O75914
SS
Gene name |
PAK3 (OPHN3) |
Protein name |
Serine/threonine-protein kinase PAK 3 |
Names |
EC 2.7.11.1 , Beta-PAK , Oligophrenin-3 , p21-activated kinase 3 , PAK-3 |
Species |
Homo sapiens (Human) |
KEGG Pathway |
hsa:5063 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
The p21-activated kinases (PAKs) control cytoskeletal actin assembly and activate Mes: (1) as an inactive homodimer in which kinase activity is autoinhibited by binding of the inhibitory segment of a second PAK molecule, and (2) as an active monomer. <br> Inhibitory segment hinders the kinase domain and stabilizes a disabled catalytic site, and thus limits the ability of each kinase to autophosphorylate, a required step for activation. Inhibitory segment is thought to exist in two states that are highly conserved in PAKs. PAKs are activated by the binding of GTP-loaded Cdc42 (or Rac) to the CRIB domain, which disrupts the dimer and unfolds the inhibitory segment. After releasing the inhibitory segment, the kinase domain is then autophosphorylated for full activation. In addition, phosphorylation of Ser residue (Ser144 of PAK1) in the inhibitory segment also significantly contributes to activation. <br> Alternative modes of activation that may not require GTPase binding have been described, but less understood, including binding of sphingosine, direct phosphorylation by AKT, PDK1, and JAK2, caspase-3 binding during apoptosis, and binding of PIX with subsequent recruitment to GIT1.
Autoinhibitory domains (AIDs)
Target domain |
283-534 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
419-442 (Activation loop from InterPro)
Target domain |
263-559 (Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3) |
Relief mechanism |
|
Assay |
|
419-442 (Activation loop from InterPro)
Target domain |
263-559 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Bautista L et al. (2020) "p21-Activated Kinases in Thyroid Cancer", Endocrinology, 161,
- Chong C et al. (2001) "The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity", The Journal of biological chemistry, 276, 17347-53
- Wang J et al. (2011) "Structural insights into the autoactivation mechanism of p21-activated protein kinase", Structure (London, England : 1993), 19, 1752-61
- Lei M et al. (2000) "Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch", Cell, 102, 387-97
- Ha BH et al. (2012) "Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate", Proceedings of the National Academy of Sciences of the United States of America, 109, 16107-12
- Totaro A et al. (2007) "Identification of an intramolecular interaction important for the regulation of GIT1 functions", Molecular biology of the cell, 18, 5124-38
Autoinhibited structure
Activated structure
2 structures for O75914
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 6FD3 | X-ray | 152 A | A | 261-559 | PDB |
| AF-O75914-F1 | Predicted | AlphaFoldDB |
207 variants for O75914
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
|
RCV002314874 RCV000499388 CA10492567 RCV001169822 RCV002056863 rs140296303 |
4 | G>S | Intellectual disability, X-linked 30 Inborn genetic diseases [ClinVar] | Yes |
ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD |
|
RCV000012325 CA121581 rs121434612 VAR_023825 |
67 | R>C | Intellectual disability, X-linked 30 XLID30 [ClinVar, UniProt] | Yes |
ClinGen ClinVar UniProt Ensembl dbSNP |
|
RCV001785643 RCV000505239 CA10492630 rs780775497 |
115 | R>* | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar ExAC dbSNP gnomAD |
|
RCV000624388 CA414244769 rs1390290077 |
118 | Q>K | Inborn genetic diseases [ClinVar] | Yes |
ClinGen ClinVar dbSNP gnomAD |
|
rs2093969404 RCV001257659 |
142 | D>Y | Intellectual disability [ClinVar] | Yes |
ClinVar dbSNP |
|
rs2093969640 RCV001260293 |
150 | Q>* | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinVar dbSNP |
