Descriptions

MAP2K4 encodes for Dual specificity mitogen-activated protein kinase kinase 4, belongs to MAP2Ks family, plays an important role in MAP kinase signal transduction pathway. The part of the activation (loop) segment is forming a helical structure (activation segment helix, ASH) in its autoinhibited state, which could be destabilized by the phosphorylation of the activation segment.

Autoinhibitory domains (AIDs)

Accessory elements

246-268 (Activation loop from InterPro)

Target domain

102-367 (Protein kinase domain)

Relief mechanism

PTM

Assay

Structure analysis, Mutagenesis experiment

Autoinhibited structure

Activated structure

4 structures for P45985

Entry ID Method Resolution Chain Position Source
3ALN X-ray 230 A A/B/C 80-399 PDB
3ALO X-ray 260 A A 80-399 PDB
3VUT X-ray 350 A A/B 80-399 PDB
AF-P45985-F1 Predicted AlphaFoldDB

150 variants for P45985

Variant ID(s) Position Change Description Diseaes Association Provenance
CA398239990
rs1555550018
RCV000505661
180 L>V Neuroblastoma [ClinVar] Yes ClinGen
ClinVar
Ensembl
dbSNP
CA398214476
rs1417816691
4 P>L No ClinGen
TOPMed
CA398214482
rs1161471824
5 S>I No ClinGen
TOPMed
gnomAD
rs1161471824
CA398214480
5 S>N No ClinGen
TOPMed
gnomAD
CA288025340
rs979899636
6 P>A No ClinGen
TOPMed
gnomAD
rs989028622
CA288025362
9 G>D No ClinGen
TOPMed
CA288025359
rs959911955
9 G>R No ClinGen
TOPMed
gnomAD
CA288025358
rs959911955
9 G>S No ClinGen
TOPMed
gnomAD
CA398214514
rs1229178018
11 G>R No ClinGen
TOPMed
rs749070408
CA8398836
15 G>S No ClinGen
ExAC
TOPMed
gnomAD
CA288025374
VAR_062963
rs17855590
16 S>R No ClinGen
UniProt
TOPMed
dbSNP
gnomAD
CA398214563
rs1169380060
18 S>R No ClinGen
TOPMed
rs976985059
CA288025382
19 G>D No ClinGen
TOPMed
rs978668162
CA288025384
20 T>I No ClinGen
TOPMed
gnomAD
rs1289939331
CA398214576
21 P>A No ClinGen
TOPMed
gnomAD
CA398214582
rs527463657
22 G>C No ClinGen
1000Genomes
TOPMed
CA288025392
rs527463657
22 G>S No ClinGen
1000Genomes
TOPMed
rs1283698963
CA398214590
23 P>L No ClinGen
TOPMed
gnomAD
rs548788415
CA8398838
23 P>T No ClinGen
1000Genomes
ExAC
TOPMed
gnomAD
rs1049103069
CA288025394
26 S>Y No ClinGen
TOPMed
rs1598004807
CA398214611
27 P>L No ClinGen
Ensembl
CA288025399
rs910110079
28 A>S No ClinGen
TOPMed
CA398214626
rs1283304214
30 G>S No ClinGen
TOPMed
CA398214643
rs1326610085
32 P>Q No ClinGen
gnomAD
CA398214647
rs1404280869
33 A>T No ClinGen
TOPMed
CA288025413
rs561204979
33 A>V No ClinGen
1000Genomes
gnomAD
