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Protein

Indian hedgehog protein

Gene

Ihh

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

Functioni

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).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi94 – 941Calcium 1By similarity
Metal bindingi95 – 951Calcium 1By similarity
Metal bindingi95 – 951Calcium 2By similarity
Metal bindingi100 – 1001Calcium 1By similarity
Metal bindingi130 – 1301Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi131 – 1311Calcium 1By similarity
Metal bindingi131 – 1311Calcium 2By similarity
Metal bindingi134 – 1341Calcium 2By similarity
Metal bindingi136 – 1361Calcium 2By similarity
Metal bindingi145 – 1451ZincBy similarity
Metal bindingi152 – 1521ZincBy similarity
Metal bindingi187 – 1871ZincBy similarity
Sitei202 – 2032Cleavage; by autolysis
Sitei248 – 2481Involved in cholesterol transferBy similarity
Sitei272 – 2721Involved in auto-cleavageBy similarity
Sitei275 – 2751Essential for auto-cleavageBy similarity

GO - Molecular functioni

  • calcium ion binding Source: MGI
  • patched binding Source: BHF-UCL
  • peptidase activity Source: UniProtKB-KW

GO - Biological processi

  • bone resorption Source: MGI
  • camera-type eye development Source: MGI
  • camera-type eye photoreceptor cell fate commitment Source: MGI
  • cartilage development Source: MGI
  • cell-cell signaling Source: InterPro
  • cell differentiation Source: MGI
  • cell fate specification Source: MGI
  • cell maturation Source: MGI
  • chondrocyte proliferation Source: MGI
  • embryonic camera-type eye morphogenesis Source: MGI
  • embryonic digestive tract morphogenesis Source: MGI
  • embryonic digit morphogenesis Source: MGI
  • embryonic pattern specification Source: MGI
  • embryonic skeletal joint development Source: MGI
  • epithelial cell-cell adhesion Source: MGI
  • epithelial cell morphogenesis Source: MGI
  • head morphogenesis Source: MGI
  • heart looping Source: BHF-UCL
  • intein-mediated protein splicing Source: InterPro
  • in utero embryonic development Source: MGI
  • maternal process involved in female pregnancy Source: Ensembl
  • morphogenesis of a branching structure Source: MGI
  • multicellular organism growth Source: MGI
  • negative regulation of alpha-beta T cell differentiation Source: BHF-UCL
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of cell differentiation Source: MGI
  • negative regulation of eye pigmentation Source: MGI
  • negative regulation of immature T cell proliferation in thymus Source: BHF-UCL
  • negative regulation of signal transduction Source: Ensembl
  • negative regulation of T cell differentiation in thymus Source: BHF-UCL
  • neuron development Source: MGI
  • ossification Source: MGI
  • osteoblast differentiation Source: MGI
  • pancreas development Source: MGI
  • patterning of blood vessels Source: MGI
  • pattern specification process Source: MGI
  • positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of chondrocyte differentiation Source: Ensembl
  • positive regulation of collagen biosynthetic process Source: MGI
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of smoothened signaling pathway Source: BHF-UCL
  • positive regulation of T cell differentiation in thymus Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • proteoglycan metabolic process Source: MGI
  • regulation of growth Source: MGI
  • response to estradiol Source: Ensembl
  • retinal pigment epithelium development Source: MGI
  • skeletal system development Source: MGI
  • smoothened signaling pathway Source: MGI
  • smooth muscle tissue development Source: MGI
  • somite development Source: BHF-UCL
  • vasculature development Source: MGI
  • vitelline membrane formation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiC46.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Indian hedgehog protein
Short name:
IHH
Alternative name(s):
HHG-2
Cleaved into the following 2 chains:
Gene namesi
Name:Ihh
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:96533. Ihh.

Subcellular locationi

Indian hedgehog protein N-product :
Indian hedgehog protein C-product :

GO - Cellular componenti

  • extracellular space Source: UniProtKB-SubCell
  • plasma membrane Source: MGI
  • proteinaceous extracellular matrix Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 411384Indian hedgehog proteinPRO_0000013232Add
BLAST
Chaini28 – 202175Indian hedgehog protein N-productPRO_0000013233Add
BLAST
Chaini203 – 411209Indian hedgehog protein C-productPRO_0000013234Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi28 – 281N-palmitoyl cysteineBy similarity
Lipidationi202 – 2021Cholesterol glycine esterBy similarity
Glycosylationi282 – 2821N-linked (GlcNAc...)Sequence Analysis

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 (By similarity).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

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiP97812.
PaxDbiP97812.
PRIDEiP97812.

Expressioni

Tissue specificityi

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 stagei

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.

Gene expression databases

BgeeiP97812.
ExpressionAtlasiP97812. baseline and differential.
GenevisibleiP97812. MM.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-59800N.
STRINGi10090.ENSMUSP00000128056.

Structurei

3D structure databases

ProteinModelPortaliP97812.
SMRiP97812. Positions 41-197, 203-349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

Sequence similaritiesi

Belongs to the hedgehog family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG250647.
HOVERGENiHBG005480.
InParanoidiP97812.
KOiK11989.
PhylomeDBiP97812.

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.

P97812-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK
60 70 80 90 100
QFSPNVPEKT LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD
110 120 130 140 150
RLMTQRCKDR LNSLAISVMN QWPGVKLRVT EGWDEDGHHS EESLHYEGRA
160 170 180 190 200
VDITTSDRDR NKYGLLARLA VEAGFDWVYY ESKAHVHCSV KSEHSAAAKT
210 220 230 240 250
GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF SDVLIFLDRE
260 270 280 290 300
PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP
310 320 330 340 350
GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA
360 370 380 390 400
VADHHLAQLA FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST
410
FHPLGMSGAG S
Length:411
Mass (Da):45,485
Last modified:July 15, 1999 - v2
Checksum:i08BE7AD8507C0D9B
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti383 – 3831W → S (PubMed:7916661).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85610 mRNA. Translation: AAB49692.1. Different initiation.
X76291 mRNA. Translation: CAA53923.1.
PIRiC49425.
RefSeqiNP_034674.1. NM_010544.2.
UniGeneiMm.439736.

Genome annotation databases

GeneIDi16147.
KEGGimmu:16147.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85610 mRNA. Translation: AAB49692.1. Different initiation.
X76291 mRNA. Translation: CAA53923.1.
PIRiC49425.
RefSeqiNP_034674.1. NM_010544.2.
UniGeneiMm.439736.

3D structure databases

ProteinModelPortaliP97812.
SMRiP97812. Positions 41-197, 203-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59800N.
STRINGi10090.ENSMUSP00000128056.

Protein family/group databases

MEROPSiC46.003.

Proteomic databases

MaxQBiP97812.
PaxDbiP97812.
PRIDEiP97812.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi16147.
KEGGimmu:16147.

Organism-specific databases

CTDi3549.
MGIiMGI:96533. Ihh.

Phylogenomic databases

eggNOGiNOG250647.
HOVERGENiHBG005480.
InParanoidiP97812.
KOiK11989.
PhylomeDBiP97812.

Miscellaneous databases

ChiTaRSiIhh. mouse.
NextBioi288931.
PROiP97812.
SOURCEiSearch...

Gene expression databases

BgeeiP97812.
ExpressionAtlasiP97812. baseline and differential.
GenevisibleiP97812. MM.

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...

Publicationsi

  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], PROTEOLYTIC PROCESSING, 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.

Entry informationi

Entry nameiIHH_MOUSE
AccessioniPrimary (citable) accession number: P97812
Secondary accession number(s): Q61724
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: June 24, 2015
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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 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.