Reviewed,
UniProtKB/Swiss-Prot Q5VT25 (MRCKA_HUMAN)
Last modified
February 9, 2010.
Version 61.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Serine/threonine-protein kinase MRCK alpha EC=2.7.11.1 Alternative name(s): Myotonic dystrophy kinase-related CDC42-binding kinase alpha Short name=Myotonic dystrophy protein kinase-like alpha Short name=MRCK alpha CDC42-binding protein kinase alpha DMPK-like alpha | ||||
| Gene names |
| ||||
| 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 | 1732 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. Ref.1 Ref.5 Ref.8 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. Ref.5 |
| Cofactor | Magnesium. Ref.5 |
| 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. Ref.9 |
| Subunit structure | Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. Ref.8 Ref.9 |
| Subcellular location | Cytoplasm 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. |
| Tissue specificity | Abundant in the heart, brain, skeletal muscle, kidney, and pancreas, with little or no expression in the lung and liver. Ref.5 |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 3 | EBI-689171,EBI-689171 | ||
| CDC42 | P60953 | 3 | EBI-689171,EBI-81752 | |
| RHOQ | P17081 | 1 | EBI-689171,EBI-689202 |
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q5VT25-1) 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. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 2 (identifier: Q5VT25-2) The sequence of this isoform differs from the canonical sequence as follows: 969-969: R → TDPVENTYVWNPSVKFHIQSRST 973-981: CTPASKGRR → TSSEAEPVK | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 Ref.1 (identifier: Q5VT25-3) The sequence of this isoform differs from the canonical sequence as follows: 550-630: Missing. 969-981: Missing. | ||||||
| Isoform 4 Ref.4 (identifier: Q5VT25-4) The sequence of this isoform differs from the canonical sequence as follows: 969-1009: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 5 Ref.1 (identifier: Q5VT25-5) The sequence of this isoform differs from the canonical sequence as follows: 969-981: Missing. | ||||||
| Isoform 6 (identifier: Q5VT25-6) The sequence of this isoform differs from the canonical sequence as follows: 969-981: Missing. 1597-1597: M → MPGFPYPSPHHHSGLISSPINFEHIYHMTVNSAEKFLSPDSINPEYSPSLRSVPGTPSFMTLR |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1732 | 1732 | Serine/threonine-protein kinase MRCK alpha | PRO_0000086392 | |||||
Regions | |||||||||
| Domain | 77 – 343 | 267 | Protein kinase Ref.5 | ||||||
| Domain | 344 – 414 | 71 | AGC-kinase C-terminal | ||||||
| Domain | 1082 – 1201 | 120 | PH | ||||||
| Domain | 1227 – 1499 | 273 | CNH | ||||||
| Domain | 1571 – 1584 | 14 | CRIB | ||||||
| Nucleotide binding | 83 – 91 | 9 | ATP By similarity UniProtKB P54265 | ||||||
| Zinc finger | 1012 – 1062 | 51 | Phorbol-ester/DAG-type | ||||||
| Coiled coil | 437 – 820 | 384 | Potential | ||||||
| Coiled coil | 880 – 943 | 64 | Potential | ||||||
Sites | |||||||||
| Active site | 201 | 1 | Proton acceptor By similarity UniProtKB P54265 | ||||||
| Binding site | 106 | 1 | ATP Ref.9 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 222 | 1 | Phosphoserine; by autocatalysis Ref.9 | ||||||
| Modified residue | 234 | 1 | Phosphoserine; by autocatalysis Ref.9 | ||||||
| Modified residue | 240 | 1 | Phosphothreonine; by autocatalysis Ref.9 | ||||||
| Modified residue | 1545 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 1651 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1719 | 1 | Phosphoserine Ref.10 Ref.11 | ||||||
| Modified residue | 1721 | 1 | Phosphoserine Ref.10 | ||||||
Natural variations | |||||||||
