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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)DescriptionActionsGraphical viewLength
Metal bindingi94Calcium 1By similarity1
Metal bindingi95Calcium 1By similarity1
Metal bindingi95Calcium 2By similarity1
Metal bindingi100Calcium 1By similarity1
Metal bindingi130Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi131Calcium 1By similarity1
Metal bindingi131Calcium 2By similarity1
Metal bindingi134Calcium 2By similarity1
Metal bindingi136Calcium 2By similarity1
Metal bindingi145ZincBy similarity1
Metal bindingi152ZincBy similarity1
Metal bindingi187ZincBy similarity1
Sitei248Involved in cholesterol transferBy similarity1
Sitei272Involved in auto-cleavageBy similarity1
Sitei275Essential for auto-cleavageBy similarity1

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 differentiation involved in endochondral bone morphogenesis 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
  • 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 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 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 collagen biosynthetic process Source: MGI
  • 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
  • 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
Proteomesi
  • UP000000589 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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001323228 – 411Indian hedgehog proteinAdd BLAST384
ChainiPRO_000001323328 – 202Indian hedgehog protein N-productAdd BLAST175
ChainiPRO_0000013234203 – 411Indian hedgehog protein C-productAdd BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi28N-palmitoyl cysteineBy similarity1
Lipidationi202Cholesterol glycine esterBy similarity1
Glycosylationi282N-linked (GlcNAc...)Sequence analysis1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei202 – 203Cleavage; by autolysis2

Keywords - PTMi

Autocatalytic cleavage, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiP97812.
PaxDbiP97812.
PeptideAtlasiP97812.
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

BgeeiENSMUSG00000006538.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • patched binding Source: BHF-UCL

Protein-protein interaction databases

DIPiDIP-59800N.
STRINGi10090.ENSMUSP00000128056.

Structurei

3D structure databases

ProteinModelPortaliP97812.
SMRiP97812.
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

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
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.
IPR033385. IHH.
IPR006141. Intein_N.
[Graphical view]
PANTHERiPTHR11889:SF39. PTHR11889:SF39. 1 hit.
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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti383W → S (PubMed:7916661).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85610 mRNA. Translation: AAB49692.1. Different initiation.
X76291 mRNA. Translation: CAA53923.1.
CCDSiCCDS15061.1.
PIRiC49425.
RefSeqiNP_034674.2. NM_010544.3.
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.
CCDSiCCDS15061.1.
PIRiC49425.
RefSeqiNP_034674.2. NM_010544.3.
UniGeneiMm.439736.

3D structure databases

ProteinModelPortaliP97812.
SMRiP97812.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59800N.
STRINGi10090.ENSMUSP00000128056.

Protein family/group databases

MEROPSiC46.003.

Proteomic databases

MaxQBiP97812.
PaxDbiP97812.
PeptideAtlasiP97812.
PRIDEiP97812.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi16147.
KEGGimmu:16147.

Organism-specific databases

CTDi3549.
MGIiMGI:96533. Ihh.

Phylogenomic databases

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
HOVERGENiHBG005480.
InParanoidiP97812.
KOiK11989.
PhylomeDBiP97812.

Miscellaneous databases

ChiTaRSiIhh. mouse.
PROiP97812.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006538.

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.
IPR033385. IHH.
IPR006141. Intein_N.
[Graphical view]
PANTHERiPTHR11889:SF39. PTHR11889:SF39. 1 hit.
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 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: November 2, 2016
This is version 157 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

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.