dbPTM

E2AK3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	E2AK3_HUMAN
UniProt AC	Q9NZJ5
Protein Name	Eukaryotic translation initiation factor 2-alpha kinase 3
Gene Name	EIF2AK3
Organism	Homo sapiens (Human).
Sequence Length	1116
Subcellular Localization	Endoplasmic reticulum membrane Single-pass type I membrane protein.
Protein Description	Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' during the unfolded protein response (UPR) and in response to low amino acid availability. Converts phosphorylated eIF-2-alpha/EIF2S1 either in a global protein synthesis inhibitor, leading to a reduced overall utilization of amino acids, or to a translation initiation activator of specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function..
Protein Sequence	MERAISPGLLVRALLLLLLLLGLAARTVAAGRARGLPAPTAEAAFGLGAAAAPTSATRVPAAGAVAAAEVTVEDAEALPAAAGEQEPRGPEPDDETELRPRGRSLVIISTLDGRIAALDPENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGALFQWDQDRESMETVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKVRYICSALGCRQWDSDEMEQEEDILLLQRTQKTVRAVGPRSGNEKWNFSVGHFELRYIPDMETRAGFIESTFKPNENTEESKIISDVEEQEAAIMDIVIKVSVADWKVMAFSKKGGHLEWEYQFCTPIASAWLLKDGKVIPISLFDDTSYTSNDDVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRISEKFPSSPKALESVTNENAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKFSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDNPHYNKNIRKKDPVLLLHWWKEIVATILFCIIATTFIVRRLFHPHPHRQRKESETQCQTENKYDSVSGEANDSSWNDIKNSGYISRYLTDFEPIQCLGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLEAPPEKWQEKMDEIWLKDESTDWPLSSPSPMDAPSVKIRRMDPFATKEHIEIIAPSPQRSRSFSVGISCDQTSSSESQFSPLEFSGMDHEDISESVDAAYNLQDSCLTDCDVEDGTMDGNDEGHSFELCPSEASPYVRSRERTSSSIVFEDSGCDNASSKEEPKTNRLHIGNHCANKLTAFKPTSSKSSSEATLSISPPRPTTLSLDLTKNTTEKLQPSSPKVYLYIQMQLCRKENLKDWMNGRCTIEERERSVCLHIFLQIAEAVEFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYARHTGQVGTKLYMSPEQIHGNSYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPCEYVMVQDMLSPSPMERPEAINIIENAVFEDLDFPGKTVLRQRSRSLSSSGTKHSRQSNNSHSPLPSN

