SIX3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SIX3_HUMAN
• UniProt AC: O95343
• Protein Name: Homeobox protein SIX3
• Gene Name: SIX3
• Organism: Homo sapiens (Human).
• Sequence Length: 332
• Subcellular Localization: Nucleus .
• Protein Description: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is AES and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 functions also in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway..
• Protein Sequence: MVFRSPLDLYSSHFLLPNFADSHHRSILLASSGGGNGAGGGGGAGGGSGGGNGAGGGGAGGAGGGGGGGSRAPPEELSMFQLPTLNFSPEQVASVCETLEETGDIERLGRFLWSLPVAPGACEAINKHESILRARAVVAFHTGNFRDLYHILENHKFTKESHGKLQAMWLEAHYQEAEKLRGRPLGPVDKYRVRKKFPLPRTIWDGEQKTHCFKERTRSLLREWYLQDPYPNPSKKRELAQATGLTPTQVGNWFKNRRQRDRAAAAKNRLQHQAIGPSGMRSLAEPGCPTHGSAESPSTAASPTTSVSSLTERADTGTSILSVTSSDSECDV

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
26	Phosphorylation	FADSHHRSILLASSG CCCCCCCCEEEEECC	17.15	25954137
31	Phosphorylation	HRSILLASSGGGNGA CCCEEEEECCCCCCC	29.50	25954137
32	Phosphorylation	RSILLASSGGGNGAG CCEEEEECCCCCCCC	35.53	25954137
48	Phosphorylation	GGGAGGGSGGGNGAG CCCCCCCCCCCCCCC	37.22	-
149	Phosphorylation	TGNFRDLYHILENHK CCCHHHHHHHHHHCC	7.36	-
158	Phosphorylation	ILENHKFTKESHGKL HHHHCCCCHHHHHHH	38.41	-
190	Ubiquitination	RPLGPVDKYRVRKKF CCCCCCCHHCCCCCC	34.88	29967540
209	Ubiquitination	TIWDGEQKTHCFKER CCCCCCCCCHHHHHH	35.61	-
214	Ubiquitination	EQKTHCFKERTRSLL CCCCHHHHHHHHHHH	52.24	-
225	Phosphorylation	RSLLREWYLQDPYPN HHHHHHHHHHCCCCC	6.96	22461510
230	Phosphorylation	EWYLQDPYPNPSKKR HHHHHCCCCCHHHHH	24.75	-
234	Phosphorylation	QDPYPNPSKKRELAQ HCCCCCHHHHHHHHH	58.40	-
282	Phosphorylation	IGPSGMRSLAEPGCP CCCCHHHHHCCCCCC	24.04	27732954
290	Phosphorylation	LAEPGCPTHGSAESP HCCCCCCCCCCCCCC	42.84	28450419
293	Phosphorylation	PGCPTHGSAESPSTA CCCCCCCCCCCCCCC	22.66	30108239
296	Phosphorylation	PTHGSAESPSTAASP CCCCCCCCCCCCCCC	24.70	28450419
298	Phosphorylation	HGSAESPSTAASPTT CCCCCCCCCCCCCCC	39.70	28450419
299	Phosphorylation	GSAESPSTAASPTTS CCCCCCCCCCCCCCC	29.63	28450419
302	Phosphorylation	ESPSTAASPTTSVSS CCCCCCCCCCCCHHH	21.95	28450419
304	Phosphorylation	PSTAASPTTSVSSLT CCCCCCCCCCHHHHH	29.25	28450419
305	Phosphorylation	STAASPTTSVSSLTE CCCCCCCCCHHHHHH	30.43	28450419
306	Phosphorylation	TAASPTTSVSSLTER CCCCCCCCHHHHHHC	23.60	28450419
308	Phosphorylation	ASPTTSVSSLTERAD CCCCCCHHHHHHCCC	21.28	30108239
309	Phosphorylation	SPTTSVSSLTERADT CCCCCHHHHHHCCCC	36.84	28450419
311	Phosphorylation	TTSVSSLTERADTGT CCCHHHHHHCCCCCC	25.93	30108239
316	Phosphorylation	SLTERADTGTSILSV HHHHCCCCCCEEEEE	41.18	27732954
318	Phosphorylation	TERADTGTSILSVTS HHCCCCCCEEEEEEC	18.06	27732954
319	Phosphorylation	ERADTGTSILSVTSS HCCCCCCEEEEEECC	23.91	27732954
322	Phosphorylation	DTGTSILSVTSSDSE CCCCEEEEEECCCCC	22.98	27732954
324	Phosphorylation	GTSILSVTSSDSECD CCEEEEEECCCCCCC	21.09	27732954
325	Phosphorylation	TSILSVTSSDSECDV CEEEEEECCCCCCCC	29.96	27732954
326	Phosphorylation	SILSVTSSDSECDV- EEEEEECCCCCCCC-	35.47	27732954
328	Phosphorylation	LSVTSSDSECDV--- EEEECCCCCCCC---	41.91	27732954

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

Oops, there are no upstream regulatory protein records of SIX3_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SIX3_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 SIX3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TLE1_HUMAN	TLE1	physical	12441302
AES_HUMAN	AES	physical	12441302
NR4A3_HUMAN	NR4A3	physical	12543801
MTA1_HUMAN	MTA1	physical	20682799

Drug and Disease Associations

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