D3ZG83

SS
Gene name
Map3k10
Protein name
Mitogen-activated protein kinase kinase kinase 10
Names
EC 2.7.11.25
Species
Rattus norvegicus (Rat)
KEGG Pathway
EC number
2.7.11.25: Protein-serine/threonine kinases
Protein Class

Descriptions

Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAPKKK) that activates the c-Jun N-terminal kinase (JNK) pathway through the dual phosphorylation of mitogen-activated protein kinase kinases 4/7 (MKK4/7). The catalytic domain of MLK3 is flanked by an N-terminal SH3 domain and a centrally located zipper and Cdc42/Rac-interactive binding (CRIB) motif. Zipper-mediated homo-oligomerization is required for full activity of MLK3, proper substrate phosphorylation, and activation of the JNK pathway. MLK3 is autoinhibited through an interaction between its SH3 domain and a proline-containing sequence between the zipper and the CRIB motif. Activated forms of the small GTPases Cdc42 and Rac interact with MLK3 in a CRIB motif-dependent manner to increase the autophosphorylation of MLK3 and substrate phosphorylation activity and to potentiate MLK3-induced activation of JNK. Activated Cdc42 translocates MLK3 to membranes and induces activation loop phosphorylation of MLK3.

Autoinhibitory domains (AIDs)

18-81 (SH3 domain) SS

Target domain

444-467 (Proline-rich region)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for D3ZG83

Entry ID Method Resolution Chain Position Source
AF-D3ZG83-F1 Predicted AlphaFoldDB

No variants for D3ZG83

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for D3ZG83

No associated diseases with D3ZG83

6 regional properties for D3ZG83

Type Name Position InterPro Accession
domain Protein kinase domain 98 - 360 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 98 - 357 IPR001245
domain SH3 domain 16 - 81 IPR001452
active_site Serine/threonine-protein kinase, active site 218 - 230 IPR008271
binding_site Protein kinase, ATP binding site 104 - 125 IPR017441
domain MLK1-3, SH3 domain 20 - 76 IPR035779

Functions

Description
EC Number 2.7.11.25 Protein-serine/threonine kinases
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

1 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
bHLH transcription factor binding Binding to a basic Helix-Loop-Helix (bHLH) superfamily of transcription factors, important regulatory components in transcriptional networks of many developmental pathways.
JUN kinase kinase kinase activity Catalysis of the reaction
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions
transcription corepressor activity A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators.

5 GO annotations of biological process

Name Definition
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
positive regulation of apoptotic process Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of JNK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
smoothened signaling pathway The series of molecular signals generated as a consequence of activation of the transmembrane protein Smoothened.