CA288025420
rs940014479
34 V>F No ClinGen
TOPMed
gnomAD
CA398214651
rs940014479
34 V>I No ClinGen
TOPMed
gnomAD
rs1036999303
CA288025426
35 S>I No ClinGen
TOPMed
rs1355620714
CA398214681
38 Q>* No ClinGen
gnomAD
CA398214686
rs1214238261
38 Q>H No ClinGen
gnomAD
CA8398850
rs760186886
41 R>H No ClinGen
ExAC
gnomAD
rs111801039
CA287997640
42 K>R No ClinGen
Ensembl
rs752767497
CA8398852
45 K>M No ClinGen
ExAC
gnomAD
CA8398853
rs559800950
46 L>M No ClinGen
1000Genomes
ExAC
gnomAD
rs1348623447
CA398203507
47 N>S No ClinGen
gnomAD
CA287997688
rs1010543298
50 N>S No ClinGen
Ensembl
rs1447612385
CA398203569
50 N>Y No ClinGen
TOPMed
rs1261150954
CA398203592
51 P>L No ClinGen
TOPMed
rs754035296
CA8398855
52 P>A No ClinGen
ExAC
gnomAD
rs1358824984
COSM1686247
CA398203612
52 P>L skin [Cosmic] No ClinGen
cosmic curated
TOPMed
rs754035296
CA398203604
52 P>S No ClinGen
ExAC
gnomAD
CA287997693
rs372872972
53 F>S No ClinGen
ESP
TOPMed
gnomAD
rs1348785378
CA398203722
57 A>G No ClinGen
gnomAD
rs757051936
CA8398856
57 A>T No ClinGen
ExAC
gnomAD
rs1213129161
CA398203759
59 F>L No ClinGen
gnomAD
CA8398858
rs750208931
63 P>L No ClinGen
ExAC
gnomAD
CA8398857
rs778746854
63 P>S No ClinGen
ExAC
gnomAD
rs758381870
CA8398859
64 N>S No ClinGen
ExAC
gnomAD
rs780013239
CA8398860
66 T>A No ClinGen
ExAC
TOPMed
gnomAD
rs201981451
CA287997743
68 V>A No ClinGen
1000Genomes
TOPMed
gnomAD
rs1394118458
CA398203862
69 Q>E No ClinGen
gnomAD
rs1434938057
CA398203876
70 N>S No ClinGen
gnomAD
CA8398886
rs377490722
76 L>V No ClinGen
ESP
ExAC
gnomAD
CA398208127
rs1290976146
90 S>Y No ClinGen
gnomAD
rs1466199105
CA398208154
94 H>Y No ClinGen
TOPMed
CA288017479
rs773665341
105 L>F No ClinGen
gnomAD
CA398208338
rs1474208027
108 I>F No ClinGen
gnomAD
CA398208341
rs1215001531
108 I>T No ClinGen
TOPMed
CA398208364
rs1164096095
COSM79380
110 R>* ovary endometrium stomach [Cosmic] No ClinGen
cosmic curated
gnomAD
rs1418420168
CA398208374
111 G>* No ClinGen
gnomAD
CA8398893
rs747647990
117 N>S No ClinGen
ExAC
TOPMed
gnomAD
CA398208467
rs1290755523
118 K>N No ClinGen
TOPMed
gnomAD
rs769619151
CA8398894
120 V>I No ClinGen
ExAC
TOPMed
gnomAD
rs769619151
CA398208496
120 V>L No ClinGen
ExAC
TOPMed
gnomAD
CA288017491
rs77267737
130 V>G No ClinGen
Ensembl
CA398239147
rs1415316526
136 T>I No ClinGen
TOPMed
gnomAD
COSM975559
CA8398968
rs775475276
137 V>M endometrium [Cosmic] No ClinGen
cosmic curated
ExAC
gnomAD
rs1444656785
CA398239163
138 D>N No ClinGen
TOPMed
rs1371329502
