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P97812 (IHH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Indian hedgehog protein

Short name=IHH
Alternative name(s):
HHG-2
Gene names
Name:Ihh
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Intercellular signal essential for a variety of patterning events during development. Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. Implicated in endochondral ossification: may regulate the balance between growth and ossification of the developing bones. Induces the expression of parathyroid hormone-related protein (PTHRP).

Subunit structure

Homooligomer (indian hedgehog protein N-product). Interacts with BOC and CDON. Interacts with PTCH1 By similarity.

Subcellular location

Indian hedgehog protein N-product: Cell membrane; Lipid-anchor; Extracellular side By similarity. Note: The N-terminal peptide remains associated with the cell surface By similarity.

Indian hedgehog protein C-product: Secretedextracellular space By similarity. Note: The C-terminal peptide diffuses from the cell By similarity.

Cell membrane By similarity.

Tissue specificity

In the embryo, detected in the developing gut, the growth zone of cartilage of developing long bones, epithelium and urogenital sinus. In the adult kidney, found in proximal convoluted and proximal straight tubule.

Developmental stage

Detected at 10 dpc in developing gut, at 14.5 days dpc in the cartilage primordium and in the developing urogenital sinus. Expression increases with gestional age in kidney and duodenum, becoming maximal in adulthood.

Domain

The indian 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.

Post-translational modification

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 By similarity.

Cholesterylation is required for N-product targeting to lipid rafts and multimerization By similarity.

N-palmitoylation is required for N-product multimerization and full activity By similarity.

Sequence similarities

Belongs to the hedgehog family.

Sequence caution

The sequence AAB49692.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   DomainSignal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionDevelopmental protein
Hydrolase
Protease
   PTMAutocatalytic cleavage
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbone resorption

Inferred from direct assay PubMed 10208865. Source: MGI

camera-type eye development

Inferred from mutant phenotype PubMed 18582859. Source: MGI

camera-type eye photoreceptor cell fate commitment

Inferred from mutant phenotype PubMed 18582859. Source: MGI

cartilage development

Inferred from mutant phenotype PubMed 17191253. Source: MGI

cell differentiation

Inferred from direct assay PubMed 15951842. Source: MGI

cell fate specification

Inferred from mutant phenotype PubMed 18582859. Source: MGI

cell maturation

Inferred from mutant phenotype PubMed 15576404. Source: MGI

cell-cell signaling

Inferred from electronic annotation. Source: InterPro

chondrocyte proliferation

Inferred from mutant phenotype PubMed 16935278. Source: MGI

embryonic camera-type eye morphogenesis

Inferred from mutant phenotype PubMed 18582859. Source: MGI

embryonic digestive tract morphogenesis

Inferred from mutant phenotype PubMed 10821773. Source: MGI

embryonic pattern specification

Inferred from mutant phenotype PubMed 18582859. Source: MGI

embryonic skeletal joint development

Inferred from mutant phenotype PubMed 17191253. Source: MGI

epithelial cell morphogenesis

Inferred from mutant phenotype PubMed 18582859. Source: MGI

epithelial cell-cell adhesion

Inferred from mutant phenotype PubMed 18582859. Source: MGI

head morphogenesis

Inferred from mutant phenotype PubMed 16935278. Source: MGI

heart looping

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

in utero embryonic development

Inferred from mutant phenotype PubMed 17881493. Source: MGI

intein-mediated protein splicing

Inferred from electronic annotation. Source: InterPro

maternal process involved in female pregnancy

Inferred from electronic annotation. Source: Ensembl

morphogenesis of a branching structure

Inferred from mutant phenotype PubMed 11044404. Source: MGI

multicellular organism growth

Inferred from mutant phenotype PubMed 10821773. Source: MGI

negative regulation of T cell differentiation in thymus

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

negative regulation of alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell differentiation

Inferred from mutant phenotype PubMed 16284117. Source: MGI

negative regulation of eye pigmentation

Inferred from mutant phenotype PubMed 17464332. Source: MGI

negative regulation of immature T cell proliferation in thymus

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

negative regulation of signal transduction

Inferred from electronic annotation. Source: Ensembl

neuron development

Inferred from mutant phenotype PubMed 10821773. Source: MGI

ossification

Inferred from mutant phenotype PubMed 11748145. Source: MGI

osteoblast differentiation

Inferred from mutant phenotype PubMed 14973297. Source: MGI

pancreas development

Inferred from mutant phenotype PubMed 10821773. Source: MGI

pattern specification process

Inferred from mutant phenotype PubMed 9671585. Source: MGI

patterning of blood vessels

Inferred from mutant phenotype PubMed 15689378. Source: MGI

positive regulation of T cell differentiation in thymus

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

positive regulation of alpha-beta T cell differentiation

Inferred from mutant phenotype PubMed 19109233. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 16284117PubMed 17191253PubMed 18582859. Source: MGI

positive regulation of chondrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of collagen biosynthetic process

