UniProtKB - Q6ZN16 (M3K15_HUMAN)
Protein
Mitogen-activated protein kinase kinase kinase 15
Gene
MAP3K15
Organism
Homo sapiens (Human)
Status
Functioni
May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.1 Publication
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-812, inhibited by phosphorylation at Ser-924 and Ser-994 (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 681 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 773 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 658 – 666 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase kinase kinase activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- protein kinase activity Source: GO_Central
- protein serine kinase activity Source: RHEA
- protein threonine kinase activity Source: RHEA
GO - Biological processi
- activation of MAPKK activity Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q6ZN16 |
SignaLinki | Q6ZN16 |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase kinase kinase 15 (EC:2.7.11.25)Alternative name(s): Apoptosis signal-regulating kinase 3 MAPK/ERK kinase kinase 15 Short name: MEK kinase 15 Short name: MEKK 15 |
Gene namesi | Name:MAP3K15 Synonyms:ASK3 |
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:31689, MAP3K15 |
MIMi | 300820, gene |
neXtProti | NX_Q6ZN16 |
VEuPathDBi | HostDB:ENSG00000180815.14 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 389840 |
OpenTargetsi | ENSG00000180815 |
PharmGKBi | PA134935369 |
Miscellaneous databases
Pharosi | Q6ZN16, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1163127 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q6ZN16 |
Genetic variation databases
BioMutai | MAP3K15 |
DMDMi | 116248533 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000253481 | 1 – 1313 | Mitogen-activated protein kinase kinase kinase 15Add BLAST | 1313 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 994 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
CPTACi | CPTAC-841 CPTAC-842 |
jPOSTi | Q6ZN16 |
MassIVEi | Q6ZN16 |
PaxDbi | Q6ZN16 |
PeptideAtlasi | Q6ZN16 |
PRIDEi | Q6ZN16 |
ProteomicsDBi | 67956 [Q6ZN16-1] 67957 [Q6ZN16-2] 67958 [Q6ZN16-3] |
PTM databases
iPTMneti | Q6ZN16 |
PhosphoSitePlusi | Q6ZN16 |
Expressioni
Tissue specificityi
Isoform 2 and isoform 3 are widely expressed. Isoform 2 highest levels are observed in fetal brain, and isoform 3 highest levels in pancreas, peripheral blood leukocytes, fetal brain and spleen.1 Publication
Gene expression databases
Bgeei | ENSG00000180815, Expressed in adrenal tissue and 84 other tissues |
ExpressionAtlasi | Q6ZN16, baseline and differential |
Organism-specific databases
HPAi | ENSG00000180815, Tissue enhanced (adrenal gland, brain) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 133293, 6 interactors |
IntActi | Q6ZN16, 8 interactors |
STRINGi | 9606.ENSP00000345629 |
Chemistry databases
BindingDBi | Q6ZN16 |
Miscellaneous databases
RNActi | Q6ZN16, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q6ZN16 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 652 – 908 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 257 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1179 – 1225 | Sequence analysisAdd BLAST | 47 |
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 | ENSGT00940000159562 |
HOGENOMi | CLU_048342_0_0_1 |
InParanoidi | Q6ZN16 |
OMAi | PRMDIAC |
OrthoDBi | 226722at2759 |
PhylomeDBi | Q6ZN16 |
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, DUF4071, 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 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q6ZN16-1) [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