|
RCV002318720 RCV001712742 rs770793505 |
190 | D>missing | Inborn genetic diseases [ClinVar] | Yes |
ClinVar dbSNP |
|
rs749370794 RCV000625953 |
197 | E>missing | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinVar dbSNP |
|
CA10492690 RCV000327728 RCV002523822 rs778585528 |
237 | P>Q | Intellectual disability, X-linked 30 Inborn genetic diseases [ClinVar] | Yes |
ClinGen ClinVar ExAC TOPMed dbSNP gnomAD |
|
rs367901722 RCV000893839 RCV002372515 CA10492693 |
246 | S>C | Inborn genetic diseases [ClinVar] | Yes |
ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD |
|
RCV001169823 rs2094566106 |
303 | I>V | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinVar dbSNP |
|
rs1603373827 CA414237805 RCV000844885 |
341 | V>L | Microcephaly [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
CA414237833 rs1603373843 RCV000850377 |
345 | D>N | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
RCV000012326 RCV003162241 rs121434613 CA121583 VAR_023826 |
380 | A>E | Intellectual disability, X-linked 30 XLID30 [ClinVar, UniProt] | Yes |
ClinGen ClinVar UniProt Ensembl dbSNP |
|
CA414238394 RCV001004826 rs1603377813 |
386 | C>Y | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
rs2094609108 RCV001267468 |
404 | K>N | Inborn genetic diseases [ClinVar] | Yes |
ClinVar dbSNP |
|
RCV000012324 CA121579 COSM1756339 rs121434611 RCV000656321 COSM254886 |
434 | R>* | Intellectual disability, X-linked 30 Variant assessed as Somatic; impact. urinary_tract [ClinVar, NCI-TCGA, Cosmic] | Yes |
ClinGen cosmic curated ClinVar Ensembl NCI-TCGA dbSNP |
|
rs1569459580 RCV000768415 CA414239384 |
439 | G>R | Intellectual disability [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
rs1603378331 RCV000824810 CA414239439 |
443 | W>R | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
RCV000012327 rs121434614 CA121585 |
461 | W>S | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar Ensembl dbSNP |
|
rs200474454 CA10492827 RCV000927169 RCV000655945 |
542 | S>G | Intellectual disability, X-linked 30 [ClinVar] | Yes |
ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD |
| rs1039228196 | 1 | M>? | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA10492565 rs780898950 |
3 | D>G | No |
ClinGen ExAC TOPMed gnomAD |
|
|
CA414238373 rs140296303 |
4 | G>R | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
| TCGA novel | 5 | L>P | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1189894083 CA414238424 |
7 | N>K | No |
ClinGen gnomAD |
|
|
CA414238504 rs1464727079 |
11 | P>T | No |
ClinGen gnomAD |
|
|
CA414238690 rs1164331815 |
19 | N>S | No |
ClinGen gnomAD |
|
|
CA414238747 rs1393421677 |
22 | N>D | No |
ClinGen gnomAD |
|
|
CA10492570 RCV000502998 rs768347607 |
23 | R>Q | No |
ClinGen ClinVar ExAC TOPMed dbSNP gnomAD |
|
|
CA334398935 rs978487268 |
23 | R>W | No |
ClinGen TOPMed gnomAD |
|
| TCGA novel | 25 | S>Y | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs367802412 CA10492571 |
27 | A>G | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
|
CA414238962 rs1437368857 |
28 | L>P | No |
ClinGen gnomAD |
|
|
rs1171690830 CA414239001 |
29 | N>T | No |
ClinGen TOPMed |
|
|
rs1478864661 CA414239048 |
31 | S>G | No |
ClinGen TOPMed |
|
|
rs1805077 CA334398936 |
31 | S>R | No |
ClinGen Ensembl |
|
|
rs1312938810 CA414239112 |
33 | K>R | No |
ClinGen gnomAD |
|
|
CA246059 rs370566075 RCV000178869 |
34 | P>L | No |
ClinGen ClinVar ESP dbSNP |
|
|
rs1382106067 CA414239204 |
37 | M>V | No |
ClinGen gnomAD |
|
|
rs1244057948 CA414239246 |
38 | A>G | No |
ClinGen gnomAD |
|
| TCGA novel | 38 | A>T | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1265925413 CA414239312 |
40 | E>D | No |
ClinGen TOPMed gnomAD |
|
|
rs926951840 CA334398937 |
45 | K>I | No |
ClinGen TOPMed |
|
|
rs150741170 CA10492572 |
54 | G>V | No |
ClinGen ESP ExAC TOPMed |
|
|
