Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Mitogen-activated protein kinase 3  

UniProtKB / Swiss-Prot ID :  MK03_HUMAN

Gene Name (Synonyms) : 
MAPK3, ERK1, PRKM3  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. Nucleus. Note=Autophosphorylation at Thr-207 promotes nuclear localization. 

Protein Function :  Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The the MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additionnal cytosolic and nuclear targets, thereby extending the specificity of the cascade. 

Protein Sequence MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAI...
Predicted Secondary Structure CCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHCCCCCCCCCCEEEEEEEEECCCEEEEEEEECCCCCEEEE...
Protein Variant
LocationDescription
323E -> K (in dbSNP:rs55859133). VAR_042253
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
2N-acetylalanine.---MAAAAA
---CCCCCC
13.05UniProtKB
Link-
170PhosphoserineDLKPSNLLI
ECCCCCEEE
38.22Phosphositeplus
Link
170Phosphoserine.DLKPSNLLI
ECCCCCEEE
38.22UniProtKB
Link
181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)TCDLKICDF
CCCEEEEEC
28.21Phosphositeplus
Link
198PhosphothreonineEHDHTGFLT
CCCCCCEEE
35.37Phosphositeplus
Link
198Phosphothreonine.EHDHTGFLT
CCCCCCEEE
35.37UniProtKB
Link
202PhosphothreonineTGFLTEYVA
CCEEEEEEE
24.02Phosphositeplus
Link
202PhosphothreonineTGFLTEYVA
CCEEEEEEE
24.02SysPTM
Link
202Phosphothreonine (MAP2K2)TGFLTEYVA
CCEEEEEEE
24.02HPRD
Link
202Phosphothreonine (MAP2K_group;MAP2K1;MAP2K2)TGFLTEYVA
CCEEEEEEE
24.02PhosphoELM
Link
202Phosphothreonine (MAPK3)TGFLTEYVA
CCEEEEEEE
24.02HPRD
Link
202Phosphothreonine (MAPK3)TGFLTEYVA
CCEEEEEEE
24.02HPRD
Link
202Phosphothreonine; by MAP2K1 and MAP2K2.TGFLTEYVA
CCEEEEEEE
24.02UniProtKB
Link
204PhosphotyrosineFLTEYVATR
EEEEEEECC
7.08HPRD
Link
204PhosphotyrosineFLTEYVATR
EEEEEEECC
7.08Phosphositeplus
Link
204PhosphotyrosineFLTEYVATR
EEEEEEECC
7.08SysPTM
Link
204Phosphotyrosine (MAP2K2)FLTEYVATR
EEEEEEECC
7.08HPRD
Link
204Phosphotyrosine (MAP2K_group;MAP2K1;MAP2K2)FLTEYVATR
EEEEEEECC
7.08PhosphoELM
Link
204Phosphotyrosine (MAPK3)FLTEYVATR
EEEEEEECC
7.08HPRD
Link
204Phosphotyrosine; by MAP2K1 and MAP2K2.FLTEYVATR
EEEEEEECC
7.08UniProtKB
Link
207PhosphothreonineEYVATRWYR
EEEECCCCC
16.22Phosphositeplus
Link
207Phosphothreonine; by autocatalysis.EYVATRWYR
EEEECCCCC
16.22UniProtKB
Link
210PhosphotyrosineATRWYRAPE
ECCCCCCCC
8.13Phosphositeplus
Link
294Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)VAWAKLFPK
CCHHHHCCC
39.70Phosphositeplus
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
KS6A3_HUMANphysical interactionMINT-16738MINT9915826
CASP8_HUMANphysical interactionMINT-4329823MINT17290218
KS6A4_HUMANphysical interactionEBI-74011
intact9792677
DAPK1_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-525646
EBI-525573
EBI-525
intact15616583
15616583
15616583
15616583
STAT3_HUMANin vitro
in vivo
HPRD:03479HPRD11350938
10521505
9343414
10446219
12576423
14551213
9872331
12763138
ARRB1_HUMANin vitroHPRD:03479HPRD10347142
9388255
ARBK1_HUMANin vitro
in vivo
HPRD:03479HPRD10574913
10727525
CXA1_HUMANin vitro
in vivo
HPRD:03479HPRD12637502
8631994
9535909
9535905
DCC_HUMANin vitro
in vivo
HPRD:03479HPRD11986622
GAB1_HUMANin vitroHPRD:03479HPRD15379552
EPOR_HUMANin vivoHPRD:03479HPRD12538595
HSF1_HUMANin vitro
in vivo
HPRD:03479HPRD8940068
TFE2_HUMANin vivoHPRD:03479HPRD14592976
K2C8_HUMANin vitro
in vivo
HPRD:03479HPRD11788583
11781324
9211903
9054461
INSR_HUMANin vivoHPRD:03479HPRD11409918
ETS1_HUMANin vitroHPRD:03479HPRD11948414
12048211
TPA_HUMANin vitroHPRD:03479HPRD15861134
STMN1_HUMANin vivoHPRD:03479HPRD8376365
11135364
8325880
LIPS_HUMANin vitroHPRD:03479HPRD11581251
LYN_HUMANin vivoHPRD:03479HPRD11131153
MP2K1_HUMANin vitro
in vivo
HPRD:03479HPRD10748187
8626767
8226933
JUN_HUMANin vivo
yeast 2-hybrid
HPRD:03479HPRD1922387
PTN5_HUMANin vitro
in vivo
HPRD:03479HPRD9857190
LCK_HUMANin vitro
in vivo
HPRD:03479HPRD8506364
8618896
PTN7_HUMANin vitro
in vivo
HPRD:03479HPRD10559944
10206983
10415025
PPARA_HUMANin vitroHPRD:03479HPRD10187842
KS6A3_HUMANin vivoHPRD:03479HPRD12832467
9915826
SRBP1_HUMANin vitroHPRD:03479HPRD10915800
P53_HUMANin vivoHPRD:03479HPRD10958792
TAL2_HUMANin vitroHPRD:03479HPRD8152805
TAL1_HUMANin vitroHPRD:03479HPRD8423803
TY3H_HUMANin vivoHPRD:03479HPRD1347949
NTRK3_HUMANin vitroHPRD:03479HPRD11205744
SP1_HUMANin vitro
in vivo
HPRD:03479HPRD11904305
ELK1_HUMANin vivoHPRD:03479HPRD8208531
12473660
AT1A1_HUMANin vitroHPRD:03479HPRD15069082
C1QBP_HUMANin vitro
in vivo
HPRD:03479HPRD11866440
RAF1_HUMANin vitroHPRD:03479HPRD9446616
SRBP2_HUMANin vitroHPRD:03479HPRD10627507
KPCD_HUMANin vivoHPRD:03479HPRD12759139
MYLK_HUMANin vitroHPRD:03479HPRD10402467
HMMR_HUMANin vitroHPRD:03479HPRD11403955
MK03_HUMANin vitro
in vivo
HPRD:03479HPRD12840032
1322499
7687743
862676
CASP9_HUMANin vitro
in vivo
HPRD:03479HPRD12792650
RCAN1_HUMANin vitroHPRD:03479HPRD12063245
GAB2_HUMANin vitro
in vivo
HPRD:03479HPRD15356145
SPIB_HUMANin vitroHPRD:03479HPRD8632909
PLCB1_HUMANin vivoHPRD:03479HPRD11287604
HSPB8_HUMANin vitroHPRD:03479HPRD11342557
CNRG_HUMANin vitroHPRD:03479HPRD12624098
STMN2_HUMANin vitroHPRD:03479HPRD9525956
9126608
CCDC6_HUMANin vitro
in vivo
HPRD:03479HPRD14712216
15302935
15144186
MKNK1_HUMANin vitro
in vivo
HPRD:03479HPRD9155018
SMAD2_HUMANin vitro
in vivo
HPRD:03479HPRD12193595
11027280
DUS3_HUMANin vitro
in vivo
HPRD:03479HPRD10224087
UBF1_HUMANin vitro
in vivo
HPRD:03479HPRD11741541
DUS1_HUMANin vitro
in vivo
HPRD:03479HPRD11278799
10617468
MK14_HUMANin vitro
in vivo
HPRD:03479HPRD12697810
KPCE_HUMANin vivoHPRD:03479HPRD16461926
KPCZ_HUMANin vivoHPRD:03479HPRD15721486
GTF2I_HUMANin vitro
in vivo
HPRD:03479HPRD10648599
KS6A1_HUMANin vitro
in vivo
HPRD:03479HPRD12832467
9915826
KS6A2_HUMANin vitro
in vivo
HPRD:03479HPRD8939914
GMFB_HUMANin vivoHPRD:03479HPRD8639570
DAPK1_HUMANin vitro
in vivo
HPRD:03479HPRD15616583
STA5A_HUMANin vitro
in vivo
HPRD:03479HPRD10194762
MYC_HUMANin vitroHPRD:03479HPRD9155018