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
40	O-linked_Glycosylation	ARGLPAPTAEAAFGL HCCCCCCCHHHHHCC	38.96	OGP
54	O-linked_Glycosylation	LGAAAAPTSATRVPA CCCCCCCCCCCCCCC	26.68	OGP
57	O-linked_Glycosylation	AAAPTSATRVPAAGA CCCCCCCCCCCCCCC	31.78	OGP
139	Phosphorylation	VGSGSLVSSSLSKPE CCCCCEECCCCCCCC	21.36	22210691
177	Phosphorylation	SMETVPFTVESLLES CCCCCCEEHHHHHHH	19.79	-
201	Phosphorylation	LVGGKSLTTYGLSAY EECCEEECHHCCCCC	25.68	28985074
202	Phosphorylation	VGGKSLTTYGLSAYS ECCEEECHHCCCCCC	22.38	28985074
206	Phosphorylation	SLTTYGLSAYSGKVR EECHHCCCCCCCCHH	22.31	28985074
258	N-linked_Glycosylation	RSGNEKWNFSVGHFE CCCCCCCCEEEEEEE	30.31	UniProtKB CARBOHYD
268	Phosphorylation	VGHFELRYIPDMETR EEEEEEEECCCHHCC	29.45	-
396	Phosphorylation	GMYRGQLYLQSSVRI EEECCEEEEEEEEEE	8.53	29759185
409	Phosphorylation	RISEKFPSSPKALES EEHHCCCCCHHHHHH	63.51	23403867
410	Phosphorylation	ISEKFPSSPKALESV EHHCCCCCHHHHHHC	30.56	23403867
418	O-linked_Glycosylation	PKALESVTNENAIIP HHHHHHCCCCCCEEE	46.20	OGP
428	O-linked_Glycosylation	NAIIPLPTIKWKPLI CCEEECCCCCCEECC	42.76	OGP
441	Phosphorylation	LIHSPSRTPVLVGSD CCCCCCCCCEEECCH	23.30	-
447	Phosphorylation	RTPVLVGSDEFDKCL CCCEEECCHHHHHHH	26.87	-
452	Ubiquitination	VGSDEFDKCLSNDKF ECCHHHHHHHCCCCC	42.25	-
455	Phosphorylation	DEFDKCLSNDKFSHE HHHHHHHCCCCCCCH	53.07	-
464	Phosphorylation	DKFSHEEYSNGALSI CCCCCHHHCCCCEEE	12.40	-
474	Phosphorylation	GALSILQYPYDNGYY CCEEEEECCCCCCCC	10.58	-
480	Phosphorylation	QYPYDNGYYLPYYKR ECCCCCCCCCCCCCC	14.21	-
481	Phosphorylation	YPYDNGYYLPYYKRE CCCCCCCCCCCCCCC	11.55	-
484	Phosphorylation	DNGYYLPYYKRERNK CCCCCCCCCCCCCCC	21.01	22817900
485	Phosphorylation	NGYYLPYYKRERNKR CCCCCCCCCCCCCCC	11.13	-
493	Phosphorylation	KRERNKRSTQITVRF CCCCCCCCEEEEEEE	26.69	26074081
494	Phosphorylation	RERNKRSTQITVRFL CCCCCCCEEEEEEEC	28.20	26074081
497	Phosphorylation	NKRSTQITVRFLDNP CCCCEEEEEEECCCC	8.87	26074081
555	Phosphorylation	PHRQRKESETQCQTE CCCCCCCCHHHCCCC	49.32	30266825
557	Phosphorylation	RQRKESETQCQTENK CCCCCCHHHCCCCCC	43.88	23663014
561	Phosphorylation	ESETQCQTENKYDSV CCHHHCCCCCCCCCC	49.50	23663014
565	Phosphorylation	QCQTENKYDSVSGEA HCCCCCCCCCCCCCC	25.65	30576142
567	Phosphorylation	QTENKYDSVSGEAND CCCCCCCCCCCCCCC	18.32	30576142
569	Phosphorylation	ENKYDSVSGEANDSS CCCCCCCCCCCCCCC	34.56	28450419
575	Phosphorylation	VSGEANDSSWNDIKN CCCCCCCCCHHHHCC	36.74	26471730
576	Phosphorylation	SGEANDSSWNDIKNS CCCCCCCCHHHHCCC	32.53	23927012
581	Ubiquitination	DSSWNDIKNSGYISR CCCHHHHCCCCCCHH	48.18	-
585	Phosphorylation	NDIKNSGYISRYLTD HHHCCCCCCHHCCCC	8.78	-
619	Phosphorylation	NKVDDCNYAIKRIRL CCHHCCCHHHHHCCC	18.94	22169477
622	Ubiquitination	DDCNYAIKRIRLPNR HCCCHHHHHCCCCCH	33.33	-
669	Ubiquitination	PPEKWQEKMDEIWLK CHHHHHHHHHHHEEC	36.23	-
679	Phosphorylation	EIWLKDESTDWPLSS HHEECCCCCCCCCCC	41.63	27251275
680	Phosphorylation	IWLKDESTDWPLSSP HEECCCCCCCCCCCC	39.78	27251275
685	Phosphorylation	ESTDWPLSSPSPMDA CCCCCCCCCCCCCCC	35.80	25159151
686	Phosphorylation	STDWPLSSPSPMDAP CCCCCCCCCCCCCCC	36.76	25159151
688	Phosphorylation	DWPLSSPSPMDAPSV CCCCCCCCCCCCCCC	34.50	25159151
694	Phosphorylation	PSPMDAPSVKIRRMD CCCCCCCCCEEEECC	37.45	30576142
705	Phosphorylation	RRMDPFATKEHIEII EECCCCCCHHCEEEE	37.03	28857561
715	Phosphorylation	HIEIIAPSPQRSRSF CEEEECCCCCCCCCE	25.33	30266825
719	Phosphorylation	IAPSPQRSRSFSVGI ECCCCCCCCCEEEEE	27.33	25849741
802	Phosphorylation	YVRSRERTSSSIVFE CCCCCCCCCCEEEEE	28.36	29978859
803	Phosphorylation	VRSRERTSSSIVFED CCCCCCCCCEEEEEC	28.45	29978859
804	Phosphorylation	RSRERTSSSIVFEDS CCCCCCCCEEEEECC	24.38	30576142
805	Phosphorylation	SRERTSSSIVFEDSG CCCCCCCEEEEECCC	23.65	21815630
811	Phosphorylation	SSIVFEDSGCDNASS CEEEEECCCCCCCCC	33.84	28348404
836	Acetylation	IGNHCANKLTAFKPT ECCHHHCCCEECCCC	28.79	25953088
843	Phosphorylation	KLTAFKPTSSKSSSE CCEECCCCCCCCCCE	46.34	25159151
844	Phosphorylation	LTAFKPTSSKSSSEA CEECCCCCCCCCCEE	44.27	25849741
845	Phosphorylation	TAFKPTSSKSSSEAT EECCCCCCCCCCEEE	38.75	25159151
847	Phosphorylation	FKPTSSKSSSEATLS CCCCCCCCCCEEEEE	40.83	20068231
848	Phosphorylation	KPTSSKSSSEATLSI CCCCCCCCCEEEEEE	35.61	20068231
849	Phosphorylation	PTSSKSSSEATLSIS CCCCCCCCEEEEEEC	38.04	24719451
852	Phosphorylation	SKSSSEATLSISPPR CCCCCEEEEEECCCC	19.58	20068231
854	Phosphorylation	SSSEATLSISPPRPT CCCEEEEEECCCCCC	19.37	20068231
856	Phosphorylation	SEATLSISPPRPTTL CEEEEEECCCCCCEE	26.02	20068231
861	Phosphorylation	SISPPRPTTLSLDLT EECCCCCCEEEEECC	41.47	20068231
862	Phosphorylation	ISPPRPTTLSLDLTK ECCCCCCEEEEECCC	19.62	20068231
864	Phosphorylation	PPRPTTLSLDLTKNT CCCCCEEEEECCCCC	20.11	23312004
868	Phosphorylation	TTLSLDLTKNTTEKL CEEEEECCCCCCCCC	23.16	23312004
871	Phosphorylation	SLDLTKNTTEKLQPS EEECCCCCCCCCCCC	37.58	23312004
872	Phosphorylation	LDLTKNTTEKLQPSS EECCCCCCCCCCCCC	40.28	23312004
878	Phosphorylation	TTEKLQPSSPKVYLY CCCCCCCCCCHHHHE	46.44	28102081
879	Phosphorylation	TEKLQPSSPKVYLYI CCCCCCCCCHHHHEE	35.11	28102081
970	Phosphorylation	DQDEEEQTVLTPMPA CCCHHHCEECCCCCC	22.29	29523821
973	Phosphorylation	EEEQTVLTPMPAYAR HHHCEECCCCCCHHH	17.13	24719451
978	Phosphorylation	VLTPMPAYARHTGQV ECCCCCCHHHHCCCC	9.78	29523821
981	Phosphorylation	PMPAYARHTGQVGTK CCCCHHHHCCCCCCE	26.61	14676213
982	Phosphorylation	MPAYARHTGQVGTKL CCCHHHHCCCCCCEE	24.61	14676213
987	Phosphorylation	RHTGQVGTKLYMSPE HHCCCCCCEEECCHH	21.01	25247763
992	Phosphorylation	VGTKLYMSPEQIHGN CCCEEECCHHHHCCC	16.24	25247763
1086	Phosphorylation	DLDFPGKTVLRQRSR CCCCCCHHHHHHHHH	30.59	24719451
1092	Phosphorylation	KTVLRQRSRSLSSSG HHHHHHHHHHCCCCC	20.20	28985074
1094	Phosphorylation	VLRQRSRSLSSSGTK HHHHHHHHCCCCCCC	33.57	10026192
1096	Phosphorylation	RQRSRSLSSSGTKHS HHHHHHCCCCCCCCC	24.57	25849741
1097	Phosphorylation	QRSRSLSSSGTKHSR HHHHHCCCCCCCCCC	37.77	21406692
1098	Phosphorylation	RSRSLSSSGTKHSRQ HHHHCCCCCCCCCCC	47.29	21406692
1100	Phosphorylation	RSLSSSGTKHSRQSN HHCCCCCCCCCCCCC	27.77	21406692
1106	Phosphorylation	GTKHSRQSNNSHSPL CCCCCCCCCCCCCCC	36.55	28450419
1109	Phosphorylation	HSRQSNNSHSPLPSN CCCCCCCCCCCCCCC	29.59	28450419
1111	Phosphorylation	RQSNNSHSPLPSN-- CCCCCCCCCCCCC--	28.14	30576142
1115	Phosphorylation	NSHSPLPSN------ CCCCCCCCC------	63.96	28102081

