Reviewed,
UniProtKB/Swiss-Prot P97924 (KALRN_RAT)
Last modified
July 22, 2008.
Version 83.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Kalirin EC=2.7.11.1 Alternative name(s): Huntingtin-associated protein-interacting protein Protein Duo Serine/threonine kinase with Dbl- and pleckstrin homology domain PAM COOH-terminal interactor protein 10 Short name=P-CIP10 | ||||
| Gene names |
| ||||
| Organism | Rattus norvegicus (Rat) | ||||
| Taxonomic identifier | 10116 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 2959 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. Isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth. Isoform 6 is required for dendritic spine formation. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium By similarity. |
| Subunit structure | Interacts with the C-terminal of peptidylglycine alpha-amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1). |
| Subcellular location | Cytoplasm. Cytoplasm › cytoskeleton. Note= Isoform 6 is largely associated with synaptosomal membranes and to punctate structures in cortical neurons. Isoforms 1 and 7 are expressed in neuronal cell bodies, isoform 7 is also found in neuronal processes. |
| Tissue specificity | Highly expressed in the brain and nervous system. Isoform 6 is highly enriched in the postsynaptic density fraction of the cerebral cortex. |
| Developmental stage | Isoforms 1 and 7 are prevelant 2 dpp, isoform 6 is not detectable until 2 weeks after birth. |
| Domain | The two GEF domains catalyze nucleotide exchange for RAC1 and RhoA which are bound by DH1 and DH2 respectively. The two GEF domains appear to play differing roles in neuronal development and axonal outgrowth. SH3 1 binds to the first GEF domain inhibiting GEF activity only when in the presence of a PXXP peptide, suggesting that the SH3 domain/peptide interaction mediates binding to GEF1. CRK1 SH3 domain binds to and inhibits GEF1 activity. |
| Post-translational modification | Autophosphorylated By similarity. |
| Miscellaneous | Called DUO because the encoded protein is closely related to but shorter than TRIO. |
| Sequence similarities | Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 CRAL-TRIO domain. Contains 2 DH (DBL-homology) domains. Contains 1 fibronectin type-III domain. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 2 PH domains. Contains 1 protein kinase domain. Contains 2 SH3 domains. Contains 5 spectrin repeats. |
Ontologies
Keywords | |
|---|---|
| Cellular component | Cytoplasm Cytoskeleton |
| Coding sequence diversity | Alternative initiation Alternative splicing |
| Domain | Immunoglobulin domain Repeat SH3 domain |
| Ligand | ATP-binding Magnesium Metal-binding Nucleotide-binding |
| Molecular function | Guanine-nucleotide releasing factor Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | intracellular signaling cascade Inferred from direct assay. Source: HGNC nervous system developmentInferred from direct assay. Source: HGNC |
| Molecular function | guanyl-nucleotide exchange factor activity Traceable author statement. Source: HGNC protein binding Ref.1Inferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Pam | P97467 | 1 | EBI-1397166,EBI-1397216 | From a different organism. |
Alternative products
| This entry describes 8 isoforms produced by alternative splicing and alternative initiation. [Align] [Select] | |||||
| Isoform 1 (identifier: P97924-1) Also known as: Kalirin-12A; 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: Produced by alternative splicing. | |||||
| Isoform 2 (identifier: P97924-2) Also known as: Kalirin-8B; P-CIP10B; The sequence of this isoform differs from the canonical sequence as follows: 1-4: MVLS → MNPPEGASEEGGAADSDVDAFFRT 1860-1899: TLEGGSYRGS...LEEEQKAKAL → VSGHAGGSRV...HPDFVYSNCI 1900-2959: Missing. | |||||
| Notes: Produced by alternative splicing. | |||||
| Isoform 3 (identifier: P97924-3) Also known as: Kalirin-8A; P-CIP10A; The sequence of this isoform differs from the canonical sequence as follows: 1860-1899: TLEGGSYRGS...LEEEQKAKAL → VSGHAGGSRV...HPDFVYSNCI 1900-2959: Missing. | |||||
| Notes: Produced by alternative splicing. | |||||
| Isoform 4 (identifier: P97924-4) The sequence of this isoform differs from the canonical sequence as follows: 923-923: E → ESLFHATSLQ | |||||
| Notes: Produced by alternative splicing. | |||||
| Isoform 5 (identifier: P97924-5) Also known as: Delta Kalirin-7; The sequence of this isoform differs from the canonical sequence as follows: 1-623: Missing. 1617-1636: LSGGCELTVVLQDFSAAHSS → DGNLVPRWHLGPGDPFSTYV 1637-2959: Missing. | |||||
