UniProtKB - Q92918 (M4K1_HUMAN)
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 (PubMed:24362026).
Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585).
May play a role in hematopoietic lineage decisions and growth regulation (PubMed:8824585, PubMed:24362026).
Able to autophosphorylate (PubMed:8824585).
Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity).
By similarity2 PublicationsCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 46 | ATPPROSITE-ProRule annotation | 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: UniProtKB
- 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: UniProtKB
- JNK cascade Source: UniProtKB
- peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of MAPK cascade Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q92918 |
SignaLinki | Q92918 |
SIGNORi | Q92918 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase kinase 1 (EC:2.7.11.11 Publication)Alternative name(s): Hematopoietic progenitor kinase MAPK/ERK kinase kinase kinase 1 Short name: MEK kinase kinase 1 Short name: MEKKK 1 |
Gene namesi | Name:MAP4K1 Synonyms:HPK1 |
Organismi | Homo sapiens (Human)Imported |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6863, MAP4K1 |
MIMi | 601983, gene |
neXtProti | NX_Q92918 |
VEuPathDBi | HostDB:ENSG00000104814 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 355 | T → A: Retains kinase activity. Not degraded by the Cul7-RING ubiquitin-protein ligase complex containing FBXW8. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 11184 |
OpenTargetsi | ENSG00000104814 |
PharmGKBi | PA30609 |
Miscellaneous databases
Pharosi | Q92918, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5749 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q92918 |
Genetic variation databases
BioMutai | MAP4K1 |
DMDMi | 29427916 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086273 | 1 – 833 | Mitogen-activated protein kinase kinase kinase kinase 1Add BLAST | 833 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 165 | Phosphothreonine; by autocatalysis1 Publication | 1 | |
Modified residuei | 171 | Phosphoserine; by autocatalysis1 Publication | 1 | |
Modified residuei | 175 | Phosphothreonine; by autocatalysis1 Publication | 1 | |
Modified residuei | 355 | Phosphothreonine; by autocatalysis1 Publication | 1 | |
Modified residuei | 374 | PhosphoserineBy similarity | 1 | |
Modified residuei | 376 | PhosphoserineBy similarity | 1 | |
Modified residuei | 405 | PhosphoserineCombined sources | 1 | |
Modified residuei | 407 | PhosphoserineCombined sources | 1 | |
Modified residuei | 413 | PhosphoserineCombined sources | 1 | |
Modified residuei | 421 | PhosphoserineCombined sources | 1 | |
Modified residuei | 586 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | Q92918 |
MassIVEi | Q92918 |
MaxQBi | Q92918 |
PaxDbi | Q92918 |
PeptideAtlasi | Q92918 |
PRIDEi | Q92918 |
ProteomicsDBi | 75603 [Q92918-1] 75604 [Q92918-2] |
PTM databases
iPTMneti | Q92918 |
PhosphoSitePlusi | Q92918 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000104814, Expressed in small intestine Peyer's patch and 151 other tissues |
ExpressionAtlasi | Q92918, baseline and differential |
Genevisiblei | Q92918, HS |
Organism-specific databases
HPAi | ENSG00000104814, Tissue enhanced (intestine, lymphoid tissue) |
Interactioni
Subunit structurei
Binary interactionsi
Q92918
Protein-protein interaction databases
BioGRIDi | 116354, 79 interactors |
DIPi | DIP-31019N |
IntActi | Q92918, 35 interactors |
MINTi | Q92918 |
STRINGi | 9606.ENSP00000465039 |
Chemistry databases
BindingDBi | Q92918 |
Miscellaneous databases
