dbPTM

IF2A_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IF2A_HUMAN
UniProt AC	P05198
Protein Name	Eukaryotic translation initiation factor 2 subunit 1
Gene Name	EIF2S1
Organism	Homo sapiens (Human).
Sequence Length	315
Subcellular Localization	Cytoplasm, Stress granule . Colocalizes with NANOS3 in the stress granules.
Protein Description	Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B..
Protein Sequence	MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSINKLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLEYTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNINRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTTTLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEVDGDDDAEEMEAKAED

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
9	Phosphorylation	PGLSCRFYQHKFPEV CCCCCEEEECCCCCC	7.14	29496907
12	Acetylation	SCRFYQHKFPEVEDV CCEEEECCCCCCEEE	47.27	26051181
12	Ubiquitination	SCRFYQHKFPEVEDV CCEEEECCCCCCEEE	47.27	-
26	Phosphorylation	VVMVNVRSIAEMGAY EEEEEHHHHHHHCCE	23.13	26552605
33	Phosphorylation	SIAEMGAYVSLLEYN HHHHHCCEEEEEHCC	5.71	27251275
35	Phosphorylation	AEMGAYVSLLEYNNI HHHCCEEEEEHCCCC	17.98	27251275
39	Phosphorylation	AYVSLLEYNNIEGMI CEEEEEHCCCCCHHH	17.30	27251275
49	Phosphorylation	IEGMILLSELSRRRI CCHHHHHHHHHHHHH	32.80	21082442
52	Phosphorylation	MILLSELSRRRIRSI HHHHHHHHHHHHHHH	21.49	14676213
58	Phosphorylation	LSRRRIRSINKLIRI HHHHHHHHHHHHHHC	28.30	20068231
61	Ubiquitination	RRIRSINKLIRIGRN HHHHHHHHHHHCCCC	43.55	21890473
61	Malonylation	RRIRSINKLIRIGRN HHHHHHHHHHHCCCC	43.55	26320211
61	Acetylation	RRIRSINKLIRIGRN HHHHHHHHHHHCCCC	43.55	25953088
78	Ubiquitination	VVVIRVDKEKGYIDL EEEEEEECCCCEEEC	59.47	-
80	Ubiquitination	VIRVDKEKGYIDLSK EEEEECCCCEEECCC	63.86	-
80	2-Hydroxyisobutyrylation	VIRVDKEKGYIDLSK EEEEECCCCEEECCC	63.86	-
82	Phosphorylation	RVDKEKGYIDLSKRR EEECCCCEEECCCCC	11.43	28152594
86	Phosphorylation	EKGYIDLSKRRVSPE CCCEEECCCCCCCHH	21.99	24719451
87	2-Hydroxyisobutyrylation	KGYIDLSKRRVSPEE CCEEECCCCCCCHHH	52.07	-
87	Acetylation	KGYIDLSKRRVSPEE CCEEECCCCCCCHHH	52.07	25953088
87	Ubiquitination	KGYIDLSKRRVSPEE CCEEECCCCCCCHHH	52.07	21906983
91	Phosphorylation	DLSKRRVSPEEAIKC ECCCCCCCHHHHHCC	25.45	23927012
97	Ubiquitination	VSPEEAIKCEDKFTK CCHHHHHCCCHHCCC	38.32	-
97	Acetylation	VSPEEAIKCEDKFTK CCHHHHHCCCHHCCC	38.32	26051181
101	Acetylation	EAIKCEDKFTKSKTV HHHCCCHHCCCHHHH	32.41	25825284
101	Ubiquitination	EAIKCEDKFTKSKTV HHHCCCHHCCCHHHH	32.41	-
103	Phosphorylation	IKCEDKFTKSKTVYS HCCCHHCCCHHHHHH	39.90	23312004
104	Ubiquitination	KCEDKFTKSKTVYSI CCCHHCCCHHHHHHH	53.76	-
106	Malonylation	EDKFTKSKTVYSILR CHHCCCHHHHHHHHH	43.49	26320211
106	Ubiquitination	EDKFTKSKTVYSILR CHHCCCHHHHHHHHH	43.49	21890473
107	Phosphorylation	DKFTKSKTVYSILRH HHCCCHHHHHHHHHH	31.59	23186163
109	Phosphorylation	FTKSKTVYSILRHVA CCCHHHHHHHHHHHH	8.67	28152594
110	Phosphorylation	TKSKTVYSILRHVAE CCHHHHHHHHHHHHH	15.71	21815630
123	Ubiquitination	AEVLEYTKDEQLESL HHHHHHCCHHHHHHH	59.37	21906983
123	2-Hydroxyisobutyrylation	AEVLEYTKDEQLESL HHHHHHCCHHHHHHH	59.37	-
