SHH_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SHH_HUMAN
• UniProt AC: Q15465
• Protein Name: Sonic hedgehog protein
• Gene Name: SHH {ECO:0000312|HGNC:HGNC:10848}
• Organism: Homo sapiens (Human).
• Sequence Length: 462
• Subcellular Localization: Sonic hedgehog protein N-product: Cell membrane ; Lipid-anchor . The dual-lipidated sonic hedgehog protein N-product (ShhNp) is firmly tethered to the cell membrane where it forms multimers (PubMed:24522195). Further solubilization and release from t
• Protein Description: Sonic hedgehog protein: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).; Sonic hedgehog protein N-product: The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites. [PubMed: 24863049 Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity Essential for axon guidance (By similarity Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes]
• Protein Sequence: MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
24	N-palmitoylation	LVCSGLACGPGRGFG HHHCCCCCCCCCCCC	8.98	9593755
32	Acetylation	GPGRGFGKRRHPKKL CCCCCCCCCCCCCCC	43.95	7367451
37	Acetylation	FGKRRHPKKLTPLAY CCCCCCCCCCCHHHH	55.05	7367461
197	Cholesterol ester	SVAAKSGGCFPGSAT CCCCCCCCCCCCCEE	19.58	-
253	Phosphorylation	DGAKKVFYVIETREP CCCEEEEEEEECCCH	11.96	-
278	N-linked_Glycosylation	LLFVAPHNDSATGEP HHHHCCCCCCCCCCC	43.82	16335952
316	Phosphorylation	VRPGQRVYVVAERDG CCCCCEEEEEEEECC	7.44	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of SHH_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SHH_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of SHH_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SHH_HUMAN	SHH	physical	11395778
DERL1_HUMAN	DERL1	physical	23867461
DERL2_HUMAN	DERL2	physical	23867461
EDEM1_HUMAN	EDEM1	physical	24910992
EDEM2_HUMAN	EDEM2	physical	24910992
EDEM3_HUMAN	EDEM3	physical	24910992

Drug and Disease Associations

• Kegg Disease
• H00039: Basal cell carcinoma
• H00267: Holoprosencephaly (HPE)
• H00652: Solitary median maxillary central incisor syndrome
• H01027: Anophthalmia and microphthalmia (A/M)
• H01160: Schizencephaly
• OMIM Disease
• 611638: Microphthalmia, isolated, with coloboma, 5 (MCOPCB5)
• 142945: Holoprosencephaly 3 (HPE3)
• 147250: Solitary median maxillary central incisor (SMMCI)
• 174500: Triphalangeal thumb-polysyndactyly syndrome (TPTPS)
• 174500: Preaxial polydactyly 2 (PPD2)
• 188740: Hypoplasia or aplasia of tibia with polydactyly (THYP)
• 135750: Laurin-Sandrow syndrome (LSS)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278, AND MASSSPECTROMETRY.
PubMed: 16335952

Palmitoylation

"Identification of a palmitic acid-modified form of human Sonichedgehog.";
Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P.,Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R.,Wang E.A., Galdes A.;
J. Biol. Chem. 273:14037-14045(1998).
Cited for: PROTEIN SEQUENCE OF 24-32, PALMITOYLATION AT CYS-24, CHOLESTERYLATION,MUTAGENESIS OF CYS-24, AND MASS SPECTROMETRY.
PubMed: 9593755