Q3UU96
SS
Gene name |
Cdc42bpa (Kiaa0451) |
Protein name |
Serine/threonine-protein kinase MRCK alpha |
Names |
CDC42-binding protein kinase alpha |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:226751 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
CDC42BPA(MRCK) is a Cdc42-binding serine/threonine kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. A region containing the two distal CC domains (CC2 and CC3; residues 658-930) interacts intramolecularly with the kinase domain and negatively regulates its activity.
Autoinhibitory domains (AIDs)
Target domain |
77-343 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
218-242 (Activation loop from InterPro)
Target domain |
4-412 (Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase, MRCK, alpha) |
Relief mechanism |
|
Assay |
|
References
- Tan I et al. (2001) "Intermolecular and intramolecular interactions regulate catalytic activity of myotonic dystrophy kinase-related Cdc42-binding kinase alpha", Molecular and cellular biology, 21, 2767-78
- Riento K et al. (2003) "Rocks: multifunctional kinases in cell behaviour", Nature reviews. Molecular cell biology, 4, 446-56
- Amano M et al. (1999) "The COOH terminus of Rho-kinase negatively regulates rho-kinase activity", The Journal of biological chemistry, 274, 32418-24
- Chen XQ et al. (2002) "Characterization of RhoA-binding kinase ROKalpha implication of the pleckstrin homology domain in ROKalpha function using region-specific antibodies", The Journal of biological chemistry, 277, 12680-8
- Leung T et al. (1996) "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton", Molecular and cellular biology, 16, 5313-27
Autoinhibited structure
Activated structure
1 structures for Q3UU96
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q3UU96-F1 | Predicted | AlphaFoldDB |
7 variants for Q3UU96
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs226076961 | 521 | R>Q | No | Ensembl | |
| rs864274343 | 592 | Q>R | No | Ensembl | |
| rs864305301 | 809 | D>E | No | Ensembl | |
| rs864261631 | 894 | Q>R | No | Ensembl | |
| rs864283303 | 895 | A>T | No | Ensembl | |
| rs864302567 | 935 | T>I | No | Ensembl | |
| rs32676625 | 1099 | K>T | No | Ensembl |
No associated diseases with Q3UU96
12 regional properties for Q3UU96
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | CRIB domain | 1558 - 1593 | IPR000095 |
| domain | Protein kinase domain | 77 - 343 | IPR000719 |
| domain | AGC-kinase, C-terminal | 344 - 414 | IPR000961 |
| domain | Citron homology (CNH) domain | 1214 - 1492 | IPR001180 |
| domain | Pleckstrin homology domain | 1069 - 1190 | IPR001849 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 999 - 1050 | IPR002219 |
| active_site | Serine/threonine-protein kinase, active site | 197 - 209 | IPR008271 |
| domain | Myotonic dystrophy protein kinase, coiled coil | 881 - 941 | IPR014930 |
| binding_site | Protein kinase, ATP binding site | 83 - 106 | IPR017441 |
| domain | Protein kinase, C-terminal | 362 - 404 | IPR017892 |
| domain | Serine/threonine-protein kinase MRCK alpha, catalytic domain | 4 - 412 | IPR026611 |
| domain | KELK-motif containing domain | 529 - 608 | IPR031597 |
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 | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| actomyosin | Any complex of actin, myosin, and accessory proteins. |
