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UniProtKB - O95382 (M3K6_HUMAN)
Protein
Mitogen-activated protein kinase kinase kinase 6
Gene
MAP3K6
Organism
Homo sapiens (Human)
Status
Functioni
Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
2 PublicationsCatalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Activated by phosphorylation on Thr-806. Catalytically active only when complexed with MAP3K5, with MAP3K5 supporting the stability and the active configuration of MAP3K6 and MAP3K6 activating MAP3K5 by direct phosphorylation.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 677 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 771 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 654 – 662 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- MAP kinase kinase kinase activity Source: UniProtKB
- protein kinase activity Source: GO_Central
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine kinase activity Source: RHEA
GO - Biological processi
- protein phosphorylation Source: UniProtKB
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.25, 2681 |
PathwayCommonsi | O95382 |
SignaLinki | O95382 |
SIGNORi | O95382 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase 6 (EC:2.7.11.25)Alternative name(s): Apoptosis signal-regulating kinase 2 |
Gene namesi | Name:MAP3K6 Synonyms:ASK2, MAPKKK6, MEKK6 |
Organismi | Homo sapiens (Human) |
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:6858, MAP3K6 |
MIMi | 604468, gene |
neXtProti | NX_O95382 |
VEuPathDBi | HostDB:ENSG00000142733 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 9064 |
MalaCardsi | MAP3K6 |
OpenTargetsi | ENSG00000142733 |
Orphaneti | 26106, Hereditary diffuse gastric cancer |
PharmGKBi | PA30602 |
Miscellaneous databases
Pharosi | O95382, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1163123 |
DrugBanki | DB12010, Fostamatinib |
GuidetoPHARMACOLOGYi | 2081 |
Genetic variation databases
BioMutai | MAP3K6 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086251 | 1 – 1288 | Mitogen-activated protein kinase kinase kinase 6Add BLAST | 1288 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 806 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 964 | PhosphoserineCombined sources | 1 | |
Modified residuei | 984 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1129 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1149 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
CPTACi | CPTAC-851 CPTAC-852 |
EPDi | O95382 |
jPOSTi | O95382 |
MassIVEi | O95382 |
MaxQBi | O95382 |
PaxDbi | O95382 |
PeptideAtlasi | O95382 |
PRIDEi | O95382 |
ProteomicsDBi | 50834 [O95382-1] 50835 [O95382-2] 50836 [O95382-3] |
PTM databases
GlyGeni | O95382, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O95382 |
PhosphoSitePlusi | O95382 |
Expressioni
Gene expression databases
Bgeei | ENSG00000142733, Expressed in left lobe of thyroid gland and 180 other tissues |
ExpressionAtlasi | O95382, baseline and differential |
Genevisiblei | O95382, HS |
Organism-specific databases
HPAi | ENSG00000142733, Low tissue specificity |
Interactioni
Subunit structurei
Binds both upstream activators and downstream substrates in multimolecular complexes.
