Reviewed, UniProtKB/Swiss-Prot Q6DT37 (MRCKG_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase MRCK gamma
    EC=2.7.11.1
Alternative name(s):
    CDC42-binding protein kinase gamma
    Myotonic dystrophy kinase-related CDC42-binding kinase gamma
      Short name=Myotonic dystrophy protein kinase-like gamma
      Short name=MRCK gamma
    Myotonic dystrophy protein kinase-like alpha
    DMPK-like gamma

Gene names

Name:	CDC42BPG
Synonyms:	DMPK2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1551 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation By similarity. Ref.1 UniProtKB Q5VT25
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
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 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.
Subcellular location	Cytoplasm. Note: Concentrates at the leading edge of cells. Ref.1
Tissue specificity	Expressed in heart and skeletal muscle. Ref.1
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	Cytoplasm
Coding sequence diversity	Polymorphism
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
Gene Ontology (GO)
Biological process	actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	cell leading edge Ref.1 Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	1	EBI-689124,EBI-81752
RHOQ	P17081	1	EBI-689124,EBI-689202

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1551	1551	Serine/threonine-protein kinase MRCK gamma		PRO_0000086397
Regions
	Domain	71 – 337	267	Protein kinase Ref.1
	Domain	338 – 408	71	AGC-kinase C-terminal
	Domain	947 – 1066	120	PH
	Domain	1092 – 1366	275	CNH
	Domain	1437 – 1450	14	CRIB
	Nucleotide binding	77 – 85	9	ATP By similarity UniProtKB P54265
	Zinc finger	878 – 927	50	Phorbol-ester/DAG-type
	Coiled coil	406 – 678	273	Potential
	Coiled coil	730 – 802	73	Potential
Sites
	Active site	195	1	Proton acceptor By similarity UniProtKB P54265
	Binding site	100	1	ATP By similarity Ref.1
Amino acid modifications
	Modified residue	216	1	Phosphoserine; by autocatalysis By similarity Ref.1
	Modified residue	228	1	Phosphoserine; by autocatalysis By similarity Ref.1
	Modified residue	234	1	Phosphothreonine; by autocatalysis By similarity Ref.1
	Modified residue	1540	1	Phosphoserine
Natural variations
	Natural variant	168	1	P → L: dbSNP rs34454471. Ref.4		VAR_040840
	Natural variant	280	1	S → F in a glioblastoma multiforme sample; somatic mutation. Ref.4		VAR_040841
	Natural variant	362	1	T → P: dbSNP rs55688429. Ref.4		VAR_040842
	Natural variant	537	1	A → D: dbSNP rs34241745. Ref.4		VAR_040843
	Natural variant	1135	1	Q → R: dbSNP rs3741395.		VAR_057105

