UniProtKB - P70218 (M4K1_MOUSE)
Mitogen-activated protein kinase kinase kinase kinase 1
Map4k1
Functioni
Serine/threonine-protein kinase, which may play a role in the response to environmental stress (By similarity).
Appears to act upstream of the JUN N-terminal pathway (PubMed:9003777).
May play a role in hematopoietic lineage decisions and growth regulation (PubMed:9003777).
Able to autophosphorylate (PubMed:9003777).
Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (PubMed:11509653).
By similarity2 PublicationsCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 46 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 137 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 23 – 31 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- MAP kinase kinase kinase kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cell population proliferation Source: UniProtKB
- cellular response to phorbol 13-acetate 12-myristate Source: MGI
- intracellular signal transduction Source: UniProtKB
- JNK cascade Source: MGI
- peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of MAPK cascade Source: MGI
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase kinase 1 (EC:2.7.11.12 Publications)Alternative name(s): Hematopoietic progenitor kinase Short name: HPK MAPK/ERK kinase kinase kinase 1 Short name: MEK kinase kinase 1 Short name: MEKKK 1 |
Gene namesi | Name:Map4k1 Synonyms:Hpk1 |
Organismi | Mus musculus (Mouse)Imported |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1346882, Map4k1 |
VEuPathDBi | HostDB:ENSMUSG00000037337 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 46 | K → E: Loss of kinase activity and ability to activate JNK family. Inhibits the ability of CLNK to up-regulate CD3-triggered activation of the IL2 promoter. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086274 | 1 – 827 | Mitogen-activated protein kinase kinase kinase kinase 1Add BLAST | 827 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 165 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 171 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 175 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 354 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 373 | PhosphoserineCombined sources | 1 | |
Modified residuei | 375 | PhosphoserineCombined sources | 1 | |
Modified residuei | 403 | PhosphoserineBy similarity | 1 | |
Modified residuei | 405 | PhosphoserineBy similarity | 1 | |
Modified residuei | 419 | PhosphoserineCombined sources | 1 | |
Modified residuei | 592 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P70218 |
jPOSTi | P70218 |
MaxQBi | P70218 |
PaxDbi | P70218 |
PeptideAtlasi | P70218 |
PRIDEi | P70218 |
ProteomicsDBi | 291987 |
PTM databases
iPTMneti | P70218 |
PhosphoSitePlusi | P70218 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000037337, Expressed in spleen and 161 other tissues |
Genevisiblei | P70218, MM |
Interactioni
Subunit structurei
Interacts with MAP3K1 (By similarity).
Interacts with FBXW8 (By similarity).
Interacts with CLNK (via its SH2 domain) (PubMed:11509653).
By similarity1 PublicationBinary interactionsi
P70218
With | #Exp. | IntAct |
---|---|---|
CARD11 [Q9BXL7] from Homo sapiens. | 2 | EBI-2906801,EBI-7006141 |
MAP3K11 [Q16584] from Homo sapiens. | 3 | EBI-2906801,EBI-49961 |
Protein-protein interaction databases
BioGRIDi | 204964, 6 interactors |
DIPi | DIP-42073N |
IntActi | P70218, 7 interactors |
MINTi | P70218 |
STRINGi | 10090.ENSMUSP00000082995 |
Miscellaneous databases
RNActi | P70218, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P70218 |
SMRi | P70218 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P70218 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 274 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 501 – 806 | CNHPROSITE-ProRule annotationAdd BLAST | 306 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 296 – 315 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 359 – 485 | DisorderedSequence analysisAdd BLAST | 127 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 296 – 312 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 387 – 401 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 430 – 444 | Pro residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000160308 |
HOGENOMi | CLU_006347_1_1_1 |
InParanoidi | P70218 |
OMAi | FLCCALD |
OrthoDBi | 996262at2759 |
PhylomeDBi | P70218 |
TreeFami | TF105121 |
Family and domain databases
IDEALi | IID50083 |
InterProi | View protein in InterPro IPR001180, CNH_dom IPR011009, Kinase-like_dom_sf IPR021160, MAPKKKK IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS |
Pfami | View protein in Pfam PF00780, CNH, 1 hit PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF038172, MAPKKKK, 1 hit |
