Reviewed, UniProtKB/Swiss-Prot P97812 (IHH_MOUSE)

Names and origin

Protein names

Recommended name:
    Indian hedgehog protein
      Short name=IHH
Alternative name(s):
    HHG-2
Cleaved into the following 2 chains:
    1- Recommended name:
            Indian hedgehog protein N-product
    2- Recommended name:
            Indian hedgehog protein C-product

Gene names

Name:

Ihh

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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).
Subcellular location	Indian hedgehog protein N-product: Cell membrane; Lipid-anchor; Extracellular sideBy similarity. Note= The N-terminal peptide remains associated with the cell surface By similarity. Indian hedgehog protein C-product: Secreted › extracellular spaceBy similarity. Note= The C-terminal peptide diffuses from the cell By similarity.
Tissue specificity	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 stage	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.
Post-translational modification	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.
Sequence similarities	Belongs to the hedgehog family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Domain	Signal
Molecular function	Developmental protein Hydrolase Protease
PTM	Autocatalytic cleavage Glycoprotein Lipoprotein Palmitate
Gene Ontology (GO)
Biological process	cell maturation Inferred from mutant phenotype. Source: MGI negative regulation of cell differentiation Inferred from mutant phenotype. Source: MGI osteoblast differentiation Inferred from mutant phenotype. Source: MGI patterning of blood vessels Inferred from mutant phenotype. Source: MGI positive regulation of cell proliferation Inferred from mutant phenotype. Source: MGI skeletal development Inferred from mutant phenotype. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 411	384	Indian hedgehog protein
	Chain	28 – 202	175	Indian hedgehog protein N-product
	Chain	203 – 411	209	Indian hedgehog protein C-product
Sites
	Site	202 – 203	2	Cleavage; by autolysis
	Site	248	1	Involved in cholesterol transfer By similarity
	Site	272	1	Involved in auto-cleavage By similarity
	Site	275	1	Essential for auto-cleavage By similarity
Amino acid modifications
	Lipidation	28	1	N-palmitoyl cysteine By similarity
	Lipidation	202	1	Cholesterol glycine ester By similarity
	Glycosylation	282	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	383	1	W → S Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P97812-1 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: 08BE7AD8507C0D9B	FASTA	411	45,485
	10 20 30 40 50 60 MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK QFSPNVPEKT 70 80 90 100 110 120 LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD RLMTQRCKDR LNSLAISVMN 130 140 150 160 170 180 QWPGVKLRVT EGWDEDGHHS EESLHYEGRA VDITTSDRDR NKYGLLARLA VEAGFDWVYY 190 200 210 220 230 240 ESKAHVHCSV KSEHSAAAKT GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF 250 260 270 280 290 300 SDVLIFLDRE PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP 310 320 330 340 350 360 GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA VADHHLAQLA 370 380 390 400 410 FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST FHPLGMSGAG S

References

[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: 9079674] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOPROTEOLYTIC 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: 7916661] [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: 7720571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 124-172.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U85610 mRNA. Translation: AAB49692.1. Different initiation. X76291 mRNA. Translation: CAA53923.1.
PIR	C49425.
UniGene	Mm.439736
3D structure databases
HSSP	HSSP built from PDB template 1VHH based on UniProtKB Q62226.
SMR	P97812. Positions 43-199.
ModBase	Search...
Protein family/group databases
MEROPS	C46.003.
Genome annotation databases
Ensembl	ENSMUSG00000006538. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:96533. Ihh.
Phylogenomic databases
HOVERGEN	P97812.
Gene expression databases
ArrayExpress	P97812.
GermOnline	ENSMUSG00000006538. Mus musculus.
Family and domain databases
InterPro	IPR003586. Hedgehog_hint_C. IPR003587. Hedgehog_hint_N. IPR000320. HH_signal. IPR006141. Intein_splicing_site. IPR001657. Peptidase_C46. IPR001767. Peptidase_C46_hint. [Graphical view]
Pfam	PF01085. HH_signal. 1 hit. PF01079. Hint. 1 hit. [Graphical view]
PIRSF	PIRSF009400. Peptidase_C46. 1 hit.
PRINTS	PR00632. SONICHHOG.
SMART	SM00305. HintC. 1 hit. SM00306. HintN. 1 hit. [Graphical view]
PROSITE	PS50817. INTEIN_N_TER. 1 hit. [Graphical view]
ProDom	P97812. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

IHH_MOUSE

Accession

Primary (citable) accession number: P97812
Secondary accession number(s): Q61724

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	September 2, 2008
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)