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Hedgehog Signaling

Hedgehog (Hh) signaling is highly conserved across chordates of different taxonomical classification. It is essential for development of the embryo. The Hedehog pathway was first described and characterized in the fruit fly, Drosophila melanogaster. In mammals, Hh signaling regulates cell-fate, tissue polarity, and patterning during early embryogenesis and the morphogenesis of specific organs and tissues. It is subsequently silenced in most adult tissues but can be reactivated following injury to promote repair and regeneration.

Different Hh ligands, including homologs sonic hedgehog (SHH), indian hedgehog (IHH), and desert hedgehog (DHH) are produced as precursors that undergo autocatalytic cleavage, C-terminal cholesterol attachment, and N-terminal palmitoylation prior to secretion. Release and extracellular accumulation of the mature ligands is regulated by the homologs of the Drosophila dispatched (Disp) protein. Binding of secreted Hh ligands to the receptor homolog (PTCH1, PTCH2) triggers the stimulation of the signaling network: the repressive effect of PTCH on the transmembrane receptor SMO is relieved which leads to the activation of glioma-associated oncogene (GLI) transcription factors.

A key specialized structure in this process is the microtubule-based primary cilium. In the absence of the Hh signal unprocessed, non-activating GLI proteins as well as their regulator SUFU are concentrated in the distal tip of the primary cilium. Upon binding of the Hh ligand, PTCH relocates to the cell surface, thus rendering translocation of SMO to the primary cilium and the down-regulation of SUFU possible. Several structurally essential primary cilium proteins have also regulatory effects on the Hh signaling cascade.

Aberrant Hh/GLI regulation leads to major tissular disorders and the development of a wide variety of aggressive cancers. The Hh/GLI cascade has also been linked to the regulation of stemness genes and the survival of cancer stem cells.

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SHH - Sonic Hedgehog

This gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Of three human proteins showing sequence and functional similarity to the sonic hedgehog protein of Drosophila, this protein is the most similar. The protein is...   More...

IHH - Indian Hedgehog

This gene encodes a member of the hedgehog family of secreted signaling molecules. Hedgehog proteins are essential regulators of a variety of...

DHH - desert Hedgehog

This gene encodes a member of the hedgehog family. The hedgehog gene family encodes signaling molecules that play an important role in regulating...

Hh Processing

HHAT - Hedgehog Acyltransferase

Skinny hedgehog' (SKI1) encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of 'hedgehog' (see MIM 600725).[supplied by OMIM, Jul 2002].   More...
Antigens in this category:
HHATL - Hedgehog Acyltransferase-Like: HHATL antibodies   HHATL Proteins
PRKACA (Protein Kinase A, alpha): PRKACA antibodies PRKACA ELISA Kits PRKACA Proteins
PRKACB (Protein Kinase, CAMP Dependent, Catalytic, beta): PRKACB antibodies PRKACB ELISA Kits PRKACB Proteins
PRKACG (Protein Kinase, CAMP-Dependent, Catalytic, gamma): PRKACG antibodies   PRKACG Proteins
PROKR1 - Prokineticin Receptor 1: PROKR1 antibodies PROKR1 ELISA Kits PROKR1 Proteins
PRKAR1A - Protein Kinase, CAMP-Dependent, Regulatory, Type I, alpha (Tissue Specific Extinguisher 1): PRKAR1A antibodies PRKAR1A ELISA Kits PRKAR1A Proteins
PRKAR1B (Protein Kinase, CAMP-Dependent, Regulatory, Type I, beta): PRKAR1B antibodies PRKAR1B ELISA Kits PRKAR1B Proteins
PROKR2 - Prokineticin Receptor 2: PROKR2 antibodies PROKR2 ELISA Kits PROKR2 Proteins
PRKAR2A - Protein Kinase, CAMP-Dependent, Regulatory, Type II, alpha: PRKAR2A antibodies PRKAR2A ELISA Kits PRKAR2A Proteins
PRKAR2B - Protein Kinase, CAMP-Dependent, Regulatory, Type II, beta: PRKAR2B antibodies PRKAR2B ELISA Kits PRKAR2B Proteins
CSNK1A1 (Casein Kinase 1, alpha 1): CSNK1A1 antibodies CSNK1A1 ELISA Kits CSNK1A1 Proteins
CSNK1D - Casein Kinase 1 delta: CSNK1D antibodies CSNK1D ELISA Kits CSNK1D Proteins
CSNK1E - CK1 epsilon: CSNK1E antibodies CSNK1E ELISA Kits CSNK1E Proteins
CSNK1G1 - Casein Kinase 1, gamma 1: CSNK1G1 antibodies CSNK1G1 ELISA Kits CSNK1G1 Proteins
CSNK1G2 - Casein Kinase 1 gamma 2: CSNK1G2 antibodies CSNK1G2 ELISA Kits CSNK1G2 Proteins
CSNK1G3 - Casein Kinase 1, gamma 3: CSNK1G3 antibodies CSNK1G3 ELISA Kits CSNK1G3 Proteins
GSK3b - GSK3 beta: GSK3b antibodies    
SKP1 (S-Phase Kinase-Associated Protein 1): SKP1 antibodies SKP1 ELISA Kits SKP1 Proteins
CUL1 - Cullin 1: CUL1 antibodies CUL1 ELISA Kits CUL1 Proteins
BTRC (beta-Transducin Repeat Containing): BTRC antibodies BTRC ELISA Kits BTRC Proteins

Hh Receptors

PTCH1 - Patched 1

This gene encodes a member of the patched gene family. The encoded protein is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis, as well as the desert hedgehog and indian hedgehog proteins. This gene functions as a tumor suppressor. Mutations of this gene have been associated with basal cell nevus syndrome, esophageal...   More...
Antigens in this category:
PTCH2 - Patched 2: PTCH2 antibodies   PTCH2 Proteins

Hh Effectors

GLI1 (Zinc Finger Protein GLI1):

This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for...   More...

