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)

Target domain

312-401 (PH domain);427-549 (Arf GAP domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for A1Z7A6

Entry ID Method Resolution Chain Position Source
AF-A1Z7A6-F1 Predicted AlphaFoldDB

No variants for A1Z7A6

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for A1Z7A6

No associated diseases with A1Z7A6

3 regional properties for A1Z7A6

Type Name Position InterPro Accession
domain Cation-transporting P-type ATPase, N-terminal 21 - 93 IPR004014
ptm P-type ATPase, phosphorylation site 337 - 343 IPR018303
domain P-type ATPase, haloacid dehalogenase domain 317 - 645 IPR044492

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

5 GO annotations of cellular component

Name Definition
apical part of cell The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
microvillus Thin cylindrical membrane-covered projections on the surface of an animal cell containing a core bundle of actin filaments. Present in especially large numbers on the absorptive surface of intestinal cells.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

3 GO annotations of molecular function

Name Definition
GTPase activator activity Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP.
metal ion binding Binding to a metal ion.
phosphatidylinositol phosphate binding Binding to phosphatidylinositol phosphate.

5 GO annotations of biological process

Name Definition
compound eye morphogenesis The morphogenetic process in which the anatomical structures of the compound eye are generated and organized. The adult compound eye is a precise assembly of 700-800 ommatidia. Each ommatidium is composed of 20 cells, identified by cell type and position. An example of compound eye morphogenesis is found in Drosophila melanogaster.
mitotic cleavage furrow ingression Advancement of the mitotic cleavage furrow from the outside of the cell inward towards the center of the cell. The cleavage furrow acts as a 'purse string' which draws tight to separate daughter cells during mitotic cytokinesis and partition the cytoplasm between the two daughter cells. The furrow ingresses until a cytoplasmic bridge is formed.
positive regulation of protein localization Any process that activates or increases the frequency, rate or extent of a protein localization.
regulation of Golgi organization Any process that modulates the frequency, rate or extent of Golgi organization.
regulation of GTPase activity Any process that modulates the rate of GTP hydrolysis by a GTPase.

15 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A5PK26 ACAP1 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1 Bos taurus (Bovine) SS
O97902 ASAP1 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 Bos taurus (Bovine) SS
Q15027 ACAP1 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1 Homo sapiens (Human) EV
Q15057 ACAP2 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 Homo sapiens (Human) PR
Q9ULH1 ASAP1 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 Homo sapiens (Human) EV
Q8TDY4 ASAP3 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 Homo sapiens (Human) SS
O43150 ASAP2 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 Homo sapiens (Human) SS
Q8K2H4 Acap1 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1 Mus musculus (Mouse) SS
Q6ZQK5 Acap2 Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 Mus musculus (Mouse) PR
Q9QWY8 Asap1 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 Mus musculus (Mouse) SS
Q7SIG6 Asap2 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 Mus musculus (Mouse) SS
Q5U464 Asap3 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 Mus musculus (Mouse) SS
Q1AAU6 Asap1 Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 Rattus norvegicus (Rat) SS
Q9C6C3 AGD2 ADP-ribosylation factor GTPase-activating protein AGD2 Arabidopsis thaliana (Mouse-ear cress) PR
Q9SMX5 AGD4 ADP-ribosylation factor GTPase-activating protein AGD4 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MEEEEGAAAR EWGATPAGPV WTAVFDYEAV GDEELTLRRG DRVQVLSQDC AVSGDEGWWT
70 80 90 100 110 120
GQLPSGRVGV FPSNYVAPAA PAAPSDLQLP QEIPFHELQL EEIIGVGGFG KVYRAVWRGE
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 MDCGGSSGSG TWSRSGPPKK
550 560 570 580 590 600
EELVGGKKKG RTWGPSSTLQ KERAGGEERL KALGEGSKQW SSSAPNLGKS PKHTPMAPGF
610 620 630 640 650 660
ASLNEMEEFA EADEGNNVPP SPYSTPSYLK VPLPAEPSPC VQAPWEPPAV TPSRPGHGAR
670 680 690 700 710 720
RRCDLALLSC ATLLSAVGLG ADVAEARAGD GEEQRRWLDS LFFPRPGRFP RGLSPTGRPG
730 740 750 760 770 780
GRREDTAPGL GLAPSATLVS LSSVSDCNST RSLLRSDSDE AAPAAPSPPP SPLAPSPSTN
790 800 810 820 830 840
PLVDVELESF KKDPRQSLTP THVTAAHAVS RGHRRTPSDG ALRQREPLEL TNHGPRDPLD
850 860 870 880 890 900
FPRLPDPQAL FPTRRRPLEF PGRPTTLTFA PRPRPAASRP RLDPWKLVSF GRTLSISPPS
910 920 930
RPDTPESPGP PSVQPTLLDM DMEGQSQDNT VPLCGVYGSH