SMARTi | View protein in SMART SM00036, CNH, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50219, CNH, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MALVDPDIFN KDPREHYDLL QRLGGGTYGE VFKARDKVSK DLVALKMVKM
60 70 80 90 100
EPDDDVATLQ KEILMLKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ
110 120 130 140 150
DIYQVTGSLS ELQISYVCRE VLQGLAYLHS EKKIHRDIKG ANILINDCGE
160 170 180 190 200
VKLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS
210 220 230 240 250
LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK SRWSSSFHNF
260 270 280 290 300
VKVTLTKNSK KRPSATKMLS HQLVSQPGLN RGLILDLLDK MKNPGKGLPV
310 320 330 340 350
DIEDEEPEPP PAIPRRIRST YRASSLGIPD ADCCRRQMEF QRPRCVDCRP
360 370 380 390 400
QAETVRLYPP AHFGSTSPRS QLSDSDDDYD DVDIPAPSEN IPPPLPPKPK
410 420 430 440 450
FRSPSDDGSG GIRDDGQLSP GVLVRCASGP PPRTPRPGPP PATCSPHLTA
460 470 480 490 500
RSDPSLWNPA APEPGQPPLV PPRKEKMRGK MENEKRREKY PLLVKLFNGC
510 520 530 540 550
PLQIHSTAAW THPSTKDQNL LLGAEEGIFI LNRNDQEATL EMIFPGRTTW
560 570 580 590 600
LYCINNLLMS LSGKTPYLYS HSILGLLERK DGRTGSPIAH ISPHRLLARK
610 620 630 640 650
NMVSSKIQDT KGCRACCVAE SASSGGPFLC GALETSVVLL QWYQPMNKFL
660 670 680 690 700
LVRQVLFPLP TPLPVFTLLT TPGSELPAVC IGVSPGQAAK SVLFHTVRFG
710 720 730 740 750
ALSCWLDDSS TEHKGPVQVI QVKEDMVMVL MDGSLKLVTP EGAPAPGLRT
760 770 780 790 800
PEIPMTEAVE AVAMVEDRLE AFWKHGVQVW APGLKQPLQE LRDPTLTFRL
810 820
LCSPRPVVVE TRPTDDPTAP SNLYIQE
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A140LJF0 | A0A140LJF0_MOUSE | Non-specific serine/threonine prote... | Map4k1 | 641 | Annotation score: | ||
Q3UPT4 | Q3UPT4_MOUSE | Mitogen-activated protein kinase ki... | Map4k1 | 750 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 411 | G → V in AAH24832 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 444 | C → R in AAH05433 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 444 | C → R in AAH24832 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 807 | V → I in AAH24832 (PubMed:15489334).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y09010 mRNA Translation: CAA70213.1 BC005433 mRNA Translation: AAH05433.1 Sequence problems. BC024832 mRNA Translation: AAH24832.1 |
CCDSi | CCDS39865.1 |
RefSeqi | NP_032305.2, NM_008279.2 |
Genome annotation databases
Ensembli | ENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337 |
GeneIDi | 26411 |
KEGGi | mmu:26411 |
UCSCi | uc009gam.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y09010 mRNA Translation: CAA70213.1 BC005433 mRNA Translation: AAH05433.1 Sequence problems. BC024832 mRNA Translation: AAH24832.1 |
CCDSi | CCDS39865.1 |
RefSeqi | NP_032305.2, NM_008279.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1UTI | X-ray | 1.50 | D | 465-480 | [»] | |
AlphaFoldDBi | P70218 | |||||
SMRi | P70218 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 204964, 6 interactors |
DIPi | DIP-42073N |
IntActi | P70218, 7 interactors |
MINTi | P70218 |
STRINGi | 10090.ENSMUSP00000082995 |
PTM databases
iPTMneti | P70218 |
PhosphoSitePlusi | P70218 |
Proteomic databases
EPDi | P70218 |
jPOSTi | P70218 |
MaxQBi | P70218 |
PaxDbi | P70218 |
PeptideAtlasi | P70218 |
PRIDEi | P70218 |
ProteomicsDBi | 291987 |
Protocols and materials databases
Antibodypediai | 2067, 573 antibodies from 40 providers |
DNASUi | 26411 |
Genome annotation databases
Ensembli | ENSMUST00000085835; ENSMUSP00000082995; ENSMUSG00000037337 |
GeneIDi | 26411 |
KEGGi | mmu:26411 |
UCSCi | uc009gam.1, mouse |
Organism-specific databases
CTDi | 11184 |
MGIi | MGI:1346882, Map4k1 |
VEuPathDBi | HostDB:ENSMUSG00000037337 |
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000160308 |
HOGENOMi | CLU_006347_1_1_1 |
InParanoidi | P70218 |
OMAi | FLCCALD |
OrthoDBi | 996262at2759 |
PhylomeDBi | P70218 |
TreeFami | TF105121 |
Miscellaneous databases
BioGRID-ORCSi | 26411, 1 hit in 74 CRISPR screens |
ChiTaRSi | Map4k1, mouse |
EvolutionaryTracei | P70218 |
PROi | PR:P70218 |
RNActi | P70218, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000037337, Expressed in spleen and 161 other tissues |
Genevisiblei | P70218, MM |
Family and domain databases
IDEALi | IID50083 |
InterProi | View protein in InterPro IPR001180, CNH_dom IPR011009, Kinase-like_dom_sf IPR021160, MAPKKKK IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS |
Pfami | View protein in Pfam PF00780, CNH, 1 hit PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF038172, MAPKKKK, 1 hit |
SMARTi | View protein in SMART SM00036, CNH, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50219, CNH, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | M4K1_MOUSE | |
Accessioni | P70218Primary (citable) accession number: P70218 Secondary accession number(s): Q8R3R0, Q99K62 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 28, 2003 |
Last sequence update: | February 1, 1997 | |
Last modified: | May 25, 2022 | |
This is version 183 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families