EGLN2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: EGLN2_HUMAN
• UniProt AC: Q96KS0
• Protein Name: Egl nine homolog 2 {ECO:0000305}
• Gene Name: EGLN2 {ECO:0000312|HGNC:HGNC:14660}
• Organism: Homo sapiens (Human).
• Sequence Length: 407
• Subcellular Localization: Nucleus .
• 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. 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. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death. Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation. Hydroxylates IKBKB, mediating NF-kappaB activation in hypoxic conditions. Target proteins are preferentially recognized via a LXXLAP motif..
• Protein Sequence: MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEASAGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEAPKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAPERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPPRSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGNGLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLLIFWSDRRNPHEVKPAYATRYAITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTPT

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
67	Phosphorylation	GSGTPRATATSTTAS CCCCCCCCCEECCCC	31.57	28348404
69	Phosphorylation	GTPRATATSTTASPL CCCCCCCEECCCCCC	23.42	28348404
70	Phosphorylation	TPRATATSTTASPLR CCCCCCEECCCCCCC	22.69	28348404
71	Phosphorylation	PRATATSTTASPLRD CCCCCEECCCCCCCC	23.25	22210691
72	Phosphorylation	RATATSTTASPLRDG CCCCEECCCCCCCCC	25.55	28348404
74	Phosphorylation	TATSTTASPLRDGFG CCEECCCCCCCCCCC	23.52	30631047
130	Phosphorylation	EDGGDAPSPSKRPWA CCCCCCCCCCCCCCH	43.45	11595184
132	Phosphorylation	GGDAPSPSKRPWARQ CCCCCCCCCCCCHHH	45.71	25850435
151	Phosphorylation	AEREGGMSCSCSSGS HHHHCCCCCCCCCCC	13.22	-
153	Phosphorylation	REGGMSCSCSSGSGE HHCCCCCCCCCCCCC	15.10	-
155	Phosphorylation	GGMSCSCSSGSGEAS CCCCCCCCCCCCCCC	22.80	-
156	Phosphorylation	GMSCSCSSGSGEASA CCCCCCCCCCCCCCC	41.11	-
226	Phosphorylation	LRDGQLVSQRAIPPR CCCCCEECCCCCCCC	23.65	22817900
234	Phosphorylation	QRAIPPRSIRGDQIA CCCCCCCCCCCCEEE	23.55	22817900
252	Phosphorylation	GHEPGCRSIGALMAH CCCCCHHHHHHHHHH	29.47	22210691
374	Phosphorylation	RYAITVWYFDAKERA CEEEEEEEECHHHHH	6.30	-
386	Ubiquitination	ERAAAKDKYQLASGQ HHHHHHHHHHHCCCC	33.90	-
401	Phosphorylation	KGVQVPVSQPPTPT- CCCCCCCCCCCCCC-	30.79	-
405	Phosphorylation	VPVSQPPTPT----- CCCCCCCCCC-----	46.36	24719451

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
130	S	Phosphorylation	Kinase	CDK2	P24941	PSP
130	S	Phosphorylation	Kinase	CDK4	P11802	PSP
130	S	Phosphorylation	Kinase	CDK6	Q00534	PSP
132	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
226	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
234	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
401	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
405	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH1	Q8IUQ4	PMID:17047048
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH2	O43255	PMID:15210114

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of EGLN2_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 EGLN2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SIAH2_HUMAN	SIAH2	physical	16958618
EGLN3_HUMAN	EGLN3	physical	16958618
EGLN2_HUMAN	EGLN2	physical	16958618
PRP19_HUMAN	PRPF19	physical	20599946
SPY2_HUMAN	SPRY2	physical	22006925
SIAH2_HUMAN	SIAH2	physical	15210114
MAGAB_HUMAN	MAGEA11	physical	19147576
DYR1A_HUMAN	DYRK1A	physical	26735018
DYR1B_HUMAN	DYRK1B	physical	26735018
CUL3_HUMAN	CUL3	physical	28089830
SPOP_HUMAN	SPOP	physical	28089830

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