rs1175985940 CA414242411 |
59 | T>I | No |
ClinGen TOPMed |
|
|
CA414242440 rs1481398266 |
61 | K>T | No |
ClinGen gnomAD |
|
| TCGA novel | 66 | E>V | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs867801165 CA334400338 |
74 | S>P | No |
ClinGen Ensembl |
|
| TCGA novel | 79 | T>A | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1260832880 CA414242735 |
79 | T>M | No |
ClinGen gnomAD |
|
|
CA414242748 rs1398096161 |
80 | I>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen Ensembl NCI-TCGA |
| TCGA novel | 84 | F>L | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA10492590 rs191705141 |
86 | A>E | No |
ClinGen 1000Genomes ExAC gnomAD |
|
| TCGA novel | 94 | D>E | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 95 | L>F | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 95 | L>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs867206818 CA334400669 |
98 | S>* | No |
ClinGen TOPMed |
|
|
CA414244096 rs867206818 |
98 | S>L | No |
ClinGen TOPMed |
|
|
CA10492619 rs200670003 |
100 | M>I | No |
ClinGen ExAC TOPMed gnomAD |
|
|
CA414244120 rs1189219056 |
100 | M>V | No |
ClinGen gnomAD |
|
|
CA10492620 rs762131584 |
102 | P>S | No |
ClinGen ExAC gnomAD |
|
|
CA414244150 rs762131584 |
102 | P>T | No |
ClinGen ExAC gnomAD |
|
|
rs1349157941 CA414244173 |
105 | L>I | No |
ClinGen gnomAD |
|
|
rs1166600861 CA414244740 |
113 | W>* | No |
ClinGen gnomAD |
|
|
rs1386028872 CA414244747 |
114 | A>S | No |
ClinGen gnomAD |
|
|
CA414244753 rs1320774876 |
115 | R>Q | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
| TCGA novel | 129 | K>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs375144673 CA10492633 |
137 | V>I | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
|
rs1286789180 CA414244972 |
146 | T>A | No |
ClinGen gnomAD |
|
| TCGA novel | 154 | S>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414245048 rs1266581016 |
156 | T>A | No |
ClinGen TOPMed |
|
|
CA414245062 rs1229316649 |
158 | G>E | No |
ClinGen gnomAD |
|
|
CA334401130 rs371827969 |
161 | S>N | No |
ClinGen Ensembl |
|
|
CA414236210 rs1569413428 |
165 | Y>C | No |
ClinGen Ensembl |
|
|
CA10492640 rs760977173 |
166 | I>K | No |
ClinGen ExAC gnomAD |
|
|
CA414236219 rs1429172600 |
166 | I>M | No |
ClinGen TOPMed |
|
|
CA414236242 rs1306718587 |
170 | P>A | No |
ClinGen TOPMed gnomAD |
|
| TCGA novel | 170 | P>H | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA10492641 COSM1133853 COSM422267 rs139949467 |
171 | S>L | Variant assessed as Somatic; 0.0 impact. urinary_tract [NCI-TCGA, Cosmic] | No |
ClinGen cosmic curated ESP ExAC NCI-TCGA TOPMed gnomAD |
|
CA414236273 rs1415674453 |
173 | T>A | No |
ClinGen TOPMed gnomAD |
|
|
COSM1113156 CA10492654 rs748267883 COSM1598678 |
174 | K>E | Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic] | No |
ClinGen cosmic curated ExAC NCI-TCGA gnomAD |
| TCGA novel | 176 | A>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA334401926 rs541818337 |
176 | A>T | No |
ClinGen Ensembl |
|
|
rs1410864522 CA414236294 |
176 | A>V | No |
ClinGen gnomAD |
|
|
RCV001090397 rs2094208830 |
179 | P>missing | No |
ClinVar dbSNP |
|
|
COSM404357 rs866361777 CA334401927 |
179 | P>S | lung [Cosmic] | No |
ClinGen cosmic curated Ensembl |
|
COSM1464863 COSM1464864 CA10492660 rs371211507 |
190 | D>G | large_intestine [Cosmic] | No |
ClinGen cosmic curated ESP ExAC TOPMed gnomAD |
|
rs374572591 CA10492663 |
193 | E>G | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
|
COSM1155208 COSM1113159 rs764106735 CA10492664 |
197 | E>D | Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic] | No |
ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD |
|
rs1205632953 CA414236448 |
198 | D>E | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
|
CA10492665 rs751517340 RCV000489603 RCV001821410 |
200 | N>T | No |
ClinGen ClinVar ExAC dbSNP gnomAD |
|
|
CA414236478 rs1237460765 |
202 | P>L | No |
ClinGen gnomAD |
|
| TCGA novel | 206 | I>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA334401930 rs1029470602 |
207 | A>T | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
|
rs1246873798 CA414236528 |
211 | E>K | No |
ClinGen TOPMed gnomAD |
|
| TCGA novel | 214 | K>Q | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs374367630 CA10492684 |
217 | Y>C | No |
ClinGen ESP ExAC gnomAD |
|
|
rs1472675895 CA414236597 |
219 | R>C | No |
ClinGen gnomAD |
|
|
rs749953063 CA10492685 |
221 | V>M | No |
ClinGen ExAC gnomAD |
|
|
rs760116222 CA10492686 |
222 | V>F | No |
ClinGen ExAC TOPMed gnomAD |
|
|
CA10492687 rs766056089 |
223 | E>A | No |
ClinGen ExAC gnomAD |
|
| TCGA novel | 226 | A>D | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs753498985 CA10492688 |
229 | A>E | No |
ClinGen ExAC gnomAD |
|
|
rs753498985 CA414236660 |
229 | A>V | No |
ClinGen ExAC gnomAD |
|
|
CA334401958 rs1044245561 |
236 | T>P | No |
ClinGen TOPMed gnomAD |
|
|
rs754649748 CA10492689 |
237 | P>A | No |
ClinGen ExAC gnomAD |
|
| TCGA novel | 237 | P>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414236716 rs1226264908 |
238 | P>L | No |
ClinGen TOPMed gnomAD |
|
|
rs1336640754 CA414236714 |
238 | P>S | No |
ClinGen gnomAD |
|
| TCGA novel | 239 | S>T | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs759005736 CA10492692 |
239 | S>Y | No |
ClinGen ExAC TOPMed gnomAD |
|
|
rs1464966968 CA414236739 |
242 | N>D | No |
ClinGen TOPMed gnomAD |
|
|
rs1206315228 CA414236756 |
244 | N>S | No |
ClinGen TOPMed gnomAD |
|
|
CA334401959 rs1050534399 |
245 | S>F | No |
ClinGen TOPMed |
|
|
rs370810599 CA10492694 |
251 | N>S | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
|
CA334401960 rs761542913 |
253 | D>G | No |
ClinGen 1000Genomes |
|
|
CA414236821 rs1188823579 |
254 | R>Q | No |
ClinGen TOPMed gnomAD |
|
|
CA10492695 rs770850940 |
255 | Q>P | No |
ClinGen ExAC TOPMed gnomAD |
|
|
CA414236846 rs1460944698 |
258 | K>E | No |
ClinGen TOPMed |
|
|
CA10492696 rs781317832 |
258 | K>R | No |
ClinGen ExAC gnomAD |
|
| TCGA novel | 259 | S>F | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 259 | S>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1261292931 CA414236856 |
259 | S>Y | No |
ClinGen TOPMed |
|
| TCGA novel | 260 | K>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 263 | D>G | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1603349367 CA414237166 |
272 | S>R | No |
ClinGen Ensembl |
|
|
CA10492715 rs781169107 |
276 | V>D | No |
ClinGen ExAC gnomAD |
|
|
rs1330059263 CA414237208 |
278 | D>Y | No |
ClinGen gnomAD |
|
|
rs866468719 CA334402776 |
279 | P>T | No |
ClinGen Ensembl |
|
| TCGA novel | 282 | K>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 283 | Y>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 288 | K>E | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 289 | I>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414237289 rs1395819172 |
289 | I>V | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
|
rs2094364755 RCV001280726 |
292 | G>A | No |
ClinVar dbSNP |
|
|
rs776040802 CA10492724 |
295 | G>A | No |
ClinGen ExAC gnomAD |
|
|
rs1206499470 CA414237575 |
309 | V>A | No |
ClinGen TOPMed |
|
| TCGA novel | 309 | V>E | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 321 | K>R | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs777586956 CA10492740 |
324 | L>V | No |
ClinGen ExAC |
|
| TCGA novel | 328 | E>D | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 331 | V>A | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 331 | V>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs868441369 CA334404185 |
334 | E>K | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen Ensembl NCI-TCGA |
|
CA334404186 rs756304087 |
337 | N>H | No |
ClinGen TOPMed gnomAD |
|
