Reviewed,
UniProtKB/Swiss-Prot Q5VT25 (MRCKA_HUMAN)
Last modified
September 2, 2008.
Version 43.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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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 Short name=CDC42-binding protein kinase alpha DMPK-like alpha | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| 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. |
| Sequence processing | The displayed sequence is not processed. |
| 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. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. |
| 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. |
| Subunit structure | Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. |
| Subcellular location | CytoplasmBy 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. |
| 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. | |||||
| Notes: 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 | |||||
| Notes: No experimental confirmation available. | |||||
| Isoform 3 (identifier: Q5VT25-3) The sequence of this isoform differs from the canonical sequence as follows: 550-630: Missing. 969-981: Missing. | |||||
| Isoform 4 (identifier: Q5VT25-4) The sequence of this isoform differs from the canonical sequence as follows: 969-1009: Missing. | |||||
| Notes: No experimental confirmation available. | |||||
| Isoform 5 (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 | ||||
Molecule processing | ||||||||
|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1732 | 1732 | Serine/threonine-protein kinase MRCK alpha | |||||
Regions | ||||||||
| Domain | 77 – 343 | 267 | Protein kinase | |||||
| Domain | 344 – 414 | 71 | AGC-kinase C-terminal | |||||
| Domain | 1082 – 1201 | 120 | PH | |||||
| Domain | 1228 – 1499 | 272 | CNH | |||||
| Domain | 1571 – 1584 | 14 | CRIB | |||||
| Nucleotide binding | 83 – 91 | 9 | ATP By similarity | |||||
| 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 | |||||
| Binding site | 106 | 1 | ATP | |||||
Amino acid modifications | ||||||||
| Modified residue | 222 | 1 | Phosphoserine; by autocatalysis | |||||
| Modified residue | 234 | 1 | Phosphoserine; by autocatalysis | |||||
| Modified residue | 240 | 1 | Phosphothreonine; by autocatalysis | |||||
Natural variations | ||||||||
| Alternative sequence | 550 – 630 | 81 | Missing in isoform 3. | |||||
| Alternative sequence | 969 – 1009 | 41 | Missing in isoform 4. | |||||
| Alternative sequence | 969 – 981 | 13 | Missing in isoform 3, isoform 5 and isoform 6. | |||||
| Alternative sequence | 969 | 1 | R → TDPVENTYVWNPSVKFHIQS RST in isoform 2. | |||||
| Alternative sequence | 973 – 981 | 9 | CTPASKGRR → TSSEAEPVK in isoform 2. | |||||
| Alternative sequence | 1597 | 1 | M → MPGFPYPSPHHHSGLISSPI NFEHIYHMTVNSAEKFLSPD SINPEYSPSLRSVPGTPSFM TLR in isoform 6. | |||||
| Natural variant | 50 | 1 | E → K in a lung neuroendocrine carcinoma sample; somatic mutation. | |||||
| Natural variant | 231 | 1 | T → M | |||||
| Natural variant | 537 | 1 | I → T | |||||
| Natural variant | 780 | 1 | T → M: dbSNP rs56119119. | |||||
| Natural variant | 790 | 1 | Y → C: dbSNP rs34943764. | |||||
| Natural variant | 1148 | 1 | A → T | |||||
| Natural variant | 1211 | 1 | R → H | |||||
| Natural variant | 1317 | 1 | V → I | |||||
| Natural variant | 1418 | 1 | I → K | |||||
| Natural variant | 1469 | 1 | A → V: dbSNP rs55687355. | |||||
| Natural variant | 1618 | 1 | T → A | |||||
| Natural variant | 1699 | 1 | A → V: dbSNP rs2802269. | |||||
Experimental info | ||||||||
| Mutagenesis | 106 | 1 | K → A: Loss of kinase activity | |||||
| Mutagenesis | 222 | 1 | S → L: Increase in autophosphorylation but not kinase activity | |||||
| Mutagenesis | 234 | 1 | S → A: Loss of autophosphorylation and kinase activity | |||||
| Mutagenesis | 240 | 1 | T → A: Loss of autophosphorylation and kinase activity | |||||
| Mutagenesis | 403 | 1 | T → A: Loss of autophosphorylation and kinase activity | |||||
| Mutagenesis | 1579 | 1 | H → A: Loss of CDC42 binding; when associated with A-1582 | |||||
| Mutagenesis | 1582 | 1 | H → A: Loss of CDC42 binding; when associated with A-1579 | |||||
| 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 | |||||
| Sequence conflict | 1712 | 1 | A → V in CAD57745 and CAD57746. Ref.1 | |||||
| Sequence conflict | 1712 | 1 | A → V in BAD92205. Ref.2 | |||||
| Sequence conflict | 1712 | 1 | A → V in CAI46252. Ref.3 | |||||
| Sequence conflict | 1712 | 1 | A → V in BAA32296. Ref.6 | |||||
Sequences
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Clusters with