Inferred from direct assay PubMed 10208865. Source: MGI

positive regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 18582859. Source: MGI

positive regulation of smoothened signaling pathway

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 17881493. Source: MGI

proteoglycan metabolic process

Inferred from genetic interaction PubMed 16935278. Source: MGI

regulation of growth

Inferred from genetic interaction PubMed 19590577. Source: MGI

response to estradiol

Inferred from electronic annotation. Source: Ensembl

retinal pigment epithelium development

Inferred from mutant phenotype PubMed 18582859. Source: MGI

skeletal system development

Inferred from mutant phenotype PubMed 16278811. Source: MGI

smooth muscle tissue development

Inferred from mutant phenotype PubMed 10821773. Source: MGI

smoothened signaling pathway

Inferred from genetic interaction PubMed 19590577. Source: MGI

somite development

Inferred from mutant phenotype PubMed 11517919. Source: BHF-UCL

vasculature development

Inferred from mutant phenotype PubMed 17881493. Source: MGI

vitelline membrane formation

Inferred from mutant phenotype PubMed 17881493. Source: MGI

   Cellular_componentextracellular matrix

Inferred from direct assay PubMed 11476578. Source: MGI

extracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: Ensembl

patched binding

Inferred from physical interaction PubMed 9811851. Source: BHF-UCL

peptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 411384Indian hedgehog protein
PRO_0000013232
Chain28 – 202175Indian hedgehog protein N-product
PRO_0000013233
Chain203 – 411209Indian hedgehog protein C-product
PRO_0000013234

Sites

Metal binding941Calcium 1 By similarity
Metal binding951Calcium 1 By similarity
Metal binding951Calcium 2 By similarity
Metal binding1001Calcium 1 By similarity
Metal binding1301Calcium 1; via carbonyl oxygen By similarity
Metal binding1311Calcium 1 By similarity
Metal binding1311Calcium 2 By similarity
Metal binding1341Calcium 2 By similarity
Metal binding1361Calcium 2 By similarity
Metal binding1451Zinc By similarity
Metal binding1521Zinc By similarity
Metal binding1871Zinc By similarity
Site202 – 2032Cleavage; by autolysis
Site2481Involved in cholesterol transfer By similarity
Site2721Involved in auto-cleavage By similarity
Site2751Essential for auto-cleavage By similarity

Amino acid modifications

Lipidation281N-palmitoyl cysteine By similarity
Lipidation2021Cholesterol glycine ester By similarity
Glycosylation2821N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict3831W → S Ref.2

Sequences

Sequence LengthMass (Da)Tools
P97812 [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 08BE7AD8507C0D9B

FASTA41145,485
        10         20         30         40         50         60 
MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK QFSPNVPEKT 

        70         80         90        100        110        120 
LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD RLMTQRCKDR LNSLAISVMN 

       130        140        150        160        170        180 
QWPGVKLRVT EGWDEDGHHS EESLHYEGRA VDITTSDRDR NKYGLLARLA VEAGFDWVYY 

       190        200        210        220        230        240 
ESKAHVHCSV KSEHSAAAKT GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF 

       250        260        270        280        290        300 
SDVLIFLDRE PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP 

       310        320        330        340        350        360 
GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA VADHHLAQLA 

       370        380        390        400        410 
FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST FHPLGMSGAG S 

« Hide

References

[1]"Post-translational processing and renal expression of mouse indian hedgehog."
Valentini R.P., Brookhiser W.T., Park J., Yang T., Briggs J., Dressler G., Holzman L.B.
J. Biol. Chem. 272:8466-8473(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOCATALYTIC CLEAVAGE.
Strain: CD-1.
Tissue: Kidney.
[2]"Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity."
Echelard Y., Epstein D.J., St Jacques B., Shen L., Mohler J., McMahon J.A., McMahon A.P.
Cell 75:1417-1430(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-411.
Strain: C57BL/6J.
Tissue: Embryo.
[3]St Jacques B.
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[4]"Products, genetic linkage and limb patterning activity of a murine hedgehog gene."
Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.
Development 120:3339-3353(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-172.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U85610 mRNA. Translation: AAB49692.1. Different initiation.
X76291 mRNA. Translation: CAA53923.1.
PIRC49425.
RefSeqNP_034674.1. NM_010544.2.
UniGeneMm.439736.

3D structure databases

ProteinModelPortalP97812.
SMRP97812. Positions 41-197, 203-349.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59800N.

Protein family/group databases

MEROPSC46.003.

Proteomic databases

PaxDbP97812.
PRIDEP97812.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID16147.
KEGGmmu:16147.

Organism-specific databases

CTD3549.
MGIMGI:96533. Ihh.

Phylogenomic databases

eggNOGNOG250647.
HOVERGENHBG005480.
InParanoidP97812.
KOK11989.
PhylomeDBP97812.

Gene expression databases

ArrayExpressP97812.
BgeeP97812.
GenevestigatorP97812.

Family and domain databases

Gene3D2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProIPR001657. 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_splice_site.
[Graphical view]
PfamPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFPIRSF009400. Peptidase_C46. 1 hit.
PRINTSPR00632. SONICHHOG.
SMARTSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMSSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEPS50817. INTEIN_N_TER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio288931.
PROP97812.
SOURCESearch...

Entry information

Entry nameIHH_MOUSE
AccessionPrimary (citable) accession number: P97812
Secondary accession number(s): Q61724
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: July 9, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot