O35099

SS
Gene name
Map3k5 (Ask1, Mekk5)
Protein name
Mitogen-activated protein kinase kinase kinase 5
Names
Apoptosis signal-regulating kinase 1, ASK-1, MAPK/ERK kinase kinase 5, MEK kinase 5, MEKK 5
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:26408
EC number
2.7.11.25: Protein-serine/threonine kinases
Protein Class

Descriptions

MAP3K5 mediates signaling for determination of cell fate such as differentiation and survival. Truncation experiments with human MAP3K5 (Q99683) showed that an autoinhibitory region is included in N-terminal region and mutation of S1034A further increased the activity of N-terminal-truncated MAP3K5. These results represent the existence of autoinhibitory regions within N- and C-terminal regions.

Autoinhibitory domains (AIDs)

1-655 (N-terminal autoinhibitory region) SS

Target domain

687-945 (Protein kinase domain)

Relief mechanism

Assay

946-1380 (C-terminal autoinhibitory region) SS

Target domain

687-945 (Protein kinase domain)

Relief mechanism

Assay

Accessory elements

828-851 (Activation loop from InterPro)

Target domain

687-945 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for O35099

Entry ID Method Resolution Chain Position Source
AF-O35099-F1 Predicted AlphaFoldDB

10 variants for O35099

Variant ID(s) Position Change Description Diseaes Association Provenance
rs250866542 97 R>S No Ensembl
rs243298531 248 N>K No Ensembl
rs212585693 251 L>V No Ensembl
rs245400464 261 V>A No Ensembl
rs29347953 420 D>A No Ensembl
rs50042747 612 G>S No Ensembl
rs1133304319 900 K>E No Ensembl
rs50326540 1081 A>V No Ensembl
rs1132727820 1168 K>N No Ensembl
rs223981959 1203 D>E No Ensembl

No associated diseases with O35099

17 regional properties for O35099

Type Name Position InterPro Accession
domain Flavodoxin-like 523 - 536 IPR001094-1
domain Flavodoxin-like 570 - 581 IPR001094-2
domain Flavodoxin-like 646 - 656 IPR001094-3
domain Flavodoxin-like 670 - 689 IPR001094-4
domain Oxidoreductase FAD/NAD(P)-binding 1013 - 1125 IPR001433
domain Flavoprotein pyridine nucleotide cytochrome reductase 795 - 805 IPR001709-1
domain Flavoprotein pyridine nucleotide cytochrome reductase 940 - 947 IPR001709-2
domain Flavoprotein pyridine nucleotide cytochrome reductase 976 - 985 IPR001709-3
domain Flavoprotein pyridine nucleotide cytochrome reductase 1012 - 1031 IPR001709-4
domain Flavoprotein pyridine nucleotide cytochrome reductase 1042 - 1051 IPR001709-5
domain Flavoprotein pyridine nucleotide cytochrome reductase 1055 - 1066 IPR001709-6
domain Flavoprotein pyridine nucleotide cytochrome reductase 1087 - 1103 IPR001709-7
domain Flavoprotein pyridine nucleotide cytochrome reductase 1112 - 1120 IPR001709-8
domain Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding 754 - 981 IPR003097
domain Nitric oxide synthase, N-terminal 122 - 483 IPR004030
domain Flavodoxin/nitric oxide synthase 522 - 705 IPR008254
domain FAD-binding domain, ferredoxin reductase-type 758 - 1004 IPR017927

Functions

Description
EC Number 2.7.11.25 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Endoplasmic reticulum
  • Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
external side of plasma membrane The leaflet of the plasma membrane that faces away from the cytoplasm and any proteins embedded or anchored in it or attached to its surface.
IRE1-TRAF2-ASK1 complex A protein complex of the endoplasmic reticulum membrane that consists of IRE1 (Inositol-requiring enzyme-1), TRAF2 (TNF receptor-associated factor 2) and ASK1 (Apoptosis signal-regulating kinase 1, a MAP3K).
protein kinase complex A protein complex which is capable of protein kinase activity.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

