[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
TISSUE=Hippocampus;
DOI=10.1074/jbc.271.45.28636; PubMed=8910496 [NCBI, ExPASy, EBI, Israel, Japan]
Alam M.R.,
Caldwell B.D.,
Johnson R.C.,
Darlington D.N.,
Mains R.E.,
Eipper B.A.;
"Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme.";
J. Biol. Chem. 271:28636-28640(1996).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND INTERACTION WITH PAM.
TISSUE=Hippocampus;
DOI=10.1074/jbc.272.19.12667; PubMed=9139723 [NCBI, ExPASy, EBI, Israel, Japan]
Alam M.R.,
Johnson R.C.,
Darlington D.N.,
Hand T.A.,
Mains R.E.,
Eipper B.A.;
"Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange factor-like domains that interacts with peptidylglycine alpha-amidating monooxygenase, an integral membrane peptide-processing enzyme.";
J. Biol. Chem. 272:12667-12675(1997).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.275.9.6395; PubMed=10692441 [NCBI, ExPASy, EBI, Israel, Japan]
Penzes P.,
Johnson R.C.,
Alam M.R.,
Kambampati V.,
Mains R.E.,
Eipper B.A.;
"An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction.";
J. Biol. Chem. 275:6395-6403(2000).
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[4]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 5 AND 7), ALTERNATIVE INITIATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.M000676200; PubMed=10777487 [NCBI, ExPASy, EBI, Israel, Japan]
Johnson R.C.,
Penzes P.,
Eipper B.A.,
Mains R.E.;
"Isoforms of kalirin, a neuronal Dbl family member, generated through use of different 5'- and 3'-ends along with an internal translational initiation site.";
J. Biol. Chem. 275:19324-19333(2000).
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[5]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), AND FUNCTION.
DOI=10.1016/j.yexcr.2005.03.024; PubMed=15950621 [NCBI, ExPASy, EBI, Israel, Japan]
Schiller M.R.,
Blangy A.,
Huang J.,
Mains R.E.,
Eipper B.A.;
"Induction of lamellipodia by Kalirin does not require its guanine nucleotide exchange factor activity.";
Exp. Cell Res. 307:402-417(2005).
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[6]
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NUCLEOTIDE SEQUENCE [MRNA] OF 638-1216 (ISOFORM 4).
TISSUE=Brain cortex, and Hippocampus;
DOI=10.1093/hmg/6.9.1519; PubMed=9285789 [NCBI, ExPASy, EBI, Israel, Japan]
Colomer V.,
Engelender S.,
Sharp A.H.,
Duan K.,
Cooper J.K.,
Lanahan A.,
Lyford G.,
Worley P.,
Ross C.A.;
"Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain.";
Hum. Mol. Genet. 6:1519-1525(1997).
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[7]
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FUNCTION, DOMAIN, AND DEVELOPMENTAL STAGE.
PubMed=11606631 [NCBI, ExPASy, EBI, Israel, Japan]
Penzes P.,
Johnson R.C.,
Kambampati V.,
Mains R.E.,
Eipper B.A.;
"Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin in regulation of neurite growth and neuronal morphology.";
J. Neurosci. 21:8426-8434(2001).
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[8]
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STRUCTURE BY NMR OF 1617-1707, DOMAIN, AND INTERACTION WITH CRK1.
DOI=10.1074/jbc.M512482200; PubMed=16644733 [NCBI, ExPASy, EBI, Israel, Japan]
Schiller M.R.,
Chakrabarti K.,
King G.F.,
Schiller N.I.,
Eipper B.A.,
Maciejewski M.W.;
"Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions.";
J. Biol. Chem. 281:18774-18786(2006).
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- 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: Interacts with the C-terminal of peptidylglycine alpha-amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1).
- INTERACTION:
P97467:Pam (xeno); NbExp=1; IntAct=EBI-1397166, EBI-1397216;
- 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.
- ALTERNATIVE PRODUCTS:
8 named isoforms [FASTA] produced by alternative splicing and alternative initiation.
| Name | 1 |
| Synonyms | Kalirin-12A |
| Isoform ID | P97924-1 |
| Note: Produced by alternative splicing. |
| This is the isoform sequence displayed in this entry. |
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| Name | 2 |
| Synonyms | Kalirin-8B, P-CIP10B |
| Isoform ID | P97924-2 |
| Note: Produced by alternative splicing. |
| Features which should be applied to build the isoform sequence: VSP_028891, VSP_028899, VSP_028900. |
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| Name | 3 |
| Synonyms | Kalirin-8A, P-CIP10A |
| Isoform ID | P97924-3 |
| Note: Produced by alternative splicing. |
| Features which should be applied to build the isoform sequence: VSP_028899, VSP_028900. |
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| Name | 4 |
| Isoform ID | P97924-4 |
| Note: Produced by alternative splicing. |
| Features which should be applied to build the isoform sequence: VSP_028896. |
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| Name | 5 |
| Synonyms | Delta Kalirin-7 |
| Isoform ID | P97924-5 |
| Note: Produced by alternative initiation at Met-624 of isoform 6. |
| Features which should be applied to build the isoform sequence: VSP_028893, VSP_028897, VSP_028898. |
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| Name | 7 |
| Synonyms | Kalirin-9A |
| Isoform ID | P97924-7 |
| Note: Produced by alternative splicing. |
| Features which should be applied to build the isoform sequence: VSP_028901, VSP_028902. |
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| Name | 8 |
| Isoform ID | P97924-8 |
| Note: Produced by alternative splicing. |
| Features which should be applied to build the isoform sequence: VSP_028894, VSP_028895. |
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- 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.
- PTM: Autophosphorylated (By similarity).
- MISCELLANEOUS: Called DUO because the encoded protein is closely related to but shorter than TRIO.
- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
- SIMILARITY: Contains 1 CRAL-TRIO domain.
- SIMILARITY: Contains 2 DH (DBL-homology) domains.
- SIMILARITY: Contains 1 fibronectin type-III domain.
- SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like) domain.
- SIMILARITY: Contains 2 PH domains.
- SIMILARITY: Contains 1 protein kinase domain.
- SIMILARITY: Contains 2 SH3 domains.
- SIMILARITY: Contains 5 spectrin repeats.
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