P97812 (IHH_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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. Indian hedgehog protein N-product
2. 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 › 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 side By similarity. Note: The N-terminal peptide remains associated with the cell surface By similarity. Indian hedgehog protein C-product: Secreted › extracellular space By 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.
Sequence caution	The sequence AAB49692.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Domain	Signal
Molecular function	Developmental protein Hydrolase Protease
PTM	Autocatalytic cleavage Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	bone resorption Inferred from direct assay. Source: MGI camera-type eye photoreceptor cell fate commitment Inferred from mutant phenotype. Source: MGI cartilage development Inferred from mutant phenotype. Source: MGI cell fate specification Inferred from mutant phenotype. Source: MGI cell maturation Inferred from mutant phenotype. Source: MGI cell-cell signaling Inferred from electronic annotation. Source: InterPro embryonic camera-type eye morphogenesis Inferred from mutant phenotype. Source: MGI embryonic digestive tract morphogenesis Inferred from mutant phenotype. Source: MGI embryonic pattern specification Inferred from mutant phenotype. Source: MGI embryonic skeletal joint development Inferred from mutant phenotype. Source: MGI epithelial cell morphogenesis Inferred from mutant phenotype. Source: MGI epithelial cell-cell adhesion Inferred from mutant phenotype. Source: MGI heart looping Inferred from mutant phenotype. Source: BHF-UCL in utero embryonic development Inferred from mutant phenotype. Source: MGI intein-mediated protein splicing Inferred from electronic annotation. Source: InterPro multicellular organism growth Inferred from mutant phenotype. Source: MGI negative regulation of T cell differentiation in thymus Inferred from mutant phenotype. Source: BHF-UCL negative regulation of alpha-beta T cell differentiation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of eye pigmentation Inferred from mutant phenotype. Source: MGI negative regulation of immature T cell proliferation in thymus Inferred from mutant phenotype. Source: BHF-UCL neuron development Inferred from mutant phenotype. Source: MGI osteoblast differentiation Inferred from mutant phenotype. Source: MGI pancreas development Inferred from mutant phenotype. Source: MGI patterning of blood vessels Inferred from mutant phenotype. Source: MGI positive regulation of T cell differentiation in thymus Inferred from mutant phenotype. Source: BHF-UCL positive regulation of alpha-beta T cell differentiation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of collagen biosynthetic process Inferred from direct assay. Source: MGI positive regulation of mesenchymal cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of smoothened signaling pathway Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of growth Inferred from genetic interaction. Source: MGI retinal pigment epithelium development Inferred from mutant phenotype. Source: MGI smooth muscle tissue development Inferred from mutant phenotype. Source: MGI smoothened signaling pathway Inferred from genetic interaction. Source: MGI somite development Inferred from mutant phenotype. Source: BHF-UCL vitelline membrane formation Inferred from mutant phenotype. Source: MGI
Cellular component	extracellular matrix Inferred from direct assay. Source: MGI extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	patched binding Inferred from physical interaction. Source: BHF-UCL peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 411	384	Indian hedgehog protein		PRO_0000013232
	Chain	28 – 202	175	Indian hedgehog protein N-product		PRO_0000013233
	Chain	203 – 411	209	Indian hedgehog protein C-product		PRO_0000013234
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 [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], 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: 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
EMBL GenBank DDBJ	U85610 mRNA. Translation: AAB49692.1. Different initiation. X76291 mRNA. Translation: CAA53923.1.
IPI	IPI00987856.
PIR	C49425.
RefSeq	NP_034674.1. NM_010544.2.
UniGene	Mm.439736.
3D structure databases
ProteinModelPortal	P97812.
SMR	P97812. Positions 41-197, 203-349.
ModBase	Search...
Protein-protein interaction databases
STRING	P97812.
Protein family/group databases
MEROPS	C46.003.
Proteomic databases
PRIDE	P97812.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006713; ENSMUSP00000006713; ENSMUSG00000006538.
GeneID	16147.
KEGG	mmu:16147.
Organism-specific databases
CTD	3549.
MGI	MGI:96533. Ihh.
Phylogenomic databases
eggNOG	roNOG09706.
HOVERGEN	HBG005480.
InParanoid	P97812.
OrthoDB	EOG46WZ8G.
Gene expression databases
ArrayExpress	P97812.
Bgee	P97812.
Genevestigator	P97812.
GermOnline	ENSMUSG00000006538. Mus musculus.
Family and domain databases
InterPro	IPR009045. Hedgehog/DD-peptidase. IPR003586. Hedgehog_hint_C. IPR003587. Hedgehog_hint_N. IPR000320. Hedgehog_signaling_dom. IPR006141. Intein_splice_site. IPR001657. Peptidase_C46. IPR001767. Peptidase_C46_hint. [Graphical view]
Gene3D	G3DSA:3.30.1380.10. Hedgehog/DD-pept_Zn-bd. 1 hit.
KO	K11989.
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]
SUPFAM	SSF55166. Hedgehog_sig_N. 1 hit.
PROSITE	PS50817. INTEIN_N_TER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	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:	January 25, 2012
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program