Reviewed, UniProtKB/Swiss-Prot Q91035 (SHH_CHICK)

Names and origin

Protein names

Recommended name:
    Sonic hedgehog protein
      Short name=SHH
Cleaved into the following 2 chains:
    1- Recommended name:
            Sonic hedgehog protein N-product
    2- Recommended name:
            Sonic hedgehog protein C-product

Gene names

Name:

SHH

Organism

Gallus gallus (Chicken)

Taxonomic identifier

9031 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galliformes › Phasianidae › Phasianinae › Gallus

Protein attributes

Sequence length	425 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	Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction.
Subunit structure	N-product is active as a multimer By similarity.
Subcellular location	Sonic hedgehog protein C-product: Secreted › extracellular spaceBy similarity. Note= The C-terminal peptide diffuses from the cell By similarity. Sonic hedgehog protein N-product: Cell membrane; Lipid-anchorBy similarity. Note= The N-product either remains associated with lipid rafts at the cell surface, or forms freely diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside By similarity.
Tissue specificity	Expressed in the posterior limb bud mesenchyme, the Hensen node, the notochord, and the floor plate of the neural tube.
Developmental stage	First detectable at stage 17 during the initiation of limb bud formation. From that point onwards, the expression pattern exactly matches the location of the zone of polarizing activity (ZPA).
Induction	By retinoic acid.
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. Cholesterylation is required for N-product targeting to lipid rafts and multimerization By similarity. N-palmitoylation of Cys-27 by HHAT 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 Lipoprotein Palmitate
Gene Ontology (GO)
Biological process	embryonic digit morphogenesis Inferred from mutant phenotype. Source: Roslin induction of apoptosis by extracellular signals Inferred from direct assay. Source: Roslin intein-mediated protein splicing Inferred from electronic annotation. Source: InterPro negative regulation of apoptosis Inferred from direct assay. Source: Roslin polarity specification of anterior/posterior axis Inferred from mutant phenotype. Source: Roslin response to retinoic acid Ref.1 Inferred from direct assay. Source: Roslin
Cellular component	plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	morphogen activity Ref.1 Non-traceable author statement. Source: Roslin peptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 425	399	Sonic hedgehog protein		PRO_0000013217
	Chain	27 – 200	174	Sonic hedgehog protein N-product		PRO_0000013218
	Chain	201 – 425	225	Sonic hedgehog protein C-product		PRO_0000013219
Regions
	Compositional bias	390 – 393	4	Poly-Thr
Sites
	Site	200 – 201	2	Cleavage; by autolysis Probable
	Site	246	1	Involved in cholesterol transfer By similarity
	Site	270	1	Involved in auto-cleavage By similarity
	Site	273	1	Essential for auto-cleavage By similarity
Amino acid modifications
	Lipidation	27	1	N-palmitoyl cysteine By similarity
	Lipidation	200	1	Cholesterol glycine ester By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q91035-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: DA9627443D4A0173	FASTA	425	46,474
	10 20 30 40 50 60 MVEMLLLTRI LLVGFICALL VSSGLTCGPG RGIGKRRHPK KLTPLAYKQF IPNVAEKTLG 70 80 90 100 110 120 ASGRYEGKIT RNSERFKELT PNYNPDIIFK DEENTGADRL MTQRCKDKLN ALAISVMNQW 130 140 150 160 170 180 PGVKLRVTEG WDEDGHHSEE SLHYEGRAVD ITTSDRDRSK YGMLARLAVE AGFDWVYYES 190 200 210 220 230 240 KAHIHCSVKA ENSVAAKSGG CFPGSATVHL EHGGTKLVKD LSPGDRVLAA DADGRLLYSD 250 260 270 280 290 300 FLTFLDRMDS SRKLFYVIET RQPRARLLLT AAHLLFVAPQ HNQSEATGST SGQALFASNV 310 320 330 340 350 360 KPGQRVYVLG EGGQQLLPAS VHSVSLREEA SGAYAPLTAQ GTILINRVLA SCYAVIEEHS 370 380 390 400 410 420 WAHWAFAPFR LAQGLLAALC PDGAIPTAAT TTTGIHWYSR LLYRIGSWVL DGDALHPLGM VAPAS

References

[1]	"Sonic hedgehog mediates the polarizing activity of the ZPA." Riddle R.D., Johnson R.L., Laufer E., Tabin C. Cell 75:1401-1416(1993) [PubMed: 8269518] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Limb bud.
[2]	"Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis." Roelink H., Porter J.A., Chiang C., Tanabe Y., Chang D.T., Beachy P.A., Jessell T.M. Cell 81:445-455(1995) [PubMed: 7736596] [Abstract] Cited for: FUNCTION, AUTOPROTEOLYTIC CLEAVAGE.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L28099 mRNA. Translation: AAA72428.1.
PIR	A49424.
RefSeq	NP_990152.1.
UniGene	Gga.345
3D structure databases
HSSP	HSSP built from PDB template 1VHH based on UniProtKB Q62226.
SMR	Q91035. Positions 41-197.
ModBase	Search...
Protein family/group databases
MEROPS	C46.002.
Genome annotation databases
Ensembl	ENSGALG00000006379. Gallus gallus. [Contig view]
GeneID	395615.
KEGG	gga:395615.
Phylogenomic databases
HOGENOM	Q91035.
HOVERGEN	Q91035.
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]
ProtoNet	Search...

Entry information

Entry name

SHH_CHICK

Accession

Primary (citable) accession number: Q91035

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 71 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)