RNActi | Q92918, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q92918 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 17 – 274 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 495 – 800 | CNHPROSITE-ProRule annotationAdd BLAST | 306 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 296 – 478 | DisorderedSequence analysisAdd BLAST | 183 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 299 – 313 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 333 – 347 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 389 – 405 | Pro residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 432 – 446 | Pro residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000160308 |
InParanoidi | Q92918 |
OMAi | FLCCALD |
OrthoDBi | 996262at2759 |
PhylomeDBi | Q92918 |
TreeFami | TF105121 |
Family and domain databases
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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDVVDPDIFN RDPRDHYDLL QRLGGGTYGE VFKARDKVSG DLVALKMVKM
60 70 80 90 100
EPDDDVSTLQ KEILILKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ
110 120 130 140 150
DIYQVTGSLS ELQISYVCRE VLQGLAYLHS QKKIHRDIKG ANILINDAGE
160 170 180 190 200
VRLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS
210 220 230 240 250
LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK GKWSAAFHNF
260 270 280 290 300
IKVTLTKSPK KRPSATKMLS HQLVSQPGLN RGLILDLLDK LKNPGKGPSI
310 320 330 340 350
GDIEDEEPEL PPAIPRRIRS THRSSSLGIP DADCCRRHME FRKLRGMETR
360 370 380 390 400
PPANTARLQP PRDLRSSSPR KQLSESSDDD YDDVDIPTPA EDTPPPLPPK
410 420 430 440 450
PKFRSPSDEG PGSMGDDGQL SPGVLVRCAS GPPPNSPRPG PPPSTSSPHL
460 470 480 490 500
TAHSEPSLWN PPSRELDKPP LLPPKKEKMK RKGCALLVKL FNGCPLRIHS
510 520 530 540 550
TAAWTHPSTK DQHLLLGAEE GIFILNRNDQ EATLEMLFPS RTTWVYSINN
560 570 580 590 600
VLMSLSGKTP HLYSHSILGL LERKETRAGN PIAHISPHRL LARKNMVSTK
610 620 630 640 650
IQDTKGCRAC CVAEGASSGG PFLCGALETS VVLLQWYQPM NKFLLVRQVL
660 670 680 690 700
FPLPTPLSVF ALLTGPGSEL PAVCIGVSPG RPGKSVLFHT VRFGALSCWL
710 720 730 740 750
GEMSTEHRGP VQVTQVEEDM VMVLMDGSVK LVTPEGSPVR GLRTPEIPMT
760 770 780 790 800
EAVEAVAMVG GQLQAFWKHG VQVWALGSDQ LLQELRDPTL TFRLLGSPRL
810 820 830
ECSGTISPHC NLLLPGSSNS PASASRVAGI TGL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7ER95 | K7ER95_HUMAN | Mitogen-activated protein kinase ki... | MAP4K1 | 817 | Annotation score: | ||
K7EJS6 | K7EJS6_HUMAN | Non-specific serine/threonine prote... | MAP4K1 | 525 | Annotation score: | ||
K7EKT6 | K7EKT6_HUMAN | Mitogen-activated protein kinase ki... | MAP4K1 | 395 | Annotation score: | ||
K7ERT2 | K7ERT2_HUMAN | Mitogen-activated protein kinase ki... | MAP4K1 | 69 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040739 | 312 | P → T1 PublicationCorresponds to variant dbSNP:rs55924696Ensembl. | 1 | |
Natural variantiVAR_040740 | 351 | P → S1 PublicationCorresponds to variant dbSNP:rs34591617Ensembl. | 1 | |
Natural variantiVAR_040741 | 361 | P → L1 PublicationCorresponds to variant dbSNP:rs56060067Ensembl. | 1 | |
Natural variantiVAR_040742 | 737 | S → F in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1238066548Ensembl. | 1 | |
Natural variantiVAR_051643 | 811 | N → S. Corresponds to variant dbSNP:rs12975825Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_040340 | 800 – 833 | LECSG…GITGL → PVVVETRPVDDPTAPSNLYI QE in isoform 2. CuratedAdd BLAST | 34 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U66464 mRNA Translation: AAB97983.1 AC005933 Genomic DNA No translation available. AC008649 Genomic DNA No translation available. |
CCDSi | CCDS42564.1 [Q92918-2] CCDS59385.1 [Q92918-1] |
RefSeqi | NP_001036065.1, NM_001042600.2 [Q92918-2] NP_009112.1, NM_007181.5 [Q92918-1] |
Genome annotation databases
Ensembli | ENST00000396857; ENSP00000380066; ENSG00000104814 [Q92918-2] ENST00000591517; ENSP00000465039; ENSG00000104814 ENST00000634395; ENSP00000489001; ENSG00000282928 ENST00000634494; ENSP00000489158; ENSG00000282928 [Q92918-2] |
