Protein Shh

URN urn:agi-llid:3243
Total Entities 0
Connectivity 1269
Name Shh
Description sonic hedgehog
Notes 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 made as a precursor that is autocatalytically cleaved; the N-terminal portion is soluble and contains the signalling activity while the C-terminal portion is involved in precursor processing. More importantly, the C-terminal product covalently attaches a cholesterol moiety to the N-terminal product, restricting the N-terminal product to the cell surface and preventing it from freely diffusing throughout the developing embryo. Defects in this protein or in its signalling pathway are a cause of holoprosencephaly (HPE), a disorder in which the developing forebrain fails to correctly separate into right and left hemispheres. HPE is manifested by facial deformities. It is also thought that mutations in this gene or in its signalling pathway may be responsible for VACTERL syndrome, which is characterized by vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, cardiac anomalies, and limb abnormalities. Additionally, mutations in a long range enhancer located approximately 1 megabase upstream of this gene disrupt limb patterning and can result in preaxial polydactyly. [provided by RefSeq]

Ariadne Ontology SHH
Secreted proteins
Biofluids assayable substances

GO Molecular Function morphogen activity
receptor binding
glycoprotein binding
patched binding
laminin-1 binding
glycosaminoglycan binding
calcium ion binding
zinc ion binding
hydrolase activity
peptidase activity
signal transducer activity

GO Cellular Component membrane
extracellular matrix
extracellular region
membrane raft
plasma membrane
cell surface
endoplasmic reticulum
Golgi apparatus
transport vesicle
nucleus
axon
dendrite
neuronal cell body
extracellular space

GO Biological Process cell proliferation
positive regulation of penile erection
cell communication
cell death
epithelial-mesenchymal signaling involved in prostate gland development
mesenchymal smoothened signaling pathway involved in prostate gland development
regulation of epithelial cell proliferation involved in prostate gland development
positive regulation of epithelial cell proliferation involved in prostate gland development
regulation of mesenchymal cell proliferation involved in prostate gland development
cell-cell signaling
epithelial-mesenchymal cell signaling
negative regulation of Wnt receptor signaling pathway
negative regulation of canonical Wnt receptor signaling pathway
positive regulation of smoothened signaling pathway
positive regulation of Wnt receptor signaling pathway
regulation of nodal signaling pathway involved in determination of lateral mesoderm left-right asymmetry
signal transduction
regulation of cell proliferation
smoothened signaling pathway
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
canonical Wnt receptor signaling pathway
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of transcription, DNA-dependent
positive regulation of transcription from RNA polymerase II promoter
negative regulation of transcription from RNA polymerase II promoter
negative regulation of transcription elongation from RNA polymerase II promoter
regulation of transcription, DNA-dependent
positive regulation of hh target transcription factor activity
negative regulation of cell differentiation
negative regulation of alpha-beta T cell differentiation
negative regulation of ureter smooth muscle cell differentiation
negative regulation of kidney smooth muscle cell differentiation
negative regulation of T cell proliferation
negative regulation of cell migration
negative regulation of apoptotic process
positive regulation of cell division
positive regulation of cell differentiation
positive regulation of cell proliferation
positive regulation of skeletal muscle cell proliferation
positive regulation of mesenchymal cell proliferation
positive regulation of mesenchymal cell proliferation involved in ureter development
positive regulation of neuroblast proliferation
positive regulation of cerebellar granule cell precursor proliferation
positive regulation of oligodendrocyte progenitor proliferation
positive regulation of immature T cell proliferation in thymus
positive regulation of alpha-beta T cell differentiation
positive regulation of T cell differentiation in thymus
positive regulation of neuron differentiation
positive regulation of oligodendrocyte differentiation
positive regulation of photoreceptor cell differentiation
positive regulation of striated muscle cell differentiation
