Kalirin

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]

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] Band 3q21.1-q21.2 Start 124,080,023 bp[1] End 124,726,325 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B3 Start 33,969,073 bp[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 • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • Rac guanyl-nucleotide exchange factor activity Cellular component • cytoplasm • actin cytoskeleton • extracellular exosome • cytoskeleton • nucleoplasm • cytosol • GO:0097483, GO:0097481 postsynaptic density Biological process • GO:0007243 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 • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 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
Species	Human	Mouse
Entrez	8997	545156
Ensembl	ENSG00000160145	ENSMUSG00000061751
UniProt	O60229	A2CG49
RefSeq (mRNA)	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
RefSeq (protein)	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
Location (UCSC)	Chr 3: 124.08 – 124.73 Mb	Chr 16: 33.97 – 34.57 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000160145 - Ensembl, May 2017
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

External links

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