Top MAP3K4
Localization (UniProt annotation) Cytoplasm, perinuclear region Note=Localized in perinuclear vesicular-like structures, probablyGolgi-associated vesicles Function (UniProt annotation) Component of a protein kinase signal transductioncascade Activates the CSBP2, P38 and JNK MAPK pathways, but notthe ERK pathway Specifically phosphorylates and activates MAP2K4and MAP2K6 Catalytic Activity (UniProt annotation) ATP + a protein = ADP + a phosphoprotein Protein Sequence MREAAAALVPPPAFAVTPAAAMEEPPPPPPPPPPPPEPETESEPECCLAARQEGTLGDSACKSPESDLEDFSDETNTENL
YGTSPPSTPRQMKRMSTKHQRNNVGRPASRSNLKEKMNAPNQPPHKDTGKTVENVEEYSYKQEKKIRAALRTTERDRKKN
VQCSFMLDSVGGSLPKKSIPDVDLNKPYLSLGCSNAKLPVSVPMPIARPARQTSRTDCPADRLKFFETLRLLLKLTSVSK
KKDREQRGQENTSGFWLNRSNELIWLELQAWHAGRTINDQDFFLYTARQAIPDIINEILTFKVDYGSFAFVRDRAGFNGT
SVEGQCKATPGTKIVGYSTHHEHLQRQRVSFEQVKRIMELLEYIEALYPSLQALQKDYEKYAAKDFQDRVQALCLWLNIT
KDLNQKLRIMGTVLGIKNLSDIGWPVFEIPSPRPSKGNEPEYEGDDTEGELKELESSTDESEEEQISDPRVPEIRQPIDN
SFDIQSRDCISKKLERLESEDDSLGWGAPDWSTEAGFSRHCLTSIYRPFVDKALKQMGLRKLILRLHKLMDGSLQRARIA
LVKNDRPVEFSEFPDPMWGSDYVQLSRTPPSSEEKCSAVSWEELKAMDLPSFEPAFLVLCRVLLNVIHECLKLRLEQRPA
GEPSLLSIKQLVRECKEVLKGGLLMKQYYQFMLQEVLEDLEKPDCNIDAFEEDLHKMLMVYFDYMRSWIQMLQQLPQASH
SLKNLLEEEWNFTKEITHYIRGGEAQAGKLFCDIAGMLLKSTGSFLEFGLQESCAEFWTSADDSSASDEIRRSVIEISRA
LKELFHEARERASKALGFAKMLRKDLEIAAEFRLSAPVRDLLDVLKSKQYVKVQIPGLENLQMFVPDTLAEEKSIILQLL
NAAAGKDCSKDSDDVLIDAYLLLTKHGDRARDSEDSWGTWEAQPVKVVPQVETVDTLRSMQVDNLLLVVMQSAHLTIQRK
AFQQSIEGLMTLCQEQTSSQPVIAKALQQLKNDALELCNRISNAIDRVDHMFTSEFDAEVDESESVTLQQYYREAMIQGY
NFGFEYHKEVVRLMSGEFRQKIGDKYISFARKWMNYVLTKCESGRGTRPRWATQGFDFLQAIEPAFISALPEDDFLSLQA
LMNECIGHVIGKPHSPVTGLYLAIHRNSPRPMKVPRCHSDPPNPHLIIPTPEGFSTRSMPSDARSHGSPAAAAAAAAAAV
AASRPSPSGGDSVLPKSISSAHDTRGSSVPENDRLASIAAELQFRSLSRHSSPTEERDEPAYPRGDSSGSTRRSWELRTL
ISQSKDTASKLGPIEAIQKSVRLFEEKRYREMRRKNIIGQVCDTPKSYDNVMHVGLRKVTFKWQRGNKIGEGQYGKVYTC
ISVDTGELMAMKEIRFQPNDHKTIKETADELKIFEGIKHPNLVRYFGVELHREEMYIFMEYCDEGTLEEVSRLGLQEHVI
RLYSKQITIAINVLHEHGIVHRDIKGANIFLTSSGLIKLGDFGCSVKLKNNAQTMPGEVNSTLGTAAYMAPEVITRAKGE
GHGRAADIWSLGCVVIEMVTGKRPWHEYEHNFQIMYKVGMGHKPPIPERLSPEGKDFLSHCLESDPKMRWTASQLLDHSF
VKVCTDEE
ELM Motif Motif Instance Description Motif Regex NA NA NA NA
Pathway ID Pathway Name Pathway Description (KEGG) hsa04010 MAPK signaling pathway The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. hsa04912 GnRH signaling pathway Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes.
