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Q6DT37 (MRCKG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase MRCK gamma

EC=2.7.11.1
Alternative name(s):
CDC42-binding protein kinase gamma
DMPK-like gamma
Myotonic dystrophy kinase-related CDC42-binding kinase gamma
Short name=MRCK gamma
Short name=MRCKG
Short name=Myotonic dystrophy protein kinase-like gamma
Myotonic dystrophy protein kinase-like alpha
Gene names
Name:CDC42BPG
Synonyms:DMPK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1551 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TBK1Q9UHD22EBI-689124,EBI-356402

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15511551Serine/threonine-protein kinase MRCK gamma
PRO_0000086397

Regions

Domain71 – 337267Protein kinase Ref.1
Domain338 – 40871AGC-kinase C-terminal
Domain947 – 1066120PH
Domain1092 – 1366275CNH
Domain1437 – 145014CRIB
Nucleotide binding77 – 859ATP By similarity UniProtKB P54265
Zinc finger878 – 92750Phorbol-ester/DAG-type
Coiled coil406 – 678273 Potential
Coiled coil730 – 80273 Potential

Sites

Active site1951Proton acceptor By similarity UniProtKB P54265
Binding site1001ATP By similarity Ref.1

Amino acid modifications

Modified residue2161Phosphoserine; by autocatalysis By similarity Ref.1
Modified residue2281Phosphoserine; by autocatalysis By similarity Ref.1
Modified residue2341Phosphothreonine; by autocatalysis By similarity Ref.1

Natural variations

Natural variant1681P → L. Ref.4
Corresponds to variant rs34454471 [ dbSNP | Ensembl ].
VAR_040840
Natural variant2801S → F in a glioblastoma multiforme sample; somatic mutation. Ref.4
VAR_040841
Natural variant3621T → P. Ref.4
Corresponds to variant rs55688429 [ dbSNP | Ensembl ].
VAR_040842
Natural variant5371A → D. Ref.4
Corresponds to variant rs34241745 [ dbSNP | Ensembl ].
VAR_040843
Natural variant11351Q → R.
Corresponds to variant rs3741395 [ dbSNP | Ensembl ].
VAR_057105

Experimental info

Sequence conflict6281P → R in AAT67172. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q6DT37 [UniParc].

Last modified March 2, 2010. Version 2.
Checksum: A6D042D5D11318D7

FASTA1,551172,459
        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 EQAHSHRPSG 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 

« Hide

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Colon.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 113-401.
[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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-168; PHE-280; PRO-362 AND ASP-537.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY648038 mRNA. Translation: AAT67172.1.
AP001187 Genomic DNA. No translation available.
Y12337 mRNA. Translation: CAA73006.1.
CCDSCCDS31601.1.
RefSeqNP_059995.2. NM_017525.2.
UniGeneHs.293590.

3D structure databases

ProteinModelPortalQ6DT37.
SMRQ6DT37. Positions 2-400.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120719. 5 interactions.
IntActQ6DT37. 4 interactions.
MINTMINT-3976275.
STRING9606.ENSP00000345133.

Chemistry

ChEMBLCHEMBL5615.
GuidetoPHARMACOLOGY1506.

PTM databases

PhosphoSiteQ6DT37.

Polymorphism databases

DMDM290457650.

Proteomic databases

MaxQBQ6DT37.
PaxDbQ6DT37.
PRIDEQ6DT37.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000342711; ENSP00000345133; ENSG00000171219.
GeneID55561.
KEGGhsa:55561.
UCSCuc001obs.4. human.

Organism-specific databases

CTD55561.
GeneCardsGC11M064591.
H-InvDBHIX0035842.
HGNCHGNC:29829. CDC42BPG.
HPAHPA027382.
MIM613991. gene.
neXtProtNX_Q6DT37.
PharmGKBPA134901493.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000294133.
HOVERGENHBG055933.
InParanoidQ6DT37.
KOK16307.
OMATCAPQAP.
OrthoDBEOG7F511X.
PhylomeDBQ6DT37.
TreeFamTF313551.

Enzyme and pathway databases

SignaLinkQ6DT37.

Gene expression databases

BgeeQ6DT37.
CleanExHS_CDC42BPG.
GenevestigatorQ6DT37.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR001180. Citron.
IPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR014930. Myotonic_dystrophy_kinase_coil.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. 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]
ProDomPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00109. C1. 1 hit.
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

ChiTaRSCDC42BPG. human.
GenomeRNAi55561.
NextBio60044.
PROQ6DT37.
SOURCESearch...

Entry information

Entry nameMRCKG_HUMAN
AccessionPrimary (citable) accession number: Q6DT37
Secondary accession number(s): O00565
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: March 2, 2010
Last modified: July 9, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM