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Q6DT37

- MRCKG_HUMAN

UniProt

Q6DT37 - MRCKG_HUMAN

Protein

Serine/threonine-protein kinase MRCK gamma

Gene

CDC42BPG

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 2 (02 Mar 2010)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

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

    Cofactori

    Magnesium.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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei100 – 1001ATP1 PublicationPROSITE-ProRule annotation
    Active sitei195 – 1951Proton acceptorBy similarityPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi77 – 859ATPBy similarityPROSITE-ProRule annotation
    Zinc fingeri878 – 92750Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. magnesium ion binding Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein serine/threonine kinase activity Source: UniProtKB
    5. small GTPase regulator activity Source: InterPro

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: UniProtKB
    2. intracellular signal transduction Source: InterPro
    3. protein phosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

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

    Enzyme and pathway databases

    SignaLinkiQ6DT37.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:CDC42BPGImported
    Synonyms:DMPK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:29829. CDC42BPG.

    Subcellular locationi

    Cytoplasm 1 Publication
    Note: Concentrates at the leading edge of cells.

    GO - Cellular componenti

    1. cell leading edge Source: UniProtKB
    2. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134901493.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 15511551Serine/threonine-protein kinase MRCK gammaPRO_0000086397Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei216 – 2161Phosphoserine; by autocatalysisBy similarity
    Modified residuei228 – 2281Phosphoserine; by autocatalysisBy similarity
    Modified residuei234 – 2341Phosphothreonine; by autocatalysisBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ6DT37.
    PaxDbiQ6DT37.
    PRIDEiQ6DT37.

    PTM databases

    PhosphoSiteiQ6DT37.

    Expressioni

    Tissue specificityi

    Expressed in heart and skeletal muscle.1 Publication

    Gene expression databases

    BgeeiQ6DT37.
    CleanExiHS_CDC42BPG.
    GenevestigatoriQ6DT37.

    Organism-specific databases

    HPAiHPA027382.

    Interactioni

    Subunit structurei

    Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TBK1Q9UHD22EBI-689124,EBI-356402

    Protein-protein interaction databases

    BioGridi120719. 5 interactions.
    IntActiQ6DT37. 4 interactions.
    MINTiMINT-3976275.
    STRINGi9606.ENSP00000345133.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6DT37.
    SMRiQ6DT37. Positions 2-400.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini71 – 337267Protein kinase1 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Domaini338 – 40871AGC-kinase C-terminalAdd
    BLAST
    Domaini947 – 1066120PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini1092 – 1366275CNHPROSITE-ProRule annotationAdd
    BLAST
    Domaini1437 – 145014CRIBPROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili406 – 678273Sequence AnalysisAdd
    BLAST
    Coiled coili730 – 80273Sequence AnalysisAdd
    BLAST

    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)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri878 – 92750Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Coiled coil, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000294133.
    HOVERGENiHBG055933.
    InParanoidiQ6DT37.
    KOiK16307.
    OMAiTCAPQAP.
    OrthoDBiEOG7F511X.
    PhylomeDBiQ6DT37.
    TreeFamiTF313551.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR001180. Citron.
    IPR000095. CRIB_dom.
    IPR011009. Kinase-like_dom.
    IPR014930. Myotonic_dystrophy_kinase_coil.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    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]
    PfamiPF00130. 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]
    ProDomiPD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00109. C1. 1 hit.
    SM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. 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]

    Sequencei

    Sequence statusi: Complete.