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ALK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID AP4E1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID AXIN1 Affinity Capture-Western physical 17726008 , (Europe PMC )NA BioGRID BAG3 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID BAG6 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID BTK Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID CDC42 Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 25241761 , 9079650 , (Europe PMC )0.40 BioGRID, IntAct CHUK Biochemical Activity physical 22547678 , (Europe PMC )NA BioGRID CNTRL Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct CNTROB Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID GADD45A Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct GADD45B Affinity Capture-MS, Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, dihydrofolate reductase reconstruction physical, physical association 12052864 , 16256071 , 28514442 , 9827804 , (Europe PMC )0.57 BioGRID, IntAct, MINT GADD45G Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct GOLT1B Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID GSK3B Biochemical Activity physical 17726008 , (Europe PMC )NA BioGRID HNRNPD Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID INTS14 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF21A Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF23 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF7 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID MAP2K1 Biochemical Activity physical 9841871 , (Europe PMC )NA BioGRID MAP2K3 Biochemical Activity, Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 15866172 , 25241761 , 9841871 , (Europe PMC )0.40 BioGRID, IntAct MAP2K4 Biochemical Activity, Reconstituted Complex physical 15866172 , 9841871 , (Europe PMC )NA BioGRID MAP2K6 Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, proximity ligation assay, two hybrid physical, physical association 12052864 , 15866172 , 16157600 , 17726008 , 25241761 , 9841871 , (Europe PMC )0.57 BioGRID, IntAct MAP2K7 Reconstituted Complex physical 15866172 , (Europe PMC )NA BioGRID MAP3K4 Biochemical Activity, two hybrid physical, physical association 12052864 , 17726008 , (Europe PMC )0.37 BioGRID, IntAct MAPK13 Co-localization, proximity ligation assay physical, physical association 25241761 , (Europe PMC )0.40 BioGRID, IntAct MAPK8 Affinity Capture-MS, Biochemical Activity physical 21152872 , 26496610 , (Europe PMC )NA BioGRID NEDD1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID POLR2F Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID RAC1 Reconstituted Complex physical 9079650 , (Europe PMC )NA BioGRID RAP1B Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID RIPK2 Affinity Capture-Western physical 21097508 , (Europe PMC )NA BioGRID SGTB Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SH3KBP1 Affinity Capture-Western, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical, physical association 16256071 , 20221403 , 23085457 , (Europe PMC )0.59 BioGRID, IntAct, MINT SIGLECL1 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID SORT1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SPATA1 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID SRPRA Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SYNCRIP Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID TOP1 Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TOP2A Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TOP3A Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TPR Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct TRAF4 Affinity Capture-Western physical 16157600 , 21097508 , (Europe PMC )NA BioGRID USF1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID YWHAZ Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct ZFP36 Affinity Capture-Western physical 20221403 , (Europe PMC )NA BioGRID
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source CDC42 Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 25241761 , 9079650 , (Europe PMC )0.40 BioGRID, IntAct CNTRL Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct FLNB pull down association, physical association 19270716 , (Europe PMC )0.50 IntAct, MINT GADD45A Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct GADD45B Affinity Capture-MS, Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, dihydrofolate reductase reconstruction physical, physical association 12052864 , 16256071 , 28514442 , 9827804 , (Europe PMC )0.57 BioGRID, IntAct, MINT GADD45G Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct MAP2K3 Biochemical Activity, Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 15866172 , 25241761 , 9841871 , (Europe PMC )0.40 BioGRID, IntAct MAP2K6 Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, proximity ligation assay, two hybrid physical, physical association 12052864 , 15866172 , 16157600 , 17726008 , 25241761 , 9841871 , (Europe PMC )0.57 BioGRID, IntAct MAP3K4 Biochemical Activity, two hybrid physical, physical association 12052864 , 17726008 , (Europe PMC )0.37 BioGRID, IntAct MAPK13 Co-localization, proximity ligation assay physical, physical association 25241761 , (Europe PMC )0.40 BioGRID, IntAct MFHAS1 protein array direct interaction 29513927 , (Europe PMC )0.44 IntAct PTK2B anti bait coimmunoprecipitation, imaging technique colocalization, physical association 15601262 , (Europe PMC )0.46 IntAct, MINT PTPN6 experimental interaction detection, imaging technique colocalization, dephosphorylation reaction 15601262 , (Europe PMC )0.40 IntAct, MINT SH3KBP1 Affinity Capture-Western, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical, physical association 16256071 , 20221403 , 23085457 , (Europe PMC )0.59 BioGRID, IntAct, MINT TPR Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct UBC anti bait coimmunoprecipitation, anti tag coimmunoprecipitation physical association 16256071 , (Europe PMC )0.52 IntAct, MINT YWHAZ Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source FLNB pull down association, physical association 19270716 , (Europe PMC )0.50 IntAct, MINT GADD45B Affinity Capture-MS, Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, dihydrofolate reductase reconstruction physical, physical association 12052864 , 16256071 , 28514442 , 9827804 , (Europe PMC )0.57 BioGRID, IntAct, MINT PTK2B anti bait coimmunoprecipitation, imaging technique colocalization, physical association 15601262 , (Europe PMC )0.46 IntAct, MINT PTPN6 experimental interaction detection, imaging technique colocalization, dephosphorylation reaction 15601262 , (Europe PMC )0.40 IntAct, MINT SH3KBP1 Affinity Capture-Western, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical, physical association 16256071 , 20221403 , 23085457 , (Europe PMC )0.59 BioGRID, IntAct, MINT UBC anti bait coimmunoprecipitation, anti tag coimmunoprecipitation physical association 16256071 , (Europe PMC )0.52 IntAct, MINT
