dbPTM

E2AK1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	E2AK1_HUMAN
UniProt AC	Q9BQI3
Protein Name	Eukaryotic translation initiation factor 2-alpha kinase 1
Gene Name	EIF2AK1
Organism	Homo sapiens (Human).
Sequence Length	630
Subcellular Localization	Cytoplasm.
Protein Description	Inhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity)..
Protein Sequence	MQGGNSGVRKREEEGDGAGAVAAPPAIDFPAEGPDPEYDESDVPAEIQVLKEPLQQPTFPFAVANQLLLVSLLEHLSHVHEPNPLRSRQVFKLLCQTFIKMGLLSSFTCSDEFSSLRLHHNRAITHLMRSAKERVRQDPCEDISRIQKIRSREVALEAQTSRYLNEFEELAILGKGGYGRVYKVRNKLDGQYYAIKKILIKGATKTVCMKVLREVKVLAGLQHPNIVGYHTAWIEHVHVIQPRADRAAIELPSLEVLSDQEEDREQCGVKNDESSSSSIIFAEPTPEKEKRFGESDTENQNNKSVKYTTNLVIRESGELESTLELQENGLAGLSASSIVEQQLPLRRNSHLEESFTSTEESSEENVNFLGQTEAQYHLMLHIQMQLCELSLWDWIVERNKRGREYVDESACPYVMANVATKIFQELVEGVFYIHNMGIVHRDLKPRNIFLHGPDQQVKIGDFGLACTDILQKNTDWTNRNGKRTPTHTSRVGTCLYASPEQLEGSEYDAKSDMYSLGVVLLELFQPFGTEMERAEVLTGLRTGQLPESLRKRCPVQAKYIQHLTRRNSSQRPSAIQLLQSELFQNSGNVNLTLQMKIIEQEKEIAELKKQLNLLSQDKGVRDDGKDGGVG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
6	Phosphorylation	--MQGGNSGVRKREE --CCCCCCCCCCCCC	41.77	23663014
10	Ubiquitination	GGNSGVRKREEEGDG CCCCCCCCCCCCCCC	62.85	-
38	Phosphorylation	AEGPDPEYDESDVPA CCCCCCCCCCCCCCC	30.33	18691976
41	Phosphorylation	PDPEYDESDVPAEIQ CCCCCCCCCCCCHHH	40.80	27642862
115	Phosphorylation	TCSDEFSSLRLHHNR CCCCCCCHHHHHHHH	23.88	24719451
144	Phosphorylation	QDPCEDISRIQKIRS CCCCCHHHHHHHHHH	35.34	27251275
175 (in isoform 2)	Ubiquitination	-	45.80	21906983
175	Ubiquitination	EELAILGKGGYGRVY HHHHCCCCCCCCEEE	45.80	21906983
175 (in isoform 1)	Ubiquitination	-	45.80	21906983
187	Ubiquitination	RVYKVRNKLDGQYYA EEEEEEECCCCCEEE	37.07	-
196	Ubiquitination	DGQYYAIKKILIKGA CCCEEEEEEHHHCCC	26.11	-
201	Ubiquitination	AIKKILIKGATKTVC EEEEHHHCCCCHHHH	38.76	-
210	Ubiquitination	ATKTVCMKVLREVKV CCHHHHHHHHHHHHH	32.75	-
253	Phosphorylation	RAAIELPSLEVLSDQ CCCEECCCEEECCCC	50.19	30266825
257 (in isoform 2)	Phosphorylation	-	3.22	25849741
258	Phosphorylation	LPSLEVLSDQEEDRE CCCEEECCCCHHHHH	42.28	19664994
274	Phosphorylation	CGVKNDESSSSSIIF HCCCCCCCCCCEEEE	38.08	25159151
275	Phosphorylation	GVKNDESSSSSIIFA CCCCCCCCCCEEEEE	31.99	25159151
276	Phosphorylation	VKNDESSSSSIIFAE CCCCCCCCCEEEEEE	37.07	25159151
277	Phosphorylation	KNDESSSSSIIFAEP CCCCCCCCEEEEEEC	27.75	23663014
278	Phosphorylation	NDESSSSSIIFAEPT CCCCCCCEEEEEECC	22.96	23663014
285	Phosphorylation	SIIFAEPTPEKEKRF EEEEEECCCHHHHCC	35.27	28985074
288	Ubiquitination	FAEPTPEKEKRFGES EEECCCHHHHCCCCC	70.51	-
295	Phosphorylation	KEKRFGESDTENQNN HHHCCCCCCCCCCCC	50.65	25159151
297	Phosphorylation	KRFGESDTENQNNKS HCCCCCCCCCCCCCC	46.22	25849741
302 (in isoform 2)	Ubiquitination	-	28.37	21906983
303	Ubiquitination	DTENQNNKSVKYTTN CCCCCCCCCCEEEEE	65.26	2190698
303 (in isoform 1)	Ubiquitination	-	65.26	21906983
304	Phosphorylation	TENQNNKSVKYTTNL CCCCCCCCCEEEEEE	26.43	26434776
307	Phosphorylation	QNNKSVKYTTNLVIR CCCCCCEEEEEEEEE	19.35	27642862
467	Phosphorylation	GDFGLACTDILQKNT CCHHHHHHHHHHHCC	22.07	27050516
472	Ubiquitination	ACTDILQKNTDWTNR HHHHHHHHCCCCCCC	59.37	-
486	Phosphorylation	RNGKRTPTHTSRVGT CCCCCCCCCCCCCCC	36.85	-
488	Phosphorylation	GKRTPTHTSRVGTCL CCCCCCCCCCCCCEE	22.24	-
493	Phosphorylation	THTSRVGTCLYASPE CCCCCCCCEEECCHH	9.11	-
498	Phosphorylation	VGTCLYASPEQLEGS CCCEEECCHHHHCCC	18.53	25159151
538	Phosphorylation	MERAEVLTGLRTGQL HHHHHHHHCCCCCCC	39.07	24719451
558	Ubiquitination	KRCPVQAKYIQHLTR HHCHHHHHHHHHHHH	26.29	-
602	Ubiquitination	MKIIEQEKEIAELKK EEHHHHHHHHHHHHH	54.86	-
609	Ubiquitination	KEIAELKKQLNLLSQ HHHHHHHHHHHHHHC	73.05	-
618	Ubiquitination	LNLLSQDKGVRDDGK HHHHHCCCCCCCCCC	52.23	-

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
Oops, there are no upstream regulatory protein records of E2AK1_HUMAN !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
488	T	Phosphorylation		-
Autophosphorylation at Thr-488 is required for kinase 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 E2AK1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CDC37_HUMAN	CDC37	physical	11036079
HS90A_HUMAN	HSP90AA1	physical	11036079
EAF1_HUMAN	EAF1	physical	27173435
DDX20_HUMAN	DDX20	physical	27173435
NAF1_HUMAN	NAF1	physical	27173435
ATRX_HUMAN	ATRX	physical	27173435
AP3B1_HUMAN	AP3B1	physical	27173435
DPOD1_HUMAN	POLD1	physical	27173435
RBM14_HUMAN	RBM14	physical	27173435
MFAP1_HUMAN	MFAP1	physical	27173435

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.

Regulatory Network of E2AK1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6; SER-258 AND SER-295,AND MASS SPECTROMETRY.	18691976 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275; SER-276; SER-277AND SER-278, AND MASS SPECTROMETRY.	17081983 [Abstract]

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