GeneIDi | 11184 |
KEGGi | hsa:11184 |
MANE-Selecti | ENST00000396857.7; ENSP00000380066.1; NM_001042600.3; NP_001036065.1 [Q92918-2] |
UCSCi | uc002oix.3, human [Q92918-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U66464 mRNA Translation: AAB97983.1 AC005933 Genomic DNA No translation available. AC008649 Genomic DNA No translation available. |
CCDSi | CCDS42564.1 [Q92918-2] CCDS59385.1 [Q92918-1] |
RefSeqi | NP_001036065.1, NM_001042600.2 [Q92918-2] NP_009112.1, NM_007181.5 [Q92918-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6CQD | X-ray | 2.12 | A/B | 2-293 | [»] | |
6CQE | X-ray | 1.89 | A/B | 2-293 | [»] | |
6CQF | X-ray | 2.25 | A | 2-293 | [»] | |
6NFY | X-ray | 2.17 | A/B | 10-307 | [»] | |
6NFZ | X-ray | 2.97 | A/B | 1-307 | [»] | |
6NG0 | X-ray | 2.05 | A/B | 1-307 | [»] | |
7KAC | X-ray | 1.85 | A/B | 1-319 | [»] | |
7L24 | X-ray | 2.68 | A/B/C/D | 7-294 | [»] | |
7L25 | X-ray | 1.85 | A/B | 6-294 | [»] | |
7L26 | X-ray | 2.30 | A/B/C/D | 8-294 | [»] | |
7M0K | X-ray | 2.01 | A/B/C/D | 6-294 | [»] | |
7M0L | X-ray | 2.43 | A/B/C/D | 5-294 | [»] | |
7M0M | X-ray | 1.93 | A/B | 2-294 | [»] | |
SMRi | Q92918 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116354, 79 interactors |
DIPi | DIP-31019N |
IntActi | Q92918, 35 interactors |
MINTi | Q92918 |
STRINGi | 9606.ENSP00000465039 |
Chemistry databases
BindingDBi | Q92918 |
ChEMBLi | CHEMBL5749 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q92918 |
PTM databases
iPTMneti | Q92918 |
PhosphoSitePlusi | Q92918 |
Genetic variation databases
BioMutai | MAP4K1 |
DMDMi | 29427916 |
Proteomic databases
jPOSTi | Q92918 |
MassIVEi | Q92918 |
MaxQBi | Q92918 |
PaxDbi | Q92918 |
PeptideAtlasi | Q92918 |
PRIDEi | Q92918 |
ProteomicsDBi | 75603 [Q92918-1] 75604 [Q92918-2] |
Protocols and materials databases
Antibodypediai | 2067, 573 antibodies from 40 providers |
DNASUi | 11184 |
Genome annotation databases
Ensembli | ENST00000396857; ENSP00000380066; ENSG00000104814 [Q92918-2] ENST00000591517; ENSP00000465039; ENSG00000104814 ENST00000634395; ENSP00000489001; ENSG00000282928 ENST00000634494; ENSP00000489158; ENSG00000282928 [Q92918-2] |
GeneIDi | 11184 |
KEGGi | hsa:11184 |
MANE-Selecti | ENST00000396857.7; ENSP00000380066.1; NM_001042600.3; NP_001036065.1 [Q92918-2] |
UCSCi | uc002oix.3, human [Q92918-1] |
Organism-specific databases
CTDi | 11184 |
DisGeNETi | 11184 |
GeneCardsi | MAP4K1 |
HGNCi | HGNC:6863, MAP4K1 |
HPAi | ENSG00000104814, Tissue enhanced (intestine, lymphoid tissue) |
MIMi | 601983, gene |
neXtProti | NX_Q92918 |
OpenTargetsi | ENSG00000104814 |
PharmGKBi | PA30609 |
VEuPathDBi | HostDB:ENSG00000104814 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000160308 |
InParanoidi | Q92918 |
OMAi | FLCCALD |
OrthoDBi | 996262at2759 |
PhylomeDBi | Q92918 |
TreeFami | TF105121 |
Enzyme and pathway databases
PathwayCommonsi | Q92918 |
SignaLinki | Q92918 |
SIGNORi | Q92918 |
Miscellaneous databases
BioGRID-ORCSi | 11184, 11 hits in 1071 CRISPR screens |
ChiTaRSi | MAP4K1, human |
GeneWikii | MAP4K1 |
GenomeRNAii | 11184 |
Pharosi | Q92918, Tchem |
PROi | PR:Q92918 |
RNActi | Q92918, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000104814, Expressed in small intestine Peyer's patch and 151 other tissues |
ExpressionAtlasi | Q92918, baseline and differential |
Genevisiblei | Q92918, HS |
Family and domain databases
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_HUMAN | |
Accessioni | Q92918Primary (citable) accession number: Q92918 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 28, 2003 |
Last sequence update: | February 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 198 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) 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