O08648

SS
Gene name
Map3k4 (Mekk4)
Protein name
Mitogen-activated protein kinase kinase kinase 4
Names
MAPK/ERK kinase kinase 4, MEK kinase 4, MEKK 4
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:26407
EC number
2.7.11.25: Protein-serine/threonine kinases
Protein Class

Descriptions

MAP3K4 is mitogen-activated protein kinase kinase kinase 4, activates two families of stress-responsive MAPKs, JNK and p38, in response to stimuli such as UV radiation, ionizing radiation, hyperosmolarity, oxidative stress, and translation inhibitors, as well as cytokines. In human MAP3K4 (Q9Y6R4), autoinhibitory region locates at N-terminal region. The MAP3K4 autoinhibitory region interacts with its C-terminal kinase domain via multiple interactions, thus preventing C-terminal kinase domain from interacting with its substrate, MKK6.

Autoinhibitory domains (AIDs)

246-544 (Autoinhibitory region) SS

Target domain

1332-1590 (Protein kinase domain)

Relief mechanism

Partner binding

Assay

Accessory elements

1469-1478 (Activation loop from InterPro)

Target domain

1332-1590 (Protein kinase domain)

Relief mechanism

Assay

1490-1496 (Activation loop from InterPro)

Target domain

1332-1590 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for O08648

Entry ID Method Resolution Chain Position Source
AF-O08648-F1 Predicted AlphaFoldDB

20 variants for O08648

Variant ID(s) Position Change Description Diseaes Association Provenance
rs47127344 54 R>H No Ensembl
rs47150245 231 V>A No Ensembl
rs238449748 304 S>A No Ensembl
rs107752070 307 G>E No Ensembl
rs51990131 314 L>S No Ensembl
rs108210665 323 Q>H No Ensembl
rs247349527 378 D>E No Ensembl
rs52454427 425 P>L No Ensembl
rs52640142 437 V>G No Ensembl
rs52644682 464 V>A No Ensembl
rs252363238 473 A>T No Ensembl
rs248532987 478 R>H No Ensembl
rs223948827 485 R>G No Ensembl
rs236432086 497 I>V No Ensembl
rs1133525477 670 G>R No Ensembl
rs51233076 835 A>T No Ensembl
rs259191799 835 A>V No Ensembl
rs47570998 915 A>T No Ensembl
rs33476886 1187 A>T No Ensembl
rs46379368 1227 I>V No Ensembl

No associated diseases with O08648

3 regional properties for O08648

Type Name Position InterPro Accession
domain SUN domain 622 - 784 IPR012919
domain SUN domain-containing protein 1, N-terminal 63 - 291 IPR032680
domain SUN coiled coil domain 2 547 - 605 IPR040994

Functions

Description
EC Number 2.7.11.25 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm, perinuclear region
  • Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.

6 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
MAP kinase kinase kinase activity Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases.
metal ion binding Binding to a metal ion.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

13 GO annotations of biological process

Name Definition
chorionic trophoblast cell differentiation The process in which relatively unspecialized cells of the ectoplacental cone acquire specialized structural and/or functional features that characterize chorionic trophoblasts. These cells will migrate towards the spongiotrophoblast layer and give rise to syncytiotrophoblasts of the labyrinthine layer.
determination of dorsal identity Determination of the identity of part of an organism or organ where those parts are of the type that occur in the dorsal region. Identity is considered to be the aggregate of characteristics by which a structure is recognized.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
male germ-line sex determination The determination of sex and sexual phenotype in a male organism's germ line.
MAPK cascade An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell.
placenta development The process whose specific outcome is the progression of the placenta over time, from its formation to the mature structure. The placenta is an organ of metabolic interchange between fetus and mother, partly of embryonic origin and partly of maternal origin.
positive regulation of JUN kinase activity Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of p38MAPK cascade Any process that activates or increases the frequency, rate or extent of p38MAPK cascade.
positive regulation of telomerase activity Any process that activates or increases the frequency, rate or extent of telomerase activity, the catalysis of the reaction: deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
positive regulation of telomere capping Any process that activates or increases the frequency, rate or extent of telomere capping.
positive regulation of telomere maintenance via telomerase Any process that activates or increases the frequency, rate or extent of the addition of telomeric repeats by telomerase.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
response to UV-C Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a UV-C radiation stimulus. UV-C radiation (UV-C light) spans the wavelengths 100 to 280 nm.