GLI2 (GLI Family Zinc Finger 2):

This gene encodes a protein which belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are...

GLI3 (GLI Family Zinc Finger 3):

This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding...

Primary Cilium

DZIP1 (DAZ Interacting Protein 1):

Acts as a permissive factor that is required for the proper regulation of Hedgehog (Hh) target genes in response to Hh signals. Acts downstream of the Smoothened protein to modulate Gli activity in the somites of the developing embryo.   More...

EVC (Ellis Van Creveld Syndrome):

This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld...

KIF7 (Kinesin Family Member 7):

This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling...
Antigens in this category:
EVC2 - Ellis Van Creveld Syndrome 2: EVC2 antibodies EVC2 ELISA Kits EVC2 Proteins
DYNC2H1 (Dynein, Cytoplasmic 2, Heavy Chain 1):   DYNC2H1 ELISA Kits  
DYNC2LI1 (Dynein, Cytoplasmic 2, Light Intermediate Chain 1): DYNC2LI1 antibodies DYNC2LI1 ELISA Kits DYNC2LI1 Proteins
KIF3A (Kinesin Family Member 3A): KIF3A antibodies KIF3A ELISA Kits KIF3A Proteins
KIF3B (Kinesin Family Member 3B): KIF3B antibodies KIF3B ELISA Kits KIF3B Proteins
KIF3C - Kinesin Family Member 3C: KIF3C antibodies KIF3C ELISA Kits KIF3C Proteins
KIFAP3 - Kinesin Associated Protein 3: KIFAP3 antibodies KIFAP3 ELISA Kits KIFAP3 Proteins
TRIM28 - Tripartite Motif Containing 28: TRIM28 antibodies TRIM28 ELISA Kits TRIM28 Proteins
IFT43 (Intraflagellar Transport 43 Homolog (Chlamydomonas)): IFT43 antibodies IFT43 ELISA Kits IFT43 Proteins
WDR35 (WD Repeat Domain 35): WDR35 antibodies WDR35 ELISA Kits  
TTC21B (Tetratricopeptide Repeat Domain 21B): TTC21B antibodies TTC21B ELISA Kits  
IFT140 - Intraflagellar Transport 140 Homolog (Chlamydomonas): IFT140 antibodies    
WDR19 - WD Repeat Domain 19: WDR19 antibodies WDR19 ELISA Kits WDR19 Proteins
IFT20 (Intraflagellar Transport 20 Homolog (Chlamydomonas)): IFT20 antibodies IFT20 ELISA Kits IFT20 Proteins
PDK4 (Pyruvate Dehydrogenase Kinase, Isozyme 4): PDK4 antibodies PDK4 ELISA Kits PDK4 Proteins
IFT27 (Intraflagellar Transport 27 Homolog (Chlamydomonas)): IFT27 antibodies IFT27 ELISA Kits IFT27 Proteins
IFT46 (Intraflagellar Transport 46 Homolog (Chlamydomonas)): IFT46 antibodies IFT46 ELISA Kits IFT46 Proteins
TRAF3IP1 (TNF Receptor-Associated Factor 3 Interacting Protein 1): TRAF3IP1 antibodies TRAF3IP1 ELISA Kits TRAF3IP1 Proteins
IFT57 (Intraflagellar Transport 57 Homolog (Chlamydomonas)): IFT57 antibodies IFT57 ELISA Kits IFT57 Proteins
TTC30B (Tetratricopeptide Repeat Domain 30B): TTC30B antibodies TTC30B ELISA Kits TTC30B Proteins
IFT74 (Intraflagellar Transport Protein 74 Homolog): IFT74 antibodies    
IFT80 (Intraflagellar Transport 80 Homolog (Chlamydomonas)): IFT80 antibodies IFT80 ELISA Kits IFT80 Proteins
IFT81 - Intraflagellar Transport 81 Homolog (Chlamydomonas): IFT81 antibodies IFT81 ELISA Kits IFT81 Proteins
IFT88 (Intraflagellar Transport 88 Homolog (Chlamydomonas)): IFT88 antibodies IFT88 ELISA Kits IFT88 Proteins
BBS1 (Bardet-Biedl Syndrome 1): BBS1 antibodies   BBS1 Proteins
BBS2 (Bardet-Biedl Syndrome 2): BBS2 antibodies   BBS2 Proteins
BBS4 (Bardet-Biedl Syndrome 4): BBS4 antibodies   BBS4 Proteins
BBS5 - Bardet-Biedl Syndrome 5: BBS5 antibodies   BBS5 Proteins
BBS7 (Bardet-Biedl Syndrome 7): BBS7 antibodies   BBS7 Proteins
TTC8 (Tetratricopeptide Repeat Domain 8): TTC8 antibodies TTC8 ELISA Kits TTC8 Proteins
BBS9 (Bardet-Biedl Syndrome 9): BBS9 antibodies   BBS9 Proteins

Hh Regulators

DISP1 (Dispatched Homolog 1 (Drosophila)):

The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the...   More...

DISP2 (Dispatched Homolog 2 (Drosophila)):

The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized...

SUFUH (Suppressor of Fused Homolog (Drosophila)):

The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern...
Antigens in this category:
HHIP (Hedgehog Interacting Protein): HHIP antibodies HHIP ELISA Kits HHIP Proteins
KCTD11 - Potassium Channel Tetramerisation Domain Containing 11: KCTD11 antibodies KCTD11 ELISA Kits KCTD11 Proteins