MESGGGNAPA GALGAASESP QCPPPPGVEG AAGPAEPDGA AEGAAGGSGE
60 70 80 90 100
GESGGGPRRA LRAVYVRSES SQGGAAGGPE AGARQCLLRA CEAEGAHLTS
110 120 130 140 150
VPFGELDFGE TAVLDAFYDA DVAVVDMSDV SRQPSLFYHL GVRESFDMAN
160 170 180 190 200
NVILYHDTDA DTALSLKDMV TQKNTASSGN YYFIPYIVTP CADYFCCESD
210 220 230 240 250
AQRRASEYMQ PNWDNILGPL CMPLVDRFIS LLKDIHVTSC VYYKETLLND
260 270 280 290 300
IRKAREKYQG EELAKELARI KLRMDNTEVL TSDIIINLLL SYRDIQDYDA
310 320 330 340 350
MVKLVETLEM LPTCDLADQH NIKFHYAFAL NRRNSTGDRE KALQIMLQVL
360 370 380 390 400
QSCDHPGPDM FCLCGRIYKD IFLDSDCKDD TSRDSAIEWY RKGFELQSSL
410 420 430 440 450
YSGINLAVLL IVAGQQFETS LELRKIGVRL NSLLGRKGSL EKMNNYWDVG
460 470 480 490 500
QFFSVSMLAH DVGKAVQAAE RLFKLKPPVW YLRSLVQNLL LIRRFKKTII
510 520 530 540 550
EHSPRQERLN FWLDIIFEAT NEVTNGLRFP VLVIEPTKVY QPSYVSINNE
560 570 580 590 600
AEERTVSLWH VSPTEMKQMH EWNFTASSIK GISLSKFDER CCFLYVHDNS
610 620 630 640 650
DDFQIYFSTE EQCSRFFSLV KEMITNTAGS TVELEGETDG DTLEYEYDHD
660 670 680 690 700
ANGERVVLGK GTYGIVYAGR DLSNQVRIAI KEIPERDSRY SQPLHEEIAL
710 720 730 740 750
HKYLKHRNIV QYLGSVSENG YIKIFMEQVP GGSLSALLRS KWGPMKEPTI
760 770 780 790 800
KFYTKQILEG LKYLHENQIV HRDIKGDNVL VNTYSGVVKI SDFGTSKRLA
810 820 830 840 850
GVNPCTETFT GTLQYMAPEI IDQGPRGYGA PADIWSLGCT IIEMATSKPP
860 870 880 890 900
FHELGEPQAA MFKVGMFKIH PEIPEALSAE ARAFILSCFE PDPHKRATTA
910 920 930 940 950
ELLREGFLRQ VNKGKKNRIA FKPSEGPRGV VLALPTQGEP MATSSSEHGS
960 970 980 990 1000
VSPDSDAQPD ALFERTRAPR HHLGHLLSVP DESSALEDRG LASSPEDRDQ
1010 1020 1030 1040 1050
GLFLLRKDSE RRAILYKILW EEQNQVASNL QECVAQSSEE LHLSVGHIKQ
1060 1070 1080 1090 1100
IIGILRDFIR SPEHRVMATT ISKLKVDLDF DSSSISQIHL VLFGFQDAVN
1110 1120 1130 1140 1150
KILRNHLIRP HWMFAMDNII RRAVQAAVTI LIPELRAHFE PTCETEGVDK
1160 1170 1180 1190 1200
DMDEAEEGYP PATGPGQEAQ PHQQHLSLQL GELRQETNRL LEHLVEKERE
1210 1220 1230 1240 1250
YQNLLRQTLE QKTQELYHLQ LKLKSNCITE NPAGPYGQRT DKELIDWLRL
1260 1270 1280 1290 1300
QGADAKTIEK IVEEGYTLSD ILNEITKEDL RYLRLRGGLL CRLWSAVSQY
1310
RRAQEASETK DKA
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A140T8W5 | A0A140T8W5_HUMAN | Mitogen-activated protein kinase ki... | MAP3K15 | 283 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 793 | F → L in BAD18622 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040716 | 192 | A → T1 PublicationCorresponds to variant dbSNP:rs5909299Ensembl. | 1 | |
Natural variantiVAR_040717 | 199 | S → N1 PublicationCorresponds to variant dbSNP:rs55916006EnsemblClinVar. | 1 | |
Natural variantiVAR_040718 | 226 | D → H1 PublicationCorresponds to variant dbSNP:rs56338727Ensembl. | 1 | |
Natural variantiVAR_040719 | 255 | R → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040720 | 456 | S → G1 PublicationCorresponds to variant dbSNP:rs56212339Ensembl. | 1 | |
Natural variantiVAR_040721 | 494 | R → C1 PublicationCorresponds to variant dbSNP:rs41305349Ensembl. | 1 | |
Natural variantiVAR_040722 | 562 | S → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040723 | 677 | R → Q in a metastatic melanoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040724 | 838 | G → S1 PublicationCorresponds to variant dbSNP:rs56381411Ensembl. | 1 | |
Natural variantiVAR_040725 | 993 | S → L1 PublicationCorresponds to variant dbSNP:rs56233219Ensembl. | 1 | |
Natural variantiVAR_040726 | 1029 | N → H1 PublicationCorresponds to variant dbSNP:rs55787622Ensembl. | 1 | |
Natural variantiVAR_040727 | 1247 | W → R in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_040728 | 1251 | Q → E1 PublicationCorresponds to variant dbSNP:rs15943Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_021038 | 1 – 565 | Missing in isoform 2. 1 PublicationAdd BLAST | 565 | |
