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UniProtKB - Q8IVH8 (M4K3_HUMAN)
Protein
Mitogen-activated protein kinase kinase kinase kinase 3
Gene
MAP4K3
Organism
Homo sapiens (Human)
Status
Functioni
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
1 PublicationCatalytic activityi
Cofactori
Mg2+1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 45 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 48 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 136 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 22 – 30 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- MAP kinase kinase kinase kinase activity Source: GO_Central
- protein kinase activity Source: ProtInc
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- intracellular signal transduction Source: UniProtKB
- JNK cascade Source: ProtInc
- protein phosphorylation Source: UniProtKB
- response to tumor necrosis factor Source: UniProtKB
- response to UV Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q8IVH8 |
SignaLinki | Q8IVH8 |
SIGNORi | Q8IVH8 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase kinase 3 (EC:2.7.11.1)Alternative name(s): Germinal center kinase-related protein kinase Short name: GLK MAPK/ERK kinase kinase kinase 3 Short name: MEK kinase kinase 3 Short name: MEKKK 3 |
Gene namesi | Name:MAP4K3 Synonyms:RAB8IPL1 |
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:6865, MAP4K3 |
MIMi | 604921, gene |
neXtProti | NX_Q8IVH8 |
VEuPathDBi | HostDB:ENSG00000011566 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 48 | K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8491 |
OpenTargetsi | ENSG00000011566 |
PharmGKBi | PA30611 |
Miscellaneous databases
Pharosi | Q8IVH8, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5432 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q8IVH8 |
GuidetoPHARMACOLOGYi | 2087 |
Genetic variation databases
BioMutai | MAP4K3 |
DMDMi | 29427817 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086277 | 1 – 894 | Mitogen-activated protein kinase kinase kinase kinase 3Add BLAST | 894 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 329 | PhosphoserineBy similarity | 1 | |
Modified residuei | 398 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-864 CPTAC-865 |
EPDi | Q8IVH8 |
jPOSTi | Q8IVH8 |
MassIVEi | Q8IVH8 |
MaxQBi | Q8IVH8 |
PaxDbi | Q8IVH8 |
PeptideAtlasi | Q8IVH8 |
PRIDEi | Q8IVH8 |
ProteomicsDBi | 70709 [Q8IVH8-1] 70710 [Q8IVH8-2] 70711 [Q8IVH8-3] |
PTM databases
iPTMneti | Q8IVH8 |
PhosphoSitePlusi | Q8IVH8 |
SwissPalmi | Q8IVH8 |
Expressioni
Tissue specificityi
Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.1 Publication
Gene expression databases
Bgeei | ENSG00000011566, Expressed in kidney and 239 other tissues |
ExpressionAtlasi | Q8IVH8, baseline and differential |
Genevisiblei | Q8IVH8, HS |
Organism-specific databases
HPAi | ENSG00000011566, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).