CA398239180
139 E>K No ClinGen
TOPMed
CA398239277
rs1307654543
146 L>V No ClinGen
TOPMed
rs760515884
CA8398969
147 M>T No ClinGen
ExAC
TOPMed
gnomAD
CA8398971
rs776387940
151 V>I No ClinGen
ExAC
gnomAD
CA8398972
rs761402309
153 M>V No ClinGen
ExAC
gnomAD
CA398239334
rs1208900089
154 R>Q No ClinGen
gnomAD
CA398239332
rs1567657403
VAR_040819
COSM20411
154 R>W large_intestine a colorectal adenocarcinoma sample; somatic mutation [Cosmic, UniProt] No ClinGen
cosmic curated
UniProt
Ensembl
dbSNP
rs1314005490
CA398239360
157 D>E No ClinGen
TOPMed
gnomAD
rs764582118
CA8398973
159 P>A No ClinGen
ExAC
gnomAD
rs1248970628
CA398239377
160 Y>C No ClinGen
TOPMed
gnomAD
rs749942107
CA8398974
160 Y>H No ClinGen
ExAC
gnomAD
CA398239412
rs1418890158
165 Y>N No ClinGen
gnomAD
rs534883661
CA287984272
178 M>V No ClinGen
Ensembl
rs1191386417
CA398240022
182 S>C No ClinGen
gnomAD
rs766050183
CA8398995
185 F>L No ClinGen
ExAC
gnomAD
CA8398996
rs150905259
191 Y>C No ClinGen
ESP
ExAC
TOPMed
gnomAD
rs760844487
CA287984326
195 V>A No ClinGen
Ensembl
rs764298113
CA8398998
195 V>I No ClinGen
ExAC
gnomAD
rs754217305
CA8398999
196 L>S No ClinGen
ExAC
gnomAD
CA398240251
rs1371909082
200 I>V No ClinGen
TOPMed
gnomAD
rs1040630581
CA287984336
203 E>D No ClinGen
TOPMed
CA8399001
rs765746113
207 K>R No ClinGen
ExAC
gnomAD
rs1307489818
CA398240352
208 I>T No ClinGen
gnomAD
CA398240362
rs1260446708
209 T>S No ClinGen
gnomAD
CA398240370
rs1240723113
210 L>S No ClinGen
gnomAD
rs1354928111
CA398241122
222 N>S No ClinGen
TOPMed
CA287988423
rs748395840
230 I>T No ClinGen
gnomAD
CA398241369
rs1597480176
231 K>N No ClinGen
Ensembl
rs536223681
CA8399033
231 K>R No ClinGen
1000Genomes
ExAC
gnomAD
rs1025397785
CA287988437
242 N>S No ClinGen
TOPMed
CA398241507
rs1160578914
243 I>T No ClinGen
gnomAD
rs1361335563
CA398241605
255 V>L No ClinGen
gnomAD
CA287988456
rs200798818
264 A>S No ClinGen
1000Genomes
rs76726054
CA287988466
266 C>W No ClinGen
Ensembl
rs1455763623
CA398241772
277 P>A No ClinGen
TOPMed
COSM21292
VAR_040822
CA8399062
rs753665559
279 A>T large_intestine haematopoietic_and_lymphoid_tissue a colorectal adenocarcinoma sample; somatic mutation [Cosmic, UniProt] No ClinGen
cosmic curated
UniProt
ExAC
dbSNP
gnomAD
rs1183392154
COSM1563407
CA398241789
279 A>V large_intestine [Cosmic] No ClinGen
cosmic curated
Ensembl
CA8399063
rs537815982
286 V>I No ClinGen
1000Genomes
ExAC
TOPMed
gnomAD
CA398241845
rs1334746981
288 S>C No ClinGen
gnomAD
CA8399090