Protein-protein interaction databases
BioGRIDi | 114524, 40 interactors |
IntActi | O95382, 24 interactors |
MINTi | O95382 |
STRINGi | 9606.ENSP00000419591 |
Chemistry databases
BindingDBi | O95382 |
Miscellaneous databases
RNActi | O95382, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 648 – 906 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 259 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 899 – 997 | DisorderedSequence analysisAdd BLAST | 99 | |
Regioni | 1123 – 1157 | DisorderedSequence analysisAdd BLAST | 35 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1004 – 1029 | Sequence analysisAdd BLAST | 26 | |
Coiled coili | 1166 – 1205 | Sequence analysisAdd BLAST | 40 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 930 – 948 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 1134 – 1151 | Polar residuesSequence analysisAdd BLAST | 18 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.Curated
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG4279, Eukaryota |
GeneTreei | ENSGT00940000159398 |
HOGENOMi | CLU_003687_3_0_1 |
InParanoidi | O95382 |
OMAi | VWYVASI |
OrthoDBi | 1019877at2759 |
PhylomeDBi | O95382 |
TreeFami | TF105115 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR043969, MAP3K_PH IPR025136, MAP3K_TRAF-bd IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR013761, SAM/pointed_sf IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF19039, ASK_PH, 1 hit PF13281, MAP3K_TRAF_bd, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47769, SSF47769, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 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 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: O95382-1) [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
MAGPCPRSGA ERAGSCWQDP LAVALSRGRQ LAAPPGRGCA RSRPLSVVYV
60 70 80 90 100
LTREPQPGLE PREGTEAEPL PLRCLREACA QVPRPRPPPQ LRSLPFGTLE
110 120 130 140 150
LGDTAALDAF YNADVVVLEV SSSLVQPSLF YHLGVRESFS MTNNVLLCSQ
160 170 180 190 200
ADLPDLQALR EDVFQKNSDC VGSYTLIPYV VTATGRVLCG DAGLLRGLAD
210 220 230 240 250
GLVQAGVGTE ALLTPLVGRL ARLLEATPTD SCGYFRETIR RDIRQARERF
260 270 280 290 300
SGPQLRQELA RLQRRLDSVE LLSPDIIMNL LLSYRDVQDY SAIIELVETL
310 320 330 340 350
QALPTCDVAE QHNVCFHYTF ALNRRNRPGD RAKALSVLLP LVQLEGSVAP
360 370 380 390 400
DLYCMCGRIY KDMFFSSGFQ DAGHREQAYH WYRKAFDVEP SLHSGINAAV
410 420 430 440 450
LLIAAGQHFE DSKELRLIGM KLGCLLARKG CVEKMQYYWD VGFYLGAQIL
460 470 480 490 500
ANDPTQVVLA AEQLYKLNAP IWYLVSVMET FLLYQHFRPT PEPPGGPPRR
510 520 530 540 550
AHFWLHFLLQ SCQPFKTACA QGDQCLVLVL EMNKVLLPAK LEVRGTDPVS
560 570 580 590 600
TVTLSLLEPE TQDIPSSWTF PVASICGVSA SKRDERCCFL YALPPAQDVQ
610 620 630 640 650
LCFPSVGHCQ WFCGLIQAWV TNPDSTAPAE EAEGAGEMLE FDYEYTETGE
660 670 680 690 700
RLVLGKGTYG VVYAGRDRHT RVRIAIKEIP ERDSRFSQPL HEEIALHRRL
710 720 730 740 750
RHKNIVRYLG SASQGGYLKI FMEEVPGGSL SSLLRSVWGP LKDNESTISF
760 770 780 790 800
YTRQILQGLG YLHDNHIVHR DIKGDNVLIN TFSGLLKISD FGTSKRLAGI
810 820 830 840 850
TPCTETFTGT LQYMAPEIID QGPRGYGKAA DIWSLGCTVI EMATGRPPFH
860 870 880 890 900
ELGSPQAAMF QVGMYKVHPP MPSSLSAEAQ AFLLRTFEPD PRLRASAQTL
910 920 930 940 950
LGDPFLQPGK RSRSPSSPRH APRPSDAPSA SPTPSANSTT QSQTFPCPQA
960 970 980 990 1000
PSQHPPSPPK RCLSYGGTSQ LRVPEEPAAE EPASPEESSG LSLLHQESKR
1010 1020 1030 1040 1050
RAMLAAVLEQ ELPALAENLH QEQKQEQGAR LGRNHVEELL RCLGAHIHTP
1060 1070 1080 1090 1100
NRRQLAQELR ALQGRLRAQG LGPALLHRPL FAFPDAVKQI LRKRQIRPHW
1110 1120 1130 1140 1150
MFVLDSLLSR AVRAALGVLG PEVEKEAVSP RSEELSNEGD SQQSPGQQSP