12 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding Binding to an identical protein or proteins.
JUN kinase kinase kinase activity Catalysis of the reaction: JNKK + ATP = JNKK phosphate + ADP. This reaction is the phosphorylation and activation of JUN kinase kinases (JNKKs).
magnesium ion binding Binding to a magnesium (Mg) ion.
MAP kinase kinase kinase activity Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases.
protein domain specific binding Binding to a specific domain of a protein.
protein homodimerization activity Binding to an identical protein to form a homodimer.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein phosphatase binding Binding to a protein phosphatase.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

30 GO annotations of biological process

Name Definition
cellular response to amino acid starvation Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of amino acids.
cellular response to hydrogen peroxide Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
cellular response to reactive nitrogen species Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a reactive nitrogen species stimulus.
cellular response to tumor necrosis factor Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
endothelial cell apoptotic process Any apoptotic process in an endothelial cell. An endothelial cell comprises the outermost layer or lining of anatomical structures and can be squamous or cuboidal.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to a stimulus indicating endoplasmic reticulum (ER) stress, and ends when the execution phase of apoptosis is triggered. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
intrinsic apoptotic signaling pathway in response to oxidative stress The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, and ends when the execution phase of apoptosis is triggered.
JNK cascade An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
MAPK cascade An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell.
p38MAPK cascade An intracellular protein kinase cascade containing at least a p38 MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
positive regulation of apoptotic process Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process.
positive regulation of cardiac muscle cell apoptotic process Any process that increases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death.
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Any process that activates or increases the activity of a cysteine-type endopeptidase involved in the apoptotic process.
positive regulation of JNK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade.
positive regulation of JUN kinase activity Any process that activates or increases the frequency, rate or extent of JUN kinase activity.
positive regulation of MAPK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
positive regulation of myoblast differentiation Any process that activates or increases the frequency, rate or extent of myoblast differentiation. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into skeletal muscle fibers.
positive regulation of neuron death Any process that activates or increases the frequency, rate or extent of neuron death.
positive regulation of p38MAPK cascade Any process that activates or increases the frequency, rate or extent of p38MAPK cascade.
positive regulation of protein kinase activity Any process that activates or increases the frequency, rate or extent of protein kinase activity.
positive regulation of transcription, DNA-templated Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
positive regulation of vascular associated smooth muscle cell proliferation Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation.