rs144008624
301 A>G No ClinGen
ESP
ExAC
rs781002756
CA8399089
301 A>S No ClinGen
ExAC
gnomAD
rs1194360851
CA398241966
304 R>Q No ClinGen
TOPMed
gnomAD
rs755823478
CA8399091
309 K>R No ClinGen
ExAC
gnomAD
rs779390733
CA8399092
311 N>D No ClinGen
ExAC
gnomAD
rs1480785686
CA398242019
311 N>K No ClinGen
TOPMed
rs1396947681
COSM98424
CA398242084
321 V>M large_intestine [Cosmic] No ClinGen
cosmic curated
TOPMed
gnomAD
CA288003875
COSM98425
rs267604739
326 P>L large_intestine [Cosmic] No ClinGen
cosmic curated
Ensembl
rs1311024915
CA398242129
327 Q>H No ClinGen
gnomAD
CA398242154
rs1597497681
331 S>Y No ClinGen
Ensembl
CA398242159
rs1355543573
332 E>K No ClinGen
gnomAD
rs908877597
CA288003883
335 E>Q No ClinGen
TOPMed
gnomAD
CA8399100
rs371746849
338 P>L No ClinGen
ESP
ExAC
TOPMed
gnomAD
CA398242205
rs371746849
338 P>R No ClinGen
ESP
ExAC
TOPMed
gnomAD
CA288003902
rs367710581
341 I>T No ClinGen
ESP
TOPMed
rs1239669542
CA398242223
341 I>V No ClinGen
gnomAD
rs1355990355
CA398242234
342 N>K No ClinGen
gnomAD
CA8399102
rs191244765
342 N>S No ClinGen
1000Genomes
ExAC
TOPMed
gnomAD
rs755523599
CA8399132
COSM975566
349 T>M endometrium [Cosmic] No ClinGen
cosmic curated
ExAC
gnomAD
rs1293062852
CA398242297
349 T>S No ClinGen
gnomAD
rs1294064382
CA398242316
351 D>E No ClinGen
gnomAD
rs1340390247
CA398242321
352 E>G No ClinGen
gnomAD
CA288014390
rs1024493228
355 R>M No ClinGen
TOPMed
CA8399135
rs769700685
359 K>T No ClinGen
ExAC
gnomAD
CA398242410
rs1567679461
363 K>R No ClinGen
Ensembl
CA398242415
rs1323806098
364 H>Y No ClinGen
TOPMed
CA398242443
rs1425777448
368 L>V No ClinGen
gnomAD
CA398242461
rs1379788876
370 Y>C No ClinGen
gnomAD
rs749364956
CA8399156
370 Y>N No ClinGen
ExAC
gnomAD
CA398242465
rs1168805084
371 E>K No ClinGen
gnomAD
rs1300593472
CA398242483
373 R>C No ClinGen
gnomAD
rs1372846289
CA398242484
373 R>H No ClinGen
gnomAD
CA398242487
rs1052408848
374 A>S No ClinGen
TOPMed
CA288015641
rs1052408848
374 A>T No ClinGen
TOPMed
rs889363169
CA288015651
374 A>V No ClinGen
TOPMed
rs367662793
CA8399158
375 V>I No ClinGen
1000Genomes
ESP
ExAC
TOPMed
gnomAD
rs771926980
CA8399160
378 A>S No ClinGen
ExAC
gnomAD
rs771926980
CA8399161
COSM975568
378 A>T endometrium [Cosmic] No ClinGen
cosmic curated
ExAC
gnomAD
CA398242567
rs1192323091
386 D>A No ClinGen
TOPMed
CA398242633
rs1209244324
396 M>V No ClinGen
gnomAD
rs538492504
CA8399165
397 Y>C No ClinGen
ExAC
TOPMed
gnomAD
rs1177038824
CA398242655
399 D>N No ClinGen
gnomAD