    Q6DT37-1 [UniParc]FASTAAdd to Basket

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    MERRLRALEQ LARGEAGGCP GLDGLLDLLL ALHHELSSGP LRRERSVAQF     50
    LSWASPFVSK VKELRLQRDD FEILKVIGRG AFGEVTVVRQ RDTGQIFAMK 100
    MLHKWEMLKR AETACFREER DVLVKGDSRW VTTLHYAFQD EEYLYLVMDY 150
    YAGGDLLTLL SRFEDRLPPE LAQFYLAEMV LAIHSLHQLG YVHRDVKPDN 200
    VLLDVNGHIR LADFGSCLRL NTNGMVDSSV AVGTPDYISP EILQAMEEGK 250
    GHYGPQCDWW SLGVCAYELL FGETPFYAES LVETYGKIMN HEDHLQFPPD 300
    VPDVPASAQD LIRQLLCRQE ERLGRGGLDD FRNHPFFEGV DWERLASSTA 350
    PYIPELRGPM DTSNFDVDDD TLNHPGTLPP PSHGAFSGHH LPFVGFTYTS 400
    GSHSPESSSE AWAALERKLQ CLEQEKVELS RKHQEALHAP TDHRELEQLR 450
    KEVQTLRDRL PEMLRDKASL SQTDGPPAGS PGQDSDLRQE LDRLHRELAE 500
    GRAGLQAQEQ ELCRAQGQQE ELLQRLQEAQ EREAATASQT RALSSQLEEA 550
    RAAQRELEAQ VSSLSRQVTQ LQGQWEQRLE ESSQAKTIHT ASETNGMGPP 600
    EGGPQEAQLR KEVAALREQL EQAHSHRPSG KEEALCQLQE ENRRLSREQE 650
    RLEAELAQEQ ESKQRLEGER RETESNWEAQ LADILSWVND EKVSRGYLQA 700
    LATKMAEELE SLRNVGTQTL PARPLDHQWK ARRLQKMEAS ARLELQSALE 750
    AEIRAKQGLQ ERLTQVQEAQ LQAERRLQEA EKQSQALQQE LAMLREELRA 800
    RGPVDTKPSN SLIPFLSFRS SEKDSAKDPG ISGEATRHGG EPDLRPEGRR 850
    SLRMGAVFPR APTANTASTE GLPAKPGSHT LRPRSFPSPT KCLRCTSLML 900
    GLGRQGLGCD ACGYFCHTTC APQAPPCPVP PDLLRTALGV HPETGTGTAY 950
    EGFLSVPRPS GVRRGWQRVF AALSDSRLLL FDAPDLRLSP PSGALLQVLD 1000
    LRDPQFSATP VLASDVIHAQ SRDLPRIFRV TTSQLAVPPT TCTVLLLAES 1050
    EGERERWLQV LGELQRLLLD ARPRPRPVYT LKEAYDNGLP LLPHTLCAAI 1100
    LDQDRLALGT EEGLFVIHLR SNDIFQVGEC RRVQQLTLSP SAGLLVVLCG 1150
    RGPSVRLFAL AELENIEVAG AKIPESRGCQ VLAAGSILQA RTPVLCVAVK 1200
    RQVLCYQLGP GPGPWQRRIR ELQAPATVQS LGLLGDRLCV GAAGGFALYP 1250
    LLNEAAPLAL GAGLVPEELP PSRGGLGEAL GAVELSLSEF LLLFTTAGIY 1300
    VDGAGRKSRG HELLWPAAPM GWGYAAPYLT VFSENSIDVF DVRRAEWVQT 1350
    VPLKKVRPLN PEGSLFLYGT EKVRLTYLRN QLAEKDEFDI PDLTDNSRRQ 1400
    LFRTKSKRRF FFRVSEEQQK QQRREMLKDP FVRSKLISPP TNFNHLVHVG 1450
    PANGRPGARD KSPAPEEKGR VARGSGPQRP HSFSEALRRP ASMGSEGLGG 1500
    DADPMKRKPW TSLSSESVSC PQGSLSPATS LMQVSERPRS LPLSPELESS 1550
    P 1551
    Length:1,551
    Mass (Da):172,459
    Last modified:March 2, 2010 - v2
    Checksum:iA6D042D5D11318D7
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti628 – 6281P → R in AAT67172. (PubMed:15194684)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti168 – 1681P → L.1 Publication
    Corresponds to variant rs34454471 [ dbSNP | Ensembl ].
    VAR_040840
    Natural varianti280 – 2801S → F in a glioblastoma multiforme sample; somatic mutation. 1 Publication
    VAR_040841
    Natural varianti362 – 3621T → P.1 Publication
    Corresponds to variant rs55688429 [ dbSNP | Ensembl ].
    VAR_040842
    Natural varianti537 – 5371A → D.1 Publication
    Corresponds to variant rs34241745 [ dbSNP | Ensembl ].
    VAR_040843
    Natural varianti1135 – 11351Q → R.
    Corresponds to variant rs3741395 [ dbSNP | Ensembl ].
    VAR_057105

