ID   IHH_MOUSE               Reviewed;         411 AA.
AC   P97812; Q61724;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   02-SEP-2008, entry version 87.
DE   RecName: Full=Indian hedgehog protein;
DE            Short=IHH;
DE   AltName: Full=HHG-2;
DE   Contains:
DE     RecName: Full=Indian hedgehog protein N-product;
DE   Contains:
DE     RecName: Full=Indian hedgehog protein C-product;
DE   Flags: Precursor;
GN   Name=Ihh;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND AUTOPROTEOLYTIC CLEAVAGE.
RC   STRAIN=CD-1; TISSUE=Kidney;
RX   MEDLINE=97236802; PubMed=9079674; DOI=10.1074/jbc.272.13.8466;
RA   Valentini R.P., Brookhiser W.T., Park J., Yang T., Briggs J.,
RA   Dressler G., Holzman L.B.;
RT   "Post-translational processing and renal expression of mouse indian
RT   hedgehog.";
RL   J. Biol. Chem. 272:8466-8473(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 76-411.
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RX   MEDLINE=94094334; PubMed=7916661; DOI=10.1016/0092-8674(93)90627-3;
RA   Echelard Y., Epstein D.J., St Jacques B., Shen L., Mohler J.,
RA   McMahon J.A., McMahon A.P.;
RT   "Sonic hedgehog, a member of a family of putative signaling molecules,
RT   is implicated in the regulation of CNS polarity.";
RL   Cell 75:1417-1430(1993).
RN   [3]
RP   SEQUENCE REVISION.
RA   St Jacques B.;
RL   Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 124-172.
RX   MEDLINE=95236997; PubMed=7720571;
RA   Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K.,
RA   Zhao R., Seldin M.F., Fallon J.F., Beachy P.A.;
RT   "Products, genetic linkage and limb patterning activity of a murine
RT   hedgehog gene.";
RL   Development 120:3339-3353(1994).
CC   -!- FUNCTION: Intercellular signal essential for a variety of
CC       patterning events during development. Binds to the patched (PTC)
CC       receptor, which functions in association with smoothened (SMO), to
CC       activate the transcription of target genes. Implicated in
CC       endochondral ossification: may regulate the balance between growth
CC       and ossification of the developing bones. Induces the expression
CC       of parathyroid hormone-related protein (PTHRP).
CC   -!- SUBCELLULAR LOCATION: Indian hedgehog protein N-product: Cell
CC       membrane; Lipid-anchor; Extracellular side (By similarity).
CC       Note=The N-terminal peptide remains associated with the cell
CC       surface (By similarity).
CC   -!- SUBCELLULAR LOCATION: Indian hedgehog protein C-product: Secreted,
CC       extracellular space (By similarity). Note=The C-terminal peptide
CC       diffuses from the cell (By similarity).
CC   -!- TISSUE SPECIFICITY: In the embryo, detected in the developing gut,
CC       the growth zone of cartilage of developing long bones, epithelium
CC       and urogenital sinus. In the adult kidney, found in proximal
CC       convoluted and proximal straight tubule.
CC   -!- DEVELOPMENTAL STAGE: Detected at 10 dpc in developing gut, at 14.5
CC       days dpc in the cartilage primordium and in the developing
CC       urogenital sinus. Expression increases with gestional age in
CC       kidney and duodenum, becoming maximal in adulthood.
CC   -!- PTM: The C-terminal domain displays an autoproteolysis activity
CC       and a cholesterol transferase activity. Both activities result in
CC       the cleavage of the full-length protein and covalent attachment of
CC       a cholesterol moiety to the C-terminal of the newly generated N-
CC       terminal fragment (N-product). The N-product is the active species
CC       in both local and long-range signaling, whereas the C-product has
CC       no signaling activity (By similarity).
CC   -!- PTM: Cholesterylation is required for N-product targeting to lipid
CC       rafts and multimerization (By similarity).
CC   -!- PTM: N-palmitoylation is required for N-product multimerization
CC       and full activity (By similarity).
CC   -!- SIMILARITY: Belongs to the hedgehog family.
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DR   EMBL; U85610; AAB49692.1; ALT_INIT; mRNA.
DR   EMBL; X76291; CAA53923.1; -; mRNA.
DR   PIR; C49425; C49425.
DR   UniGene; Mm.439736; -.
DR   HSSP; Q62226; 1VHH.
DR   SMR; P97812; 43-199.
DR   MEROPS; C46.003; -.
DR   Ensembl; ENSMUSG00000006538; Mus musculus.
DR   MGI; MGI:96533; Ihh.
DR   HOVERGEN; P97812; -.
DR   ArrayExpress; P97812; -.
DR   GermOnline; ENSMUSG00000006538; Mus musculus.
DR   GO; GO:0005515; F:protein binding; IPI:MGI.
DR   GO; GO:0048469; P:cell maturation; IMP:MGI.
DR   GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI.
DR   GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR   GO; GO:0001569; P:patterning of blood vessels; IMP:MGI.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IMP:MGI.
DR   GO; GO:0001501; P:skeletal development; IMP:MGI.
DR   InterPro; IPR003586; Hedgehog_hint_C.
DR   InterPro; IPR003587; Hedgehog_hint_N.
DR   InterPro; IPR000320; HH_signal.
DR   InterPro; IPR006141; Intein_splicing_site.
DR   InterPro; IPR001657; Peptidase_C46.
DR   InterPro; IPR001767; Peptidase_C46_hint.
DR   Pfam; PF01085; HH_signal; 1.
DR   Pfam; PF01079; Hint; 1.
DR   PIRSF; PIRSF009400; Peptidase_C46; 1.
DR   PRINTS; PR00632; SONICHHOG.
DR   SMART; SM00305; HintC; 1.
DR   SMART; SM00306; HintN; 1.
DR   PROSITE; PS50817; INTEIN_N_TER; 1.
PE   1: Evidence at protein level;
KW   Autocatalytic cleavage; Cell membrane; Developmental protein;
KW   Glycoprotein; Hydrolase; Lipoprotein; Membrane; Palmitate; Protease;
KW   Secreted; Signal.
FT   SIGNAL        1     27       Potential.
FT   CHAIN        28    411       Indian hedgehog protein.
FT                                /FTId=PRO_0000013232.
FT   CHAIN        28    202       Indian hedgehog protein N-product.
FT                                /FTId=PRO_0000013233.
FT   CHAIN       203    411       Indian hedgehog protein C-product.
FT                                /FTId=PRO_0000013234.
FT   SITE        202    203       Cleavage; by autolysis.
FT   SITE        248    248       Involved in cholesterol transfer (By
FT                                similarity).
FT   SITE        272    272       Involved in auto-cleavage (By
FT                                similarity).
FT   SITE        275    275       Essential for auto-cleavage (By
FT                                similarity).
FT   LIPID        28     28       N-palmitoyl cysteine (By similarity).
FT   LIPID       202    202       Cholesterol glycine ester (By
FT                                similarity).
FT   CARBOHYD    282    282       N-linked (GlcNAc...) (Potential).
FT   CONFLICT    383    383       W -> S (in Ref. 2).
SQ   SEQUENCE   411 AA;  45485 MW;  08BE7AD8507C0D9B CRC64;
     MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK QFSPNVPEKT
     LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD RLMTQRCKDR LNSLAISVMN
     QWPGVKLRVT EGWDEDGHHS EESLHYEGRA VDITTSDRDR NKYGLLARLA VEAGFDWVYY
     ESKAHVHCSV KSEHSAAAKT GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF
     SDVLIFLDRE PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP
     GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA VADHHLAQLA
     FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST FHPLGMSGAG S
//