ZNF7_HUMANin vitroHPRD:03479HPRD9155018
GNDS_HUMANin vitroHPRD:03479HPRD9155018
TOP2B_HUMANin vitroHPRD:03479HPRD9155018
PAXI_HUMANin vitroHPRD:03479HPRD11784715
TGIF1_HUMANin vitro
in vivo
HPRD:03479HPRD11226163
PAK2_HUMANin vitroHPRD:03479HPRD12226077
FCG2B_HUMANin vivoHPRD:03479HPRD15081531
PP1A_HUMANin vitroHPRD:03479HPRD12624094
HSF4_HUMANin vivoHPRD:03479HPRD16581800
TNR16_HUMANENSP00000263025STRING
KLF6_HUMANENSP00000263025STRING
ESR1_HUMANENSP00000263025STRING
MK01_HUMANENSP00000263025STRING
IKBA_HUMANENSP00000263025STRING
KS6B1_HUMANENSP00000263025STRING
CCL2_HUMANENSP00000263025STRING
DUS3_HUMANENSP00000263025STRING
MK1I1_HUMANENSP00000263025STRING
CCND1_HUMANENSP00000263025STRING
PAXI_HUMANENSP00000263025STRING
IFNG_HUMANENSP00000263025STRING
2A5D_HUMANENSP00000263025STRING
STMN1_HUMANENSP00000263025STRING
STMN1_HUMANENSP00000263025STRING
CREB1_HUMANENSP00000263025STRING
DUS1_HUMANENSP00000263025STRING
TNF11_HUMANENSP00000263025STRING
EGR1_HUMANENSP00000263025STRING
DUS4_HUMANENSP00000263025STRING
CDN1A_HUMANENSP00000263025STRING
SOX9_HUMANENSP00000263025STRING
ELK1_HUMANENSP00000263025STRING
INS_HUMANENSP00000263025STRING
INS_HUMANENSP00000263025STRING
RAF1_HUMANENSP00000263025STRING
TLR2_HUMANENSP00000263025STRING
P52K_HUMANENSP00000263025STRING
PGFRB_HUMANENSP00000263025STRING
KS6A5_HUMANENSP00000263025STRING
MP2K4_HUMANENSP00000263025STRING
MP2K2_HUMANENSP00000263025STRING
SL9A1_HUMANENSP00000263025STRING
ATF2_HUMANENSP00000263025STRING
STAT3_HUMANENSP00000263025STRING
ICAM1_HUMANENSP00000263025STRING
KS6A2_HUMANENSP00000263025STRING
NALP1_HUMANENSP00000263025STRING
P53_HUMANENSP00000263025STRING
ERBB2_HUMANENSP00000263025STRING
AKT1_HUMANENSP00000263025STRING
AGTR1_HUMANENSP00000263025STRING
RASA1_HUMANENSP00000263025STRING
EGFR_HUMANENSP00000263025STRING
LYN_HUMANENSP00000263025STRING
DUS6_HUMANENSP00000263025STRING
IL18_HUMANENSP00000263025STRING
CXA1_HUMANENSP00000263025STRING
CXA1_HUMANENSP00000263025STRING
IKZF3_HUMANENSP00000263025STRING
MITF_HUMANENSP00000263025STRING
IL3_HUMANENSP00000263025STRING
CSF2_HUMANENSP00000263025STRING
NOS3_HUMANENSP00000263025STRING
FRS2_HUMANENSP00000263025STRING
MMP3_HUMANENSP00000263025STRING
CRK_HUMANENSP00000263025STRING
CRK_HUMANENSP00000263025STRING
MP2K1_HUMANENSP00000263025STRING
UBF1_HUMANENSP00000263025STRING
IGF1B_HUMANENSP00000263025STRING
INSR_HUMANENSP00000263025STRING
IRS1_HUMANENSP00000263025STRING
KPCE_HUMANENSP00000263025STRING
FOS_HUMANENSP00000263025STRING
IL8_HUMANENSP00000263025STRING
BAD_HUMANENSP00000263025STRING
TERT_HUMANENSP00000263025STRING
RASH_HUMANENSP00000263025STRING
ARBK1_HUMANENSP00000263025STRING
PA21B_HUMANENSP00000263025STRING
VEGFA_HUMANENSP00000263025STRING
APOA_HUMANENSP00000263025STRING
MPIP3_HUMANENSP00000263025STRING
ETS1_HUMANENSP00000263025STRING
NOS2A_HUMANENSP00000263025STRING
SP1_HUMANENSP00000263025STRING
CASP9_HUMANENSP00000263025STRING
HSF1_HUMANENSP00000263025STRING
SMAD3_HUMANENSP00000263025STRING
HIF1A_HUMANENSP00000263025STRING