| cell leading edge | The area of a motile cell closest to the direction of movement. |
| cell-cell junction | A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoskeleton | A cellular structure that forms the internal framework of eukaryotic and prokaryotic cells. The cytoskeleton includes intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
6 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. |
| magnesium ion binding | Binding to a magnesium (Mg) ion. |
| 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 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. |
10 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton reorganization | A process that is carried out at the cellular level which results in dynamic structural changes to the arrangement of constituent parts of cytoskeletal structures comprising actin filaments and their associated proteins. |
| actomyosin structure organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures containing both actin and myosin or paramyosin. The myosin may be organized into filaments. |
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms. |
| cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures. |
| 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. |
| microtubule cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins. |
| nuclear migration | The directed movement of the nucleus to a specific location within a cell. |
| peptidyl-threonine phosphorylation | The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of small GTPase mediated signal transduction | Any process that modulates the frequency, rate or extent of small GTPase mediated signal transduction. |
15 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q28021 | ROCK2 | Rho-associated protein kinase 2 | Bos taurus (Bovine) | SS |
| Q9W1B0 | gek | Serine/threonine-protein kinase Genghis Khan | Drosophila melanogaster (Fruit fly) | SS |
| O75116 | ROCK2 | Rho-associated protein kinase 2 | Homo sapiens (Human) | SS |
| Q9Y5S2 | CDC42BPB | Serine/threonine-protein kinase MRCK beta | Homo sapiens (Human) | SS |
| Q13464 | ROCK1 | Rho-associated protein kinase 1 | Homo sapiens (Human) | SS |
| Q5VT25 | CDC42BPA | Serine/threonine-protein kinase MRCK alpha | Homo sapiens (Human) | EV |
| Q80UW5 | Cdc42bpg | Serine/threonine-protein kinase MRCK gamma | Mus musculus (Mouse) | PR |
| Q7TT50 | Cdc42bpb | Serine/threonine-protein kinase MRCK beta | Mus musculus (Mouse) | SS |
| P70335 | Rock1 | Rho-associated protein kinase 1 | Mus musculus (Mouse) | SS |
| P70336 | Rock2 | Rho-associated protein kinase 2 | Mus musculus (Mouse) | SS |
| M3TYT0 | ROCK2 | Rho-associated protein kinase 2 | Sus scrofa (Pig) | SS |
| Q62868 | Rock2 | Rho-associated protein kinase 2 | Rattus norvegicus (Rat) | EV |
| Q7TT49 | Cdc42bpb | Serine/threonine-protein kinase MRCK beta | Rattus norvegicus (Rat) | SS |
| Q63644 | Rock1 | Rho-associated protein kinase 1 | Rattus norvegicus (Rat) | SS |
| O54874 | Cdc42bpa | Serine/threonine-protein kinase MRCK alpha | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSGEVRLRQL | EQFILDGPAQ | TNGQCFSVET | LLDILICLYD | ECNNSPLRRE | KNILEYLEWA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KPFTSKVKQM | RLHREDFEIL | KVIGRGAFGE | VAVVKLKNAD | KVFAMKILNK | WEMLKRAETA |
| 130 | 140 | 150 | 160 | 170 | 180 |