2 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9Y6R4 MAP3K4 Mitogen-activated protein kinase kinase kinase 4 Homo sapiens (Human) EV
Q07174 Map3k8 Mitogen-activated protein kinase kinase kinase 8 Mus musculus (Mouse) SS
10 20 30 40 50 60
MRDAIAEPVP PPALADTPAA AMEELRPAPP PQPEPDPECC PAARQECMLG ESARKSMESD
70 80 90 100 110 120
PEDFSDETNT ETLYGTSPPS TPRQMKRLSA KHQRNSAGRP ASRSNLKEKM NTPSQSPHKD
130 140 150 160 170 180
LGKGVETVEE YSYKQEKKIR ATLRTTERDH KKNAQCSFML DSVAGSLPKK SIPDVDLNKP
190 200 210 220 230 240
YLSLGCSNAK LPVSMPMPIA RTARQTSRTD CPADRLKFFE TLRLLLKLTS VSKKKDREQR
250 260 270 280 290 300
GQENTAAFWF NRSNELIWLE LQAWHAGRTI NDQDLFLYTA RQAIPDIINE ILTFKVNYGS
310 320 330 340 350 360
IAFSSNGAGF NGPLVEGQCR TPQETNRVGC SSYHEHLQRQ RVSFEQVKRI MELLEYMEAL
370 380 390 400 410 420
YPSLQALQKD YERYAAKDFE DRVQALCLWL NITKDLNQKL RIMGTVLGIK NLSDIGWPVF
430 440 450 460 470 480
EIPSPRPSKG YEPEDEVEDT EVELRELESG TEESDEEPTP SPRVPELRLS TDAILDSRSQ
490 500 510 520 530 540
GCVSRKLERL ESEEDSIGWG TADCGPEASR HCLTSIYRPF VDKALKQMGL RKLILRLHKL
550 560 570 580 590 600
MNGSLQRARV ALVKDDRPVE FSDFPGPMWG SDYVQLSGTP PSSEQKCSAV SWEELRAMDL
610 620 630 640 650 660
PSFEPAFLVL CRVLLNVIHE CLKLRLEQRP AGEPSLLSIK QLVRECKEVL KGGLLMKQYY
670 680 690 700 710 720
QFMLQEVLGG LEKTDCNMDA FEEDLQKMLM VYFDYMRSWI QMLQQLPQAS HSLKNLLEEE
730 740 750 760 770 780
WNFTKEITHY IRGGEAQAGK LFCDIAGMLL KSTGSFLESG LQESCAELWT SADDNGAADE
790 800 810 820 830 840
LRRSVIEISR ALKELFHEAR ERASKALGFA KMLRKDLEIA AEFVLSASAR ELLDALKAKQ
850 860 870 880 890 900
YVKVQIPGLE NLHVFVPDSL AEEKKIILQL LNAATGKDCS KDPDDVFMDA FLLLTKHGDR
910 920 930 940 950 960
ARDSEDGWGT WEARAVKIVP QVETVDTLRS MQVDNLLLVV MESAHLVLQR KAFQQSIEGL
970 980 990 1000 1010 1020
MTVRHEQTSS QPIIAKGLQQ LKNDALELCN RISDAIDRVD HMFTLEFDAE VEESESATLQ
1030 1040 1050 1060 1070 1080
QYYREAMIQG YNFGFEYHKE VVRLMSGEFR QKIGDKYISF AQKWMNYVLT KCESGRGTRP
1090 1100 1110 1120 1130 1140
RWATQGFDFL QAIEPAFISA LPEDDFLSLQ ALMNECIGHV IGKPHSPVTA IHRNSPRPVK
1150 1160 1170 1180 1190 1200
VPRCHSDPPN PHLIIPTPEG FSTRSVPSDA RTHGNSVAAA AAVAAAATTA AGRPGPGGGD
1210 1220 1230 1240 1250 1260
SVPAKPVNTA PDTRGSSVPE NDRLASIAAE LQFRSLSRHS SPTEERDEPA YPRSDSSGST
1270 1280 1290 1300 1310 1320
RRSWELRTLI SQTKDSASKQ GPIEAIQKSV RLFEERRYRE MRRKNIIGQV CDTPKSYDNV
1330 1340 1350 1360 1370 1380
MHVGLRKVTF KWQRGNKIGE GQYGKVYTCI SVDTGELMAM KEIRFQPNDH KTIKETADEL
1390 1400 1410 1420 1430 1440
KIFEGIKHPN LVRYFGVELH REEMYIFMEY CDEGTLEEVS RLGLQEHVIR LYTKQITVAI
1450 1460 1470 1480 1490 1500
NVLHEHGIVH RDIKGANIFL TSSGLIKLGD FGCSVKLKNN AQTMPGEVNS TLGTAAYMAP
1510 1520 1530 1540 1550 1560
EVITRAKGEG HGRAADIWSL GCVVIEMVTG KRPWHEYEHN FQIMYKVGMG HKPPIPERLS
1570 1580 1590
PEGKAFLSHC LESDPKIRWT ASQLLDHAFV KVCTDEE