Kalirin

KALRN
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1WFW
Identifiers
Aliases	KALRN, ARHGEF24, CHD5, CHDS5, DUET, DUO, HAPIP, TRAD, kalirin, RhoGEF kinase, kalirin RhoGEF kinase
External IDs	OMIM: 604605 MGI: 2685385 HomoloGene: 57160 GeneCards: KALRN
Gene location (Human)
Chr.	Chromosome 3 (human)[1]
End	124,726,325 bp[1]
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)[2]
End	34,573,532 bp[2]
Gene ontology
Molecular function	• transferase activity; • nucleotide binding; • protein kinase activity; • guanyl-nucleotide exchange factor activity; • metal ion binding; • kinase activity; • protein serine/threonine kinase activity; • GO:0001948 protein binding; • ATP binding; • Rho guanyl-nucleotide exchange factor activity; • GTPase activator activity; • Rac guanyl-nucleotide exchange factor activity;
Cellular component	• cytoplasm; • actin cytoskeleton; • extracellular exosome; • cytoskeleton; • nucleoplasm; • cytosol; • postsynaptic density;
Biological process	• intracellular signal transduction; • phosphorylation; • ephrin receptor signaling pathway; • nervous system development; • protein phosphorylation; • positive regulation of apoptotic process; • regulation of Rho protein signal transduction; • regulation of small GTPase mediated signal transduction; • vesicle-mediated transport; • signal transduction; • positive regulation of dendritic spine morphogenesis; • behavioral response to cocaine; • behavioral fear response; • social organism behavior; • regulation of protein localization to plasma membrane; • positive regulation of GTPase activity; • regulation of synaptic transmission, glutamatergic; • memory; • positive regulation of dendritic spine development; • Rho protein signal transduction; • neuromuscular junction development; • lactation; • adult locomotory behavior; • response to mechanical stimulus; • smooth muscle cell migration; • maternal behavior; • habituation; • regulation of neuronal synaptic plasticity; • smooth muscle cell proliferation; • negative regulation of growth hormone secretion; • maternal process involved in parturition; • behavioral response to formalin induced pain; • positive regulation of long-term synaptic potentiation; • G-protein coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	8997
	545156
	ENSG00000160145
	ENSMUSG00000061751
	O60229
	A2CG49
NM_001024660; NM_003947; NM_007064; NM_001322988; NM_001322989;
	NM_001322990; NM_001322991; NM_001322992; NM_001322993; NM_001322994; NM_001322995; NM_001322996; NM_001322997; NM_001322998; NM_001322999; NM_001323000; NM_001323001
	NM_001164268; NM_177357
NP_001019831; NP_001309917; NP_001309918; NP_001309919; NP_001309920;
	NP_001309921; NP_001309922; NP_001309923; NP_001309924; NP_001309925; NP_001309926; NP_001309927; NP_001309928; NP_001309929; NP_001309930; NP_003938; NP_008995
	NP_001157740; NP_796331
	Wikidata
View/Edit Human	View/Edit Mouse

Kalirin, also known as Huntingtin-associated protein-interacting protein (HAPIP), protein duo (DUO), or serine/threonine-protein kinase with Dbl- and pleckstrin homology domain, is a protein that in humans is encoded by the KALRN gene.[5][6] Kalirin was first identified in 1997 as a protein interacting with huntingtin-associated protein 1.[5] Is also known to play an important role in nerve growth and axonal development.[7]

Kalirin is a member of the Dbl family of proteins and is a Rho guanine nucleotide exchange factor.

It is named after the multiple-handed Hindu goddess Kali for its ability to interact with numerous other proteins. Kalirin's other name, DUO, comes from the fact that it is 98% identical to rat DUO protein and 80.6% identical to a human protein named TRIO. Unlike TRIO, which is expressed in numerous tissues, Kalirin isoforms are mainly found in the brain.

Clinical significance

Several isoforms of Kalirin are produced through alternative splicing.[8] One of the isoforms, Kalirin-7, was found to be necessary for the remodeling of synapses in mature cortical neurons and is thought to be important in the development of schizophrenia,[9][10][11][12] as demonstrated by adolescent development of schizophrenia-like symptoms in kalirin knockout mice.[13] Alzheimer's disease may also be linked to kalirin-7.[12][14][15]