| CFREERDVLV | NGDSKWITTL | HYAFQDDNNL | YLVMDYYVGG | DLLTLLSKFE | DRLPEEMARF |
| 190 | 200 | 210 | 220 | 230 | 240 |
| YLAEMVIAID | SVHQLHYVHR | DIKPDNILMD | MNGHIRLADF | GSCLKLMEDG | TVQSSVAVGT |
| 250 | 260 | 270 | 280 | 290 | 300 |
| PDYISPEILQ | AMEDGKGRYG | PECDWWSLGV | CMYEMLYGET | PFYAESLVET | YGKIMNHKER |
| 310 | 320 | 330 | 340 | 350 | 360 |
| FQFPAQVTDV | SENAKDLIRR | LICSREHRLG | QNGIEDFKKH | PFFSGIDWDN | IRNCEAPYIP |
| 370 | 380 | 390 | 400 | 410 | 420 |
| EVSSPTDTSN | FDVDDDCLKN | SETMPPPTHT | AFSGHHLPFV | GFTYTSSCVL | SDRSCLRVTA |
| 430 | 440 | 450 | 460 | 470 | 480 |
| GPTSLDLDVS | VQRTLDNNLA | TEAYERRIKR | LEQEKLELTR | KLQESTQTVQ | ALQYSTVDGP |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LTASKDLEIK | SLKEEIEKLR | KQVAEVNHLE | QQLEEANSVR | RELDDAFRQI | KASEKQIKTL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| QQEREELNKE | LVQASERLKN | QSKELKDAHC | QRKLAMQEFM | EINERLTELH | TQKQKLARHV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| RDKEEEVDLV | MQKAESLRQE | LRRAERAKKE | LEVHTEALIA | EASKDKKLRE | QSEHYSKQLE |
| 670 | 680 | 690 | 700 | 710 | 720 |
| NELEGLKQKQ | ISYSPGICSI | EHQQEITKLK | TDLEKKSIFY | EEEISKREGI | HASEIKNLKK |
| 730 | 740 | 750 | 760 | 770 | 780 |
| ELHDSEGQQL | ALNKEILVLK | DKLEKTRRES | QSEREEFENE | FKQQYEREKV | LLTEENKKLT |
| 790 | 800 | 810 | 820 | 830 | 840 |
| SELDKLTSLY | ESLSLRNQHL | EEEVKDLADK | KESVAHWEAQ | ITEIIQWVSD | EKDARGYLQA |
| 850 | 860 | 870 | 880 | 890 | 900 |
| LASKMTEELE | ALRNSSLGTR | ATDMPWKMRR | FAKLDMSARL | ELQSALDAEI | RAKQAIQEEL |
| 910 | 920 | 930 | 940 | 950 | 960 |
| NKVKASNILT | ECKLKDSEKK | NLELLSEIEQ | LIKDTEELRS | EKGIEHQDSQ | HSFLAFLNTP |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| TDALDQFEIA | DCAPLPAHTP | TLRKKGCPAS | TGFPPKRKTH | QFFVKSFTAP | TKCHQCTSLM |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| VGLIRQGCSC | EVCGFSCHIT | CVNKAPTVCP | VPPEQTKGPL | GIDPQKGVGT | AYEGHVRIPK |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| PAGVKKGWQR | ALAVVCDFKL | FLYDIAEGKA | SQPTSVISQV | IDMRDEEFSV | SSVLASDVIH |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| ASRKDIPCIF | RVTASQLSAP | SNKCSILMLA | DSENERSKWV | GVLSELHKIL | KKNKFRDRSV |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| YVPKEAYDST | LPLIKTTQAA | AIIDHERIAL | GNEEGLFVVH | VTKDEIVRVG | DNKKIHQIEL |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| IPSDQLVAVI | SGRNRHVRLF | PMSALDGRET | DFYKLAETKG | CQTIAAGKVR | HGALSCLCVA |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| MKRQVLCYEL | FQSKTRHRKF | KEIQVPCNVQ | WMAIFSEHLC | VGFQSGFLRY | PLNGEGGPCN |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| MLHSNDHTLS | FISHQPMDAL | CAVEISNKEY | LLCFNSIGIY | TDCQGRRSRQ | QELMWPANPS |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| SCCYNAPYLS | VYSENAVDIF | DVNSMEWIQT | LPLKKVRPLN | TEGSLNLLGL | ETIRLIYFKN |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| KMAEGDELVV | PETSDNSRKQ | MVRNINNKRR | YSFRVPEEER | MQQRREMLRD | PEMRNKLISN |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| PTNFNHIAHM | GPGDGIQILK | DLPMNPRPQE | SRTVFSGSVS | IPSITKSRPE | PGRSMSASSG |
| 1630 | 1640 | 1650 | 1660 | 1670 | 1680 |
| LSARSSAQNG | SALKREFSGG | SYNTKRQPMP | SPSEGSLSSG | GMDQGSDAPA | RDYDGEDSDS |
| 1690 | 1700 | 1710 | |||
| PRHSTASNSS | NLSSPPSPIS | PQKTKSLSLE | STDRGSWDP |