P49025 (CTRO_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified
November 16, 2011.
Version 111.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Citron Rho-interacting kinase Short name=CRIK EC=2.7.11.1 Alternative name(s): Rho-interacting, serine/threonine-protein kinase 21 | ||||
| Gene names |
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| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus |
Protein attributes
| Sequence length | 2055 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Probable RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2 By similarity. Ref.1 Ref.2 Ref.5 Ref.7 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. Ref.2 |
| Subunit structure | Interacts with TTC3 By similarity. Homodimer Probable. Directly interacts with KIF14 depending on the activation state (stronger interaction with the kinase-dead form). |
| Subcellular location | |
| Tissue specificity | A major signal was observed in testis and brain, but it was also detected in thymus, spleen, kidney, heart and lung. Ref.2 Ref.7 |
| Developmental stage | Detected at E10.5 with highest expression in the developing central nervous system. After E16.5 expression decreases and at two weeks after birth is restricted to the proliferating neuronal precursor cells in the external germinal layer of the cerebellum and subventricular migratory stream. Ref.7 |
| Disruption phenotype | Death before reaching adulthood, probably due to lethal epilepsy. Mice display severe defects in the olfactory bulbs, the hippocampus, and the cerebellum. These defects appear to result from impaired cytokinesis followed by the induction of apoptosis in specific neuroblast populations. Ref.7 |
| Sequence similarities | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. Contains 1 AGC-kinase C-terminal domain. Contains 1 CNH domain. Contains 1 PH domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. |
| Sequence caution | The sequence AAC72822.1 differs from that shown. Reason: Frameshift at positions 396 and 408. The sequence AAC72823.1 differs from that shown. Reason: Frameshift at positions 396 and 408. The sequence AAH23775.1 differs from that shown. Reason: Frameshift at position 1011. The sequence AAH51165.1 differs from that shown. Reason: Frameshift at position 1011. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist. | ||||||
| Isoform 1 (identifier: P49025-1) Also known as: CRIK; 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. | ||||||
| Isoform 2 (identifier: P49025-2) Also known as: CRIK-SK; The sequence of this isoform differs from the canonical sequence as follows: 467-494: MEQEMTRLHRRVSEVEAVLSQKEVELKA → VSISTAGLRPCSRILQSIYAEGSAGGHC 495-2055: Missing. | ||||||
| Isoform 3 (identifier: P49025-3) Also known as: Citron; The sequence of this isoform differs from the canonical sequence as follows: 1-458: Missing. 459-466: DSQDKCHK → MLLGEEAM | ||||||
| Isoform 4 (identifier: P49025-4) The sequence of this isoform differs from the canonical sequence as follows: 693-735: Missing. | ||||||
| Isoform 5 (identifier: P49025-5) The sequence of this isoform differs from the canonical sequence as follows: 1279-1279: K → KGLFSRRKEDPALPTQ 1602-1602: A → AARDHTSSEHQPVWVE | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2055 | 2055 | Citron Rho-interacting kinase | PRO_0000085909 | |||||
Regions | |||||||||
| Domain | 97 – 359 | 263 | Protein kinase | ||||||
| Domain | 360 – 430 | 71 | AGC-kinase C-terminal | ||||||
| Domain | 1469 – 1589 | 121 | PH | ||||||
| Domain | 1617 – 1907 | 291 | CNH | ||||||
| Nucleotide binding | 103 – 111 | 9 | ATP By similarity | ||||||
| Zinc finger | 1388 – 1437 | 50 | Phorbol-ester/DAG-type | ||||||
| Region | 1132 – 1328 | 197 | Interaction with Rho/Rac | ||||||
| Coiled coil | 441 – 1086 | 646 | Potential | ||||||
| Coiled coil | 1091 – 1247 | 157 | Potential | ||||||
| Coiled coil | 1275 – 1325 | 51 | Potential | ||||||
| Motif | 1979 – 1984 | 6 | SH3-binding Potential | ||||||
| Compositional bias | 550 – 962 | 413 | Glu-rich | ||||||
| Compositional bias | 1276 – 1279 | 4 | Poly-Lys | ||||||
Sites | |||||||||
| Active site | 221 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 126 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 432 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 439 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 479 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 1237 | 1 | Phosphotyrosine Ref.9 | ||||||
| Modified residue | 1504 | 1 | Phosphotyrosine Ref.9 | ||||||
| Modified residue | 1608 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 1747 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 1999 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 2021 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 458 | 458 | Missing in isoform 3. | VSP_012436 | |||||
| Alternative sequence | 459 – 466 | 8 | DSQDKCHK → MLLGEEAM in isoform 3. | VSP_012437 | |||||
| Alternative sequence | 467 – 494 | 28 | MEQEM…VELKA → VSISTAGLRPCSRILQSIYA EGSAGGHC in isoform 2. | VSP_012438 | |||||