123	Acetylation	AEVLEYTKDEQLESL HHHHHHCCHHHHHHH	59.37	26051181
133	Methylation	QLESLFQRTAWVFDD HHHHHHHHHHHHCCC	21.05	-
141	2-Hydroxyisobutyrylation	TAWVFDDKYKRPGYG HHHHCCCCCCCCCCC	55.29	-
141	Acetylation	TAWVFDDKYKRPGYG HHHHCCCCCCCCCCC	55.29	19608861
141	Ubiquitination	TAWVFDDKYKRPGYG HHHHCCCCCCCCCCC	55.29	21890473
143	Malonylation	WVFDDKYKRPGYGAY HHCCCCCCCCCCCHH	58.83	32601280
143	Acetylation	WVFDDKYKRPGYGAY HHCCCCCCCCCCCHH	58.83	26051181
143	Ubiquitination	WVFDDKYKRPGYGAY HHCCCCCCCCCCCHH	58.83	21890473
147	Phosphorylation	DKYKRPGYGAYDAFK CCCCCCCCCHHHHHH	10.98	28152594
150	Phosphorylation	KRPGYGAYDAFKHAV CCCCCCHHHHHHHHC	11.93	28152594
154	Ubiquitination	YGAYDAFKHAVSDPS CCHHHHHHHHCCCHH	32.16	21906983
154	Methylation	YGAYDAFKHAVSDPS CCHHHHHHHHCCCHH	32.16	-
158	Phosphorylation	DAFKHAVSDPSILDS HHHHHHCCCHHHHHC	44.58	30266825
161	Phosphorylation	KHAVSDPSILDSLDL HHHCCCHHHHHCCCC	40.55	23663014
165	Phosphorylation	SDPSILDSLDLNEDE CCHHHHHCCCCCHHH	21.97	29214152
185	Phosphorylation	NNINRRLTPQAVKIR HHHHCCCCCCCEEEC	16.14	30266825
190	Ubiquitination	RLTPQAVKIRADIEV CCCCCCEEECCCEEE	29.50	1906983
190	2-Hydroxyisobutyrylation	RLTPQAVKIRADIEV CCCCCCEEECCCEEE	29.50	-
199	Glutathionylation	RADIEVACYGYEGID CCCEEEEECCCCCHH	3.06	22555962
200	Phosphorylation	ADIEVACYGYEGIDA CCEEEEECCCCCHHH	17.01	22817900
202	Phosphorylation	IEVACYGYEGIDAVK EEEEECCCCCHHHHH	5.63	27642862
209	Ubiquitination	YEGIDAVKEALRAGL CCCHHHHHHHHHCCC	38.70	-
219	O-linked_Glycosylation	LRAGLNCSTENMPIK HHCCCCCCCCCCCEE	37.37	28657654
219	Phosphorylation	LRAGLNCSTENMPIK HHCCCCCCCCCCCEE	37.37	21712546
223	Sulfoxidation	LNCSTENMPIKINLI CCCCCCCCCEEEEEE	2.71	21406390
226	Ubiquitination	STENMPIKINLIAPP CCCCCCEEEEEECCC	21.48	-
235	Phosphorylation	NLIAPPRYVMTTTTL EEECCCCEEEEECCE	10.59	29496907
237	Sulfoxidation	IAPPRYVMTTTTLER ECCCCEEEEECCEEC	1.72	30846556
239	O-linked_Glycosylation	PPRYVMTTTTLERTE CCCEEEEECCEECCC	10.33	28657654
240	O-linked_Glycosylation	PRYVMTTTTLERTEG CCEEEEECCEECCCC	21.88	28657654
241	O-linked_Glycosylation	RYVMTTTTLERTEGL CEEEEECCEECCCCH	25.24	28657654
245	Phosphorylation	TTTTLERTEGLSVLS EECCEECCCCHHHHH	25.65	21406692
249	Phosphorylation	LERTEGLSVLSQAMA EECCCCHHHHHHHHH	31.69	21406692
252	Phosphorylation	TEGLSVLSQAMAVIK CCCHHHHHHHHHHHH	17.46	21406692
259	Ubiquitination	SQAMAVIKEKIEEKR HHHHHHHHHHHHHHC	46.48	21906983
261	Ubiquitination	AMAVIKEKIEEKRGV HHHHHHHHHHHHCCC	50.87	-
265	Ubiquitination	IKEKIEEKRGVFNVQ HHHHHHHHCCCCEEE	41.48	-
266	Methylation	KEKIEEKRGVFNVQM HHHHHHHCCCCEEEE	50.19	-
273	Sulfoxidation	RGVFNVQMEPKVVTD CCCCEEEECCEEECC	9.19	21406390
276	Ubiquitination	FNVQMEPKVVTDTDE CEEEECCEEECCCCH	35.71	21906983
276	Acetylation	FNVQMEPKVVTDTDE CEEEECCEEECCCCH	35.71	26051181
279	Phosphorylation	QMEPKVVTDTDETEL EECCEEECCCCHHHH	35.85	30266825
281	Phosphorylation	EPKVVTDTDETELAR CCEEECCCCHHHHHH	26.77	30266825
284	Phosphorylation	VVTDTDETELARQME EECCCCHHHHHHHHH	38.82	30266825
309	Sulfoxidation	GDDDAEEMEAKAED- CCCCHHHHHHHHCC-	4.58	28465586
312	Ubiquitination	DAEEMEAKAED---- CHHHHHHHHCC----	38.72	-