| Alternative sequence | 550 – 630 | 81 | Missing in isoform 3. Ref.1 | VSP_051859 | |||||
| Alternative sequence | 969 – 1009 | 41 | Missing in isoform 4. Ref.4 | VSP_051862 | |||||
| Alternative sequence | 969 – 981 | 13 | Missing in isoform 3, isoform 5 and isoform 6. Ref.1 | VSP_051860 | |||||
| Alternative sequence | 969 | 1 | R → TDPVENTYVWNPSVKFHIQS RST in isoform 2. | VSP_051861 | |||||
| Alternative sequence | 973 – 981 | 9 | CTPASKGRR → TSSEAEPVK in isoform 2. | VSP_051863 | |||||
| Alternative sequence | 1597 | 1 | M → MPGFPYPSPHHHSGLISSPI NFEHIYHMTVNSAEKFLSPD SINPEYSPSLRSVPGTPSFM TLR in isoform 6. | VSP_035286 | |||||
| Natural variant | 50 | 1 | E → K in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.12 | VAR_040830 | |||||
| Natural variant | 231 | 1 | T → M: dbSNP rs34614709. Ref.12 | VAR_040831 | |||||
| Natural variant | 537 | 1 | I → T: dbSNP rs56364976. Ref.12 | VAR_040832 | |||||
| Natural variant | 780 | 1 | T → M: dbSNP rs56119119. Ref.12 | VAR_045583 | |||||
| Natural variant | 790 | 1 | Y → C: dbSNP rs34943764. Ref.12 | VAR_045584 | |||||
| Natural variant | 1148 | 1 | A → T | VAR_045585 | |||||
| Natural variant | 1211 | 1 | R → H | VAR_045586 | |||||
| Natural variant | 1317 | 1 | V → I | VAR_045587 | |||||
| Natural variant | 1418 | 1 | I → K | VAR_040833 | |||||
| Natural variant | 1469 | 1 | A → V: dbSNP rs55687355. Ref.12 | VAR_045588 | |||||
| Natural variant | 1618 | 1 | T → A | VAR_045589 | |||||
| Natural variant | 1699 | 1 | A → V: dbSNP rs2802269. | VAR_045590 | |||||
| Natural variant | 1712 | 1 | A → V: dbSNP rs2802269. Ref.2 Ref.3 Ref.6 | VAR_057104 | |||||
Experimental info | |||||||||
| Mutagenesis | 106 | 1 | K → A: Loss of kinase activity. Ref.9 | ||||||
| Mutagenesis | 222 | 1 | S → L: Increase in autophosphorylation but not kinase activity. Ref.9 | ||||||
| Mutagenesis | 234 | 1 | S → A: Loss of autophosphorylation and kinase activity. Ref.9 | ||||||
| Mutagenesis | 240 | 1 | T → A: Loss of autophosphorylation and kinase activity. Ref.9 | ||||||
| Mutagenesis | 403 | 1 | T → A: Loss of autophosphorylation and kinase activity. Ref.9 | ||||||
| Mutagenesis | 1579 | 1 | H → A: Loss of CDC42 binding; when associated with A-1582. Ref.8 | ||||||
| Mutagenesis | 1582 | 1 | H → A: Loss of CDC42 binding; when associated with A-1579. Ref.8 | ||||||
| Sequence conflict | 25 | 1 | C → Y in AAB37126. Ref.5 | ||||||
| Sequence conflict | 809 | 1 | D → N in CAI46252. Ref.3 | ||||||
| Sequence conflict | 1521 | 1 | L → V Ref.8 | ||||||
| Sequence conflict | 1688 | 1 | G → K in BAA32296. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion." Wilkinson S., Paterson H.F., Marshall C.J. Nat. Cell Biol. 7:255-261(2005) [PubMed: 15723050] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5), FUNCTION. Tissue: Colon. |
| [2] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), VARIANT VAL-1712. Tissue: Brain. |
| [3] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ILE-1317 AND VAL-1712. Tissue: Testis. |
| [4] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "Cloning and chromosomal location of a novel member of the myotonic dystrophy family of protein kinases." Zhao Y., Loyer P., Li H., Valentine V., Kidd V., Kraft A.S. J. Biol. Chem. 272:10013-10020(1997) [PubMed: 9092543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-496, FUNCTION, TISSUE SPECIFICITY. Tissue: Mammary gland. |
| [6] | "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain." Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O. DNA Res. 4:345-349(1997) [PubMed: 9455484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 799-1732 (ISOFORM 6), VARIANT VAL-1712. Tissue: Brain. |
| [7] | Ohara O. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION. |
