dbPTM

EPAS1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	EPAS1_MOUSE
UniProt AC	P97481
Protein Name	Endothelial PAS domain-containing protein 1
Gene Name	Epas1
Organism	Mus musculus (Mouse).
Sequence Length	874
Subcellular Localization	Nucleus . Nucleus speckle . Colocalizes with HIF3A isoform 2 in the nucleus and speckles.
Protein Description	Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. [PubMed: 26245371 Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity]
Protein Sequence	MTADKEKKRSSSELRKEKSRDAARCRRSKETEVFYELAHELPLPHSVSSHLDKASIMRLAISFLRTHKLLSSVCSENESEAEADQQMDNLYLKALEGFIAVVTQDGDMIFLSENISKFMGLTQVELTGHSIFDFTHPCDHEEIRENLTLKNGSGFGKKSKDVSTERDFFMRMKCTVTNRGRTVNLKSATWKVLHCTGQVRVYNNCPPHSSLCGSKEPLLSCLIIMCEPIQHPSHMDIPLDSKTFLSRHSMDMKFTYCDDRILELIGYHPEELLGRSAYEFYHALDSENMTKSHQNLCTKGQVVSGQYRMLAKHGGYVWLETQGTVIYNPRNLQPQCIMCVNYVLSEIEKNDVVFSMDQTESLFKPHLMAMNSIFDSSDDVAVTEKSNYLFTKLKEEPEELAQLAPTPGDAIISLDFGSQNFDEPSAYGKAILPPGQPWVSGLRSHSAQSESGSLPAFTVPQADTPGNTTPSASSSSSCSTPSSPEDYYSSLENPLKIEVIEKLFAMDTEPRDPGSTQTDFSELDLETLAPYIPMDGEDFQLSPICPEEPLMPESPQPTPQHCFSTMTSIFQPLTPGATHGPFFLDKYPQQLESRKTESEHWPMSSIFFDAGSKGSLSPCCGQASTPLSSMGGRSNTQWPPDPPLHFGPTKWPVGDQSAESLGALPVGSSQLEPPSAPPHVSMFKMRSAKDFGARGPYMMSPAMIALSNKLKLKRQLEYEEQAFQDTSGGDPPGTSSSHLMWKRMKSLMGGTCPLMPDKTISANMAPDEFTQKSMRGLGQPLRHLPPPQPPSTRSSGENAKTGFPPQCYASQFQDYGPPGAQKVSGVASRLLGPSFEPYLLPELTRYDCEVNVPVPGSSTLLQGRDLLRALDQAT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
10	Phosphorylation	ADKEKKRSSSELRKE CHHHHHCCHHHHHHH	47.28	23832136
12	Phosphorylation	KEKKRSSSELRKEKS HHHHCCHHHHHHHHH	41.73	22802335
28	Phosphorylation	DAARCRRSKETEVFY HHHHHHHHHHHHHHH	18.58	-
31	Phosphorylation	RCRRSKETEVFYELA HHHHHHHHHHHHHHH	40.98	-
62	Phosphorylation	SIMRLAISFLRTHKL HHHHHHHHHHHHHHH	16.78	27841257
79	Phosphorylation	SVCSENESEAEADQQ HHCCCCCCHHHHHHH	54.40	22802335
91	Phosphorylation	DQQMDNLYLKALEGF HHHHHHHHHHHHCCC	16.65	22802335
103	Phosphorylation	EGFIAVVTQDGDMIF CCCEEEECCCCCEEE	17.84	22802335
112	Phosphorylation	DGDMIFLSENISKFM CCCEEEEECCHHHHH	20.18	22802335
247	Methylation	DSKTFLSRHSMDMKF CCCHHHHHHCCCCEE	28.22	58857815
405	Hydroxylation	EELAQLAPTPGDAII HHHHHHCCCCCCEEE	47.95	-
530	Hydroxylation	LDLETLAPYIPMDGE CCHHHHCCCCCCCCC	30.60	-
834	Phosphorylation	ASRLLGPSFEPYLLP HHHHHCCCCCCCCCH	40.21	11983697
844	Phosphorylation	PYLLPELTRYDCEVN CCCCHHCCCCEEEEC	26.06	11983697
846	Phosphorylation	LLPELTRYDCEVNVP CCHHCCCCEEEECCC	21.51	11983697
851	Hydroxylation	TRYDCEVNVPVPGSS CCCEEEECCCCCCCC	15.30	11823643
857	Phosphorylation	VNVPVPGSSTLLQGR ECCCCCCCCHHHCHH	17.68	11983697

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
-	K	Ubiquitination	E3 ubiquitin ligase	Vhl	P40338	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
405	P	Hydroxylation	-
In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3.
530	P	Hydroxylation	12080085
In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3.
851	N	Hydroxylation	12080085
In normoxia, is hydroxylated on Asn-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.

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 EPAS1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
VHL_MOUSE	Vhl	physical	20211142

Drug and Disease Associations

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

Regulatory Network of EPAS1_MOUSE

Related Literatures of Post-Translational Modification

Hydroxylation
Reference	PubMed
"Asparagine hydroxylation of the HIF transactivation domain a hypoxicswitch."; Lando D., Peet D.J., Whelan D.A., Gorman J.J., Whitelaw M.L.; Science 295:858-861(2002). Cited for: HYDROXYLATION AT ASN-851.	11823643 [Abstract]
Phosphorylation
Reference	PubMed
"The transcriptional activation function of the HIF-like factorrequires phosphorylation at a conserved threonine."; Gradin K., Takasaki C., Fujii-Kuriyama Y., Sogawa K.; J. Biol. Chem. 277:23508-23514(2002). Cited for: INTERACTION WITH CREBBP, PHOSPHORYLATION AT THR-844, AND MUTAGENESISOF THR-844.	11983697 [Abstract]

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