References

GRCh38: Ensembl release 89: ENSG00000160145 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000061751 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Colomer V, Engelender S, Sharp AH, Duan K, Cooper JK, Lanahan A, Lyford G, Worley P, Ross CA (September 1997). "Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain". Hum. Mol. Genet. 6 (9): 1519–25. doi:10.1093/hmg/6.9.1519. PMID 9285789.
Kawai T, Sanjo H, Akira S (February 1999). "Duet is a novel serine/threonine kinase with Dbl-Homology (DH) and Pleckstrin-Homology (PH) domains". Gene. 227 (2): 249–55. doi:10.1016/S0378-1119(98)00605-2. PMID 10023074.
Chakrabarti K, Lin R, Schiller NI, Wang Y, Koubi D, Fan YX, Rudkin BB, Johnson GR, Schiller MR (June 2005). "Critical role for Kalirin in nerve growth factor signaling through TrkA". Mol. Cell. Biol. 25 (12): 5106–18. doi:10.1128/MCB.25.12.5106-5118.2005. PMC 1140581. PMID 15923627.
McPherson CE, Eipper BA, Mains RE (February 2002). "Genomic organization and differential expression of Kalirin isoforms". Gene. 284 (1–2): 41–51. doi:10.1016/S0378-1119(02)00386-4. PMID 11891045.
Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM, Shum CY, Surmeier DJ, Penzes P (2007). "Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines". Neuron. 56 (4): 640–56. doi:10.1016/j.neuron.2007.10.005. PMC 2118058. PMID 18031682.
Ma XM, Kiraly DD, Gaier ED, Wang Y, Kim EJ, Levine ES, Eipper BA, Mains RE (November 2008). "Kalirin-7 is required for synaptic structure and function". Journal of Neuroscience. 28 (47): 12368–82. doi:10.1523/JNEUROSCI.4269-08.2008. PMC 2586970. PMID 19020030.
Sommer JE, Budreck EC (April 2009). "Kalirin-7: linking spine plasticity and behavior". Journal of Neuroscience. 29 (17): 5367–9. doi:10.1523/JNEUROSCI.0235-09.2009. PMC 2684031. PMID 19403804.
Penzes P, Jones KA (August 2008). "Dendritic spine dynamics--a key role for kalirin-7". Trends in Neurosciences. 31 (8): 419–427. doi:10.1016/j.tins.2008.06.001. PMC 3973420. PMID 18597863.
Cahill ME, Xie Z, Day M, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ, Penzes P (July 2009). "Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes". Proceedings of the National Academy of Sciences of the United States of America. 106 (31): 13058–63. doi:10.1073/pnas.0904636106. PMC 2722269. PMID 19625617.
Youn H, Ji I, Ji HP, Markesbery WR, Ji TH (November 2007). "Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampus". J. Alzheimers Dis. 12 (3): 271–81. PMID 18057561.
Youn H, Jeoung M, Koo Y, Ji H, Markesbery WR, Ji I, Ji TH (June 2007). "Kalirin is under-expressed in Alzheimer's disease hippocampus". J. Alzheimers Dis. 11 (3): 385–97. PMID 17851188.

External links

Traffic jam in brain causes schizophrenia symptoms
Architect of Synaptic Plasticity Links Spine Form and Function - Schizophrenia Research Forum, 2007-11-30

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160145 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000061751 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9285789-5] Colomer V, Engelender S, Sharp AH, Duan K, Cooper JK, Lanahan A, Lyford G, Worley P, Ross CA (September 1997). "Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain". Hum. Mol. Genet. 6 (9): 1519–25. doi:10.1093/hmg/6.9.1519. PMID 9285789.

[pmid10023074-6] Kawai T, Sanjo H, Akira S (February 1999). "Duet is a novel serine/threonine kinase with Dbl-Homology (DH) and Pleckstrin-Homology (PH) domains". Gene. 227 (2): 249–55. doi:10.1016/S0378-1119(98)00605-2. PMID 10023074.

[pmid15923627-7] Chakrabarti K, Lin R, Schiller NI, Wang Y, Koubi D, Fan YX, Rudkin BB, Johnson GR, Schiller MR (June 2005). "Critical role for Kalirin in nerve growth factor signaling through TrkA". Mol. Cell. Biol. 25 (12): 5106–18. doi:10.1128/MCB.25.12.5106-5118.2005. PMC 1140581. PMID 15923627.

[pmid11891045-8] McPherson CE, Eipper BA, Mains RE (February 2002). "Genomic organization and differential expression of Kalirin isoforms". Gene. 284 (1–2): 41–51. doi:10.1016/S0378-1119(02)00386-4. PMID 11891045.

[pmid18031682-9] Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM, Shum CY, Surmeier DJ, Penzes P (2007). "Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines". Neuron. 56 (4): 640–56. doi:10.1016/j.neuron.2007.10.005. PMC 2118058. PMID 18031682.

[pmid19020030-10] Ma XM, Kiraly DD, Gaier ED, Wang Y, Kim EJ, Levine ES, Eipper BA, Mains RE (November 2008). "Kalirin-7 is required for synaptic structure and function". Journal of Neuroscience. 28 (47): 12368–82. doi:10.1523/JNEUROSCI.4269-08.2008. PMC 2586970. PMID 19020030.

[pmid19403804-11] Sommer JE, Budreck EC (April 2009). "Kalirin-7: linking spine plasticity and behavior". Journal of Neuroscience. 29 (17): 5367–9. doi:10.1523/JNEUROSCI.0235-09.2009. PMC 2684031. PMID 19403804.

[pmid_18597863-12] Penzes P, Jones KA (August 2008). "Dendritic spine dynamics--a key role for kalirin-7". Trends in Neurosciences. 31 (8): 419–427. doi:10.1016/j.tins.2008.06.001. PMC 3973420. PMID 18597863.

[pmid19625617-13] Cahill ME, Xie Z, Day M, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ, Penzes P (July 2009). "Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes". Proceedings of the National Academy of Sciences of the United States of America. 106 (31): 13058–63. doi:10.1073/pnas.0904636106. PMC 2722269. PMID 19625617.

[pmid18057561-14] Youn H, Ji I, Ji HP, Markesbery WR, Ji TH (November 2007). "Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampus". J. Alzheimers Dis. 12 (3): 271–81. PMID 18057561.

[pmid17851188-15] Youn H, Jeoung M, Koo Y, Ji H, Markesbery WR, Ji I, Ji TH (June 2007). "Kalirin is under-expressed in Alzheimer's disease hippocampus". J. Alzheimers Dis. 11 (3): 385–97. PMID 17851188.

Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)