Q7TT50 (MRCKB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase MRCK beta
EC=2.7.11.1

Alternative name(s):
CDC42-binding protein kinase beta
DMPK-like beta
Myotonic dystrophy kinase-related CDC42-binding kinase beta
Short name=MRCK beta
Short name=Myotonic dystrophy protein kinase-like beta

Gene names

Name:	Cdc42bpb
Synonyms:	Kiaa1124

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1713 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q5VT25
Cofactor	Magnesium By similarity. UniProtKB Q5VT25
Enzyme regulation	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. Inhibited by chelerythrine chloride By similarity. UniProtKB Q5VT25
Subunit structure	Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42 By similarity. Interacts with TJP1; this interaction requires the presence of catalytically active CDC42. Forms a tripartite complex with MYO18A and LURAP1 with the latter acting as an adapter connecting CDC42BPB and MYO18A. LURAP1 binding results in activation of CDC42BPB by abolition of its negative autoregulation By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell junction By similarity. 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 By similarity. Detected at the leading edge of migrating and wounded cells; this localization requires the presence of catalytically active CDC42 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 CNH domain. Contains 1 CRIB domain. Contains 1 PH domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane
Domain	Coiled coil Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB actomyosin structure organization Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	actomyosin Inferred from electronic annotation. Source: Compara cell leading edge Inferred from sequence or structural similarity. Source: UniProtKB cell-cell junction Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB phospholipid binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1713	1713	Serine/threonine-protein kinase MRCK beta		PRO_0000086395
Regions
	Domain	76 – 342	267	Protein kinase UniProtKB Q5VT25
	Domain	343 – 413	71	AGC-kinase C-terminal
	Domain	1096 – 1215	120	PH
	Domain	1241 – 1515	275	CNH
	Domain	1585 – 1598	14	CRIB
	Nucleotide binding	82 – 90	9	ATP By similarity UniProtKB P54265
	Zinc finger	1026 – 1076	51	Phorbol-ester/DAG-type
	Coiled coil	434 – 649	216	Potential
	Coiled coil	681 – 815	135	Potential
	Coiled coil	878 – 939	62	Potential
Sites
	Active site	200	1	Proton acceptor By similarity UniProtKB P54265
	Binding site	105	1	ATP By similarity UniProtKB Q5VT25
Amino acid modifications
	Modified residue	221	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q5VT25
	Modified residue	233	1	Phosphoserine; by autocatalysis By similarity UniProtKB Q5VT25
	Modified residue	239	1	Phosphothreonine; by autocatalysis By similarity UniProtKB Q5VT25
	Modified residue	954	1	Phosphotyrosine Ref.6
	Modified residue	1692	1	Phosphoserine Ref.7 Ref.8
	Modified residue	1695	1	Phosphoserine Ref.7
Experimental info
	Sequence conflict	96	1	K → R in AAP34402. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q7TT50 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: CD809A3743986A4D	FASTA	1,713	194,753
	10 20 30 40 50 60 MSAKVRLKKL EQLLLDGPWR NDSALSVETL LDVLVCLYTE CSHSALRRDK YVAEFLEWAK 70 80 90 100 110 120 PFTQLVKDMQ LHREDFEIIK VIGRGAFGEV AVVKMKNTER IYAMKILNKW EMLKRAETAC 130 140 150 160 170 180 FREERDVLVN GDCQWITALH YAFQDENYLY LVMDYYVGGD LLTLLSKFED KLPEDMARFY 190 200 210 220 230 240 IGEMVLAIDS IHQLHYVHRD IKPDNVLLDV NGHIRLADFG SCLKMNDDGT VQSSVAVGTP 250 260 270 280 290 300 DYISPEILQA MEDGMGKYGP ECDWWSLGVC MYEMLYGETP FYAESLVETY GKIMNHEERF 310 320 330 340 350 360 QFPSHVTDVS EEAKDLIQRL ICSRERRLGQ NGIEDFKKHA FFEGLNWENI RNLEAPYIPD 370 380 390 400 410 420 VSSPSDTSNF DVDDDMLRNI EILPPGSHTG FSGLHLPFIG FTFTTESCFS DRGSLKSMTQ 430 440 450 460 470 480 SNTLTKDEDV QRDLENSLQI EAYERRIRRL EQEKLELSRK LQESTQTVQS LHGSTRALGN 490 500 510 520 530 540 SNRDKEIKRL NEELERMKSK MADSNRLERQ LEDTVTLRQE HEDSTHRLKG LEKQYRLARQ 550 560 570 580 590 600 EKEELHKQLV EASERLKSQT KELKDAHQQR KRALQEFSEL NERMSELRSL KQKVSRQLRD 610 620 630 640 650 660 KEEEMEVAMQ KIDSMRQDLR KSEKSRKELE ARLEDAAAEA SKERKLREHS ESFCKQMERE 670 680 690 700 710 720 LEALKVKQGG RGPGAASEHQ QEISKIRSEL EKKVLFYEEE LVRREASHVL EVKNVKKEVH 