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ALK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID ANXA2 coimmunoprecipitation physical association 15601262 , (Europe PMC )0.40 IntAct, MINT AP4E1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID AXIN1 Affinity Capture-Western physical 17726008 , (Europe PMC )NA BioGRID BAG3 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID BAG6 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID BTK Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID CDC42 Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 25241761 , 9079650 , (Europe PMC )0.40 BioGRID, IntAct CHUK Biochemical Activity physical 22547678 , (Europe PMC )NA BioGRID CNTRL Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct CNTROB Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID FLNB pull down association, physical association 19270716 , (Europe PMC )0.50 IntAct, MINT GADD45A Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct GADD45B Affinity Capture-MS, Affinity Capture-Western, Two-hybrid, anti bait coimmunoprecipitation, dihydrofolate reductase reconstruction physical, physical association 12052864 , 16256071 , 28514442 , 9827804 , (Europe PMC )0.57 BioGRID, IntAct, MINT GADD45G Affinity Capture-Western, Two-hybrid, dihydrofolate reductase reconstruction physical, physical association 12052864 , 9827804 , (Europe PMC )0.37 BioGRID, IntAct GOLT1B Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID GSK3B Biochemical Activity physical 17726008 , (Europe PMC )NA BioGRID HNRNPD Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID INTS14 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF21A Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF23 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID KIF7 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID MAP2K1 Biochemical Activity physical 9841871 , (Europe PMC )NA BioGRID MAP2K3 Biochemical Activity, Co-localization, Reconstituted Complex, proximity ligation assay physical, physical association 15866172 , 25241761 , 9841871 , (Europe PMC )0.40 BioGRID, IntAct MAP2K4 Biochemical Activity, Reconstituted Complex physical 15866172 , 9841871 , (Europe PMC )NA BioGRID MAP2K6 Biochemical Activity, Co-localization, Reconstituted Complex, Two-hybrid, proximity ligation assay, two hybrid physical, physical association 12052864 , 15866172 , 16157600 , 17726008 , 25241761 , 9841871 , (Europe PMC )0.57 BioGRID, IntAct MAP2K7 Reconstituted Complex physical 15866172 , (Europe PMC )NA BioGRID MAP3K4 Biochemical Activity, two hybrid physical, physical association 12052864 , 17726008 , (Europe PMC )0.37 BioGRID, IntAct MAPK13 Co-localization, proximity ligation assay physical, physical association 25241761 , (Europe PMC )0.40 BioGRID, IntAct MAPK8 Affinity Capture-MS, Biochemical Activity physical 21152872 , 26496610 , (Europe PMC )NA BioGRID MFHAS1 protein array direct interaction 29513927 , (Europe PMC )0.44 IntAct NEDD1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID POLR2F Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID PTK2B anti bait coimmunoprecipitation, imaging technique colocalization, physical association 15601262 , (Europe PMC )0.46 IntAct, MINT PTPN6 experimental interaction detection, imaging technique colocalization, dephosphorylation reaction 15601262 , (Europe PMC )0.40 IntAct, MINT RAC1 Reconstituted Complex physical 9079650 , (Europe PMC )NA BioGRID RAP1B Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID RIPK2 Affinity Capture-Western physical 21097508 , (Europe PMC )NA BioGRID SGTB Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SH3KBP1 Affinity Capture-Western, Reconstituted Complex, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, pull down physical, physical association 16256071 , 20221403 , 23085457 , (Europe PMC )0.59 BioGRID, IntAct, MINT SIGLECL1 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID SORT1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SPATA1 Affinity Capture-MS physical 28514442 , (Europe PMC )NA BioGRID SRPRA Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID SYNCRIP Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID TOP1 Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TOP2A Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TOP3A Synthetic Lethality genetic 27453043 , (Europe PMC )NA BioGRID TPR Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct TRAF4 Affinity Capture-Western physical 16157600 , 21097508 , (Europe PMC )NA BioGRID UBC anti bait coimmunoprecipitation, anti tag coimmunoprecipitation physical association 16256071 , (Europe PMC )0.52 IntAct, MINT USF1 Affinity Capture-MS physical 26496610 , (Europe PMC )NA BioGRID YWHAZ Two-hybrid, two hybrid pooling approach physical, physical association 20936779 , (Europe PMC )0.37 BioGRID, IntAct ZFP36 Affinity Capture-Western physical 20221403 , (Europe PMC )NA BioGRID
Phosphorylating Kinases Phosphoresidues Detection Method PubMed IDs Source
Visualize a network of protein kinases and phosphatases phosphorylating and dephosphorylating this protein respectively
MAP3K4 T1494_KLKNNAQtMPGEVNS , NA NA PhosphoSitePlus , Unknown S431_WPVFEIPsPRPSKGN , S456_GELKELEsSTDESEE , S457_ELKELESsTDESEEE , S461_LESSTDEsEEEQISD , S499_KKLERLEsEDDSLGW , T447_PEYEGDDtEGELKEL , T458_LKELESStDESEEEQ , in vivo 19413330 , 19651622 ,(Europe PMC )HPRD,
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