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Protein

Sonic hedgehog protein

Gene

shh

Organism
Xenopus laevis (African clawed frog)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Intercellular signal essential for a variety of patterning events during development and metamorphosis. Involved in limb formation, patterning of the central nervous system and ventral somite differentiation. Induces ectopic cement gland formation in embryos. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO (By similarity).By similarity3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi90 – 901Calcium 1By similarity
Metal bindingi91 – 911Calcium 1By similarity
Metal bindingi91 – 911Calcium 2By similarity
Metal bindingi96 – 961Calcium 1By similarity
Metal bindingi126 – 1261Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi127 – 1271Calcium 1By similarity
Metal bindingi127 – 1271Calcium 2By similarity
Metal bindingi130 – 1301Calcium 2By similarity
Metal bindingi132 – 1321Calcium 2By similarity
Metal bindingi141 – 1411ZincBy similarity
Metal bindingi148 – 1481ZincBy similarity
Metal bindingi183 – 1831ZincBy similarity
Sitei266 – 2661Involved in auto-cleavageBy similarity
Sitei269 – 2691Essential for auto-cleavageBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiC46.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Sonic hedgehog protein
Alternative name(s):
VHH-1
X-SHH
Cleaved into the following 2 chains:
Gene namesi
Name:shh
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Organism-specific databases

XenbaseiXB-GENE-864913. 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 444420Sonic hedgehog proteinPRO_0000013220Add
BLAST
Chaini25 – 198174Sonic hedgehog protein N-productPRO_0000013221Add
BLAST
Chaini199 – 444246Sonic hedgehog protein C-productPRO_0000013222Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi25 – 251N-palmitoyl cysteineBy similarity
Lipidationi198 – 1981Cholesterol glycine esterBy similarity

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-25 by HHAT is required for N-product multimerization and full activity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei198 – 1992Cleavage; by autolysisBy similarity

Keywords - PTMi

Autocatalytic cleavage, Lipoprotein, Palmitate

Expressioni

Tissue specificityi

Strongly expressed in notochord and neural floor plate during embryogenesis. In tadpole, high expression is observed in pancreas/stomach, moderate expression in tail, and low expression in intestine, brain, and hind limb.3 Publications

Developmental stagei

First detected at the neurula (stages 16-17). First peak of expression around tadpole hatching (stages 33-40). High expression observed in intestine at the climax of morphogenesis (stages 60-62) when intestine epithelial undergoes morphogenesis.3 Publications

Inductioni

By thyroid hormone.1 Publication

Interactioni

Subunit structurei

N-product is active as a multimer.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ92000.
SMRiQ92000. Positions 39-195.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati386 – 39381
Repeati394 – 40182
Repeati403 – 40973

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni386 – 409243 X 8 AA tandem repeats of Q-V-D-L-Q-S-H-HAdd
BLAST

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.By similarity

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

HOVERGENiHBG005480.
KOiK11988.

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.

Q92000-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLVATQSLLL LSFICTLVTP PGLACGPGRG IGKRRHPKKL TPLAYKQFIP
60 70 80 90 100
NVAEKTLGAS GRYEGKITRN SDCFKELTPN YNPDIMFKDE ESTGADRLMT
110 120 130 140 150
QRCKDKLNAL AISVMNQWPG VKLRVTEGWD EDGHHLEESL HYEGRAVDIT
160 170 180 190 200
TSDRDRSKYG MLGRLAVEAG FDWVYYESKA HIHCSVKAEN SVAAKSGGCF
210 220 230 240 250
PAGARVMVEF GGTKAVKDLR PGDRVLSSDP QGNLLYSDFL MFIDQERDVK
260 270 280 290 300
KLFYVIETSQ RKIRLTAAHL LFVAQTKVNG TRSFKSVFAS NIQPGDLIYT
310 320 330 340 350
ADPKTMTLKA VKVEKVDLEE DTGAYAPLTA HGTVVIDQVL ASCYAVIEEH
360 370 380 390 400
TWAHLAFAPL RFGMSLSSYI YPRDSSPPSG LQPHHQVDLQ SHHQVDLQSH
410 420 430 440
HQVDLQSHHQ LEGIHWYSQL LYQIGTWLLD SNSLHPLGMA TKSS
Length:444
Mass (Da):49,453
Last modified:November 1, 1996 - v1
Checksum:i73B4E4932FA2EFF2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 95TQSLL → NSNLCW in AAA49981 (PubMed:7551564).Curated
Sequence conflicti302 – 31918DPKTM…KVDLE → ESQDHDLEGRGKWRRLILR in AAA49981 (PubMed:7551564).CuratedAdd
BLAST
Sequence conflicti432 – 4321N → S in AAA49981 (PubMed:7551564).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L39213 mRNA. Translation: AAC42227.1.
U26314 mRNA. Translation: AAA85162.1.
L35248 mRNA. Translation: AAA49981.1.
PIRiS56765.
RefSeqiNP_001081782.1. NM_001088313.1.
UniGeneiXl.866.

Genome annotation databases

GeneIDi398047.
KEGGixla:398047.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L39213 mRNA. Translation: AAC42227.1.
U26314 mRNA. Translation: AAA85162.1.
L35248 mRNA. Translation: AAA49981.1.
PIRiS56765.
RefSeqiNP_001081782.1. NM_001088313.1.
UniGeneiXl.866.

3D structure databases

ProteinModelPortaliQ92000.
SMRiQ92000. Positions 39-195.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiC46.002.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi398047.
KEGGixla:398047.

Organism-specific databases

CTDi6469.
XenbaseiXB-GENE-864913. shh.

Phylogenomic databases

HOVERGENiHBG005480.
KOiK11988.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiSHH_XENLA
AccessioniPrimary (citable) accession number: Q92000
Secondary accession number(s): Q91894
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: May 11, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.