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Protein

Mitogen-activated protein kinase kinase kinase 6

Gene

MAP3K6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei677ATPPROSITE-ProRule annotation1
Active sitei771Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi654 – 662ATPPROSITE-ProRule annotation9

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

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.25 2681
SignaLinkiO95382

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000142733.14
HGNCiHGNC:6858 MAP3K6
MIMi604468 gene
neXtProtiNX_O95382

Subcellular locationi

Pathology & Biotechi

Organism-specific databases

DisGeNETi9064
MalaCardsiMAP3K6
OpenTargetsiENSG00000142733
Orphaneti26106 Hereditary diffuse gastric cancer
PharmGKBiPA30602

Chemistry databases

ChEMBLiCHEMBL1163123
GuidetoPHARMACOLOGYi2081

Polymorphism and mutation databases

BioMutaiMAP3K6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862511 – 1288Mitogen-activated protein kinase kinase kinase 6Add BLAST1288

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei806PhosphothreonineBy similarity1
Modified residuei964PhosphoserineCombined sources1
Modified residuei984PhosphoserineCombined sources1
Modified residuei1129PhosphoserineCombined sources1
Modified residuei1149PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO95382
MaxQBiO95382
PaxDbiO95382
PeptideAtlasiO95382
PRIDEiO95382
ProteomicsDBi50834
50835 [O95382-2]
50836 [O95382-3]

PTM databases

iPTMnetiO95382
PhosphoSitePlusiO95382

Expressioni

Gene expression databases

BgeeiENSG00000142733 Expressed in 161 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_MAP3K6
ExpressionAtlasiO95382 baseline and differential
GenevisibleiO95382 HS

Organism-specific databases

HPAiHPA051192

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes.

Protein-protein interaction databases

BioGridi114524, 21 interactors
IntActiO95382, 8 interactors
MINTiO95382
STRINGi9606.ENSP00000350195

Chemistry databases

BindingDBiO95382

Structurei

3D structure databases

ProteinModelPortaliO95382
SMRiO95382
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini648 – 906Protein kinasePROSITE-ProRule annotationAdd BLAST259

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1004 – 1029Sequence analysisAdd BLAST26
Coiled coili1166 – 1205Sequence analysisAdd BLAST40

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4279 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00800000124036
HOVERGENiHBG006305
InParanoidiO95382
KOiK04425
OMAiACPQGDQ
OrthoDBiEOG091G00SJ
PhylomeDBiO95382
TreeFamiTF105115

Family and domain databases

InterProiView protein in InterPro
IPR025136 DUF4071
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR013761 SAM/pointed_sf
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13281 DUF4071, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This 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 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:1,288
Mass (Da):142,596
Last modified:November 3, 2009 - v3
Checksum:i013AF3729698080F
GO
Isoform 2 (identifier: O95382-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.
     1065-1074: RLRAQGLGPA → WMNGEDKGSF
     1075-1288: Missing.

Note: No experimental confirmation available.
Show »
Length:797
Mass (Da):88,674
Checksum:i8EA06171D8396464
GO
Isoform 3 (identifier: O95382-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-168: Missing.

Note: No experimental confirmation available.
Show »
Length:1,280
Mass (Da):141,648
Checksum:iC9763EC2F44C5790
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y894H0Y894_HUMAN
Mitogen-activated protein kinase ki...
MAP3K6
798Annotation score:
H0Y8A3H0Y8A3_HUMAN
Mitogen-activated protein kinase ki...
MAP3K6
82Annotation score:

Sequence cautioni

The sequence AAD05304 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti435 – 440MQYYWD → ALWVPV in AAI29952 (PubMed:15489334).Curated6
Sequence conflicti435 – 440MQYYWD → HTWVPV in AAI29951 (PubMed:15489334).Curated6