| TCGA novel | 340 | I>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414237822 rs1242658535 |
343 | Y>C | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
|
rs770801401 CA10492742 |
346 | S>N | No |
ClinGen ExAC gnomAD |
|
|
rs182843813 CA334404312 |
347 | Y>C | No |
ClinGen 1000Genomes |
|
| TCGA novel | 350 | G>C | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1249190198 CA414237915 |
350 | G>D | No |
ClinGen TOPMed gnomAD |
|
|
rs1249190198 CA414237918 |
350 | G>V | No |
ClinGen TOPMed gnomAD |
|
|
rs1228989985 CA414238012 |
357 | M>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
| TCGA novel | 361 | A>T | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
RCV000432791 rs1057524312 CA16609112 |
370 | T>K | No |
ClinGen ClinVar Ensembl dbSNP |
|
|
CA10492764 rs779740979 |
383 | C>S | No |
ClinGen ExAC gnomAD |
|
| TCGA novel | 390 | L>V | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 401 | R>K | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
RCV000524035 rs1556298136 CA414238707 |
402 | D>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen ClinVar Ensembl NCI-TCGA dbSNP |
| TCGA novel | 409 | L>I | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414238883 rs1396231947 |
410 | L>P | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen NCI-TCGA gnomAD |
|
CA414238898 rs1167261829 |
412 | M>K | No |
ClinGen gnomAD |
|
|
CA334404407 rs996264683 |
416 | V>I | No |
ClinGen TOPMed |
|
|
CA414238966 COSM1113170 rs1603377889 COSM1598668 |
417 | K>T | endometrium breast [Cosmic] | No |
ClinGen cosmic curated Ensembl |
| VAR_046764 | 440 | T>S | a colorectal adenocarcinoma sample; somatic mutation [UniProt] | No | UniProt |
| TCGA novel | 441 | P>L | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 445 | A>T | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 446 | P>H | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 452 | K>N | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 454 | Y>* | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 456 | P>L | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1603378370 CA414239853 |
467 | A>E | No |
ClinGen Ensembl |
|
| TCGA novel | 476 | P>H | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
RCV000656290 rs1556298855 CA414240445 |
483 | L>R | No |
ClinGen ClinVar Ensembl dbSNP |
|
| TCGA novel | 484 | R>M | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 485 | A>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 488 | L>M | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs1285721029 CA414241909 |
494 | T>I | No |
ClinGen TOPMed |
|
|
CA414241911 rs1448130142 |
495 | P>A | No |
ClinGen gnomAD |
|
|
rs1055614465 CA334405877 |
501 | E>G | No |
ClinGen TOPMed gnomAD |
|
|
CA414241963 rs1344292761 |
502 | R>I | No |
ClinGen TOPMed gnomAD |
|
| TCGA novel | 503 | L>M | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs747573909 CA10492808 |
504 | S>P | No |
ClinGen ExAC gnomAD |
|
|
RCV000499611 CA414241976 rs1295610191 |
505 | A>T | No |
ClinGen ClinVar TOPMed dbSNP |
|
|
COSM1715416 rs758092787 CA10492809 COSM1715417 |
508 | R>H | skin [Cosmic] | No |
ClinGen cosmic curated ExAC gnomAD |
|
CA10492810 rs777234110 COSM4137604 COSM4137603 |
513 | R>C | ovary Variant assessed as Somatic; 0.0 impact. [Cosmic, NCI-TCGA] | No |
ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD |
|
CA10492811 rs747379000 |
513 | R>H | Variant assessed as Somatic; 0.0 impact. [NCI-TCGA] | No |
ClinGen ExAC NCI-TCGA TOPMed gnomAD |
| TCGA novel | 516 | E>D | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs771356919 CA10492812 |
518 | D>G | No |
ClinGen ExAC gnomAD |
|
|
rs377693111 CA414242093 |
521 | R>S | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
| TCGA novel | 528 | L>P | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414236956 rs1267762162 |
531 | H>N | No |