By similarityBinary interactionsi
Q8IVH8
With | #Exp. | IntAct |
---|---|---|
GRB2 [P62993] | 2 | EBI-1758170,EBI-401755 |
LCP2 [Q13094] | 5 | EBI-1758170,EBI-346946 |
PRKCQ [Q04759] | 4 | EBI-1758170,EBI-374762 |
Prkcq [Q02111] from Mus musculus. | 4 | EBI-1758170,EBI-2639157 |
Protein-protein interaction databases
BioGRIDi | 114063, 70 interactors |
DIPi | DIP-48924N |
IntActi | Q8IVH8, 17 interactors |
STRINGi | 9606.ENSP00000263881 |
Chemistry databases
BindingDBi | Q8IVH8 |
Miscellaneous databases
RNActi | Q8IVH8, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8IVH8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 16 – 273 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 258 | |
Domaini | 556 – 867 | CNHPROSITE-ProRule annotationAdd BLAST | 312 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 410 – 536 | DisorderedSequence analysisAdd BLAST | 127 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 410 – 427 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 448 – 462 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 469 – 487 | Pro residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 494 – 516 | Polar residuesSequence analysisAdd BLAST | 23 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000155483 |
InParanoidi | Q8IVH8 |
OMAi | VIKLEPX |
PhylomeDBi | Q8IVH8 |
TreeFami | TF105121 |
Family and domain databases
DisProti | DP02822 |
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 (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 11 PublicationCurated (identifier: Q8IVH8-1) [UniParc]FASTAAdd to basket
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
MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE
60 70 80 90 100
PGEDFAVVQQ EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD
110 120 130 140 150
IYHVTGPLSE LQIAYVSRET LQGLYYLHSK GKMHRDIKGA NILLTDNGHV
160 170 180 190 200
KLADFGVSAQ ITATIAKRKS FIGTPYWMAP EVAAVERKGG YNQLCDLWAV
210 220 230 240 250
GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKM KWSNSFHHFV
260 270 280 290 300
KMALTKNPKK RPTAEKLLQH PFVTQHLTRS LAIELLDKVN NPDHSTYHDF
310 320 330 340 350
DDDDPEPLVA VPHRIHSTSR NVREEKTRSE ITFGQVKFDP PLRKETEPHH
360 370 380 390 400
ELPDSDGFLD SSEEIYYTAR SNLDLQLEYG QGHQGGYFLG ANKSLLKSVE
410 420 430 440 450
EELHQRGHVA HLEDDEGDDD ESKHSTLKAK IPPPLPPKPK SIFIPQEMHS
460 470 480 490 500
TEDENQGTIK RCPMSGSPAK PSQVPPRPPP PRLPPHKPVA LGNGMSSFQL
510 520 530 540 550
NGERDGSLCQ QQNEHRGTNL SRKEKKDVPK PISNGLPPTP KVHMGACFSK
560 570 580 590 600
VFNGCPLKIH CASSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF
610 620 630 640 650
PRRCTWLYVM NNCLLSISGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK
660 670 680 690 700
LPDRILPRKF SVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE
710 720 730 740 750
WVEPMQKFML IKHIDFPIPC PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ
760 770 780 790 800
VVRFETVNPN STSSWFTESD TPQTNVTHVT QLERDTILVC LDCCIKIVNL
810 820 830 840 850
QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG RSFRSNEVTQ
860 870 880 890
EISDSTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H5A3 | F5H5A3_HUMAN | Mitogen-activated protein kinase ki... | MAP4K3 | 810 | Annotation score: | ||
F8WAZ1 | F8WAZ1_HUMAN | Mitogen-activated protein kinase ki... | MAP4K3 | 131 | Annotation score: | ||
V9GY95 | V9GY95_HUMAN | Mitogen-activated protein kinase ki... | MAP4K3 | 92 | Annotation score: | ||
H7C1A4 | H7C1A4_HUMAN | Mitogen-activated protein kinase ki... | MAP4K3 | 143 | Annotation score: | ||