1160 1170 1180 1190 1200
LPVEPEQGPA PLMVQLSLLR AETDRLREIL AGKEREYQAL VQRALQRLNE
1210 1220 1230 1240 1250
EARTYVLAPE PPTALSTDQG LVQWLQELNV DSGTIQMLLN HSFTLHTLLT
1260 1270 1280
YATRDDLIYT RIRGGMVCRI WRAILAQRAG STPVTSGP
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0Y8A3 | H0Y8A3_HUMAN | Mitogen-activated protein kinase ki... | MAP3K6 | 82 | Annotation score: | ||
A0A590UJN3 | A0A590UJN3_HUMAN | Mitogen-activated protein kinase ki... | MAP3K6 | 25 | Annotation score: |
Sequence cautioni
The sequence AAD05304 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 435 – 440 | MQYYWD → ALWVPV in AAI29952 (PubMed:15489334).Curated | 6 | |
Sequence conflicti | 435 – 440 | MQYYWD → HTWVPV in AAI29951 (PubMed:15489334).Curated | 6 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032832 | 455 | T → I2 PublicationsCorresponds to variant dbSNP:rs1138294Ensembl. | 1 | |
Natural variantiVAR_046050 | 499 | R → C. Corresponds to variant dbSNP:rs11247641EnsemblClinVar. | 1 | |
Natural variantiVAR_046051 | 544 | R → W1 PublicationCorresponds to variant dbSNP:rs55671988Ensembl. | 1 | |
Natural variantiVAR_032833 | 622 | N → K2 PublicationsCorresponds to variant dbSNP:rs35659744EnsemblClinVar. | 1 | |
Natural variantiVAR_046052 | 668 | R → G1 PublicationCorresponds to variant dbSNP:rs55869163Ensembl. | 1 | |
Natural variantiVAR_046053 | 673 | R → L1 PublicationCorresponds to variant dbSNP:rs56359841Ensembl. | 1 | |
Natural variantiVAR_035629 | 869 | P → T in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_046054 | 925 | S → L in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_046055 | 968 | T → I in an ovarian endometrioid cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_032834 | 969 | S → N1 PublicationCorresponds to variant dbSNP:rs17856498Ensembl. | 1 | |
Natural variantiVAR_046056 | 1061 | A → T1 PublicationCorresponds to variant dbSNP:rs55990440Ensembl. | 1 | |
Natural variantiVAR_046057 | 1233 | G → A. Corresponds to variant dbSNP:rs17162549Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026201 | 1 – 277 | Missing in isoform 2. 1 PublicationAdd BLAST | 277 | |
Alternative sequenceiVSP_026202 | 161 – 168 | Missing in isoform 3. 1 Publication | 8 | |
Alternative sequenceiVSP_026203 | 1065 – 1074 | RLRAQGLGPA → WMNGEDKGSF in isoform 2. 1 Publication | 10 | |
Alternative sequenceiVSP_026204 | 1075 – 1288 | Missing in isoform 2. 1 PublicationAdd BLAST | 214 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB167411 mRNA Translation: BAD12485.1 FO393419 Genomic DNA No translation available. BC015914 mRNA Translation: AAH15914.1 BC129950 mRNA Translation: AAI29951.1 BC129951 mRNA Translation: AAI29952.1 AB208805 mRNA Translation: BAD92042.1 AF100318 mRNA Translation: AAD05304.1 Different initiation. |
CCDSi | CCDS299.1 [O95382-1] CCDS72738.1 [O95382-3] |
RefSeqi | NP_001284538.1, NM_001297609.1 [O95382-3] NP_004663.3, NM_004672.4 [O95382-1] |
Genome annotation databases
Ensembli | ENST00000357582; ENSP00000350195; ENSG00000142733 ENST00000374040; ENSP00000363152; ENSG00000142733 [O95382-3] |
GeneIDi | 9064 |
KEGGi | hsa:9064 |
MANE-Selecti | ENST00000357582.3; ENSP00000350195.2; NM_004672.5; NP_004663.3 |
UCSCi | uc001bny.2, human [O95382-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB167411 mRNA Translation: BAD12485.1 FO393419 Genomic DNA No translation available. BC015914 mRNA Translation: AAH15914.1 BC129950 mRNA Translation: AAI29951.1 BC129951 mRNA Translation: AAI29952.1 AB208805 mRNA Translation: BAD92042.1 AF100318 mRNA Translation: AAD05304.1 Different initiation. |