programmed necrotic cell death A necrotic cell death process that results from the activation of endogenous cellular processes, such as signaling involving death domain receptors or Toll-like receptors.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of cell death Any process that modulates the rate or frequency of cell death. Cell death is the specific activation or halting of processes within a cell so that its vital functions markedly cease, rather than simply deteriorating gradually over time, which culminates in cell death.
response to endoplasmic reticulum stress Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stress acting at the endoplasmic reticulum. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
response to ischemia Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a inadequate blood supply.
stress-activated MAPK cascade The series of molecular signals in which a stress-activated MAP kinase cascade relays a signal; MAP kinase cascades involve at least three protein kinase activities and culminate in the phosphorylation and activation of a MAP kinase.
wound healing The series of events that restore integrity to a damaged tissue, following an injury.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
O95382 MAP3K6 Mitogen-activated protein kinase kinase kinase 6 Homo sapiens (Human) SS
Q6ZN16 MAP3K15 Mitogen-activated protein kinase kinase kinase 15 Homo sapiens (Human) SS
Q99683 MAP3K5 Mitogen-activated protein kinase kinase kinase 5 Homo sapiens (Human) EV
A2AQW0 Map3k15 Mitogen-activated protein kinase kinase kinase 15 Mus musculus (Mouse) PR
Q9WTR2 Map3k6 Mitogen-activated protein kinase kinase kinase 6 Mus musculus (Mouse) SS
10 20 30 40 50 60
MGTEAGEGIT FSVPPFASVG FCTIPEGGSC RRGGGAATAA EGEPSLQPLL VPPPPPPPGS
70 80 90 100 110 120
FWNVESAAAP GTSCPTTAPG SSATRGRGNS GSGGGRRTTV AYVINEASQG QLVVAESEAL
130 140 150 160 170 180
QSLREACEAV GATLETLHFG KLDFGETAVL DRFYNADIAV VEMSDAFRQP SLFYHLGVRE
190 200 210 220 230 240
SFSMANNIIL YCDTNSDSLQ SLKEIICQKN TVCTGNYTFI PYMVTPHNKV YCCDSSFMKG
250 260 270 280 290 300
LTELMQPNFE LLLGPICLPL VDRFVQLLKV AQASSSQYFR ESILSDIRKA RNLYTGKELA
310 320 330 340 350 360
AELARIRQRV DNIEVLTADI VINLLLSYRD IQDYDSIVKL VETLEKLPTF DLASHHHVKF
370 380 390 400 410 420
HYAFALNRRN LPGDRAKALD IMIPMVQSEE QVASDMYCLV GRIYKDMFLD SNFTDTESRD
430 440 450 460 470 480
HGASWFKKAF ESEPTLQSGI NYAVLLLAAG HQFESSFELR KVGVKLSSLL GKKGNLEKLQ
490 500 510 520 530 540
SYWEVGFFLG ASVLANDHLR VIQASEKLFR LKTPAWYLKS IVETILIYKH FVKLTTEQPS
550 560 570 580 590 600
AKQELVDFWM DFLVEATKTD VTVVRFPVLI LEPTKIYQPS YLSINNEVEE KTISIWHVLP
610 620 630 640 650 660
DDKKGIHEWN FGASSVRGVS ISKFEERCCF LYVLHNSDDF QIYFCTELHC KRFFEMVNTI
670 680 690 700 710 720
TEEKGRGAED GDCEGDSLEY DYEYDENGDR VVLGKGTYGI VYAGRDLSNQ VRIAIKEIPE
730 740 750 760 770 780
RDSRYSQPLH EEIALHKHLK HKNIVQYLGS FSENGFIKIF MEQVPGGSLS ALLRSKWGPL
790 800 810 820 830 840
KDNEQTIGFY TKQILEGLKY LHDNQIVHRD IKGDNVLINT YSGVLKISDF GTSKRLAGIN
850 860 870 880 890 900
PCTETFTGTL QYMAPEIIDK GPRGYGKAAD IWSLGCTIIE MATGKPPFYE LGEPQAAMFK
910 920 930 940 950 960
VGMFKVHPEI PESMSAEAKA FILKCFEPDP DKRACANDLL IDEFLKVSSK KKKTQPKLSA
970 980 990 1000 1010 1020
LSTGSNEYLR SISLPVPVLV EDTSSSSEYG SVSPDTELKA DPFSFKARAK SCGEKDGKGI
1030 1040 1050 1060 1070 1080
RTLFLGIPDE NFEDHSAPPS PEEKDSGFFM LRKDSERRAT LHRILTEDQD KVVRNLMESL
1090 1100 1110 1120 1130 1140
AQGAEEPKLK WEHITTLISS LREFVRSTDR KIIATTLSKL KLELDFDSHG ISQVQVVLFG
1150 1160 1170 1180 1190 1200
FQDAVNKVLR NHNIKPHWMF ALDSIIRKAV QTAITILVPE LRPHFSLASE SDTADPEDLD
1210 1220 1230 1240 1250 1260
VEDEHEELSS NQTVRRPQAI TEDAVATSGV STLSSTVSHD SQNAHRSLNV QLGRMKIETN
1270 1280 1290 1300 1310 1320
RLLEELVRKE RELQALLHQA IEEKDQEIRH LKLKSQPIDI PGFPVCHLNS PGTTTEDSEL
1330 1340 1350 1360 1370
PGWLRENGAD EDTISRFLAE DYTLVDVLYY VTRDDLKCLR LRGGMLCTLW KAIIDFRNKC