ClinGen TOPMed |
|
|
rs1013735234 CA334406130 |
532 | P>R | No |
ClinGen TOPMed |
|
|
CA334406131 rs977704299 |
536 | L>S | No |
ClinGen TOPMed gnomAD |
|
|
rs377015001 CA414237019 |
540 | L>F | Variant assessed as Somatic; impact. [NCI-TCGA] | No |
ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD |
|
rs377015001 CA10492826 |
540 | L>V | No |
ClinGen ESP ExAC TOPMed gnomAD |
|
| TCGA novel | 542 | S>C | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA414237077 rs1212193470 |
549 | A>V | No |
ClinGen gnomAD |
|
|
rs751275118 CA10492830 |
550 | A>E | No |
ClinGen ExAC |
|
| TCGA novel | 552 | E>* | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
CA10492831 rs756883277 |
552 | E>K | No |
ClinGen ExAC |
|
| TCGA novel | 556 | N>S | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
| TCGA novel | 557 | S>R | Variant assessed as Somatic; impact. [NCI-TCGA] | No | NCI-TCGA |
|
rs746179709 CA10492833 |
557 | S>T | No |
ClinGen ExAC gnomAD |
|
|
COSM1569765 CA414237146 COSM1569766 rs1251435916 |
559 | R>H | Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic] | No |
ClinGen cosmic curated NCI-TCGA gnomAD |
|
rs1251435916 CA414237147 |
559 | R>P | No |
ClinGen gnomAD |
No associated diseases with O75914
7 regional properties for O75914
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Calcineurin-like phosphoesterase domain, ApaH type | 212 - 406 | IPR004843 |
| domain | Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase | 179 - 456 | IPR006186 |
| domain | PPP domain | 113 - 203 | IPR013235 |
| repeat | Tetratricopeptide repeat | 5 - 38 | IPR019734-1 |
| repeat | Tetratricopeptide repeat | 39 - 72 | IPR019734-2 |
| repeat | Tetratricopeptide repeat | 73 - 106 | IPR019734-3 |
| domain | PP5, C-terminal metallophosphatase domain | 152 - 467 | IPR041753 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
5 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. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| postsynaptic density | An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| 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. |
| metal ion binding | Binding to a metal ion. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| SH3 domain binding | Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins. |
| small GTPase binding | Binding to a small monomeric GTPase. |
14 GO annotations of biological process
| Name | Definition |
|---|---|
| axonogenesis | De novo generation of a long process of a neuron, including the terminal branched region. Refers to the morphogenesis or creation of shape or form of the developing axon, which carries efferent (outgoing) action potentials from the cell body towards target cells. |
| cellular response to organic cyclic compound | 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 an organic cyclic compound stimulus. |
| dendrite development | The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure. |
| dendritic spine morphogenesis | The process in which the anatomical structures of a dendritic spine are generated and organized. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| ephrin receptor signaling pathway | The series of molecular signals initiated by ephrin binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| regulation of actin cytoskeleton organization | Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| regulation of actin filament polymerization | Any process that modulates the frequency, rate or extent of the assembly of actin filaments by the addition of actin monomers to a filament. |
| regulation of axonogenesis | Any process that modulates the frequency, rate or extent of axonogenesis, the generation of an axon, the long process of a neuron. |
| regulation of MAPK cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the MAP kinase (MAPK) cascade. |
