Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase MRCK alpha

Gene

Cdc42bpa

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2. In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Phosphorylates: PPP1R12A, LIMK1 and LIMK2. May play a role in TFRC-mediated iron uptake.3 Publications

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Enzyme regulationi

Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation (By similarity). Inhibited by chelerythrine chloride.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei106ATPPROSITE-ProRule annotation1 Publication1
Active sitei201Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi83 – 91ATPPROSITE-ProRule annotationBy similarity9
Zinc fingeri1012 – 1062Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • actomyosin structure organization Source: UniProtKB
  • cell migration Source: UniProtKB
  • cytoskeleton organization Source: RGD
  • intracellular signal transduction Source: InterPro
  • protein phosphorylation Source: UniProtKB
  • regulation of small GTPase mediated signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase MRCK alpha (EC:2.7.11.1)
Alternative name(s):
CDC42-binding protein kinase alpha
Myotonic dystrophy kinase-related CDC42-binding kinase alpha
Short name:
MRCK alpha
Short name:
Myotonic dystrophy protein kinase-like alpha
Gene namesi
Name:Cdc42bpaBy similarity
Synonyms:Pk428Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621406. Cdc42bpa.

Subcellular locationi

  • Cytoplasm 1 Publication

  • Note: Displays a dispersed punctate distribution and concentrates along the cell periphery, especially at the leading edge and cell-cell junction. This concentration is PH-domain dependent.

GO - Cellular componenti

  • actomyosin Source: UniProtKB
  • cell-cell junction Source: UniProtKB
  • cell leading edge Source: UniProtKB
  • cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106K → A: Loss of kinase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863931 – 1732Serine/threonine-protein kinase MRCK alphaAdd BLAST1732

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei222Phosphoserine; by autocatalysisBy similarity1
Modified residuei234Phosphoserine; by autocatalysisBy similarity1
Modified residuei240Phosphothreonine; by autocatalysisBy similarity1
Modified residuei1127PhosphoserineCombined sources1
Modified residuei1545PhosphoserineBy similarity1
Modified residuei1611PhosphoserineBy similarity1
Modified residuei1613PhosphoserineBy similarity1
Modified residuei1629PhosphoserineBy similarity1
Modified residuei1651PhosphoserineCombined sources1
Modified residuei1664PhosphoserineBy similarity1
Modified residuei1669PhosphoserineBy similarity1
Modified residuei1693PhosphoserineBy similarity1
Modified residuei1719PhosphoserineBy similarity1
Modified residuei1721PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO54874.
PRIDEiO54874.

PTM databases

iPTMnetiO54874.
PhosphoSitePlusiO54874.

Expressioni

Tissue specificityi

Highly expressed in the brain and lung and present in lower levels in all other tissues tested.1 Publication

Interactioni

Subunit structurei

Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. Forms a tripartite complex with MYO18A and LURAP1 with the latter acting as an adapter connecting CDC42BPA and MYO18A. LURAP1 binding results in activation of CDC42BPA by abolition of its negative autoregulation.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-689253,EBI-689253
Lurap1D4A8G38EBI-689253,EBI-2015467

GO - Molecular functioni

  • identical protein binding Source: UniProtKB

Protein-protein interaction databases

IntActiO54874. 7 interactors.
STRINGi10116.ENSRNOP00000003837.

Structurei

Secondary structure

11732
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 16Combined sources14
Helixi18 – 20Combined sources3
Turni21 – 23Combined sources3
Helixi28 – 43Combined sources16
Turni46 – 49Combined sources4
Helixi51 – 70Combined sources20
Helixi74 – 76Combined sources3
Beta strandi77 – 85Combined sources9
Beta strandi87 – 96Combined sources10
Turni97 – 99Combined sources3
Beta strandi102 – 109Combined sources8
Helixi110 – 115Combined sources6
Turni116 – 119Combined sources4
Helixi122 – 131Combined sources10
Turni134 – 136Combined sources3
Beta strandi140 – 145Combined sources6
Beta strandi147 – 154Combined sources8
Helixi162 – 167Combined sources6
Turni168 – 171Combined sources4
Helixi175 – 194Combined sources20
Helixi204 – 206Combined sources3
Beta strandi207 – 209Combined sources3
Beta strandi215 – 217Combined sources3
Helixi241 – 243Combined sources3
Helixi246 – 253Combined sources8
Helixi262 – 277Combined sources16
Helixi287 – 295Combined sources9
Helixi297 – 300Combined sources4
Helixi312 – 319Combined sources8
Helixi325 – 327Combined sources3
Turni329 – 334Combined sources6
Helixi335 – 338Combined sources4
Helixi341 – 343Combined sources3
Turni348 – 350Combined sources3
Helixi351 – 353Combined sources3
Helixi397 – 399Combined sources3
Beta strandi404 – 407Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4AW2X-ray1.70A2-424[»]
ProteinModelPortaliO54874.
SMRiO54874.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini77 – 343Protein kinasePROSITE-ProRule annotation1 PublicationAdd BLAST267
Domaini344 – 414AGC-kinase C-terminalAdd BLAST71
Domaini1082 – 1201PHPROSITE-ProRule annotationAdd BLAST120
Domaini1227 – 1499CNHPROSITE-ProRule annotationAdd BLAST273
Domaini1571 – 1584CRIBPROSITE-ProRule annotationAdd BLAST14