Sequences

	Sequence		Length	Mass (Da)
	Q6DT37-1 [UniParc]. Last modified August 16, 2004. Version 1. Checksum: 6B2DCED7BFE57B1E	FASTA	1,551	172,518
	10 20 30 40 50 60 MERRLRALEQ LARGEAGGCP GLDGLLDLLL ALHHELSSGP LRRERSVAQF LSWASPFVSK 70 80 90 100 110 120 VKELRLQRDD FEILKVIGRG AFGEVTVVRQ RDTGQIFAMK MLHKWEMLKR AETACFREER 130 140 150 160 170 180 DVLVKGDSRW VTTLHYAFQD EEYLYLVMDY YAGGDLLTLL SRFEDRLPPE LAQFYLAEMV 190 200 210 220 230 240 LAIHSLHQLG YVHRDVKPDN VLLDVNGHIR LADFGSCLRL NTNGMVDSSV AVGTPDYISP 250 260 270 280 290 300 EILQAMEEGK GHYGPQCDWW SLGVCAYELL FGETPFYAES LVETYGKIMN HEDHLQFPPD 310 320 330 340 350 360 VPDVPASAQD LIRQLLCRQE ERLGRGGLDD FRNHPFFEGV DWERLASSTA PYIPELRGPM 370 380 390 400 410 420 DTSNFDVDDD TLNHPGTLPP PSHGAFSGHH LPFVGFTYTS GSHSPESSSE AWAALERKLQ 430 440 450 460 470 480 CLEQEKVELS RKHQEALHAP TDHRELEQLR KEVQTLRDRL PEMLRDKASL SQTDGPPAGS 490 500 510 520 530 540 PGQDSDLRQE LDRLHRELAE GRAGLQAQEQ ELCRAQGQQE ELLQRLQEAQ EREAATASQT 550 560 570 580 590 600 RALSSQLEEA RAAQRELEAQ VSSLSRQVTQ LQGQWEQRLE ESSQAKTIHT ASETNGMGPP 610 620 630 640 650 660 EGGPQEAQLR KEVAALREQL EQAHSHRRSG KEEALCQLQE ENRRLSREQE RLEAELAQEQ 670 680 690 700 710 720 ESKQRLEGER RETESNWEAQ LADILSWVND EKVSRGYLQA LATKMAEELE SLRNVGTQTL 730 740 750 760 770 780 PARPLDHQWK ARRLQKMEAS ARLELQSALE AEIRAKQGLQ ERLTQVQEAQ LQAERRLQEA 790 800 810 820 830 840 EKQSQALQQE LAMLREELRA RGPVDTKPSN SLIPFLSFRS SEKDSAKDPG ISGEATRHGG 850 860 870 880 890 900 EPDLRPEGRR SLRMGAVFPR APTANTASTE GLPAKPGSHT LRPRSFPSPT KCLRCTSLML 910 920 930 940 950 960 GLGRQGLGCD ACGYFCHTTC APQAPPCPVP PDLLRTALGV HPETGTGTAY EGFLSVPRPS 970 980 990 1000 1010 1020 GVRRGWQRVF AALSDSRLLL FDAPDLRLSP PSGALLQVLD LRDPQFSATP VLASDVIHAQ 1030 1040 1050 1060 1070 1080 SRDLPRIFRV TTSQLAVPPT TCTVLLLAES EGERERWLQV LGELQRLLLD ARPRPRPVYT 1090 1100 1110 1120 1130 1140 LKEAYDNGLP LLPHTLCAAI LDQDRLALGT EEGLFVIHLR SNDIFQVGEC RRVQQLTLSP 1150 1160 1170 1180 1190 1200 SAGLLVVLCG RGPSVRLFAL AELENIEVAG AKIPESRGCQ VLAAGSILQA RTPVLCVAVK 1210 1220 1230 1240 1250 1260 RQVLCYQLGP GPGPWQRRIR ELQAPATVQS LGLLGDRLCV GAAGGFALYP LLNEAAPLAL 1270 1280 1290 1300 1310 1320 GAGLVPEELP PSRGGLGEAL GAVELSLSEF LLLFTTAGIY VDGAGRKSRG HELLWPAAPM 1330 1340 1350 1360 1370 1380 GWGYAAPYLT VFSENSIDVF DVRRAEWVQT VPLKKVRPLN PEGSLFLYGT EKVRLTYLRN 1390 1400 1410 1420 1430 1440 QLAEKDEFDI PDLTDNSRRQ LFRTKSKRRF FFRVSEEQQK QQRREMLKDP FVRSKLISPP 1450 1460 1470 1480 1490 1500 TNFNHLVHVG PANGRPGARD KSPAPEEKGR VARGSGPQRP HSFSEALRRP ASMGSEGLGG 1510 1520 1530 1540 1550 DADPMKRKPW TSLSSESVSC PQGSLSPATS LMQVSERPRS LPLSPELESS P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of the human myotonic dystrophy kinase-related Cdc42-binding kinase gamma is regulated by promoter DNA methylation and Sp1 binding." Ng Y., Tan I., Lim L., Leung T. J. Biol. Chem. 279:34156-34164(2004) [PubMed: 15194684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Colon.
[2]	"The germinal centre kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13." Kedra D., Seroussi E., Fransson I., Trifunovic J., Clark M., Lagercrantz J., Blennow E., Mehlin H., Dumanski J. Hum. Genet. 100:611-619(1997) [PubMed: 9341881] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 113-401.
[3]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1540, MASS SPECTROMETRY.
[4]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-168; PHE-280; PRO-362 AND ASP-537.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY648038 mRNA. Translation: AAT67172.1. Y12337 mRNA. Translation: CAA73006.1.
IPI	IPI00454910.
RefSeq	NP_059995.2.
UniGene	Hs.293590
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6DT37. 2 interactions.
STRING	Q6DT37.
PTM databases
PhosphoSite	Q6DT37.
Proteomic databases
PRIDE	Q6DT37.
Genome annotation databases
Ensembl	ENST00000342711; ENSP00000345133; ENSG00000171219; Homo sapiens. [Genome view]
GeneID	55561.
KEGG	hsa:55561.
UCSC	uc001obs.2. human.
Organism-specific databases
CTD	55561.
GeneCards	GC11M064348.
H-InvDB	HIX0035842.
HGNC	HGNC:29829. CDC42BPG.
HPA	HPA027382.
PharmGKB	PA134901493.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19720.
HOGENOM	HBG444706.
HOVERGEN	Q6DT37.
InParanoid	Q6DT37.
PhylomeDB	Q6DT37.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q6DT37.
Bgee	Q6DT37.
CleanEx	HS_CDC42BPG.
Genevestigator	Q6DT37.
GermOnline	ENSG00000171219. Homo sapiens.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR001180. Citron. 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. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00780. CNH. 1 hit. PF08826. DMPK_coil. 1 hit. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
ProDom	PD011252. Myotonic_dystrophy_kinase_coil. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 1 hit. SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
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 Resources
NextBio	60044.

Entry information

Entry name

MRCKG_HUMAN

Accession

Primary (citable) accession number: Q6DT37
Secondary accession number(s): O00565

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	August 16, 2004
Last modified:	February 9, 2010
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.