No associated diseases with P45985

3 regional properties for P45985

Type Name Position InterPro Accession
domain Protein kinase domain 102 - 367 IPR000719
active_site Serine/threonine-protein kinase, active site 225 - 237 IPR008271
binding_site Protein kinase, ATP binding site 108 - 131 IPR017441

2 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
JUN kinase kinase activity Catalysis of the phosphorylation of tyrosine and threonine residues in a c-Jun NH2-terminal kinase (JNK), a member of a subgroup of mitogen-activated protein kinases (MAPKs), which signal in response to cytokines and exposure to environmental stress. JUN kinase kinase (JNKK) is a dual-specificity protein kinase kinase and requires activation by a serine/threonine kinase JUN kinase kinase kinase.
MAP kinase kinase activity Catalysis of the concomitant phosphorylation of threonine (T) and tyrosine (Y) residues in a Thr-Glu-Tyr (TEY) thiolester sequence in a MAP kinase (MAPK) substrate.
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 serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein tyrosine kinase activity Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

10 GO annotations of biological process

Name Definition
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
cellular response to mechanical stimulus 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 mechanical stimulus.
cellular senescence A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest.
Fc-epsilon receptor signaling pathway The series of molecular signals initiated by the binding of the Fc portion of immunoglobulin E (IgE) to an Fc-epsilon receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. The Fc portion of an immunoglobulin is its C-terminal constant region.
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.
negative regulation of motor neuron apoptotic process Any process that stops, prevents or reduces the frequency, rate or extent of motor neuron apoptotic process.
positive regulation of smooth muscle cell apoptotic process Any process that activates or increases the frequency, rate, or extent of smooth muscle cell apoptotic process.
response to wounding Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to the organism.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

15 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q5E9X2 MAP2K6 Dual specificity mitogen-activated protein kinase kinase 6 Bos taurus (Bovine) EV
O14733 MAP2K7 Dual specificity mitogen-activated protein kinase kinase 7 Homo sapiens (Human) PR
P52564 MAP2K6 Dual specificity mitogen-activated protein kinase kinase 6 Homo sapiens (Human) EV
P46734 MAP2K3 Dual specificity mitogen-activated protein kinase kinase 3 Homo sapiens (Human) SS
Q13163 MAP2K5 Dual specificity mitogen-activated protein kinase kinase 5 Homo sapiens (Human) PR
P36507 MAP2K2 Dual specificity mitogen-activated protein kinase kinase 2 Homo sapiens (Human) EV
Q02750 MAP2K1 Dual specificity mitogen-activated protein kinase kinase 1 Homo sapiens (Human) EV
P47809 Map2k4 Dual specificity mitogen-activated protein kinase kinase 4 Mus musculus (Mouse) EV
P70236 Map2k6 Dual specificity mitogen-activated protein kinase kinase 6 Mus musculus (Mouse) EV
Q8CE90 Map2k7 Dual specificity mitogen-activated protein kinase kinase 7 Mus musculus (Mouse) PR
O09110 Map2k3 Dual specificity mitogen-activated protein kinase kinase 3 Mus musculus (Mouse) PR
G5EDF7 sek-1 Dual specificity mitogen-activated protein kinase kinase sek-1 Caenorhabditis elegans PR
G5EDT6 jkk-1 Dual specificity mitogen-activated protein kinase kinase jkk-1 Caenorhabditis elegans PR
Q21307 mek-1 Dual specificity mitogen-activated protein kinase kinase mek-1 Caenorhabditis elegans PR
Q9DGE0 map2k6 Dual specificity mitogen-activated protein kinase kinase 6 Danio rerio (Zebrafish) (Brachydanio rerio) PR
10 20 30 40 50 60
MAAPSPSGGG GSGGGSGSGT PGPVGSPAPG HPAVSSMQGK RKALKLNFAN PPFKSTARFT
70 80 90 100 110 120
LNPNPTGVQN PHIERLRTHS IESSGKLKIS PEQHWDFTAE DLKDLGEIGR GAYGSVNKMV
130 140 150 160 170 180
HKPSGQIMAV KRIRSTVDEK EQKQLLMDLD VVMRSSDCPY IVQFYGALFR EGDCWICMEL
190 200 210 220 230 240
MSTSFDKFYK YVYSVLDDVI PEEILGKITL ATVKALNHLK ENLKIIHRDI KPSNILLDRS
250 260 270 280 290 300
GNIKLCDFGI SGQLVDSIAK TRDAGCRPYM APERIDPSAS RQGYDVRSDV WSLGITLYEL
310 320 330 340 350 360
ATGRFPYPKW NSVFDQLTQV VKGDPPQLSN SEEREFSPSF INFVNLCLTK DESKRPKYKE
370 380 390
LLKHPFILMY EERAVEVACY VCKILDQMPA TPSSPMYVD