SIX4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SIX4_HUMAN
• UniProt AC: Q9UIU6
• Protein Name: Homeobox protein SIX4
• Gene Name: SIX4
• Organism: Homo sapiens (Human).
• Sequence Length: 781
• Subcellular Localization: Nucleus . Cytoplasm .
• Protein Description: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer. Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein. Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1. Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6. Controls somitic differentiation in myocyte through MYOG transactivation. Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3. Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes. During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression. During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression. Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation. During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation. Promotes survival of sensory neurons during early trigeminal gangliogenesis. In the developing dorsal root ganglia, up-regulates SLC12A2 transcription. Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression. Forms gustatory papillae during development of the tongue. Also plays a role during embryonic cranial skeleton morphogenesis..
• Protein Sequence: MSSSSPTGQIASAADIKQENGMESASEGQEAHREVAGGAAVGLSPPAPAPFPLEPGDAATAAARVSGEEGAVAAAAAGAAADQVQLHSELLGRHHHAAAAAAQTPLAFSPDHVACVCEALQQGGNLDRLARFLWSLPQSDLLRGNESLLKARALVAFHQGIYPELYSILESHSFESANHPLLQQLWYKARYTEAERARGRPLGAVDKYRLRRKFPLPRTIWDGEETVYCFKEKSRNALKELYKQNRYPSPAEKRHLAKITGLSLTQVSNWFKNRRQRDRNPSETQSKSESDGNPSTEDESSKGHEDLSPHPLSSSSDGITNLSLSSHMEPVYMQQIGNAKISLSSSGVLLNGSLVPASTSPVFLNGNSFIQGPSGVILNGLNVGNTQAVALNPPKMSSNIVSNGISMTDILGSTSQDVKEFKVLQSSANSATTTSYSPSVPVSFPGLIPSTEVKREGIQTVASQDGGSVVTFTTPVQINQYGIVQIPNSGANSQFLNGSIGFSPLQLPPVSVAASQGNISVSSSTSDGSTFTSESTTVQQGKVFLSSLAPSAVVYTVPNTGQTIGSVKQEGLERSLVFSQLMPVNQNAQVNANLSSENISGSGLHPLASSLVNVSPTHNFSLSPSTLLNPTELNRDIADSQPMSAPVASKSTVTSVSNTNYATLQNCSLITGQDLLSVPMTQAALGEIVPTAEDQVGHPSPAVHQDFVQEHRLVLQSVANMKENFLSNSESKATSSLMMLDSKSKYVLDGMVDTVCEDLETDKKELAKLQTVQLDEDMQDL