F8WBC3 | F8WBC3_HUMAN | Mitogen-activated protein kinase ki... | MAP4K3 | 44 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 392 | N → D in AAC15472 (PubMed:9275185).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040743 | 200 | V → L1 PublicationCorresponds to variant dbSNP:rs35957290EnsemblClinVar. | 1 | |
Natural variantiVAR_040744 | 424 | H → Q1 PublicationCorresponds to variant dbSNP:rs56317466Ensembl. | 1 | |
Natural variantiVAR_040745 | 669 | T → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007052 | 1 – 12 | MNPGF…SRRNP → MA in isoform 2. 1 PublicationAdd BLAST | 12 | |
Alternative sequenceiVSP_007053 | 352 – 372 | Missing in isoform 3. 1 PublicationAdd BLAST | 21 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000263881; ENSP00000263881; ENSG00000011566 ENST00000341681; ENSP00000345434; ENSG00000011566 [Q8IVH8-3] |
GeneIDi | 8491 |
KEGGi | hsa:8491 |
MANE-Selecti | ENST00000263881.8; ENSP00000263881.3; NM_003618.4; NP_003609.2 |
UCSCi | uc002rro.4, human [Q8IVH8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5J5T | X-ray | 2.85 | A | 13-380 | [»] | |
SMRi | Q8IVH8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114063, 70 interactors |
DIPi | DIP-48924N |
IntActi | Q8IVH8, 17 interactors |
STRINGi | 9606.ENSP00000263881 |
Chemistry databases
BindingDBi | Q8IVH8 |
ChEMBLi | CHEMBL5432 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q8IVH8 |
GuidetoPHARMACOLOGYi | 2087 |
PTM databases
iPTMneti | Q8IVH8 |
PhosphoSitePlusi | Q8IVH8 |
SwissPalmi | Q8IVH8 |
Genetic variation databases
BioMutai | MAP4K3 |
DMDMi | 29427817 |
Proteomic databases
CPTACi | CPTAC-864 CPTAC-865 |
EPDi | Q8IVH8 |
jPOSTi | Q8IVH8 |
MassIVEi | Q8IVH8 |
MaxQBi | Q8IVH8 |
PaxDbi | Q8IVH8 |
PeptideAtlasi | Q8IVH8 |
PRIDEi | Q8IVH8 |
ProteomicsDBi | 70709 [Q8IVH8-1] 70710 [Q8IVH8-2] 70711 [Q8IVH8-3] |
Protocols and materials databases
Antibodypediai | 29616, 359 antibodies from 33 providers |
DNASUi | 8491 |
Genome annotation databases
Ensembli | ENST00000263881; ENSP00000263881; ENSG00000011566 ENST00000341681; ENSP00000345434; ENSG00000011566 [Q8IVH8-3] |
GeneIDi | 8491 |
KEGGi | hsa:8491 |
MANE-Selecti | ENST00000263881.8; ENSP00000263881.3; NM_003618.4; NP_003609.2 |
UCSCi | uc002rro.4, human [Q8IVH8-1] |
Organism-specific databases
CTDi | 8491 |
DisGeNETi | 8491 |
GeneCardsi | MAP4K3 |
HGNCi | HGNC:6865, MAP4K3 |
HPAi | ENSG00000011566, Low tissue specificity |
MIMi | 604921, gene |
neXtProti | NX_Q8IVH8 |
OpenTargetsi | ENSG00000011566 |
PharmGKBi | PA30611 |
VEuPathDBi | HostDB:ENSG00000011566 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0576, Eukaryota |
GeneTreei | ENSGT00940000155483 |
InParanoidi | Q8IVH8 |
OMAi | VIKLEPX |
PhylomeDBi | Q8IVH8 |
TreeFami | TF105121 |
Enzyme and pathway databases
PathwayCommonsi | Q8IVH8 |
SignaLinki | Q8IVH8 |
SIGNORi | Q8IVH8 |
Miscellaneous databases
BioGRID-ORCSi | 8491, 13 hits in 1081 CRISPR screens |
ChiTaRSi | MAP4K3, human |
GenomeRNAii | 8491 |
Pharosi | Q8IVH8, Tchem |
PROi | PR:Q8IVH8 |
RNActi | Q8IVH8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000011566, Expressed in kidney and 239 other tissues |
ExpressionAtlasi | Q8IVH8, baseline and differential |
Genevisiblei | Q8IVH8, HS |
Family and domain databases
DisProti | DP02822 |
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 | M4K3_HUMAN | |
Accessioni | Q8IVH8Primary (citable) accession number: Q8IVH8 Secondary accession number(s): Q6IQ39 Q9Y6R5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 28, 2003 |
Last sequence update: | March 1, 2003 | |
Last modified: | February 23, 2022 | |
This is version 172 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 2
Human chromosome 2: 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