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY648038 mRNA. Translation: AAT67172.1.
    AP001187 Genomic DNA. No translation available.
    Y12337 mRNA. Translation: CAA73006.1.
    CCDSiCCDS31601.1.
    RefSeqiNP_059995.2. NM_017525.2.
    UniGeneiHs.293590.

    Genome annotation databases

    EnsembliENST00000342711; ENSP00000345133; ENSG00000171219.
    GeneIDi55561.
    KEGGihsa:55561.
    UCSCiuc001obs.4. human.

    Polymorphism databases

    DMDMi290457650.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY648038 mRNA. Translation: AAT67172.1 .
    AP001187 Genomic DNA. No translation available.
    Y12337 mRNA. Translation: CAA73006.1 .
    CCDSi CCDS31601.1.
    RefSeqi NP_059995.2. NM_017525.2.
    UniGenei Hs.293590.

    3D structure databases

    ProteinModelPortali Q6DT37.
    SMRi Q6DT37. Positions 2-400.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120719. 5 interactions.
    IntActi Q6DT37. 4 interactions.
    MINTi MINT-3976275.
    STRINGi 9606.ENSP00000345133.

    Chemistry

    ChEMBLi CHEMBL5615.
    GuidetoPHARMACOLOGYi 1506.

    PTM databases

    PhosphoSitei Q6DT37.

    Polymorphism databases

    DMDMi 290457650.

    Proteomic databases

    MaxQBi Q6DT37.
    PaxDbi Q6DT37.
    PRIDEi Q6DT37.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000342711 ; ENSP00000345133 ; ENSG00000171219 .
    GeneIDi 55561.
    KEGGi hsa:55561.
    UCSCi uc001obs.4. human.

    Organism-specific databases

    CTDi 55561.
    GeneCardsi GC11M064591.
    H-InvDB HIX0035842.
    HGNCi HGNC:29829. CDC42BPG.
    HPAi HPA027382.
    MIMi 613991. gene.
    neXtProti NX_Q6DT37.
    PharmGKBi PA134901493.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000294133.
    HOVERGENi HBG055933.
    InParanoidi Q6DT37.
    KOi K16307.
    OMAi TCAPQAP.
    OrthoDBi EOG7F511X.
    PhylomeDBi Q6DT37.
    TreeFami TF313551.

    Enzyme and pathway databases

    SignaLinki Q6DT37.

    Miscellaneous databases

    ChiTaRSi CDC42BPG. human.
    GenomeRNAii 55561.
    NextBioi 60044.
    PROi Q6DT37.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q6DT37.
    CleanExi HS_CDC42BPG.
    Genevestigatori Q6DT37.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR000961. AGC-kinase_C.
    IPR001180. Citron.
    IPR000095. CRIB_dom.
    IPR011009. Kinase-like_dom.
    IPR014930. Myotonic_dystrophy_kinase_coil.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    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 ]
    Pfami 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 ]
    ProDomi PD011252. Myotonic_dystrophy_kinase_coil. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00109. C1. 1 hit.
    SM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi 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 ]
    ProtoNeti Search...

    Publicationsi

    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: Colon1 Publication.
    2. 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.
      , 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.

    Entry informationi

    Entry nameiMRCKG_HUMAN
    AccessioniPrimary (citable) accession number: Q6DT37
    Secondary accession number(s): O00565
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 8, 2005
    Last sequence update: March 2, 2010
    Last modified: October 1, 2014
    This is version 105 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3