EGLN3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: EGLN3_HUMAN
• UniProt AC: Q9H6Z9
• Protein Name: Egl nine homolog 3
• Gene Name: EGLN3
• Organism: Homo sapiens (Human).
• Sequence Length: 239
• Subcellular Localization: Nucleus. Cytoplasm. Colocalizes with WDR83 in the cytoplasm..
• Protein Description: Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferentially recognized via a LXXLAP motif..
• Protein Sequence: MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSKRHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPNGDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTVWYFDAEERAEAKKKFRNLTRKTESALTED

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
48	Ubiquitination	DCVLERVKQLHCTGA HHHHHHHHHHCCCCC	54.05	-
111	Ubiquitination	YCGSRLGKYYVKERS HHCHHHCHHHHHHCC	37.69	-
115	Ubiquitination	RLGKYYVKERSKAMV HHCHHHHHHCCCCEE	31.15	-
130	Phosphorylation	ACYPGNGTGYVRHVD EEECCCCCCEEEECC	29.37	-
159	Ubiquitination	LNKNWDAKLHGGILR ECCCCCCCCCCCEEE	38.24	21890473
172	Ubiquitination	LRIFPEGKSFIADVE EEECCCCCCCEEECH	40.30	2190698
206	Phosphorylation	QPSYATRYAMTVWYF CCCHHHHHEEEEEEE	9.07	22964224
209	Phosphorylation	YATRYAMTVWYFDAE HHHHHEEEEEEECHH	10.34	22964224
212	Phosphorylation	RYAMTVWYFDAEERA HHEEEEEEECHHHHH	6.30	22964224

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	SIAH2	O43255	PMID:16958618
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH1	Q8IUQ4	PMID:17047048

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of EGLN3_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 EGLN3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MYOG_MOUSE	Myog	physical	17344222
SIAH2_HUMAN	SIAH2	physical	16958618
EGLN1_HUMAN	EGLN1	physical	16958618
EGLN3_HUMAN	EGLN3	physical	16958618
EGLN2_HUMAN	EGLN2	physical	16958618
PRP19_HUMAN	PRPF19	physical	20599946
ADRB2_HUMAN	ADRB2	physical	19584355
SPY2_HUMAN	SPRY2	physical	22006925
SIAH2_HUMAN	SIAH2	physical	15210114
EPAS1_HUMAN	EPAS1	physical	17684156
ATF4_HUMAN	ATF4	physical	17684156
MAGAB_HUMAN	MAGEA11	physical	19147576
NEMO_HUMAN	IKBKG	physical	23732909
IKKA_HUMAN	CHUK	physical	23732909
IKKB_HUMAN	IKBKB	physical	23732909
MK01_HUMAN	MAPK1	physical	21988832
MK06_HUMAN	MAPK6	physical	21988832
MK07_HUMAN	MAPK7	physical	21988832
SQSTM_HUMAN	SQSTM1	physical	23345396
TT23L_HUMAN	TTC23L	physical	25416956
HIF1A_HUMAN	HIF1A	physical	23345396
BIRC2_HUMAN	BIRC2	physical	26612615
BIRC3_HUMAN	BIRC3	physical	26612615
RIPK1_HUMAN	RIPK1	physical	26612615

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
• DB00126: Vitamin C