39 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A2VDU3 MAP3K7 Mitogen-activated protein kinase kinase kinase 7 Bos taurus (Bovine) SS
Q4TVR5 DSTYK Dual serine/threonine and tyrosine protein kinase Bos taurus (Bovine) PR
Q3SZJ2 RIPK2 Receptor-interacting serine/threonine-protein kinase 2 Bos taurus (Bovine) PR
Q6XUX0 DSTYK Dual serine/threonine and tyrosine protein kinase Gallus gallus (Chicken) PR
P83104 Takl1 Putative mitogen-activated protein kinase kinase kinase 7-like Drosophila melanogaster (Fruit fly) PR
Q95UN8 slpr Mitogen-activated protein kinase kinase kinase Drosophila melanogaster (Fruit fly) EV
O43353 RIPK2 Receptor-interacting serine/threonine-protein kinase 2 Homo sapiens (Human) PR
Q8NB16 MLKL Mixed lineage kinase domain-like protein Homo sapiens (Human) EV
Q16584 MAP3K11 Mitogen-activated protein kinase kinase kinase 11 Homo sapiens (Human) EV
P00540 MOS Proto-oncogene serine/threonine-protein kinase mos Homo sapiens (Human) PR
Q5TCX8 MAP3K21 Mitogen-activated protein kinase kinase kinase 21 Homo sapiens (Human) PR
Q6XUX3 DSTYK Dual serine/threonine and tyrosine protein kinase Homo sapiens (Human) PR
O43318 MAP3K7 Mitogen-activated protein kinase kinase kinase 7 Homo sapiens (Human) SS
Q9NYL2 MAP3K20 Mitogen-activated protein kinase kinase kinase 20 Homo sapiens (Human) PR
Q38SD2 LRRK1 Leucine-rich repeat serine/threonine-protein kinase 1 Homo sapiens (Human) EV
P80192 MAP3K9 Mitogen-activated protein kinase kinase kinase 9 Homo sapiens (Human) SS
Q02779 MAP3K10 Mitogen-activated protein kinase kinase kinase 10 Homo sapiens (Human) SS
Q80XI6 Map3k11 Mitogen-activated protein kinase kinase kinase 11 Mus musculus (Mouse) PR
Q8VDG6 Map3k21 Mitogen-activated protein kinase kinase kinase 21 Mus musculus (Mouse) PR
P58801 Ripk2 Receptor-interacting serine/threonine-protein kinase 2 Mus musculus (Mouse) PR
Q62073 Map3k7 Mitogen-activated protein kinase kinase kinase 7 Mus musculus (Mouse) EV
Q3U1V8 Map3k9 Mitogen-activated protein kinase kinase kinase 9 Mus musculus (Mouse) SS
Q9D2Y4 Mlkl Mixed lineage kinase domain-like protein Mus musculus (Mouse) SS
Q9ESL4 Map3k20 Mitogen-activated protein kinase kinase kinase 20 Mus musculus (Mouse) PR
P00536 Mos Proto-oncogene serine/threonine-protein kinase mos Mus musculus (Mouse) PR
Q66L42 Map3k10 Mitogen-activated protein kinase kinase kinase 10 Mus musculus (Mouse) SS
P0C8E4 Map3k7 Mitogen-activated protein kinase kinase kinase 7 Rattus norvegicus (Rat) SS
P00539 Mos Proto-oncogene serine/threonine-protein kinase mos Rattus norvegicus (Rat) PR
Q66HA1 Map3k11 Mitogen-activated protein kinase kinase kinase 11 Rattus norvegicus (Rat) PR
P11345 Raf1 RAF proto-oncogene serine/threonine-protein kinase Rattus norvegicus (Rat) SS
P14056 Araf Serine/threonine-protein kinase A-Raf Rattus norvegicus (Rat) PR
Q9TZM3 lrk-1 Leucine-rich repeat serine/threonine-protein kinase 1 Caenorhabditis elegans SS
Q9FPR3 EDR1 Serine/threonine-protein kinase EDR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
Q05609 CTR1 Serine/threonine-protein kinase CTR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q67E00 dstyk Dual serine/threonine and tyrosine protein kinase Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) PR
10 20 30 40 50 60
MEEEEGAAAR EWGATPAGPV WTAVFDYEAV GDEELTLRRG DRVQVLSQDC AVSGDEGWWT
70 80 90 100 110 120
GQLPSGRVGV FPSNYVAPAA PAAPTDLQLP QEIPFHELQL EEIIGVGGFG KVYRALWRGE
130 140 150 160 170 180
EVAVKAARLD PERDPAVTAE QVRQEARLFG ALQHPNIIAL RGACLSPPNL CLVMEYARGG
190 200 210 220 230 240
ALSRVLAGRR VPPHVLVNWA VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA
250 260 270 280 290 300
DTVLKITDFG LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE
310 320 330 340 350 360
VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF GSILKQLEVI
370 380 390 400 410 420
EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS REEELLRAAQ EQRFQEEQLR
430 440 450 460 470 480
RREQELAERE MDIVERELHL LMSQLSQEKP RVRKRKGNFK RSRLLKLREG SSHISLPSGF
490 500 510 520 530 540
EHKITVQASP TLDKRKGSDG ASPPASPSII PRLRAIRLTP VDCGSSGGSG TWSRSGPPKK
550 560 570 580 590 600
EELVGGKKKG RTWGPSSTLQ KERAGGEERL KALGEGSKQW SSSAPNLGKS PKHTPMAPGF
610 620 630 640 650 660
ASLNEMEEFA EADEGNNVPP SPYSTPSYLK VPLPAEASPC AQPPWEPPAA TPSRPGHGAR
670 680 690 700 710 720
RRCDLALLGC ATLLSAVGLG ADVAEARAGD GEEQRGWLDG LFFPRPGRFP RGLSPTGRPG
730 740 750 760 770 780
GRREETAPGF GLAPSATLVS LSSVSDCNST RSLLRSDSDE AAPTAPSPPP SLLPPSPSTN
790 800 810 820 830 840
PLVDVELESF KKDPRQSLTP THVTAAHAVS RGHRRTPSDG ALRQREPPEL TNHGPRDPLD
850 860 870 880 890 900
FPRLPDPQAL FPTRRRPLEF PGRPTTLTFA PRPRPAASRP RLDPWKLVSF GRTLSISPPS
910 920 930
RPDTPESPGP LSVQPTLLDM DMEGQSQDNT VPLCGAYGSH