positive regulation of kidney smooth muscle cell differentiation
positive regulation of ureter smooth muscle cell differentiation
positive regulation of protein import into nucleus
regulation of protein localization to nucleus
regulation of epithelial cell differentiation
regulation of apoptotic process
cell fate commitment
cell development
cell fate specification
osteoblast development
stem cell development
oligodendrocyte development
vasculogenesis
vasculogenesis involved in coronary vascular morphogenesis
lymphoid progenitor cell differentiation
T cell differentiation in thymus
oligodendrocyte differentiation
Bergmann glial cell differentiation
striated muscle cell differentiation
myoblast differentiation
myotube differentiation
ventral spinal cord interneuron specification
neuron fate commitment
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
androgen metabolic process
neural crest cell migration
establishment of cell polarity
cellular response to lithium ion
apoptotic process
protein localization to nucleus
intermediate filament organization
positive thymic T cell selection
negative thymic T cell selection
mesenchymal cell proliferation
epithelial cell proliferation involved in salivary gland morphogenesis
mesenchymal cell proliferation involved in lung development
metanephric mesenchymal cell proliferation involved in metanephros development
neuroblast proliferation
response to organic nitrogen
response to estradiol stimulus
response to retinoic acid
response to ethanol
axon guidance
response to hypoxia
response to axon injury
negative regulation of gene expression
negative regulation of protein catabolic process
negative regulation of cholesterol efflux
regulation of prostatic bud formation
positive regulation of sclerotome development
positive regulation of skeletal muscle tissue development
positive regulation of gene expression
regulation of gene expression
regulation of proteolysis
multicellular organismal development
anatomical structure development
pattern specification process
anatomical structure formation involved in morphogenesis
developmental growth
prostate gland development
male genitalia development
male genitalia morphogenesis
prostatic bud formation
branching involved in prostate gland morphogenesis
prostate epithelial cord elongation
primary prostatic bud elongation
embryonic digit morphogenesis
embryonic foregut morphogenesis
heart looping
embryonic digestive tract morphogenesis
branching morphogenesis of a tube
limb bud formation
hair follicle morphogenesis
angiogenesis
lung lobe morphogenesis
fungiform papilla morphogenesis
fungiform papilla formation
hindgut morphogenesis
organ formation
branching involved in salivary gland morphogenesis
formation of anatomical boundary
patterning of blood vessels
branching involved in ureteric bud morphogenesis
epithelial tube branching involved in lung morphogenesis
bud outgrowth involved in lung branching
neural tube formation
salivary gland cavitation
embryo development
forebrain development
midbrain development
ventral midline development
palate development
hindbrain development
fungiform papilla development
somite development
inner ear development
central nervous system development
vasculature development
renal system development
embryonic skeletal system development
artery development
respiratory tube development
pancreas development
embryonic organ development
lung development
trachea development
kidney development
heart development
tongue development
camera-type eye development
metanephros development
thyroid gland development
thymus development
right lung development
left lung development
ectoderm development
multicellular structure septum development
digestive tract mesoderm development
lung epithelium development
hair follicle development
skin development
lung-associated mesenchyme development
striated muscle tissue development
limb development
embryonic pattern specification
dorsal-ventral pattern formation
anterior-posterior pattern specification
telencephalon regionalization
spinal cord dorsal-ventral patterning
dorsal-ventral neural tube patterning
determination of left-right symmetry
determination of left-right asymmetry in lateral mesoderm
digestive tract morphogenesis
embryonic morphogenesis
embryonic limb morphogenesis
embryonic forelimb morphogenesis
embryonic hindlimb morphogenesis
odontogenesis
lung morphogenesis
trachea morphogenesis
tongue morphogenesis
odontogenesis of dentin-containing tooth
blood coagulation
endocytosis
proteolysis
intein-mediated protein splicing