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
585	Y	Phosphorylation	Kinase	JAK1	P23458	PSP
619	Y	Phosphorylation	Kinase	JAK1	P23458	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
982	T	Phosphorylation		22169477
Oligomerization of the N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-982 on the kinase activation loop (By similarity).

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 E2AK3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NF2L2_HUMAN	NFE2L2	physical	14517290
DNJC3_HUMAN	DNAJC3	physical	12446838
DNJC3_HUMAN	DNAJC3	genetic	12446838
GRP78_HUMAN	HSPA5	physical	11907036
ENPL_HUMAN	HSP90B1	physical	11907036
IF2A_HUMAN	EIF2S1	physical	16720581
GRP78_HUMAN	HSPA5	physical	26472337
ILF3_HUMAN	ILF3	physical	26472337
ILF2_HUMAN	ILF2	physical	26472337

Drug and Disease Associations

Kegg Disease
H00512	Permanent neonatal diabetes mellitus (PNDM)
H00766	Wolcott-Rallison syndrome; SED, Wolcott-Rallison type
OMIM Disease
226980	Wolcott-Rallison syndrome (WRS)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of E2AK3_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-715, AND MASSSPECTROMETRY.	18691976 [Abstract]
"H2s-induced sulfhydration of the phosphatase PTP1B and its role inthe endoplasmic reticulum stress response."; Krishnan N., Fu C., Pappin D.J., Tonks N.K.; Sci. Signal. 4:RA86-RA86(2011). Cited for: PHOSPHORYLATION AT TYR-619, AND DEPHOSPHORYLATION AT TYR-619.	22169477 [Abstract]

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