNAL AISVMNQWPG VKLRVTEGWD EDGHHSEESL HYEGRAVDIT
160 170 180 190 200
TSDRDRSKYG MLARLAVEAG FDWVYYESKA HIHCSVKAEN SVAAKSGGCF
210 220 230 240 250
PGSATVHLEQ GGTKLVKDLR PGDRVLAADD QGRLLYSDFL TFLDRDEGAK
260 270 280 290 300
KVFYVIETLE PRERLLLTAA HLLFVAPHND SGPTPGPSAL FASRVRPGQR
310 320 330 340 350
VYVVAERGGD RRLLPAAVHS VTLREEEAGA YAPLTAHGTI LINRVLASCY
360 370 380 390 400
AVIEEHSWAH RAFAPFRLAH ALLAALAPAR TDGGGGGSIP AAQSATEARG
410 420 430
AEPTAGIHWY SQLLYHIGTW LLDSETMHPL GMAVKSS
Length:437
Mass (Da):47,773
Last modified:June 1, 1998 - v2
Checksum:iD0EB72F08E7860EF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76290 mRNA. Translation: CAA53922.1.
AK077688 mRNA. Translation: BAC36956.1.
BC063087 mRNA. Translation: AAH63087.1.
CCDSiCCDS19146.1.
PIRiA49425.
RefSeqiNP_033196.1. NM_009170.3.
UniGeneiMm.57202.

Genome annotation databases

EnsembliENSMUST00000002708; ENSMUSP00000002708; ENSMUSG00000002633.
GeneIDi20423.
KEGGimmu:20423.
UCSCiuc008wua.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiSHH_MOUSE
AccessioniPrimary (citable) accession number: Q62226
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 22, 2017
This is version 187 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The several steps and mechanisms that permit controlled Shh dispersion and gradient formation remain controversial. The ShhNC C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity resulting in the cleavage and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN). The protein is further modified by covalent addition of palmitate at the N-terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp). ShhNp is firmly tethered to the cell membrane where it forms multimers. Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by proteolytic removal of both terminal lipidated peptides. Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range.2 Publications1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families