730 740 750 760 770 780 DSESHQLALQ KEVLMLKDKL EKSKRERHSE MEEAIGTVKD KYERERAMLF DENKKLTAEN 790 800 810 820 830 840 EKLCSFVDKL TAQNRQLEDE LQDLASKKES VAHWEAQIAE IIQWVSDEKD ARGYLQALAS 850 860 870 880 890 900 KMTEELETLR SSSLGSRTLD PLWKVRRSQK LDMSARLELQ SALEAEIRAK QLVQEELRKV 910 920 930 940 950 960 KDSSLAFESK LKESEAKNRE LLEEMQSLRK RMEEKFRADT GLKLPDFQDS IFEYFNTAPL 970 980 990 1000 1010 1020 AHDLTFRTSS ASDQETQASK MDLSPSVSVA TSTEQQEDMA RPQQRPSPVP LPSTQALAMA 1030 1040 1050 1060 1070 1080 GPKPKAHQFS IKSFPSPTQC SHCTSLMVGL IRQGYACEVC AFSCHVSCKD SAPQVCPIPP 1090 1100 1110 1120 1130 1140 EQSKRPLGVD VQRGIGTAYK GYVKVPKPTG VKKGWQRAYA VVCDCKLFLY DLPEGKSTQP 1150 1160 1170 1180 1190 1200 GVVASQVLDL RDEEFAVSSV LASDVIHATR RDIPCIFRVT ASLLGSPSKT SSLLILTENE 1210 1220 1230 1240 1250 1260 NEKRKWVGIL EGLQAILHKN RLKSQVVHVA QEAYDSSLPL IKAVLAAAIV DGDRIAVGLE 1270 1280 1290 1300 1310 1320 EGLYVIELTR DVIVRAADCK KVYQIELAPK EKIAILLCGR NHHVHLYPWS SFDGAEASNF 1330 1340 1350 1360 1370 1380 DIKLPETKGC QLIATGTLRK SSSTCLFVAV KRLILCYEIQ RTKPFHRKFS ELVAPGHVQW 1390 1400 1410 1420 1430 1440 MAVFKDRLCV GYPSGFSLLS IQGDGPPLDL VNPTDPSLAF LSQQSFDALC AVELKSEEYL 1450 1460 1470 1480 1490 1500 LCFSHMGLYV DPQGRRSRMQ ELMWPAAPVA CSCSPTHVTV YSEYGVDVFD VRTMEWVQTI 1510 1520 1530 1540 1550 1560 GLRRIRPLNS DGSLNLLGCE PPRLIYFKNK FSGTILNVPD TSDNSKKQML RTRSKRRFVF 1570 1580 1590 1600 1610 1620 KVPEEERLQQ RREMLRDPEL RSKMISNPTN FNHVAHMGPG DGMQVLMDLP LSAAPTVQEE 1630 1640 1650 1660 1670 1680 KQGPTPAGLP RQPPSRSKPY VSWPSSGGSE PGVPVPLRSM SDPDQDFDKE PDSDSTKHST 1690 1700 1710 PSNSSNPSGP PSPNSPHRSQ LPMEGLDQPS CDA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Huang C.Q., Wu S.L., Cheng Z. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H. DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 628-1713. Tissue: Fetal brain.
[4]	Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 633-642, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1139-1713. Strain: FVB/N. Tissue: Kidney.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-954, MASS SPECTROMETRY.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1692 AND SER-1695, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1692, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY277589 mRNA. Translation: AAP34402.1. AC127580 Genomic DNA. No translation available. AK173103 mRNA. Translation: BAD32381.1. BC049921 mRNA. Translation: AAH49921.1.
IPI	IPI00114613.
RefSeq	NP_898837.2. NM_183016.2.
UniGene	Mm.485798.
3D structure databases
ProteinModelPortal	Q7TT50.
SMR	Q7TT50. Positions 2-415.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7TT50. 1 interaction.
STRING	10090.ENSMUSP00000042565.
PTM databases
PhosphoSite	Q7TT50.
Proteomic databases
PaxDb	Q7TT50.
PRIDE	Q7TT50.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000041965; ENSMUSP00000042565; ENSMUSG00000021279.
GeneID	217866.
KEGG	mmu:217866.
UCSC	uc007pct.2. mouse.
Organism-specific databases
CTD	9578.
MGI	MGI:2136459. Cdc42bpb.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000101983.
HOGENOM	HOG000294133.
HOVERGEN	HBG055933.
InParanoid	Q7TT50.
KO	K16307.
OMA	TTESCFS.
OrthoDB	EOG4640B1.
Gene expression databases
Bgee	Q7TT50.
CleanEx	MM_CDC42BPB.
Genevestigator	Q7TT50.
GermOnline	ENSMUSG00000021279. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR001180. Citron. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR014930. Myotonic_dystrophy_kinase_coil. IPR000095. PAK_box_Rho-bd. IPR017892. Pkinase_C. IPR001849. Pleckstrin_homology. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. IPR026611. Ser/Thr_kinase_MRCK. [Graphical view]
PANTHER	PTHR22988:SF2. PTHR22988:SF2. 1 hit.
Pfam	PF00130. C1_1. 1 hit. PF00780. CNH. 1 hit. PF08826. DMPK_coil. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
ProDom	PD011252. Myotonic_dystrophy_kinase_coil. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. 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]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. 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]
ProtoNet	Search...
Other
NextBio	376071.
SOURCE	Search...

Entry information

Entry name

MRCKB_MOUSE

Accession

Primary (citable) accession number: Q7TT50
Secondary accession number(s): E9QK15, Q69ZR5, Q80W33

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program