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili437 – 670Sequence analysisAdd BLAST234
Coiled coili713 – 820Sequence analysisAdd BLAST108
Coiled coili880 – 943Sequence analysisAdd BLAST64

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 CNH domain.PROSITE-ProRule annotation
Contains 1 CRIB domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1012 – 1062Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG0612. Eukaryota.
ENOG410XR1Q. LUCA.
HOGENOMiHOG000294133.
HOVERGENiHBG055933.
InParanoidiO54874.
KOiK16307.
PhylomeDBiO54874.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR001180. CNH_dom.
IPR000095. CRIB_dom.
IPR031597. KELK.
IPR011009. Kinase-like_dom.
IPR014930. Myotonic_dystrophy_kinase_coil.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR026611. Ser/Thr_kinase_MRCK_alpha.
[Graphical view]
PANTHERiPTHR22988:SF31. PTHR22988:SF31. 2 hits.
PfamiPF00130. C1_1. 1 hit.
PF00780. CNH. 1 hit.
PF08826. DMPK_coil. 1 hit.
PF15796. KELK. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
ProDomiPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00109. C1. 1 hit.
SM00036. CNH. 1 hit.
SM00285. PBD. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50219. CNH. 1 hit.
PS50108. CRIB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O54874-1) [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
MSGEVRLRQL EQFILDGPAQ TNGQCFSVET LLDILICLYD ECNNSPLRRE
60 70 80 90 100
KNILEYLEWA KPFTSKVKQM RLHREDFEIL KVIGRGAFGE VAVVKLKNAD
110 120 130 140 150
KVFAMKILNK WEMLKRAETA CFREERDVLV NGDSKWITTL HYAFQDDNNL
160 170 180 190 200
YLVMDYYVGG DLLTLLSKFE DRLPEEMARF YLAEMVIAID SVHQLHYVHR
210 220 230 240 250
DIKPDNILMD MNGHIRLADF GSCLKLMEDG TVQSSVAVGT PDYISPEILQ
260 270 280 290 300
AMEDGKGRYG PECDWWSLGV CMYEMLYGET PFYAESLVET YGKIMNHKER
310 320 330 340 350
FQFPTQVTDV SENAKDLIRR LICSREHRLG QNGIEDFKKH PFFSGIDWDN
360 370 380 390 400
IRNCEAPYIP EVSSPTDTSN FDVDDDCLKN SETMPPPTHT AFSGHHLPFV
410 420 430 440 450
GFTYTSSCVL SDRSCLRVTA GPTSLDLDVN VQRTLDNNLA TEAYERRIKR
460 470 480 490 500
LEQEKLELTR KLQESTQTVQ ALQYSTVDGP LTASKDLEIK SLKEEIEKLR
510 520 530 540 550
KQVAEVNHLE QQLEEANSVR RELDDAFRQI KAFEKQIKTL QQEREELNKE
560 570 580 590 600
LVQASERLKN QSKELKDAHC QRKLAMQEFM EINERLTELH TQKQKLARHV
610 620 630 640 650
RDKEEEVDLV MQKAESLRQE LRRAERAKKE LEVHTEALIA EASKDRKLRE
660 670 680 690 700
QSRHYSKQLE NELEGLKQKQ ISYSPGICSI EHQQEITKLK TDLEKKSIFY
710 720 730 740 750
EEEISKREGI HASEIKNLKK ELHDSEGQQL ALNKEIMVLK DKLEKTRRES
760 770 780 790 800
QSEREEFENE FKQQYEREKV LLTEENKKLT SELDKLTSLY ESLSLRNQHL
810 820 830 840 850
EEEVKDLADK KESVAHWEAQ ITEIIQWVSD EKDARGYLQA LASKMTEELE
860 870 880 890 900
ALRNSSLGTR ATDMPWKMRR FAKLDMSARL ELQSALDAEI RAKQAIQEEL
910 920 930 940 950
NKVKASNIIT ECKLKDSEKK NLELLSEIEQ LIKDTEELRS EKGVEHRDSQ
960 970 980 990 1000
HSFLAFLNTP TDALDQFERS PSCTPAGKGR RIADSAPLPV HTPTLRKKGC
1010 1020 1030 1040 1050
PASAGFPPKR KTHQFFVKSF TAPTKCHQCT SLMVGLIRQG CSCEVCGFSC
1060 1070 1080 1090 1100
HITCVNKAPT TCPVPPEQTK GPLGIDPQKG VGTAYEGHVR IPKPAGVKKG
1110 1120 1130 1140 1150
WQRALAVVCD FKLFLYDIAE GKASQPSSVI SQVIDMRDEE FSVSSVLASD
1160 1170 1180 1190 1200
VIHASRKDIP CIFRVTASQL SAPSDKCSIL MLADSETERS KWVGVLSELH
1210 1220 1230 1240 1250
KVLKKNKFRD RSVYVPKEAY DSTLPLIKTT QAAAIIDHER VALGNEEGLF
1260 1270 1280 1290 1300
VVHVTKDEII RVGDNKKIHQ IELIPSDQLV AVISGRNRHV RLFPMSALDG
1310 1320 1330 1340 1350
RETDFYKLAE TKGCQTIAAG KVRHGALSCL CVAMKRQVLC YELFQSKTRH
1360 1370 1380 1390 1400
RKFKEIQVPC NVQWMAIFSE HLCVGFQSGF LRYPLNGEGS PCNMLHSNDH
1410 1420 1430 1440 1450
TLAFITHQPM DAICAVEISN KEYLLCFSSI GIYTDCQGRR SRQQELMWPA
1460 1470 1480 1490 1500
NPSSCCYNAP YLSIYSENAV DIFDVNSMEW IQTLPLKKVR PLNTEGSLNL
1510 1520 1530 1540 1550
LGLETIRLIY FKNKMAEGDE LVVPETSDNS RKQMVRNINN KRRYSFRVPE
1560 1570 1580 1590 1600
EERMQQRREM LRDPEMRNKL ISNPTNFNHI AHMGPGDGIQ ILKDLPMNPR
1610 1620 1630 1640 1650
PQESRTVFSG SVSIPSITKS RPEPGRSMSA SSGLSARSSA QNGSALKREF
1660 1670 1680 1690 1700
SGGSYNTKRQ PMPSPSEGSL SSGGVDQGSD APVRDYDGED SDSPRHSTAS
1710 1720 1730
NSSNLSSPPS PVSPRKTKSL SLESTDRGSW DP
Length:1,732
Mass (Da):197,064
Last modified:June 1, 1998 - v1
Checksum:i65F62F7872ACCD3B
GO
Isoform 2 (identifier: O54874-2)
Sequence is not available
Length:
Mass (Da):
Isoform 3 (identifier: O54874-3)
Sequence is not available
Length:
Mass (Da):
Isoform 4 (identifier: O54874-4)
Sequence is not available
Length:
Mass (Da):
Isoform 5 (identifier: O54874-5)
Sequence is not available
Length:
Mass (Da):
Isoform 6 (identifier: O54874-6)
Sequence is not available
Length:
Mass (Da):

