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Overview

Uniprot IDO95819
Protein NameMitogen-activated protein kinase kinase kinase kinase 4
Gene NameMAP4K4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
670 LLWERVEKLVPRPGS

Function

Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF. Appears to act upstream of the JUN N-terminal pathway (PubMed:9890973). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). Phosphorylates SMAD1 on Thr-322 (PubMed:21690388)

Protein Sequence

10 MANDSPAKSL 20 VDIDLSSLRD 30 PAGIFELVEV 40 VGNGTYGQVY 50 KGRHVKTGQL 60 AAIKVMDVTE 70 DEEEEIKLEI 80 NMLKKYSHHR 90 NIATYYGAFI 100 KKSPPGHDDQ 110 LWLVMEFCGA 120 GSITDLVKNT 130 KGNTLKEDWI 140 AYISREILRG 150 LAHLHIHHVI 160 HRDIKGQNVL 170 LTENAEVKLV 180 DFGVSAQLDR 190 TVGRRNTFIG 200 TPYWMAPEVI 210 ACDENPDATY 220 DYRSDLWSCG 230 ITAIEMAEGA 240 PPLCDMHPMR 250 ALFLIPRNPP 260 PRLKSKKWSK 270 KFFSFIEGCL 280 VKNYMQRPST 290 EQLLKHPFIR 300 DQPNERQVRI 310 QLKDHIDRTR 320 KKRGEKDETE 330 YEYSGSEEEE 340 EEVPEQEGEP 350 SSIVNVPGES 360 TLRRDFLRLQ 370 QENKERSEAL 380 RRQQLLQEQQ 390 LREQEEYKRQ 400 LLAERQKRIE 410 QQKEQRRRLE 420 EQQRREREAR 430 RQQEREQRRR 440 EQEEKRRLEE 450 LERRRKEEEE 460 RRRAEEEKRR 470 VEREQEYIRR 480 QLEEEQRHLE 490 VLQQQLLQEQ 500 AMLLECRWRE 510 MEEHRQAERL 520 QRQLQQEQAY 530 LLSLQHDHRR 540 PHPQHSQQPP 550 PPQQERSKPS 560 FHAPEPKAHY 570 EPADRAREVE 580 DRFRKTNHSS 590 PEAQSKQTGR 600 VLEPPVPSRS 610 ESFSNGNSES 620 VHPALQRPAE 630 PQVPVRTTSR 640 SPVLSRRDSP 650 LQGSGQQNSQ 660 AGQRNSTSIE 670 PRLLWERVEK 680 LVPRPGSGSS 690 SGSSNSGSQP 700 GSHPGSQSGS 710 GERFRVRSSS 720 KSEGSPSQRL 730 ENAVKKPEDK 740 KEVFRPLKPA 750 DLTALAKELR 760 AVEDVRPPHK 770 VTDYSSSSEE 780 SGTTDEEDDD 790 VEQEGADEST 800 SGPEDTRAAS 810 SLNLSNGETE 820 SVKTMIVHDD 830 VESEPAMTPS 840 KEGTLIVRQT 850 QSASSTLQKH 860 KSSSSFTPFI 870 DPRLLQISPS 880 SGTTVTSVVG 890 FSCDGMRPEA 900 IRQDPTRKGS 910 VVNVNPTNTR 920 PQSDTPEIRK 930 YKKRFNSEIL 940 CAALWGVNLL 950 VGTESGLMLL 960 DRSGQGKVYP 970 LINRRRFQQM 980 DVLEGLNVLV 990 TISGKKDKLR 1000 VYYLSWLRNK 1010 ILHNDPEVEK 1020 KQGWTTVGDL 1030 EGCVHYKVVK 1040 YERIKFLVIA 1050 LKSSVEVYAW 1060 APKPYHKFMA 1070 FKSFGELVHK 1080 PLLVDLTVEE 1090 GQRLKVIYGS 1100 CAGFHAVDVD 1110 SGSVYDIYLP 1120 THIQCSIKPH 1130 AIIILPNTDG 1140 MELLVCYEDE 1150 GVYVNTYGRI 1160 TKDVVLQWGE 1170 MPTSVAYIRS 1180 NQTMGWGEKA 1190 IEIRSVETGH 1200 LDGVFMHKRA 1210 QRLKFLCERN 1220 DKVFFASVRS 1230 GGSSQVYFMT LGRTSLLSW

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005925 focal adhesion
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004111 creatine kinase activity
Molecular Function GO:0008349 MAP kinase kinase kinase kinase activity
Molecular Function GO:0008017 microtubule binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0000165 MAPK cascade
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:0001953 negative regulation of cell-matrix adhesion
Biological Process GO:0048812 neuron projection morphogenesis
Biological Process GO:0032014 positive regulation of ARF protein signal transduction
Biological Process GO:0030335 positive regulation of cell migration
Biological Process GO:0051894 positive regulation of focal adhesion assembly
Biological Process GO:0120183 positive regulation of focal adhesion disassembly
Biological Process GO:0035332 positive regulation of hippo signaling
Biological Process GO:0051549 positive regulation of keratinocyte migration
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0046328 regulation of JNK cascade
Biological Process GO:0043408 regulation of MAPK cascade

Reference

[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.