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
2	Phosphorylation	------MSSSSPTGQ ------CCCCCCCCC	38.64	22199227
2	Acetylation	------MSSSSPTGQ ------CCCCCCCCC	38.64	21406692
3	Phosphorylation	-----MSSSSPTGQI -----CCCCCCCCCC	33.27	25159151
4	Phosphorylation	----MSSSSPTGQIA ----CCCCCCCCCCC	32.79	22199227
5	Phosphorylation	---MSSSSPTGQIAS ---CCCCCCCCCCCC	28.56	25159151
7	Phosphorylation	-MSSSSPTGQIASAA -CCCCCCCCCCCCHH	43.60	22199227
12	Phosphorylation	SPTGQIASAADIKQE CCCCCCCCHHHHHHH	26.14	20860994
17	Sumoylation	IASAADIKQENGMES CCCHHHHHHHHCCCC	52.70	-
24	Phosphorylation	KQENGMESASEGQEA HHHHCCCCCCHHHHH	28.36	20860994
26	Phosphorylation	ENGMESASEGQEAHR HHCCCCCCHHHHHHH	52.09	20860994
44	Phosphorylation	GGAAVGLSPPAPAPF CCCCCCCCCCCCCCC	23.94	30278072
147	Phosphorylation	DLLRGNESLLKARAL HHCCCCHHHHHHHHH	42.89	24719451
162	Phosphorylation	VAFHQGIYPELYSIL HHHHCCCCHHHHHHH	9.47	-
198	Methylation	YTEAERARGRPLGAV HHHHHHHCCCCCCCC	48.12	54559319
200	Methylation	EAERARGRPLGAVDK HHHHHCCCCCCCCCH	20.09	115917001
249	Phosphorylation	YKQNRYPSPAEKRHL HHCCCCCCHHHHHHH	28.01	25159151
286	Phosphorylation	RNPSETQSKSESDGN CCHHHHCCCCCCCCC	45.64	22496350
288	Phosphorylation	PSETQSKSESDGNPS HHHHCCCCCCCCCCC	47.80	20860994
290	Phosphorylation	ETQSKSESDGNPSTE HHCCCCCCCCCCCCC	58.89	21406692
295	Phosphorylation	SESDGNPSTEDESSK CCCCCCCCCCCCCCC	48.72	29449344
296	Phosphorylation	ESDGNPSTEDESSKG CCCCCCCCCCCCCCC	49.03	25849741
300	Phosphorylation	NPSTEDESSKGHEDL CCCCCCCCCCCCCCC	50.07	29449344
301	Phosphorylation	PSTEDESSKGHEDLS CCCCCCCCCCCCCCC	40.38	29449344
308	Phosphorylation	SKGHEDLSPHPLSSS CCCCCCCCCCCCCCC	33.22	27251275
313	Phosphorylation	DLSPHPLSSSSDGIT CCCCCCCCCCCCCCC	32.40	28348404
314	Phosphorylation	LSPHPLSSSSDGITN CCCCCCCCCCCCCCC	41.36	28348404
315	Phosphorylation	SPHPLSSSSDGITNL CCCCCCCCCCCCCCC	29.13	28348404
316	Phosphorylation	PHPLSSSSDGITNLS CCCCCCCCCCCCCCC	41.63	28348404
434	Phosphorylation	SANSATTTSYSPSVP CCCCCCCCCCCCCCC	22.70	-
437	Phosphorylation	SATTTSYSPSVPVSF CCCCCCCCCCCCCCC	15.51	-
439	Phosphorylation	TTTSYSPSVPVSFPG CCCCCCCCCCCCCCC	32.86	-
443	Phosphorylation	YSPSVPVSFPGLIPS CCCCCCCCCCCCCCC	21.47	-
451	Phosphorylation	FPGLIPSTEVKREGI CCCCCCCCCCCCCCC	39.17	-
454	Sumoylation	LIPSTEVKREGIQTV CCCCCCCCCCCCEEE	38.20	-
555	Phosphorylation	LAPSAVVYTVPNTGQ CCCCEEEEECCCCCC	8.74	27642862
568	Sumoylation	GQTIGSVKQEGLERS CCCCCCCCHHCHHHE	44.31	-
619	Phosphorylation	VNVSPTHNFSLSPST CCCCCCCCCCCCHHH	30.58	17525332
640	Phosphorylation	LNRDIADSQPMSAPV HCCCCCCCCCCCCCC	27.45	17525332
644	Phosphorylation	IADSQPMSAPVASKS CCCCCCCCCCCCCCC	35.78	28555341
649	O-linked_Glycosylation	PMSAPVASKSTVTSV CCCCCCCCCCEEEEE	27.63	30059200
727	Phosphorylation	NMKENFLSNSESKAT HHHHHHHCCCCCHHC	33.89	29083192
729	Phosphorylation	KENFLSNSESKATSS HHHHHCCCCCHHCHH	39.61	29083192
731	Phosphorylation	NFLSNSESKATSSLM HHHCCCCCHHCHHEE	27.66	29083192
736	Phosphorylation	SESKATSSLMMLDSK CCCHHCHHEECCCCC	18.87	28555341

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

Oops, there are no upstream regulatory protein records of SIX4_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of SIX4_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 SIX4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TCOF_HUMAN	TCOF1	physical	22939629

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• 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

Phosphorylation

"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage.";
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
Science 316:1160-1166(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-640, AND MASSSPECTROMETRY.
PubMed: 17525332