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF021935 mRNA. Translation: AAC02941.1.
PIRiT14039.
RefSeqiNP_446109.1. NM_053657.1. [O54874-1]
UniGeneiRn.10871.

Genome annotation databases

GeneIDi114116.
KEGGirno:114116.
UCSCiRGD:621406. rat. [O54874-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF021935 mRNA. Translation: AAC02941.1.
PIRiT14039.
RefSeqiNP_446109.1. NM_053657.1. [O54874-1]
UniGeneiRn.10871.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4AW2X-ray1.70A2-424[»]
ProteinModelPortaliO54874.
SMRiO54874.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO54874. 7 interactors.
STRINGi10116.ENSRNOP00000003837.

PTM databases

iPTMnetiO54874.
PhosphoSitePlusiO54874.

Proteomic databases

PaxDbiO54874.
PRIDEiO54874.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi114116.
KEGGirno:114116.
UCSCiRGD:621406. rat. [O54874-1]

Organism-specific databases

CTDi8476.
RGDi621406. Cdc42bpa.

Phylogenomic databases

eggNOGiKOG0612. Eukaryota.
ENOG410XR1Q. LUCA.
HOGENOMiHOG000294133.
HOVERGENiHBG055933.
InParanoidiO54874.
KOiK16307.
PhylomeDBiO54874.

Miscellaneous databases

PROiO54874.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR001180. CNH_dom.
IPR000095. CRIB_dom.
IPR031597. KELK.
IPR011009. Kinase-like_dom.
IPR014930. Myotonic_dystrophy_kinase_coil.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR026611. Ser/Thr_kinase_MRCK_alpha.
[Graphical view]
PANTHERiPTHR22988:SF31. PTHR22988:SF31. 2 hits.
PfamiPF00130. C1_1. 1 hit.
PF00780. CNH. 1 hit.
PF08826. DMPK_coil. 1 hit.
PF15796. KELK. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
ProDomiPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00109. C1. 1 hit.
SM00036. CNH. 1 hit.
SM00285. PBD. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50219. CNH. 1 hit.
PS50108. CRIB. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMRCKA_RAT
AccessioniPrimary (citable) accession number: O54874
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.