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P97812

- IHH_MOUSE

UniProt

P97812 - IHH_MOUSE

Protein

Indian hedgehog protein

Gene

Ihh

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    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

    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-cell signaling Source: InterPro
    6. cell differentiation Source: MGI
    7. cell fate specification Source: MGI
    8. cell maturation Source: MGI
    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-cell adhesion Source: MGI
    15. epithelial cell morphogenesis Source: MGI
    16. head morphogenesis Source: MGI
    17. heart looping Source: BHF-UCL
    18. intein-mediated protein splicing Source: InterPro
    19. in utero embryonic development Source: MGI
    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 alpha-beta T cell differentiation Source: BHF-UCL
    24. negative regulation of apoptotic process Source: Ensembl
    25. negative regulation of cell differentiation Source: MGI
    26. negative regulation of eye pigmentation Source: MGI
    27. negative regulation of immature T cell proliferation in thymus Source: BHF-UCL
    28. negative regulation of signal transduction Source: Ensembl
    29. negative regulation of T cell differentiation in thymus Source: BHF-UCL
    30. neuron development Source: MGI
    31. ossification Source: MGI
    32. osteoblast differentiation Source: MGI
    33. pancreas development Source: MGI
    34. patterning of blood vessels Source: MGI
    35. pattern specification process Source: MGI
    36. positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
    37. positive regulation of cell proliferation Source: MGI
    38. positive regulation of chondrocyte differentiation Source: Ensembl
    39. positive regulation of collagen biosynthetic process Source: MGI
    40. positive regulation of epithelial cell proliferation Source: Ensembl
    41. positive regulation of mesenchymal cell proliferation Source: MGI
    42. positive regulation of smoothened signaling pathway Source: BHF-UCL
    43. positive regulation of T cell differentiation in thymus 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. smoothened signaling pathway Source: MGI
    51. smooth muscle tissue development Source: MGI
    52. somite development Source: BHF-UCL
    53. vasculature development Source: MGI
    54. vitelline membrane formation Source: MGI

    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 By similarity; Lipid-anchor By similarity; 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

    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

    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.By similarity

    Protein-protein interaction databases

    DIPiDIP-59800N.

    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_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

    « Hide

    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.

    Experimental Info

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

    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: October 1, 2014
    This is version 139 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