| regulation of postsynapse organization | Any process that modulates the physical form of a postsynapse. |
| stimulatory C-type lectin receptor signaling pathway | The series of molecular signals initiated by the binding of C-type lectin to its receptor on the surface of a target cell, and resulting in cellular activation. |
| synapse organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a synapse, the junction between a neuron and a target (neuron, muscle, or secretory cell). |
24 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q12469 | SKM1 | Serine/threonine-protein kinase SKM1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q08E52 | PAK1 | Serine/threonine-protein kinase PAK 1 | Bos taurus (Bovine) | SS |
| Q7YQL4 | PAK3 | Serine/threonine-protein kinase PAK 3 | Pan troglodytes (Chimpanzee) | SS |
| Q9VXE5 | mbt | Serine/threonine-protein kinase PAK mbt | Drosophila melanogaster (Fruit fly) | PR |
| Q13043 | STK4 | Serine/threonine-protein kinase 4 | Homo sapiens (Human) | EV |
| Q13188 | STK3 | Serine/threonine-protein kinase 3 | Homo sapiens (Human) | SS |
| Q9NQU5 | PAK6 | Serine/threonine-protein kinase PAK 6 | Homo sapiens (Human) | EV |
| Q9P286 | PAK5 | Serine/threonine-protein kinase PAK 5 | Homo sapiens (Human) | EV |
| O96013 | PAK4 | Serine/threonine-protein kinase PAK 4 | Homo sapiens (Human) | EV |
| Q13177 | PAK2 | Serine/threonine-protein kinase PAK 2 | Homo sapiens (Human) | EV |
| Q13153 | PAK1 | Serine/threonine-protein kinase PAK 1 | Homo sapiens (Human) | EV |
| O95819 | MAP4K4 | Mitogen-activated protein kinase kinase kinase kinase 4 | Homo sapiens (Human) | PR |
| O88643 | Pak1 | Serine/threonine-protein kinase PAK 1 | Mus musculus (Mouse) | SS |
| Q8C015 | Pak5 | Serine/threonine-protein kinase PAK 5 | Mus musculus (Mouse) | SS |
| Q3ULB5 | Pak6 | Serine/threonine-protein kinase PAK 6 | Mus musculus (Mouse) | PR |
| Q8CIN4 | Pak2 | Serine/threonine-protein kinase PAK 2 | Mus musculus (Mouse) | SS |
| Q61036 | Pak3 | Serine/threonine-protein kinase PAK 3 | Mus musculus (Mouse) | SS |
| D4A280 | Pak5 | Serine/threonine-protein kinase PAK 5 | Rattus norvegicus (Rat) | SS |
| P35465 | Pak1 | Serine/threonine-protein kinase PAK 1 | Rattus norvegicus (Rat) | SS |
| Q64303 | Pak2 | Serine/threonine-protein kinase PAK 2 | Rattus norvegicus (Rat) | SS |
| Q62829 | Pak3 | Serine/threonine-protein kinase PAK 3 | Rattus norvegicus (Rat) | SS |
| G5EFU0 | pak-2 | Serine/threonine-protein kinase pak-2 | Caenorhabditis elegans | PR |
| Q17850 | pak-1 | Serine/threonine-protein kinase pak-1 | Caenorhabditis elegans | PR |
| G5EGQ3 | max-2 | Serine/threonine-protein kinase max-2 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSDGLDNEEK | PPAPPLRMNS | NNRDSSALNH | SSKPLPMAPE | EKNKKARLRS | IFPGGGDKTN |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KKKEKERPEI | SLPSDFEHTI | HVGFDAVTGE | FTPDLYGSQM | CPGKLPEGIP | EQWARLLQTS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| NITKLEQKKN | PQAVLDVLKF | YDSKETVNNQ | KYMSFTSGDK | SAHGYIAAHP | SSTKTASEPP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LAPPVSEEED | EEEEEEEDEN | EPPPVIAPRP | EHTKSIYTRS | VVESIASPAV | PNKEVTPPSA |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ENANSSTLYR | NTDRQRKKSK | MTDEEILEKL | RSIVSVGDPK | KKYTRFEKIG | QGASGTVYTA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LDIATGQEVA | IKQMNLQQQP | KKELIINEIL | VMRENKNPNI | VNYLDSYLVG | DELWVVMEYL |
| 370 | 380 | 390 | 400 | 410 | 420 |
| AGGSLTDVVT | ETCMDEGQIA | AVCRECLQAL | DFLHSNQVIH | RDIKSDNILL | GMDGSVKLTD |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FGFCAQITPE | QSKRSTMVGT | PYWMAPEVVT | RKAYGPKVDI | WSLGIMAIEM | VEGEPPYLNE |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NPLRALYLIA | TNGTPELQNP | ERLSAVFRDF | LNRCLEMDVD | RRGSAKELLQ | HPFLKLAKPL |
| 550 | |||||
| SSLTPLIIAA | KEAIKNSSR |