HIF1A_HUMANENSP00000263025STRING
CAV1_HUMANENSP00000263025STRING
4EBP1_HUMANENSP00000263025STRING
FAK1_HUMANENSP00000263025STRING
STA5A_HUMANENSP00000263025STRING
SMAD4_HUMANENSP00000263025STRING
MBP_HUMANENSP00000263025STRING
MBP_HUMANENSP00000263025STRING
BIM_HUMANENSP00000263025STRING
CASP8_HUMANENSP00000263025STRING
NTRK1_HUMANENSP00000263025STRING
MYLK_HUMANENSP00000263025STRING
MK08_HUMANENSP00000263025STRING
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Disease Reference
Kegg disease
There are no disease associations of PTM sites.
Drug Reference
DrugBank
DB01169Arsenic trioxide
DB00605Sulindac
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
Phosphorylation
ReferencePubMed
"Time-resolved mass spectrometry of tyrosine phosphorylation sites inthe epidermal growth factor receptor signaling network reveals dynamicmodules.";
Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J.,Lauffenburger D.A., White F.M.;
Mol. Cell. Proteomics 4:1240-1250(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-204, AND MASSSPECTROMETRY.
"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 THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-204, AND MASSSPECTROMETRY.
"Proteomics analysis of protein kinases by target class-selectiveprefractionation and tandem mass spectrometry.";
Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R.,Keri G., Wehland J., Daub H.;
Mol. Cell. Proteomics 6:537-547(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"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 THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits theRAS pathway by direct dephosphorylation of ERK1/2 kinases.";
Sacco F., Tinti M., Palma A., Ferrari E., Nardozza A.P.,Hooft van Huijsduijnen R., Takahashi T., Castagnoli L., Cesareni G.;
J. Biol. Chem. 284:22048-22058(2009).
Cited for: PHOSPHORYLATION AT TYR-204, AND DEPHOSPHORYLATION BY PTPRJ AT TYR-204.
"An extensive survey of tyrosine phosphorylation revealing new sitesin human mammary epithelial cells.";
Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,Wiley H.S., Qian W.-J.;
J. Proteome Res. 8:3852-3861(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-204, AND MASSSPECTROMETRY.
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-170; THR-198; THR-202AND TYR-204, AND MASS SPECTROMETRY.
"A new type of ERK1/2 autophosphorylation causes cardiachypertrophy.";
Lorenz K., Schmitt J.P., Schmitteckert E.M., Lohse M.J.;
Nat. Med. 15:75-83(2009).
Cited for: AUTOPHOSPHORYLATION AT THR-207, ENZYME REGULATION, SUBUNIT, ANDSUBCELLULAR LOCATION.
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, ANDMASS SPECTROMETRY.
"Crystal structure of human mono-phosphorylated ERK1 at Tyr204.";
Kinoshita T., Yoshida I., Nakae S., Okita K., Gouda M., Matsubara M.,Yokota K., Ishiguro H., Tada T.;
Biochem. Biophys. Res. Commun. 377:1123-1127(2008).
Cited for: X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS), AND PHOSPHORYLATION ATTYR-204.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures