dbPTM

ITCH_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ITCH_MOUSE
UniProt AC	Q8C863
Protein Name	E3 ubiquitin-protein ligase Itchy
Gene Name	Itch
Organism	Mus musculus (Mouse).
Sequence Length	864
Subcellular Localization	Cell membrane Peripheral membrane protein Cytoplasmic side . Cytoplasm . Nucleus . Early endosome membrane Peripheral membrane protein Cytoplasmic side . Endosome membrane Peripheral membrane protein Cytoplasmic side . May be recruited to
Protein Description	Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. [PubMed: 15358865]
Protein Sequence	MSDSGPQLDSMGSLTMKSQLQITVISAKLKENKKNWFGPSPYVEVTVDGQSKKTEKCNNTNSPKWKQPLTVIVTPTSKLCFRVWSHQTLKSDVLLGTAGLDIYETLKSNNMKLEEVVMTLQLVGDKEPTETMGDLSVCLDGLQVEAEVVTNGETSCSESTTQNDDGCRTRDDTRVSTNGSEDPEVAASGENKRANGNNSPSLSNGGFKPSRPPRPSRPPPPTPRRPASVNGSPSTNSDSDGSSTGSLPPTNTNVNTSTSEGATSGLIIPLTISGGSGPRPLNTVSQAPLPPGWEQRVDQHGRVYYVDHVEKRTTWDRPEPLPPGWERRVDNMGRIYYVDHFTRTTTWQRPTLESVRNYEQWQLQRSQLQGAMQQFNQRFIYGNQDLFATSQNKEFDPLGPLPPGWEKRTDSNGRVYFVNHNTRITQWEDPRSQGQLNEKPLPEGWEMRFTVDGIPYFVDHNRRATTYIDPRTGKSALDNGPQIAYVRDFKAKVQYFRFWCQQLAMPQHIKITVTRKTLFEDSFQQIMSFSPQDLRRRLWVIFPGEEGLDYGGVAREWFFLLSHEVLNPMYCLFEYAGKDNYCLQINPASYINPDHLKYFRFIGRFIAMALFHGKFIDTGFSLPFYKRILNKPVGLKDLESIDPEFYNSLIWVKENNIEECGLEMYFSVDKEILGEIKSHDLKPNGGNILVTEENKEEYIRMVAEWRLSRGVEEQTQAFFEGFNEILPQQYLQYFDAKELEVLLCGMQEIDLNDWQRHAIYRHYTRTSKQIMWFWQFVKEIDNEKRMRLLQFVTGTCRLPVGGFADLMGSNGPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGFGQE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSDSGPQLD ------CCCCCCCCC	40.25	-
18	Phosphorylation	MGSLTMKSQLQITVI CCCCCHHHHEEEEEE	25.87	-
26	Phosphorylation	QLQITVISAKLKENK HEEEEEEEHHHHHCC	18.27	-
66	Ubiquitination	NTNSPKWKQPLTVIV CCCCCCCCCCEEEEE	48.43	27667366
173	Phosphorylation	GCRTRDDTRVSTNGS CCCCCCCCCCCCCCC	36.94	30635358
176	Phosphorylation	TRDDTRVSTNGSEDP CCCCCCCCCCCCCCH	16.92	30635358
177	Phosphorylation	RDDTRVSTNGSEDPE CCCCCCCCCCCCCHH	40.52	30635358
180	Phosphorylation	TRVSTNGSEDPEVAA CCCCCCCCCCHHHHC	40.68	23684622
188	Phosphorylation	EDPEVAASGENKRAN CCHHHHCCCCCCCCC	36.58	20531401
192	Ubiquitination	VAASGENKRANGNNS HHCCCCCCCCCCCCC	48.89	27667366
199	Phosphorylation	KRANGNNSPSLSNGG CCCCCCCCCCCCCCC	21.62	16446428
201	Phosphorylation	ANGNNSPSLSNGGFK CCCCCCCCCCCCCCC	44.22	21743459
203	Phosphorylation	GNNSPSLSNGGFKPS CCCCCCCCCCCCCCC	37.45	21743459
222	Phosphorylation	PSRPPPPTPRRPASV CCCCCCCCCCCCCCC	34.89	16446428
232	Phosphorylation	RPASVNGSPSTNSDS CCCCCCCCCCCCCCC	15.52	16446428
311	Ubiquitination	YYVDHVEKRTTWDRP EEEECCCCCCCCCCC	54.69	27667366
346	Phosphorylation	DHFTRTTTWQRPTLE ECCCCCCCCCCCCHH	20.98	-
358	Phosphorylation	TLESVRNYEQWQLQR CHHHHHCHHHHHHHH	10.03	29514104
381	Phosphorylation	QFNQRFIYGNQDLFA HHHHHHHHCCCCCEE	13.81	29514104
393	Ubiquitination	LFATSQNKEFDPLGP CEECCCCCCCCCCCC	52.71	-
407	Ubiquitination	PLPPGWEKRTDSNGR CCCCCCEECCCCCCC	54.83	27667366
411	Phosphorylation	GWEKRTDSNGRVYFV CCEECCCCCCCEEEE	40.34	15971201
425	Phosphorylation	VNHNTRITQWEDPRS EECCCCEEECCCCCC	25.08	15971201
439	Ubiquitination	SQGQLNEKPLPEGWE CCCCCCCCCCCCCCE	51.27	27667366
474	Ubiquitination	YIDPRTGKSALDNGP EECCCCCCCCHHCCC	31.76	27667366
475	Phosphorylation	IDPRTGKSALDNGPQ ECCCCCCCCHHCCCE	35.09	-

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
199	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
199	S	Phosphorylation	Kinase	MK08	Q91Y86	PhosphoELM
222	T	Phosphorylation	Kinase	MAPK8	P45983	GPS
222	T	Phosphorylation	Kinase	MK08	Q91Y86	PhosphoELM
232	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
232	S	Phosphorylation	Kinase	MK08	Q91Y86	PhosphoELM
346	T	Phosphorylation	Kinase	SGK3	Q9ERE3	Uniprot
381	Y	Phosphorylation	Kinase	FYN	P39688	Uniprot
411	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
411	S	Phosphorylation	Kinase	SGK3	Q9ERE3	Uniprot
425	T	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
425	T	Phosphorylation	Kinase	PRKACA	P17612	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Itch	Q8C863	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
63	K	ubiquitylation		-
Autopolyubiquitinated with 'Lys-63' linkages which does not lead to protein degradation.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of ITCH_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
JUNB_MOUSE	Junb	physical	16387660
CFLAR_MOUSE	Cflar	physical	16469705
CYLD_MOUSE	Cyld	physical	22057290
PTN11_MOUSE	Ptpn11	physical	20417562
NFIP1_MOUSE	Ndfip1	physical	17137798
NOTC1_MOUSE	Notch1	physical	10940313
UB2L3_HUMAN	UBE2L3	physical	10940313
TAB1_MOUSE	Tab1	physical	25714464
RORG_MOUSE	Rorc	physical	27322655

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of ITCH_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational change."; Gallagher E., Gao M., Liu Y.C., Karin M.; Proc. Natl. Acad. Sci. U.S.A. 103:1717-1722(2006). Cited for: PHOSPHORYLATION AT SER-199; THR-222 AND SER-232, INTERACTION WITHMAPK8, AUTOUBIQUITINATION, SUBUNIT, AND MUTAGENESIS OF SER-199;THR-222; SER-232 AND 535-ARG--VAL-540.	16446428 [Abstract]

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