| Notes: Produced by alternative initiation at Met-624 of isoform 6. | |||||
| Isoform 6 (identifier: P97924-6) Also known as: Kalirin-7; HAPIP; The sequence of this isoform differs from the canonical sequence as follows: 1-4: MVLS → MTDRFWDQWYLWYLRLLRLLDR 1617-1636: LSGGCELTVVLQDFSAAHSS → DGNLVPRWHLGPGDPFSTYV 1637-2959: Missing. | |||||
| Notes: Produced by alternative splicing. | |||||
| Isoform 7 (identifier: P97924-7) Also known as: Kalirin-9A; The sequence of this isoform differs from the canonical sequence as follows: 2372-2376: KSCSW → TLLKP 2377-2959: Missing. | |||||
| Notes: Produced by alternative splicing. | |||||
| Isoform 8 (identifier: P97924-8) The sequence of this isoform differs from the canonical sequence as follows: 705-718: DSAVSNNKTPHSSS → SAWAVIPVGNASG 719-2959: Missing. | |||||
| Notes: Produced by alternative splicing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | |||||||||||||
Molecule processing | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2959 | 2959 | Kalirin | ||||||||||||||
Regions | |||||||||||||||||
| Domain | 17 – 162 | 146 | CRAL-TRIO | ||||||||||||||
| Repeat | 170 – 290 | 121 | Spectrin 1 | ||||||||||||||
| Repeat | 292 – 398 | 107 | Spectrin 2 | ||||||||||||||
| Repeat | 518 – 624 | 107 | Spectrin 3 | ||||||||||||||
| Repeat | 872 – 977 | 106 | Spectrin 4 | ||||||||||||||
| Repeat | 1103 – 1209 | 107 | Spectrin 5 | ||||||||||||||
| Domain | 1254 – 1429 | 176 | DH 1 | ||||||||||||||
| Domain | 1441 – 1553 | 113 | PH 1 | ||||||||||||||
| Domain | 1619 – 1684 | 66 | SH3 1 | ||||||||||||||
| Domain | 1901 – 2076 | 176 | DH 2 | ||||||||||||||
| Domain | 2088 – 2198 | 111 | PH 2 | ||||||||||||||
| Domain | 2293 – 2358 | 66 | SH3 2 | ||||||||||||||
| Domain | 2444 – 2537 | 94 | Ig-like C2-type | ||||||||||||||
| Domain | 2542 – 2633 | 92 | Fibronectin type-III | ||||||||||||||
| Domain | 2657 – 2911 | 255 | Protein kinase | ||||||||||||||
| Nucleotide binding | 2663 – 2671 | 9 | ATP By similarity | ||||||||||||||
| Compositional bias | 664 – 669 | 6 | Poly-Gln | ||||||||||||||
Sites | |||||||||||||||||
| Active site | 2776 | 1 | Proton acceptor By similarity | ||||||||||||||
| Binding site | 2686 | 1 | ATP By similarity | ||||||||||||||
Amino acid modifications | |||||||||||||||||
| Modified residue | 1723 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 1726 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 1729 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 1746 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 1772 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 1790 | 1 | Phosphoserine By similarity | ||||||||||||||
| Modified residue | 2234 | 1 | Phosphoserine By similarity | ||||||||||||||
| Disulfide bond | 2465 ↔ 2521 | By similarity | |||||||||||||||
Natural variations | |||||||||||||||||
| Alternative sequence | 1 – 623 | 623 | Missing in isoform 5. | ||||||||||||||
| Alternative sequence | 1 – 4 | 4 | MVLS → MNPPEGASEEGGAADSDVDA FFRT in isoform 2. | ||||||||||||||
| Alternative sequence | 1 – 4 | 4 | MVLS → MTDRFWDQWYLWYLRLLRLL DR in isoform 6. | ||||||||||||||
| Alternative sequence | 705 – 718 | 14 | DSAVS…PHSSS → SAWAVIPVGNASG in isoform 8. | ||||||||||||||
| Alternative sequence | 719 – 2959 | 2241 | Missing in isoform 8. | ||||||||||||||
| Alternative sequence | 923 | 1 | E → ESLFHATSLQ in isoform 4. | ||||||||||||||
| Alternative sequence | 1617 – 1636 | 20 | LSGGC…AAHSS → DGNLVPRWHLGPGDPFSTYV in isoform 5 and isoform 6. | ||||||||||||||
| Alternative sequence | 1637 – 2959 | 1323 | Missing in isoform 5 and isoform 6. | ||||||||||||||
| Alternative sequence | 1860 – 1899 | 40 | TLEGG…KAKAL → VSGHAGGSRVLPLTSMWLPG PQLGPQISYLHPDFVYSNCI in isoform 2 and isoform 3. | ||||||||||||||
| Alternative sequence | 1900 – 2959 | 1060 | Missing in isoform 2 and isoform 3. | ||||||||||||||
| Alternative sequence | 2372 – 2376 | 5 | KSCSW → TLLKP in isoform 7. | ||||||||||||||
| Alternative sequence | 2377 – 2959 | 583 | Missing in isoform 7. | ||||||||||||||
Experimental info | |||||||||||||||||
| Sequence conflict | 46 | 1 | T → S in AAT39517. Ref.5 | ||||||||||||||
| Sequence conflict | 62 | 1 | N → Y in AAT39517. Ref.5 | ||||||||||||||
Secondary structure | |||||||||||||||||
Helix Strand Turn | |||||||||||||||||
| Beta strand | 1642 – 1645 | 4 | |||||||||||||||
| Beta strand | 1665 – 1670 | 6 | |||||||||||||||
| Beta strand | 1678 – 1688 | 11 | |||||||||||||||
| Beta strand | 1690 – 1695 | 6 | |||||||||||||||
| Helix | 1696 – 1698 | 3 | |||||||||||||||
Sequences
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Clusters with