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P97812

- IHH_MOUSE

UniProt

P97812 - IHH_MOUSE

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Protein
Indian hedgehog protein
Gene
Ihh
Organism
Mus musculus (Mouse)
Status
Reviewed - 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 1 By similarity
Metal bindingi95 – 951Calcium 1 By similarity
Metal bindingi95 – 951Calcium 2 By similarity
Metal bindingi100 – 1001Calcium 1 By similarity
Metal bindingi130 – 1301Calcium 1; via carbonyl oxygen By similarity
Metal bindingi131 – 1311Calcium 1 By similarity
Metal bindingi131 – 1311Calcium 2 By similarity
Metal bindingi134 – 1341Calcium 2 By similarity
Metal bindingi136 – 1361Calcium 2 By similarity
Metal bindingi145 – 1451Zinc By similarity
Metal bindingi152 – 1521Zinc By similarity
Metal bindingi187 – 1871Zinc By similarity
Sitei202 – 2032Cleavage; by autolysis
Sitei248 – 2481Involved in cholesterol transfer By similarity
Sitei272 – 2721Involved in auto-cleavage By similarity
Sitei275 – 2751Essential for auto-cleavage By similarity

GO - Molecular functioni

  1. calcium ion binding Source: Ensembl
  2. patched binding Source: BHF-UCL
  3. peptidase activity Source: UniProtKB-KW

GO - Biological processi

  1. bone resorption Source: MGI
  2. camera-type eye development Source: MGI
  3. camera-type eye photoreceptor cell fate commitment Source: MGI
  4. cartilage development Source: MGI
  5. cell differentiation Source: MGI
  6. cell fate specification Source: MGI
  7. cell maturation Source: MGI
  8. cell-cell signaling Source: InterPro
  9. chondrocyte proliferation Source: MGI
  10. embryonic camera-type eye morphogenesis Source: MGI
  11. embryonic digestive tract morphogenesis Source: MGI
  12. embryonic pattern specification Source: MGI
  13. embryonic skeletal joint development Source: MGI
  14. epithelial cell morphogenesis Source: MGI
  15. epithelial cell-cell adhesion Source: MGI
  16. head morphogenesis Source: MGI
  17. heart looping Source: BHF-UCL
  18. in utero embryonic development Source: MGI
  19. intein-mediated protein splicing Source: InterPro
  20. maternal process involved in female pregnancy Source: Ensembl
  21. morphogenesis of a branching structure Source: MGI
  22. multicellular organism growth Source: MGI
  23. negative regulation of T cell differentiation in thymus Source: BHF-UCL
  24. negative regulation of alpha-beta T cell differentiation Source: BHF-UCL
  25. negative regulation of apoptotic process Source: Ensembl
  26. negative regulation of cell differentiation Source: MGI
  27. negative regulation of eye pigmentation Source: MGI
  28. negative regulation of immature T cell proliferation in thymus Source: BHF-UCL
  29. negative regulation of signal transduction Source: Ensembl
  30. neuron development Source: MGI
  31. ossification Source: MGI
  32. osteoblast differentiation Source: MGI
  33. pancreas development Source: MGI
  34. pattern specification process Source: MGI
  35. patterning of blood vessels Source: MGI
  36. positive regulation of T cell differentiation in thymus Source: BHF-UCL
  37. positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
  38. positive regulation of cell proliferation Source: MGI
  39. positive regulation of chondrocyte differentiation Source: Ensembl
  40. positive regulation of collagen biosynthetic process Source: MGI
  41. positive regulation of epithelial cell proliferation Source: Ensembl
  42. positive regulation of mesenchymal cell proliferation Source: MGI
  43. positive regulation of smoothened signaling pathway Source: BHF-UCL
  44. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  45. proteoglycan metabolic process Source: MGI
  46. regulation of growth Source: MGI
  47. response to estradiol Source: Ensembl
  48. retinal pigment epithelium development Source: MGI
  49. skeletal system development Source: MGI
  50. smooth muscle tissue development Source: MGI
  51. smoothened signaling pathway Source: MGI
  52. somite development Source: BHF-UCL
  53. vasculature development Source: MGI
  54. 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: Unplaced

Organism-specific databases

MGIiMGI:96533. Ihh.

Subcellular locationi

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

GO - Cellular componenti

  1. extracellular matrix Source: MGI
  2. extracellular space Source: UniProtKB-SubCell
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727 Reviewed prediction
Add
BLAST
Chaini28 – 411384Indian hedgehog protein
PRO_0000013232Add
BLAST
Chaini28 – 202175Indian hedgehog protein N-product
PRO_0000013233Add
BLAST
Chaini203 – 411209Indian hedgehog protein C-product
PRO_0000013234Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi28 – 281N-palmitoyl cysteine By similarity
Lipidationi202 – 2021Cholesterol glycine ester By similarity
Glycosylationi282 – 2821N-linked (GlcNAc...) Reviewed prediction

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.
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

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

ArrayExpressiP97812.
BgeeiP97812.
GenevestigatoriP97812.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-59800N.

Structurei

3D structure databases

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

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.

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_splice_site.
[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

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MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK    50
QFSPNVPEKT LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD 100
RLMTQRCKDR LNSLAISVMN QWPGVKLRVT EGWDEDGHHS EESLHYEGRA 150
VDITTSDRDR NKYGLLARLA VEAGFDWVYY ESKAHVHCSV KSEHSAAAKT 200
GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF SDVLIFLDRE 250
PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP 300
GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA 350
VADHHLAQLA FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST 400
FHPLGMSGAG S 411
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.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti383 – 3831W → S1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U85610 mRNA. Translation: AAB49692.1 . Different initiation.
X76291 mRNA. Translation: CAA53923.1 .
PIRi C49425.
RefSeqi NP_034674.1. NM_010544.2.
UniGenei Mm.439736.

3D structure databases

ProteinModelPortali P97812.
SMRi P97812. Positions 41-197, 203-349.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-59800N.

Protein family/group databases

MEROPSi C46.003.

Proteomic databases

PaxDbi P97812.
PRIDEi P97812.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 16147.
KEGGi mmu:16147.

Organism-specific databases

CTDi 3549.
MGIi MGI:96533. Ihh.

Phylogenomic databases

eggNOGi NOG250647.
HOVERGENi HBG005480.
InParanoidi P97812.
KOi K11989.
PhylomeDBi P97812.

Miscellaneous databases

NextBioi 288931.
PROi P97812.
SOURCEi Search...

Gene expression databases

ArrayExpressi P97812.
Bgeei P97812.
Genevestigatori P97812.

Family and domain databases

Gene3Di 2.170.16.10. 1 hit.
3.30.1380.10. 1 hit.
InterProi IPR001657. 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 ]
Pfami PF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view ]
PIRSFi PIRSF009400. Peptidase_C46. 1 hit.
PRINTSi PR00632. SONICHHOG.
SMARTi SM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view ]
SUPFAMi SSF51294. SSF51294. 1 hit.
SSF55166. SSF55166. 1 hit.
PROSITEi PS50817. INTEIN_N_TER. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 138 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

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