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FLASH GENE

Symbol

KIDINS220

contributors: mct - updated : 07-07-2015

HGNC name	kinase D-interacting substrate, 220kDa
HGNC id	29508

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	two potential sites for alternative splicing of KIDINS220/ARMS: the first is located between exon 24 and exon 29, while the second site replaces exon 32 by a short alternative terminal exon 33 (PMID: 26083449)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020738 30 - 7361 NP_065789 220 1771 - 2015 26083449 KIDINS220/ARMS variant 1 32 splicing - - - - 2015 26083449 isoform containing exon 32, targeted to the plasma membrane and neurite tips KIDINS220/ARMS variant 2 32 - - - - - 2015 26083449 isoform without exon 33 mainly clusters the full-length protein in a perinuclear intracellular compartment in primary neurons, leading to a change in neurotrophin receptor expression

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine         Homo sapiens Nervous brain limbic system hippocampus     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	11 ankyrin repeats
	four transmembrane domains within the N-terminal region

HOMOLOGY

Homologene

FAMILY

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus,nucleoplasm
text	interacts with the microtubule and actin cytoskeleton

basic FUNCTION	key feature of the neurotrophin signaling, shown to be critical for neuronal survival under pathologic settings
	plays an important role in NF-kappaB signaling elicited by brain-derived neurotrophic factor (BDNF)
	important for the growth of dendritic arbors and spine stability during an activity- and BDNF-dependent period of development
	key modulator of the activity of microtubule-regulating proteins known to actively regulate neuronal morphogenesis and suggest a mechanism by which it contributes to control neuronal development
	scaffold protein that has important implications in neurotrophin signalling, modulates the development and maturation of axons and dendrites
	modulation of its levels can regulate basal synaptic strength in a specific manner in hippocampal neurons
	serves as a unique downstream adaptor protein of Trk receptor tyrosine kinases
	major factor that links neurotrophin signaling to NF-kappaB
	interaction with SEPT5 suggests a possible role as a functional link between neurotrophin receptors and septins to mediate neurotrophin-induced intracellular signaling events, such as neurite outgrowth and cytoskeletal remodeling
	can be potentially regulated by neuronal activity and calpain action to influence synaptic function
	required for neuronal differentiation and survival, and its expression levels modulate synaptic plasticity
	is not essential for basal synaptic transmission and various forms of short-term plasticity, but instead plays a novel role in the mechanisms regulating the recovery of synaptic strength in GABAergic synapses
	is likely a key player in organizing the signaling complex to transduce the extracellular stimuli to cellular responses during dendrite development
	was required for optimal calcium signaling
	acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems
	role of ARMS/Kidins220 as a signaling platform to regulate tumor cell proliferation in response to the extracellular stimuli
	acts as a signaling platform at the plasma membrane and is implicated in a multitude of neuronal functions, including the control of neuronal activity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	transmembrane substrate of tropomyosin receptor kinase B (TRKB)
	intreacting with Septin 5 (SEPT5)
	integral membrane protein that was initially identified as a substrate for protein kinase D, a kinase we have found to regulate its intracellular traffic in neurons
	is rapidly cleaved by calpain during excitotoxicity, a form of neuronal death associated to phosphatases (PPs) activation
	downstream target of neurotrophin and ephrin receptors, in dendrite development
	association of NMDARs with KIDINS220 and the participation of this protein in neuronal survival and death pathways
	KIDINS220 stability and cleavage by calpain is under the control of GSK3B and PP1 activities
	is a substrate for GSK3B and is likely phosphorylated by this kinase in AD brain, as it has been demonstrated for MAPT
	is required for TCR-induced sustained, but not transient, Erk activation
	is a novel TCR-interacting protein that couples BRAF to the TCR
	transmembrane protein playing a crucial role in neuronal and cardiovascular development
	downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   to melanoma formation by preventing stress-induced apoptotic death mediated by the MEK/ERK signaling pathway, especially in acral lentiginous melanoma constitutional     --low   by excitotoxicity and cerebral ischaemia contributed to neuronal death constitutional     --over   in necropsies from AD patients where it accumulates with hyperphosphorylated MAPT, and is phosphorylated by GSK3B in AD brain, wich could be protecting KIDINS220 from calpain cleavage, contributing to accumulation of this protein in AD samples

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS