ID   SHH_CHICK               Reviewed;         425 AA.
AC   Q91035;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   13-OCT-2009, entry version 77.
DE   RecName: Full=Sonic hedgehog protein;
DE            Short=SHH;
DE   Contains:
DE     RecName: Full=Sonic hedgehog protein N-product;
DE   Contains:
DE     RecName: Full=Sonic hedgehog protein C-product;
DE   Flags: Precursor;
GN   Name=SHH;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves;
OC   Neognathae; Galliformes; Phasianidae; Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Limb bud;
RX   MEDLINE=94094333; PubMed=8269518; DOI=10.1016/0092-8674(93)90626-2;
RA   Riddle R.D., Johnson R.L., Laufer E., Tabin C.;
RT   "Sonic hedgehog mediates the polarizing activity of the ZPA.";
RL   Cell 75:1401-1416(1993).
RN   [2]
RP   FUNCTION, AND AUTOPROTEOLYTIC CLEAVAGE.
RX   MEDLINE=95254654; PubMed=7736596; DOI=10.1016/0092-8674(95)90397-6;
RA   Roelink H., Porter J.A., Chiang C., Tanabe Y., Chang D.T.,
RA   Beachy P.A., Jessell T.M.;
RT   "Floor plate and motor neuron induction by different concentrations of
RT   the amino-terminal cleavage product of sonic hedgehog
RT   autoproteolysis.";
RL   Cell 81:445-455(1995).
CC   -!- FUNCTION: Binds to the patched (PTC) receptor, which functions in
CC       association with smoothened (SMO), to activate the transcription
CC       of target genes. In the absence of SHH, PTC represses the
CC       constitutive signaling activity of SMO. Also regulates another
CC       target, the gli oncogene. Intercellular signal essential for a
CC       variety of patterning events during development: signal produced
CC       by the notochord that induces ventral cell fate in the neural tube
CC       and somites, and the polarizing signal for patterning of the
CC       anterior-posterior axis of the developing limb bud. Displays both
CC       floor plate- and motor neuron-inducing activity. The threshold
CC       concentration of N-product required for motor neuron induction is
CC       5-fold lower than that required for floor plate induction.
CC   -!- SUBUNIT: N-product is active as a multimer (By similarity).
CC   -!- SUBCELLULAR LOCATION: Sonic hedgehog protein C-product: Secreted,
CC       extracellular space (By similarity). Note=The C-terminal peptide
CC       diffuses from the cell (By similarity).
CC   -!- SUBCELLULAR LOCATION: Sonic hedgehog protein N-product: Cell
CC       membrane; Lipid-anchor (By similarity). Note=The N-product either
CC       remains associated with lipid rafts at the cell surface, or forms
CC       freely diffusible active multimers with its hydrophobic lipid-
CC       modified N- and C-termini buried inside (By similarity).
CC   -!- TISSUE SPECIFICITY: Expressed in the posterior limb bud
CC       mesenchyme, the Hensen node, the notochord, and the floor plate of
CC       the neural tube.
CC   -!- DEVELOPMENTAL STAGE: First detectable at stage 17 during the
CC       initiation of limb bud formation. From that point onwards, the
CC       expression pattern exactly matches the location of the zone of
CC       polarizing activity (ZPA).
CC   -!- INDUCTION: By retinoic acid.
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.
CC   -!- PTM: Cholesterylation is required for N-product targeting to lipid
CC       rafts and multimerization (By similarity).
CC   -!- PTM: N-palmitoylation of Cys-27 by HHAT is required for N-product
CC       multimerization and full activity (By similarity).
CC   -!- SIMILARITY: Belongs to the hedgehog family.
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DR   EMBL; L28099; AAA72428.1; -; mRNA.
DR   IPI; IPI00604018; -.
DR   PIR; A49424; A49424.
DR   RefSeq; NP_990152.1; -.
DR   UniGene; Gga.345; -.
DR   HSSP; Q62226; 1VHH.
DR   SMR; Q91035; 41-197.
DR   STRING; Q91035; -.
DR   MEROPS; C46.002; -.
DR   PRIDE; Q91035; -.
DR   Ensembl; ENSGALT00000010306; ENSGALP00000010292; ENSGALG00000006379; Gallus gallus.
DR   GeneID; 395615; -.
DR   KEGG; gga:395615; -.
DR   CTD; 395615; -.
DR   HOGENOM; Q91035; -.
DR   HOVERGEN; Q91035; -.
DR   GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR   GO; GO:0016015; F:morphogen activity; NAS:Roslin.
DR   GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0042733; P:embryonic digit morphogenesis; IMP:Roslin.
DR   GO; GO:0008624; P:induction of apoptosis by extracellular sig...; IDA:Roslin.
DR   GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR   GO; GO:0043066; P:negative regulation of apoptosis; IDA:Roslin.
DR   GO; GO:0009949; P:polarity specification of anterior/posterio...; IMP:Roslin.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   GO; GO:0032526; P:response to retinoic acid; IDA:Roslin.
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   Hydrolase; Lipoprotein; Membrane; Palmitate; Protease; Secreted;
KW   Signal.
FT   SIGNAL        1     26       Potential.
FT   CHAIN        27    425       Sonic hedgehog protein.
FT                                /FTId=PRO_0000013217.
FT   CHAIN        27    200       Sonic hedgehog protein N-product.
FT                                /FTId=PRO_0000013218.
FT   CHAIN       201    425       Sonic hedgehog protein C-product.
FT                                /FTId=PRO_0000013219.
FT   COMPBIAS    390    393       Poly-Thr.
FT   SITE        200    201       Cleavage; by autolysis (Probable).
FT   SITE        246    246       Involved in cholesterol transfer (By
FT                                similarity).
FT   SITE        270    270       Involved in auto-cleavage (By
FT                                similarity).
FT   SITE        273    273       Essential for auto-cleavage (By
FT                                similarity).
FT   LIPID        27     27       N-palmitoyl cysteine (By similarity).
FT   LIPID       200    200       Cholesterol glycine ester (By
FT                                similarity).
SQ   SEQUENCE   425 AA;  46474 MW;  DA9627443D4A0173 CRC64;
     MVEMLLLTRI LLVGFICALL VSSGLTCGPG RGIGKRRHPK KLTPLAYKQF IPNVAEKTLG
     ASGRYEGKIT RNSERFKELT PNYNPDIIFK DEENTGADRL MTQRCKDKLN ALAISVMNQW
     PGVKLRVTEG WDEDGHHSEE SLHYEGRAVD ITTSDRDRSK YGMLARLAVE AGFDWVYYES
     KAHIHCSVKA ENSVAAKSGG CFPGSATVHL EHGGTKLVKD LSPGDRVLAA DADGRLLYSD
     FLTFLDRMDS SRKLFYVIET RQPRARLLLT AAHLLFVAPQ HNQSEATGST SGQALFASNV
     KPGQRVYVLG EGGQQLLPAS VHSVSLREEA SGAYAPLTAQ GTILINRVLA SCYAVIEEHS
     WAHWAFAPFR LAQGLLAALC PDGAIPTAAT TTTGIHWYSR LLYRIGSWVL DGDALHPLGM
     VAPAS
//