Pathway EDA Expression Targets
NOTCH Expression Targets
pancreatic cancer pathway
pancreatic cancer pathway

Group SHH
cell proliferation
positive regulation of penile erection
cell communication
cell death
epithelial-mesenchymal signaling involved in prostate gland development
mesenchymal smoothened signaling pathway involved in prostate gland development
regulation of epithelial cell proliferation involved in prostate gland development
positive regulation of epithelial cell proliferation involved in prostate gland development
regulation of mesenchymal cell proliferation involved in prostate gland development
cell-cell signaling
epithelial-mesenchymal cell signaling
negative regulation of Wnt receptor signaling pathway
negative regulation of canonical Wnt receptor signaling pathway
positive regulation of smoothened signaling pathway
positive regulation of Wnt receptor signaling pathway
regulation of nodal signaling pathway involved in determination of lateral mesoderm left-right asymmetry
signal transduction
regulation of cell proliferation
smoothened signaling pathway
smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
canonical Wnt receptor signaling pathway
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of transcription, DNA-dependent
positive regulation of transcription from RNA polymerase II promoter
negative regulation of transcription from RNA polymerase II promoter
negative regulation of transcription elongation from RNA polymerase II promoter
regulation of transcription, DNA-dependent
positive regulation of hh target transcription factor activity
negative regulation of cell differentiation
negative regulation of alpha-beta T cell differentiation
negative regulation of ureter smooth muscle cell differentiation
negative regulation of kidney smooth muscle cell differentiation
negative regulation of T cell proliferation
negative regulation of cell migration
negative regulation of apoptotic process
positive regulation of cell division
positive regulation of cell differentiation
positive regulation of cell proliferation
positive regulation of skeletal muscle cell proliferation
positive regulation of mesenchymal cell proliferation
positive regulation of mesenchymal cell proliferation involved in ureter development
positive regulation of neuroblast proliferation
positive regulation of cerebellar granule cell precursor proliferation
positive regulation of oligodendrocyte progenitor proliferation
positive regulation of immature T cell proliferation in thymus
positive regulation of alpha-beta T cell differentiation
positive regulation of T cell differentiation in thymus
positive regulation of neuron differentiation
positive regulation of oligodendrocyte differentiation
positive regulation of photoreceptor cell differentiation
positive regulation of striated muscle cell differentiation
positive regulation of kidney smooth muscle cell differentiation
positive regulation of ureter smooth muscle cell differentiation
positive regulation of protein import into nucleus
regulation of protein localization to nucleus
regulation of epithelial cell differentiation
regulation of apoptotic process
cell fate commitment
cell development
cell fate specification
osteoblast development
stem cell development
oligodendrocyte development
vasculogenesis
vasculogenesis involved in coronary vascular morphogenesis
lymphoid progenitor cell differentiation
T cell differentiation in thymus
oligodendrocyte differentiation
Bergmann glial cell differentiation
striated muscle cell differentiation
myoblast differentiation
myotube differentiation
ventral spinal cord interneuron specification
neuron fate commitment
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
androgen metabolic process
neural crest cell migration
establishment of cell polarity
cellular response to lithium ion
apoptotic process
protein localization to nucleus
intermediate filament organization
positive thymic T cell selection
negative thymic T cell selection
mesenchymal cell proliferation
epithelial cell proliferation involved in salivary gland morphogenesis
mesenchymal cell proliferation involved in lung development
metanephric mesenchymal cell proliferation involved in metanephros development
neuroblast proliferation
response to organic nitrogen
response to estradiol stimulus
response to retinoic acid
response to ethanol
axon guidance
response to hypoxia
response to axon injury
negative regulation of gene expression
negative regulation of protein catabolic process
negative regulation of cholesterol efflux
regulation of prostatic bud formation
positive regulation of sclerotome development
positive regulation of skeletal muscle tissue development
positive regulation of gene expression
regulation of gene expression
regulation of proteolysis
multicellular organismal development
anatomical structure development
pattern specification process
anatomical structure formation involved in morphogenesis
developmental growth
prostate gland development
male genitalia development
male genitalia morphogenesis
prostatic bud formation
branching involved in prostate gland morphogenesis
prostate epithelial cord elongation
primary prostatic bud elongation
embryonic digit morphogenesis
embryonic foregut morphogenesis
heart looping
embryonic digestive tract morphogenesis
branching morphogenesis of a tube
limb bud formation
hair follicle morphogenesis
angiogenesis
lung lobe morphogenesis
fungiform papilla morphogenesis
fungiform papilla formation
hindgut morphogenesis
organ formation
branching involved in salivary gland morphogenesis
formation of anatomical boundary
patterning of blood vessels
branching involved in ureteric bud morphogenesis
epithelial tube branching involved in lung morphogenesis
bud outgrowth involved in lung branching
neural tube formation
salivary gland cavitation
embryo development
forebrain development
midbrain development
ventral midline development
palate development
hindbrain development
fungiform papilla development
somite development
inner ear development
central nervous system development
vasculature development
renal system development
embryonic skeletal system development
artery development
respiratory tube development
pancreas development
embryonic organ development
lung development
trachea development
kidney development
heart development
tongue development
camera-type eye development
metanephros development
thyroid gland development
thymus development
right lung development
left lung development
ectoderm development
multicellular structure septum development
digestive tract mesoderm development
lung epithelium development
hair follicle development
skin development
lung-associated mesenchyme development
striated muscle tissue development
limb development
embryonic pattern specification
dorsal-ventral pattern formation
anterior-posterior pattern specification
telencephalon regionalization
spinal cord dorsal-ventral patterning
dorsal-ventral neural tube patterning
determination of left-right symmetry
determination of left-right asymmetry in lateral mesoderm
digestive tract morphogenesis
embryonic morphogenesis
embryonic limb morphogenesis
embryonic forelimb morphogenesis
embryonic hindlimb morphogenesis
odontogenesis
lung morphogenesis
trachea morphogenesis
tongue morphogenesis
odontogenesis of dentin-containing tooth
blood coagulation
endocytosis
proteolysis
intein-mediated protein splicing
morphogen activity
receptor binding
glycoprotein binding
patched binding
laminin-1 binding
glycosaminoglycan binding
calcium ion binding
zinc ion binding
hydrolase activity
peptidase activity
signal transducer activity
membrane
extracellular matrix
extracellular region
membrane raft
plasma membrane
cell surface
endoplasmic reticulum
Golgi apparatus
transport vesicle
nucleus
axon
dendrite
neuronal cell body
extracellular space
Secreted proteins
Biofluids assayable substances