| [8] | "Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization." Leung T., Chen X.-Q., Tan I., Manser E., Lim L. Mol. Cell. Biol. 18:130-140(1998) [PubMed: 9418861] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1521-1644, FUNCTION, INTERACTION WITH CDC42, MUTAGENESIS OF HIS-1579 AND HIS-1582. Tissue: Brain. |
| [9] | "Intermolecular and intramolecular interactions regulate catalytic activity of myotonic dystrophy kinase-related Cdc42-binding kinase alpha." Tan I., Seow K.T., Lim L., Leung T. Mol. Cell. Biol. 21:2767-2778(2001) [PubMed: 11283256] [Abstract] Cited for: ENZYME REGULATION, OLIGOMERIZATION, PHOSPHORYLATION AT SER-222; SER-234 AND THR-240, MUTAGENESIS OF LYS-106; SER-222; SER-234; THR-240 AND THR-403. |
| [10] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1545; SER-1719 AND SER-1721, MASS SPECTROMETRY. |
| [11] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1719, MASS SPECTROMETRY. Tissue: T-cell. |
| [12] | "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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-50; MET-231; THR-537; MET-780; CYS-790; THR-1148; HIS-1211; ILE-1317; LYS-1418; VAL-1469 AND ALA-1618. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AJ518975 mRNA. Translation: CAD57745.1. AJ518976 mRNA. Translation: CAD57746.1. AB208968 mRNA. Translation: BAD92205.1. Different initiation. CR933723 mRNA. Translation: CAI46252.1. AL353689 Genomic DNA. Translation: CAI19113.1. AL451047, AL353689, AL627308 Genomic DNA. Translation: CAH71184.1. AL451047, AL627308, AL353689 Genomic DNA. Translation: CAH71185.1. AL627308, AL353689, AL451047 Genomic DNA. Translation: CAH71336.1. AL627308, AL353689, AL451047 Genomic DNA. Translation: CAH71337.1. AL353689, AL451047, AL627308 Genomic DNA. Translation: CAI19108.1. AL451047, AL353689, AL627308 Genomic DNA. Translation: CAH71183.1. AL627308, AL353689, AL451047 Genomic DNA. Translation: CAH71338.1. AL353689, AL627308, AL451047 Genomic DNA. Translation: CAI19109.1. AL353689, AL451047, AL627308 Genomic DNA. Translation: CAI19110.1. AB007920 mRNA. Translation: BAA32296.2. U59305 mRNA. Translation: AAB37126.1. |
| IPI | IPI00550263. IPI00640468. IPI00640957. IPI00642165. IPI00654830. IPI00903296. |
| RefSeq | NP_003598.2. NP_055641.3. |
| UniGene | Hs.35433 |
3D structure databases | |
| SMR | Q5VT25. Positions 11-409, 879-940, 1009-1078, 1085-1205. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q5VT25. 6 interactions. |
| STRING | Q5VT25. |
PTM databases | |
| PhosphoSite | Q5VT25. |
Proteomic databases | |
| PRIDE | Q5VT25. |
Genome annotation databases | |
| Ensembl | ENST00000366765; ENSP00000355727; ENSG00000143776; Homo sapiens. [Genome view] |
| GeneID | 8476. |
| KEGG | hsa:8476. |
| UCSC | uc001hqr.1. human. uc001hqs.1. human. uc009xes.1. human. |
Organism-specific databases | |
| CTD | 8476. |
| GeneCards | GC01M225244. |
| HGNC | HGNC:1737. CDC42BPA. |
| MIM | 603412. gene. |
| PharmGKB | PA26267. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG04641. |
| HOVERGEN | Q5VT25. |
| OMA | HVRLFPM. |
| PhylomeDB | Q5VT25. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 247. |
Gene expression databases | |
| ArrayExpress | Q5VT25. |
| Bgee | Q5VT25. |
| Genevestigator | Q5VT25. |
| GermOnline | ENSG00000143776. 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. 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. 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] |
| 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 | 31715. |
| SOURCE | Search... |
Entry information
| Entry name | MRCKA_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q5VT25 Secondary accession number(s): O75039 Q99646 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