| Alternative sequence | 495 – 2055 | 1561 | Missing in isoform 2. | VSP_012439 | |||||
| Alternative sequence | 693 – 735 | 43 | Missing in isoform 4. | VSP_016093 | |||||
| Alternative sequence | 1279 | 1 | K → KGLFSRRKEDPALPTQ in isoform 5. | VSP_016094 | |||||
| Alternative sequence | 1602 | 1 | A → AARDHTSSEHQPVWVE in isoform 5. | VSP_016095 | |||||
Experimental info | |||||||||
| Mutagenesis | 126 | 1 | K → A: Loss of phosphorylation. Ref.2 | ||||||
| Sequence conflict | 78 | 1 | Q → R in BAE26199. Ref.3 | ||||||
| Sequence conflict | 182 | 1 | F → L in BAE26199. Ref.3 | ||||||
| Sequence conflict | 234 | 1 | E → H in BAE26199. Ref.3 | ||||||
| Sequence conflict | 1945 | 1 | Missing in AAH51165. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A novel partner for the GTP-bound forms of rho and rac." Madaule P., Furuyashiki T., Reid T., Ishizaki T., Watanabe G., Morii N., Narumiya S. FEBS Lett. 377:243-248(1995) [PubMed: 8543060] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION. Tissue: Brain. |
| [2] | "Citron Rho-interacting kinase, a novel tissue-specific Ser/Thr kinase encompassing the Rho-Rac-binding protein Citron." Di Cunto F., Calautti E., Hsiao J., Ong L., Topley G., Turco E., Dotto G.P. J. Biol. Chem. 273:29706-29711(1998) [PubMed: 9792683] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-126. Tissue: Keratinocyte. |
| [3] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Mammary gland. |
| [4] | Lubec G., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 246-254, MASS SPECTROMETRY. Strain: OF1. Tissue: Hippocampus. |
| [5] | "Role of citron kinase as a target of the small GTPase Rho in cytokinesis." Madaule P., Eda M., Watanabe N., Fujisawa K., Matsuoka T., Bito H., Ishizaki T., Narumiya S. Nature 394:491-494(1998) [PubMed: 9697773] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 373-2055 (ISOFORM 4), FUNCTION. Tissue: Brain. |
| [6] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 992-2055 (ISOFORM 5). Strain: FVB/N. Tissue: Mammary tumor. |
| [7] | "Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis." Di Cunto F., Imarisio S., Hirsch E., Broccoli V., Bulfone A., Migheli A., Atzori C., Turco E., Triolo R., Dotto G.P., Silengo L., Altruda F. Neuron 28:115-127(2000) [PubMed: 11086988] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE. |
| [8] | "Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed: 16452087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-479, MASS SPECTROMETRY. Tissue: Brain. |
| [9] | "Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1237 AND TYR-1504, MASS SPECTROMETRY. Tissue: Brain. |
| [10] | "Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1608, MASS SPECTROMETRY. Tissue: Brain cortex. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U39904 mRNA. Translation: AAC52341.1. AF086823 mRNA. Translation: AAC72822.1. Frameshift. AF086824 mRNA. Translation: AAC72823.1. Frameshift. AK145037 mRNA. Translation: BAE26199.1. AF070066 mRNA. Translation: AAC27933.1. BC023775 mRNA. Translation: AAH23775.1. Frameshift. BC051165 mRNA. Translation: AAH51165.1. Frameshift. |
| IPI | IPI00406762. IPI00474730. IPI00655040. IPI00655108. IPI00956788. |
| PIR | S68420. |
| UniGene | Mm.426282. Mm.8321. |
3D structure databases | |
| ProteinModelPortal | P49025. |
| SMR | P49025. Positions 44-423, 1389-1437, 1471-1587. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P49025. 5 interactions. |
| STRING | P49025. |
PTM databases | |
| PhosphoSite | P49025. |
Proteomic databases | |
| PRIDE | P49025. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| UCSC | uc008zep.1. mouse. uc008zet.1. mouse. |
Organism-specific databases | |
| MGI | MGI:105313. Cit. |
Phylogenomic databases | |
| eggNOG | roNOG11544. |
| GeneTree | ENSGT00600000084128. |
| HOVERGEN | HBG071093. |
| OrthoDB | EOG402WR8. |
| PhylomeDB | P49025. |
Gene expression databases | |
| ArrayExpress | P49025. |
| Bgee | P49025. |
| CleanEx | MM_CIT. |
| Genevestigator | P49025. |
| GermOnline | ENSMUSG00000029516. Mus musculus. |
Family and domain databases | |
| InterPro | IPR000961. AGC-kinase_C. IPR001180. Citron. IPR017405. Citron_Rho-interacting_kinase. IPR011009. Kinase-like_dom. IPR011993. PH_type. 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_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view] |
| Gene3D | G3DSA:2.30.29.30. PH_type. 1 hit. |
| Pfam | PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view] |
| PIRSF | PIRSF038145. Citron_Rho-interacting_kinase. 1 hit. |
| SMART | SM00109. C1. 1 hit. SM00036. CNH. 1 hit. SM00233. PH. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS51285. AGC_KINASE_CTER. 1 hit. PS50219. CNH. 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 | |
| SOURCE | Search... |
Entry information
| Entry name | CTRO_MOUSE | ||||||||
| Accession | Primary (citable) accession number: P49025 Secondary accession number(s): O88528 Q8CIJ1 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with