MedScan ID 3243

Hugo ID 10848

Human chromosome position 7q36

GenBank ID NC_000007
NM_000193
NP_000184
NG_007504
NC_018918
AC_000068
AC_000139
AB020410
BAA34689
AC002484
AAB67604
AC078834
AAS01990
AY422195
AAQ87879
CH236954
EAL23913
CH471149
EAX04543
HM015597
ADL14518
AY927450
L38518
AAA62179
Q15465
BC111925
AAI11926
NC_000071
NM_009170
NP_033196
AC_000027
AC134530
CH466524
EDL37231
AK077688
BAC36956
BC063087
AAH63087
EU664592
ACD69663
X76290
CAA53922
Q62226
NC_005103
NM_017221
NP_058917
AC_000072
CH474057
EDL86418
AF162915
AAD45373
L27340
AAA20999
Q63673
NT_007741
NT_079596
NW_001839100
NW_923796
AC_000050
NT_162294
NW_001030787
Q8C765
NW_001084822
NW_047685
Q9R179

LocusLink ID 3243
6469
20423
29499

Alias TPT
HHG1
HLP3
HPE3
SMMCI
TPTPS
MCOPCB5
tcag7.582
sonic hedgehog protein
sonic hedgehog homolog
Hx
Dsh
Hxl3
M100081
9530036O11Rik
HHG-1
short digits
hemimelic extra toes
Vhh-1
Triphalangeal thumb-polysyndactyly syndrome protein
short digits mutant
Shh
sonic hedgehog
Sonic hedgehog , human homolog of
Triphalangeal thumb-polysyndactyly syndrome gene
sonic hedgehog homolog (Drosophila)
holoprosencephaly 3
Histocompatibility X antigen
HHG I
OTTMUSP00000023583

Organism Homo sapiens
Mus musculus
Rattus norvegicus

OMIM ID 600725
142945
611638
269160
147250
120200
174500

Unigene ID Hs.164537
Mm.57202
Rn.10432

KEGG ID hsa:6469
mmu:20423
rno:29499

Swiss-Prot Accession Q15465
Q62226
Q63673
A4D247
Q75MC9
Q8C765
Q9R179

GO ID 0005509
0001948
0005539
0043237
0016015
0005113
0008233
0004871
0008270
0060020
0043369
0033077
0008209
0009952
0006915
0060840
0007411
0007596
0060445
0001658
0048754
0060447
0043010
0060070
0048468
0001708
0007267
0071285
0007417
0003140
0007502
0021904
0009953
0007398
0009790
0048557
0042733
0048617
0035115
0035116
0030326
0009880
0048706
0006897
0060664
0060738
0030010
0030900
0048859
0031069
0007507
0001947
0030902
0007442
0048839
0016539
0045109
0060459
0060174
0030324
0060428
0060463
0060484
0002320
0030539
0048808
0060916
0060783
0072136
0001656
0030901
0080125
0045445
0014902
0042130
0046639
0043066
0090090
0045596
0030336
0090370
2000357
0032435
0034244
0000122
2000062
0045060
0001755
0001841
0007405
0048663
0042475
0014003
0048645
0002076
0060021
0031016
0007389
0001569
0033089
0030177
0046638
0051781
0008284
0060769
0007228
0033092
2000358
2000729
0002052
0048714
0070447
0060406
0046534
0042307
0061189
0014858
0048643
0045880
0051155
0045944
0045893
2000063
0045059
0060516
0060523
0030850
0034504
0006508
0042127
0030856
0060782
1900175
0060685
1900180
0030162
0072001
0048678
0032355
0045471
0001666
0010243
0032526
0060458
0060662
0043588
0007224
0021938
0061053
0048864
0021978
0048538
0030878
0043587
0060439
0001570
0007418
0021521
0005794
0009986
0005783
0031012
0005615
0045121
0005634
0005886
0030133
0016787
0048856
0048646
0001525
0060442
0007154
0008219
0045165
0008283
0007368
0048589
0048546
0048598
0048568
0060441
0060684
0061196
0061198
0061197
0001942
0001822
0060173
0060425
0010463
0007275
0030178
0010629
0042177
0042476
0048709
0045597
0021940
0010628
0002053
0045666
0060513
0042981
0060768
0010468
0006355
0030323
0007165
0021513
0051146
0014706
0043586
0060438
0001944
0060979
0030424
0030425
0005576
0016020
0043025
0005102
0016563
0048314
0010553
0051151
0010552
0051152
0045449
0005624
0043193

PIR ID A49425
B53193

Swiss-Prot ID SHH_HUMAN
SHH_MOUSE
SHH_RAT

Cell Localization Secreted
extracellular space
Cell membrane
Extracellular

IPI ID IPI00017480
IPI00123314
IPI00211101
IPI00893003
IPI00892712
IPI00894434

Mouse chromosome position 5 16.0 cM

Rat chromosome position 4q11

Homologene ID 30961

MGI ID 98297

RGD ID 3673

Primary Cell Localization Extracellular