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032832455T → I2 PublicationsCorresponds to variant dbSNP:rs1138294Ensembl.1
Natural variantiVAR_046050499R → C. Corresponds to variant dbSNP:rs11247641Ensembl.1
Natural variantiVAR_046051544R → W1 PublicationCorresponds to variant dbSNP:rs55671988Ensembl.1
Natural variantiVAR_032833622N → K2 PublicationsCorresponds to variant dbSNP:rs35659744EnsemblClinVar.1
Natural variantiVAR_046052668R → G1 PublicationCorresponds to variant dbSNP:rs55869163Ensembl.1
Natural variantiVAR_046053673R → L1 PublicationCorresponds to variant dbSNP:rs56359841Ensembl.1
Natural variantiVAR_035629869P → T in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_046054925S → L in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_046055968T → I in an ovarian endometrioid cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_032834969S → N1 PublicationCorresponds to variant dbSNP:rs17856498Ensembl.1
Natural variantiVAR_0460561061A → T1 PublicationCorresponds to variant dbSNP:rs55990440Ensembl.1
Natural variantiVAR_0460571233G → A. Corresponds to variant dbSNP:rs17162549Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0262011 – 277Missing in isoform 2. 1 PublicationAdd BLAST277
Alternative sequenceiVSP_026202161 – 168Missing in isoform 3. 1 Publication8
Alternative sequenceiVSP_0262031065 – 1074RLRAQGLGPA → WMNGEDKGSF in isoform 2. 1 Publication10
Alternative sequenceiVSP_0262041075 – 1288Missing in isoform 2. 1 PublicationAdd BLAST214

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.
CCDSiCCDS299.1 [O95382-1]
CCDS72738.1 [O95382-3]
RefSeqiNP_001284538.1, NM_001297609.1 [O95382-3]
NP_004663.3, NM_004672.4 [O95382-1]
UniGeneiHs.194694

Genome annotation databases

EnsembliENST00000357582; ENSP00000350195; ENSG00000142733 [O95382-1]
ENST00000374040; ENSP00000363152; ENSG00000142733 [O95382-3]
ENST00000493901; ENSP00000419591; ENSG00000142733 [O95382-1]
GeneIDi9064
KEGGihsa:9064
UCSCiuc001bny.2 human [O95382-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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.
CCDSiCCDS299.1 [O95382-1]
CCDS72738.1 [O95382-3]
RefSeqiNP_001284538.1, NM_001297609.1 [O95382-3]
NP_004663.3, NM_004672.4 [O95382-1]
UniGeneiHs.194694

3D structure databases

ProteinModelPortaliO95382
SMRiO95382
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114524, 21 interactors
IntActiO95382, 8 interactors
MINTiO95382
STRINGi9606.ENSP00000350195

Chemistry databases

BindingDBiO95382
ChEMBLiCHEMBL1163123
GuidetoPHARMACOLOGYi2081

PTM databases

iPTMnetiO95382
PhosphoSitePlusiO95382

Polymorphism and mutation databases

BioMutaiMAP3K6

Proteomic databases

EPDiO95382
MaxQBiO95382
PaxDbiO95382
PeptideAtlasiO95382
PRIDEiO95382
ProteomicsDBi50834
50835 [O95382-2]
50836 [O95382-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357582; ENSP00000350195; ENSG00000142733 [O95382-1]
ENST00000374040; ENSP00000363152; ENSG00000142733 [O95382-3]
ENST00000493901; ENSP00000419591; ENSG00000142733 [O95382-1]
GeneIDi9064
KEGGihsa:9064
UCSCiuc001bny.2 human [O95382-1]

Organism-specific databases

CTDi9064
DisGeNETi9064
EuPathDBiHostDB:ENSG00000142733.14
GeneCardsiMAP3K6
H-InvDBiHIX0000314
HGNCiHGNC:6858 MAP3K6
HPAiHPA051192
MalaCardsiMAP3K6
MIMi604468 gene
neXtProtiNX_O95382
OpenTargetsiENSG00000142733
Orphaneti26106 Hereditary diffuse gastric cancer
PharmGKBiPA30602
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4279 Eukaryota
ENOG410XQGS LUCA
GeneTreeiENSGT00800000124036
HOVERGENiHBG006305
InParanoidiO95382
KOiK04425
OMAiACPQGDQ
OrthoDBiEOG091G00SJ
PhylomeDBiO95382
TreeFamiTF105115

Enzyme and pathway databases

BRENDAi2.7.11.25 2681
SignaLinkiO95382

Miscellaneous databases

ChiTaRSiMAP3K6 human
GenomeRNAii9064
PROiPR:O95382
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142733 Expressed in 161 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_MAP3K6
ExpressionAtlasiO95382 baseline and differential
GenevisibleiO95382 HS

Family and domain databases

InterProiView protein in InterPro
IPR025136 DUF4071
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR013761 SAM/pointed_sf
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13281 DUF4071, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiM3K6_HUMAN
AccessioniPrimary (citable) accession number: O95382
Secondary accession number(s): A2ACE8
, A2VDG4, A2VDG5, Q59HF4, Q5SSD4, Q75PK3, Q96B75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 3, 2009
Last modified: November 7, 2018
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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