Q4W5Z4

SS
Gene name
DNMT3A
Protein name
DNA
Names
cytosine-5-methyltransferase 3A , Dnmt3a , EC 2.1.1.37 , Cysteine methyltransferase DNMT3A , EC 2.1.1.-
Species
Mus musculus (Mouse)
KEGG Pathway
gga:421991
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)

441-591 (ADD-linker) SS

Target domain

592-877 (Catalytic domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q4W5Z4

Entry ID Method Resolution Chain Position Source
AF-Q4W5Z4-F1 Predicted AlphaFoldDB

No variants for Q4W5Z4

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q4W5Z4

No associated diseases with Q4W5Z4

15 regional properties for Q4W5Z4

Type Name Position InterPro Accession
domain Protein kinase domain 460 - 739 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 460 - 734 IPR001245
domain Immunoglobulin subtype 2 46 - 108 IPR003598-1
domain Immunoglobulin subtype 2 160 - 228 IPR003598-2
domain Immunoglobulin subtype 2 259 - 339 IPR003598-3
domain Immunoglobulin subtype 40 - 118 IPR003599-1
domain Immunoglobulin subtype 154 - 239 IPR003599-2
domain Immunoglobulin subtype 253 - 350 IPR003599-3
domain Immunoglobulin-like domain 16 - 122 IPR007110-1
domain Immunoglobulin-like domain 144 - 237 IPR007110-2
domain Immunoglobulin-like domain 246 - 348 IPR007110-3
domain Immunoglobulin I-set 37 - 102 IPR013098-1
domain Immunoglobulin I-set 159 - 238 IPR013098-2
domain Immunoglobulin I-set 253 - 349 IPR013098-3
binding_site Protein kinase, ATP binding site 466 - 496 IPR017441

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

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
euchromatin A dispersed and relatively uncompacted form of chromatin that is in a transcription-competent conformation.
nuclear matrix The dense fibrillar network lying on the inner side of the nuclear membrane.
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.

4 GO annotations of molecular function

Name Definition
core promoter sequence-specific DNA binding Binding to a sequence of DNA that is part of a core promoter region. The core promoter is composed of the transcription start site and binding sites for the RNA polymerase and the basal transcription machinery. The transcribed region might be described as a gene, cistron, or operon.
DNA (cytosine-5-)-methyltransferase activity Catalysis of the reaction
metal ion binding Binding to a metal ion.
protein-cysteine methyltransferase activity Catalysis of the reaction

5 GO annotations of biological process

Name Definition
methylation The process in which a methyl group is covalently attached to a molecule.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
negative regulation of gene expression via chromosomal CpG dinucleotide methylation An epigenetic gene regulation mechanism that negatively regulates gene expression by methylation of cytosine residues in chromosomal CpG islands. CpG islands are genomic regions that contain a high frequency of the CG dinucleotide and are often associated with the transcription start site of genes.
response to fibroblast growth factor 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 fibroblast growth factor stimulus.
response to heat 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 heat stimulus, a temperature stimulus above the optimal temperature for that organism.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9UBC3 DNMT3B DNA Homo sapiens (Human) EV
Q9Y6K1 DNMT3A DNA (cytosine-5)-methyltransferase 3A Homo sapiens (Human) EV
O88509 Dnmt3b DNA Mus musculus (Mouse) SS
O88508 Dnmt3a DNA Mus musculus (Mouse) EV
Q1LZ53 Dnmt3a DNA Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MESSRSLLGC LASATAAPPG DDATGAGAEE EEDEEEAAAE LGSHAALPYW TAVFEYEAAG
70 80 90 100 110 120
EDELTLRLGD VVEVLSKDSQ VSGDEGWWTG QLNQRVGIFP SNYVTPRSAF SSRCQPGAED
130 140 150 160 170 180
PSCYPPIQLL EIDFAELTLE EIIGIGGFGK VYRAFWAGDE VAVKAARHDP DEDISQTIEN
190 200 210 220 230 240
VRQEAKLFAM LKHPNIIALR GVCLKEPNLC LVMEFARGGP LNRVLSGKRI PPDILVNWAV
250 260 270 280 290 300
QIARGMNYLH DEAIVPIIHR DLKSSNILIL QKVENGDLSN KILKITDFGL AREWHRTTKM
310 320 330 340 350 360
SAAGTYAWMA PEVIRASMFS KGSDVWSYGV LLWELLTGEV PFRGIDGLAV AYGVAMNKLA
370 380 390 400 410 420
LPIPSTCPEP FAKLMEDCWN PDPHSRPSFT SILDQLTTIE ESGFFEMPKD SFHCLQDDWK
430 440 450 460 470 480
HEIQEMFDQL RAKEKELRTW EEELTRAALQ QKNQEELLRR REQELAEREI DILERELNII
490 500 510 520 530 540
IHQLCQEKPR VKKRKGKFRK SRLKLKDGNR ISLPSDFQHK FTVQASPTMD KRKSLISNRS
550 560 570 580 590 600
SPPASPTIIP RLRAIQLTPG ESSKTWGRSS VVPKEEGEEE EKRAPKKKGR TWGPGTLGQK
610 620 630 640 650 660
ELTSGDEGLK SLVDGYKQWS SSAPNLGKGP RSSPALPGFT SLMEIEDEDS EGPGSGENHQ
670 680 690 700 710 720
QHSPNQSYLC IPFPRGEDGD GPSSDGVHEE PTPVNSATST PQLTPTNSLK RGGTHHRRCE
730 740 750 760 770 780
VALLGCGAVL AATGLGFDLL EAGKCQLLPP EEPEPPAREE KKRREGLFQR ASRPRRSTSP
790 800 810 820 830 840
PSRKLFKKEE PMTLLGDPSA SLTLLSLSSI SECNSTRSLL RSDSDEIVVY EMPVSPVEAP
850 860 870 880 890 900
PLTQCTHNPL VNVRVERFKR DPNQSLTPTH VTLTAPTQPS GHRRTPSDGA LKPTAAPAVL
910 920 930 940 950 960
GSRSPSSNGM SPSPGTGMLK TPSPSRDPGE FPRLPDPNVV FPPTPRRWNT QRDSTLERPK
970 980 990 1000 1010 1020
TLEFLPRPRP SANRQRLDPW WFVSPSHARS ASPANSSSTE TPSNLDSCFA SSSSTVEERP
1030 1040 1050 1060 1070
GLPALLPLQA GPLLPAERTL LDLDAEGQSQ DSTVPLCRAE LNAHGPSPYE IQQEFWS