CCDSi | CCDS299.1 [O95382-1] CCDS72738.1 [O95382-3] |
RefSeqi | NP_001284538.1, NM_001297609.1 [O95382-3] NP_004663.3, NM_004672.4 [O95382-1] |
3D structure databases
SMRi | O95382 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114524, 40 interactors |
IntActi | O95382, 24 interactors |
MINTi | O95382 |
STRINGi | 9606.ENSP00000419591 |
Chemistry databases
BindingDBi | O95382 |
ChEMBLi | CHEMBL1163123 |
DrugBanki | DB12010, Fostamatinib |
GuidetoPHARMACOLOGYi | 2081 |
PTM databases
GlyGeni | O95382, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | O95382 |
PhosphoSitePlusi | O95382 |
Genetic variation databases
BioMutai | MAP3K6 |
Proteomic databases
CPTACi | CPTAC-851 CPTAC-852 |
EPDi | O95382 |
jPOSTi | O95382 |
MassIVEi | O95382 |
MaxQBi | O95382 |
PaxDbi | O95382 |
PeptideAtlasi | O95382 |
PRIDEi | O95382 |
ProteomicsDBi | 50834 [O95382-1] 50835 [O95382-2] 50836 [O95382-3] |
Protocols and materials databases
Antibodypediai | 30762, 221 antibodies from 29 providers |
DNASUi | 9064 |
Genome annotation databases
Ensembli | ENST00000357582; ENSP00000350195; ENSG00000142733 ENST00000374040; ENSP00000363152; ENSG00000142733 [O95382-3] |
GeneIDi | 9064 |
KEGGi | hsa:9064 |
MANE-Selecti | ENST00000357582.3; ENSP00000350195.2; NM_004672.5; NP_004663.3 |
UCSCi | uc001bny.2, human [O95382-1] |
Organism-specific databases
CTDi | 9064 |
DisGeNETi | 9064 |
GeneCardsi | MAP3K6 |
HGNCi | HGNC:6858, MAP3K6 |
HPAi | ENSG00000142733, Low tissue specificity |
MalaCardsi | MAP3K6 |
MIMi | 604468, gene |
neXtProti | NX_O95382 |
OpenTargetsi | ENSG00000142733 |
Orphaneti | 26106, Hereditary diffuse gastric cancer |
PharmGKBi | PA30602 |
VEuPathDBi | HostDB:ENSG00000142733 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4279, Eukaryota |
GeneTreei | ENSGT00940000159398 |
HOGENOMi | CLU_003687_3_0_1 |
InParanoidi | O95382 |
OMAi | VWYVASI |
OrthoDBi | 1019877at2759 |
PhylomeDBi | O95382 |
TreeFami | TF105115 |
Enzyme and pathway databases
BRENDAi | 2.7.11.25, 2681 |
PathwayCommonsi | O95382 |
SignaLinki | O95382 |
SIGNORi | O95382 |
Miscellaneous databases
BioGRID-ORCSi | 9064, 8 hits in 1075 CRISPR screens |
ChiTaRSi | MAP3K6, human |
GenomeRNAii | 9064 |
Pharosi | O95382, Tchem |
PROi | PR:O95382 |
RNActi | O95382, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000142733, Expressed in left lobe of thyroid gland and 180 other tissues |
ExpressionAtlasi | O95382, baseline and differential |
Genevisiblei | O95382, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR043969, MAP3K_PH IPR025136, MAP3K_TRAF-bd IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR013761, SAM/pointed_sf IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF19039, ASK_PH, 1 hit PF13281, MAP3K_TRAF_bd, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF47769, SSF47769, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | M3K6_HUMAN | |
Accessioni | O95382Primary (citable) accession number: O95382 Secondary accession number(s): A2ACE8 Q96B75 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 3, 2009 | |
Last modified: | February 23, 2022 | |
This is version 186 of the entry and version 3 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
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 1
Human chromosome 1: 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 - SIMILARITY comments
Index of protein domains and families