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
49	S	Phosphorylation	Kinase	EIF2AK1	Q9BQI3	GPS
49	S	Phosphorylation	Kinase	EIF2AK2	P19525	GPS
49	S	Phosphorylation	Kinase	EIF2AK3	Q9NZJ5	GPS
52	S	Phosphorylation	Kinase	EIF2AK1	Q9BQI3	GPS
52	S	Phosphorylation	Kinase	EIF2AK2	P19525	GPS
52	S	Phosphorylation	Kinase	EIF2AK3	Q9NZJ5	GPS
52	S	Phosphorylation	Kinase	PERK	Q9Z2B5	PSP
52	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
52	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
52	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
49	S	Phosphorylation	15207627
Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs.
52	S	Phosphorylation	18032499
Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity).
52	S	Phosphorylation	15207627
Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs.

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 IF2A_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
EI2BA_HUMAN	EIF2B1	physical	9446619
E2AK2_HUMAN	EIF2AK2	physical	19364808
IF2B_HUMAN	EIF2S2	physical	22939629
IF2G_HUMAN	EIF2S3	physical	22939629
POP1_HUMAN	POP1	physical	22939629
TMED9_HUMAN	TMED9	physical	22939629
NCOA5_HUMAN	NCOA5	physical	22939629
STRN_HUMAN	STRN	physical	22939629
YBOX1_HUMAN	YBX1	physical	22939629
AIMP1_HUMAN	AIMP1	physical	22863883
SYDC_HUMAN	DARS	physical	22863883
MCA3_HUMAN	EEF1E1	physical	22863883
IF2G_HUMAN	EIF2S3	physical	22863883
MAP4_HUMAN	MAP4	physical	22863883
SYMC_HUMAN	MARS	physical	22863883
SYQ_HUMAN	QARS	physical	22863883
RL13_HUMAN	RPL13	physical	22863883
RL15_HUMAN	RPL15	physical	22863883
RL27A_HUMAN	RPL27A	physical	22863883
RL7A_HUMAN	RPL7A	physical	22863883
RLA0_HUMAN	RPLP0	physical	22863883
RS27L_HUMAN	RPS27L	physical	22863883
IF2G_HUMAN	EIF2S3	physical	26344197
RPB7_HUMAN	POLR2G	physical	26344197
RPN1_HUMAN	RPN1	physical	26344197
TOE1_HUMAN	TOE1	physical	26344197
CDC37_HUMAN	CDC37	physical	12930845
HS90A_HUMAN	HSP90AA1	physical	12930845

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 IF2A_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-141, AND MASS SPECTROMETRY.	19608861 [Abstract]

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