Alternative sequenceiVSP_021039 | 1 – 525 | Missing in isoform 3. 1 PublicationAdd BLAST | 525 | |
Alternative sequenceiVSP_021040 | 526 – 582 | GLRFP…SIKGI → MACLTHRNETDARMEFYSLF HKGNKAGVQWHDLGSLQPLP PRFKRFSCLSLQSSWDY in isoform 3. 1 PublicationAdd BLAST | 57 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK131412 mRNA Translation: BAD18559.1 AK131477 mRNA Translation: BAD18622.1 AL732326 Genomic DNA No translation available. AL732423 Genomic DNA No translation available. |
CCDSi | CCDS35212.2 [Q6ZN16-1] |
RefSeqi | NP_001001671.3, NM_001001671.3 [Q6ZN16-1] XP_011543813.1, XM_011545511.2 [Q6ZN16-2] |
Genome annotation databases
Ensembli | ENST00000338883; ENSP00000345629; ENSG00000180815 [Q6ZN16-1] |
GeneIDi | 389840 |
KEGGi | hsa:389840 |
UCSCi | uc004czj.3, human [Q6ZN16-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK131412 mRNA Translation: BAD18559.1 AK131477 mRNA Translation: BAD18622.1 AL732326 Genomic DNA No translation available. AL732423 Genomic DNA No translation available. |
CCDSi | CCDS35212.2 [Q6ZN16-1] |
RefSeqi | NP_001001671.3, NM_001001671.3 [Q6ZN16-1] XP_011543813.1, XM_011545511.2 [Q6ZN16-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6V0M | X-ray | 1.80 | A/B/C | 1241-1308 | [»] | |
SMRi | Q6ZN16 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 133293, 6 interactors |
IntActi | Q6ZN16, 8 interactors |
STRINGi | 9606.ENSP00000345629 |
Chemistry databases
BindingDBi | Q6ZN16 |
ChEMBLi | CHEMBL1163127 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q6ZN16 |
PTM databases
iPTMneti | Q6ZN16 |
PhosphoSitePlusi | Q6ZN16 |
Genetic variation databases
BioMutai | MAP3K15 |
DMDMi | 116248533 |
Proteomic databases
CPTACi | CPTAC-841 CPTAC-842 |
jPOSTi | Q6ZN16 |
MassIVEi | Q6ZN16 |
PaxDbi | Q6ZN16 |
PeptideAtlasi | Q6ZN16 |
PRIDEi | Q6ZN16 |
ProteomicsDBi | 67956 [Q6ZN16-1] 67957 [Q6ZN16-2] 67958 [Q6ZN16-3] |
Protocols and materials databases
Antibodypediai | 571, 145 antibodies |
Genome annotation databases
Ensembli | ENST00000338883; ENSP00000345629; ENSG00000180815 [Q6ZN16-1] |
GeneIDi | 389840 |
KEGGi | hsa:389840 |
UCSCi | uc004czj.3, human [Q6ZN16-1] |
Organism-specific databases
CTDi | 389840 |
DisGeNETi | 389840 |
GeneCardsi | MAP3K15 |
HGNCi | HGNC:31689, MAP3K15 |
HPAi | ENSG00000180815, Tissue enhanced (adrenal gland, brain) |
MIMi | 300820, gene |
neXtProti | NX_Q6ZN16 |
OpenTargetsi | ENSG00000180815 |
PharmGKBi | PA134935369 |
VEuPathDBi | HostDB:ENSG00000180815.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4279, Eukaryota |
GeneTreei | ENSGT00940000159562 |
HOGENOMi | CLU_048342_0_0_1 |
InParanoidi | Q6ZN16 |
OMAi | PRMDIAC |
OrthoDBi | 226722at2759 |
PhylomeDBi | Q6ZN16 |
TreeFami | TF105115 |
Enzyme and pathway databases
PathwayCommonsi | Q6ZN16 |
SignaLinki | Q6ZN16 |
Miscellaneous databases
BioGRID-ORCSi | 389840, 0 hits in 173 CRISPR screens |
ChiTaRSi | MAP3K15, human |
GenomeRNAii | 389840 |
Pharosi | Q6ZN16, Tchem |
PROi | PR:Q6ZN16 |
RNActi | Q6ZN16, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180815, Expressed in adrenal tissue and 84 other tissues |
ExpressionAtlasi | Q6ZN16, baseline and differential |
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, DUF4071, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | M3K15_HUMAN | |
Accessioni | Q6ZN16Primary (citable) accession number: Q6ZN16 Secondary accession number(s): A2AI49 Q6ZMV3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 17, 2006 |
Last sequence update: | October 17, 2006 | |
Last modified: | April 7, 2021 | |
This is version 146 of the entry and version 2 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 X
Human chromosome X: 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