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FLASH GENE

Symbol

NCK1

contributors: mct - updated : 13-04-2017

HGNC name	NCK adaptor protein 1
HGNC id	7664

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	89.40 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006153 4 - 1938 NP_006144 - 377 - 2016 26871637 NM_001291999 4 - 4455 NP_001278928 - 377 - 2016 26871637 NM_001190796 4 - 4185 NP_001177725 - 313 - 2016 26871637

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 Urinary kidney nephron renal capsule glomerulus   Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three SH3 domains
	a unique SH2 domain that recognizes a specific phosphotyrosine residue on RTKS or on substrates of RTKS like IRS1, lacking a catalytic domain
	a previously unrecognized activation motif in a linker between the first two SH3 domains, and this linker sequence, reminiscent of bacterial virulence factors, di26554011)rectly engages the WASL GTPase binding domain (GBD) and competes with verprolin-homology, connector-helix, acidic motif (VCA) binding

HOMOLOGY

Homologene

FAMILY

CATEGORY

protooncogene , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,nucleus

basic FUNCTION	adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS
	intracellular adaptor protein that is involved in actin polymerization
	independent roles and mechanisms of action of NCK1 and NCK2 in dermal fibroblast migration, which is critical for wound healing
	endogenous regulator of PKR and NCK1-PKR interaction could be a way to limit PKR activation
	NCK1 is the regulator of RASA1 activity
	proteasomal regulation is a key factor in the distinct and non-redundant effects of NCK1 on RHOA-mediated actin dynamics
	NCK1 and NCK2 have non-redundant roles in human T cell activation
	role for NCK1 in regulating gene expression through its role as the scaffold for assembly of the cytoplasmic capping complex
	crucial role for NCK1 as a master regulator within the endothelium to control actin cytoskeleton organization, vascular network remodeling, and endothelial-to-mesenchymal transition (EnMT) during cardiovascular development
	regulates preosteoblastic/osteoblastic migration and bone mass

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

LCP2/GRAP2/NCK1 adaptor protein pathway, implicated in regulation of the actin cytoskeleton by BCR-ABL kinase

a component

FYB/NCK1 complex might provide a means to link integrin activation with the actin cytoskeleton

INTERACTION

DNA

RNA

small molecule

protein	associates with BLNK, PCLG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion
	strong binding of CD3epsilon to EPS8L1 and NCK1 SH3 domains
	connection between septins, SOCS7, NCK1/NCK2 signaling, and the DNA damage response
	in podocytes, links the slit-diaphragm protein nephrin to the actin cytoskeleton (interaction essential for nephrin-dependent reorganization of actin in podocyte injury)
	connect PDGF-BB signaling to the actin cytoskeleton and cell motility
	interaction with SORBS1 (implications for a role in cytoskeletal remodelling during differentiation of skeletal muscle cells)
	functional cooperation between NCK1 and FYB mediates LCP2/WAS interactions and actin rearrangement
	directly binds and activates the GTPase-activating protein of RAS (RASA1), which is responsible for the down-regulation of RAS
	NCK1 interacts with PTPN1 and the NCK1/PTPN1 complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells
	LRFN4 complexed with SFN and NCK1 to mediate elongation in monocytic cells via RAC-1-mediated actin cytoskeleton reorganization
	NCK1 directly modulates NPHS1 phosphorylation through formation of a signaling complex with the Src family kinase FYN
	NCK1 recruitment to the TCR required for ZAP70 activation during thymic development
	WIPF1 acts as an essential link between NCK1 and WASL
	adaptor function for NCK1 in recruiting PK3AP1 to sites of BCR signaling
	ITSN1 is an important general regulator of CDC42-, NCK1- and WASL-dependent actin polymerisation
	NCK1 recruitment to the TCR is fundamental to mount an efficient T cell response, and the NCK1-CD3E interaction may represent a target for pharmacological modulation of the immune response
	NCK1-ELMO1 interaction promoting RAC1 activation and cell motility
	interacts with PTPN1 and also regulates PTPN1 expression, playing a role in regulating the PI3K/AKT1 pathway
	NCK1 was the most potent activator of WASL-driven actin assembly
	NCK1 integrates NPHS1 with the Hippo kinase cascade through association with the adaptor protein WTIP

cell & other

REGULATION

Other

phosphorylated on ser and tyr residues

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         NCK1 silencing in pancreatic beta cells promotes EIF2AK3 activation and signaling to protect beta cells against pathological stresses

Susceptibility

to diabetic nephropathy (DN) in type 1 diabetes mellitus

Variant & Polymorphism other	variant increasing the risk of diabetic nephropathy (DN) in type 1 diabetes mellitus

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS