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Protein

Mitogen-activated protein kinase kinase kinase 15

Gene

MAP3K15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei681ATPPROSITE-ProRule annotation1
Active sitei773Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi658 – 666ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS17571-MONOMER.
SignaLinkiQ6ZN16.

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

Organism-specific databases

HGNCiHGNC:31689. MAP3K15.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000180815.
PharmGKBiPA134935369.

Chemistry databases

ChEMBLiCHEMBL1163127.
GuidetoPHARMACOLOGYi2075.

Polymorphism and mutation databases

BioMutaiMAP3K15.
DMDMi116248533.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002534811 – 1313Mitogen-activated protein kinase kinase kinase 15Add BLAST1313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei994PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6ZN16.
PaxDbiQ6ZN16.
PeptideAtlasiQ6ZN16.
PRIDEiQ6ZN16.

PTM databases

iPTMnetiQ6ZN16.
PhosphoSitePlusiQ6ZN16.

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

BgeeiENSG00000180815.
CleanExiHS_MAP3K15.
ExpressionAtlasiQ6ZN16. baseline and differential.

Organism-specific databases

HPAiHPA004006.

Interactioni

Protein-protein interaction databases

BioGridi133293. 5 interactors.
IntActiQ6ZN16. 4 interactors.
STRINGi9606.ENSP00000345629.

Chemistry databases

BindingDBiQ6ZN16.

Structurei

3D structure databases

ProteinModelPortaliQ6ZN16.
SMRiQ6ZN16.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini652 – 908Protein kinasePROSITE-ProRule annotationAdd BLAST257

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili1179 – 1225Sequence analysisAdd BLAST47

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000293286.
HOVERGENiHBG006305.
InParanoidiQ6ZN16.
KOiK13986.
OMAiIPNTRKY.
OrthoDBiEOG091G00SJ.
PhylomeDBiQ6ZN16.
TreeFamiTF105115.

Family and domain databases

InterProiIPR025136. DUF4071.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR013761. SAM/pointed.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF13281. DUF4071. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q6ZN16-1) [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
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
Length:1,313
Mass (Da):147,437
Last modified:October 17, 2006 - v2
Checksum:i60751706D6AEE3E9
GO
Isoform 2 (identifier: Q6ZN16-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-565: Missing.

Note: No experimental confirmation available.
Show »
Length:748
Mass (Da):84,729
Checksum:iB062EF833B28DB1C
GO
Isoform 3 (identifier: Q6ZN16-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-525: Missing.
     526-582: GLRFPVLVIE...NFTASSIKGI → MACLTHRNET...CLSLQSSWDY

Note: No experimental confirmation available.
Show »
Length:788
Mass (Da):89,423
Checksum:i5C9C9774E3F069F3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti793F → L in BAD18622 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040716192A → T.1 PublicationCorresponds to variant rs5909299dbSNPEnsembl.1
Natural variantiVAR_040717199S → N.1 PublicationCorresponds to variant rs55916006dbSNPEnsembl.1
Natural variantiVAR_040718226D → H.1 PublicationCorresponds to variant rs56338727dbSNPEnsembl.1
Natural variantiVAR_040719255R → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040720456S → G.1 PublicationCorresponds to variant rs56212339dbSNPEnsembl.1
Natural variantiVAR_040721494R → C.1 PublicationCorresponds to variant rs41305349dbSNPEnsembl.1
Natural variantiVAR_040722562S → L in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040723677R → Q in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040724838G → S.1 PublicationCorresponds to variant rs56381411dbSNPEnsembl.1
Natural variantiVAR_040725993S → L.1 PublicationCorresponds to variant rs56233219dbSNPEnsembl.1
Natural variantiVAR_0407261029N → H.1 PublicationCorresponds to variant rs55787622dbSNPEnsembl.1
Natural variantiVAR_0407271247W → R in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0407281251Q → E.1 PublicationCorresponds to variant rs15943dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0210381 – 565Missing in isoform 2. 1 PublicationAdd BLAST565
Alternative sequenceiVSP_0210391 – 525Missing in isoform 3. 1 PublicationAdd BLAST525
Alternative sequenceiVSP_021040526 – 582GLRFP…SIKGI → MACLTHRNETDARMEFYSLF HKGNKAGVQWHDLGSLQPLP PRFKRFSCLSLQSSWDY in isoform 3. 1 PublicationAdd BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131412 mRNA. Translation: BAD18559.1.
AK131477 mRNA. Translation: BAD18622.1.
AL732423, AL732326 Genomic DNA. Translation: CAM17478.1.
AL732423, AL732326 Genomic DNA. Translation: CAM17479.1.
AL732326, AL732423 Genomic DNA. Translation: CAM23142.1.
AL732326, AL732423 Genomic DNA. Translation: CAM23143.1.
CCDSiCCDS35212.2. [Q6ZN16-1]
RefSeqiNP_001001671.3. NM_001001671.3. [Q6ZN16-1]
XP_011543813.1. XM_011545511.2. [Q6ZN16-2]
UniGeneiHs.713701.

Genome annotation databases

EnsembliENST00000338883; ENSP00000345629; ENSG00000180815. [Q6ZN16-1]
GeneIDi389840.
KEGGihsa:389840.
UCSCiuc004czj.3. human. [Q6ZN16-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK131412 mRNA. Translation: BAD18559.1.
AK131477 mRNA. Translation: BAD18622.1.
AL732423, AL732326 Genomic DNA. Translation: CAM17478.1.
AL732423, AL732326 Genomic DNA. Translation: CAM17479.1.
AL732326, AL732423 Genomic DNA. Translation: CAM23142.1.
AL732326, AL732423 Genomic DNA. Translation: CAM23143.1.
CCDSiCCDS35212.2. [Q6ZN16-1]
RefSeqiNP_001001671.3. NM_001001671.3. [Q6ZN16-1]
XP_011543813.1. XM_011545511.2. [Q6ZN16-2]
UniGeneiHs.713701.

3D structure databases

ProteinModelPortaliQ6ZN16.
SMRiQ6ZN16.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi133293. 5 interactors.
IntActiQ6ZN16. 4 interactors.
STRINGi9606.ENSP00000345629.

Chemistry databases

BindingDBiQ6ZN16.
ChEMBLiCHEMBL1163127.
GuidetoPHARMACOLOGYi2075.

PTM databases

iPTMnetiQ6ZN16.
PhosphoSitePlusiQ6ZN16.

Polymorphism and mutation databases

BioMutaiMAP3K15.
DMDMi116248533.

Proteomic databases

EPDiQ6ZN16.
PaxDbiQ6ZN16.
PeptideAtlasiQ6ZN16.
PRIDEiQ6ZN16.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338883; ENSP00000345629; ENSG00000180815. [Q6ZN16-1]
GeneIDi389840.
KEGGihsa:389840.
UCSCiuc004czj.3. human. [Q6ZN16-1]

Organism-specific databases

CTDi389840.
GeneCardsiMAP3K15.
H-InvDBHIX0028382.
HGNCiHGNC:31689. MAP3K15.
HPAiHPA004006.
MIMi300820. gene.
neXtProtiNX_Q6ZN16.
OpenTargetsiENSG00000180815.
PharmGKBiPA134935369.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4279. Eukaryota.
ENOG410XQGS. LUCA.
GeneTreeiENSGT00800000124036.
HOGENOMiHOG000293286.
HOVERGENiHBG006305.
InParanoidiQ6ZN16.
KOiK13986.
OMAiIPNTRKY.
OrthoDBiEOG091G00SJ.
PhylomeDBiQ6ZN16.
TreeFamiTF105115.

Enzyme and pathway databases

BioCyciZFISH:HS17571-MONOMER.
SignaLinkiQ6ZN16.

Miscellaneous databases

GenomeRNAii389840.
PROiQ6ZN16.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180815.
CleanExiHS_MAP3K15.
ExpressionAtlasiQ6ZN16. baseline and differential.

Family and domain databases

InterProiIPR025136. DUF4071.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR013761. SAM/pointed.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF13281. DUF4071. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K15_HUMAN
AccessioniPrimary (citable) accession number: Q6ZN16
Secondary accession number(s): A2AI49
, A2AI50, A6NJ61, Q5JPR4, Q6ZMV3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 118 of the entry and version 2 of the sequence. [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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.