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FLASH GENE

Symbol

SMG1

contributors: mct - updated : 11-09-2015

HGNC name	SMG1 homolog, phosphatidylinositol 3-kinase-related kinase (C. elegans)
HGNC id	30045

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	16p12.3      Physical location : 18.816.175 - 18.937.726
Synonym name	lambda-iota protein kinase C-interacting protein
	phosphatidylinositol 3-kinase-related protein kinase
	PI-3-kinase-related kinase SMG-1
	suppressor of morphogenesis in genitalia-1
	lambda-interacting protein
	serine/threonine-protein kinase SMG1
Synonym symbol(s)	KIAA0421, ATX, LIP, LIPKC, 61E3.4, SMG-1
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	121.55 kb     63 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_015092 63 splicing 16065 NP_055907 410.4 3661 - 2008 18326048 variant 2 - splicing 11036 isoform 2 340.7 3031 . widely . highly in heart, skeletal muscle, kidney and liver 2008 18326048 a conserved ATP-binding site, a DXXXXN and a DXX motif within the catalytic domain and a short FATC C-terminal region common in PIK-related kinases

EXPRESSION

Type	ubiquitous

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 adrenal gland       highly   neuroendocrine pituitary     predominantly   parathyroid       highly Nervous nerve cranial nerve     moderately Reproductive female system breast mammary gland   highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cell lineage
cell lines
fluid/secretion	highly in blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a FAT domain
	a HEAT repeat
	a PI3K/PI4K domain
	a FATC domain

HOMOLOGY

Homologene

FAMILY	PI3K-related kinase (PIKK) family
	phosphoinositide kinase-like kinase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1
	acting as a serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways
	functioning in NMD by phosphorylating the regulator of nonsense transcripts 1 protein
	may activate PRKCI
	may function in telomere maintenance, responses to hypoxia, and TNFA–induced apoptosis
	can phosphorylate TP53/p53 and is required for optimal TP53/p53 activation after cellular exposure to genotoxic stress
	has a critical role in the degradation of premature termination codon (PTC)–containing transcripts mediated by the nonsense-mediated mRNA decay (NMD) pathway
	recognizing the substrate consensus sequence [ST]-Q
	playing an important role in cell survival during TNFalpha-induced stress
	plays dual roles in mRNA surveillance and genotoxic stress response pathways in cells
	proximal regulator of DNA damage signaling and the G(1) checkpoint is tightly regulated during prolonged oxidative stress by both phosphatidylinositol 3-kinase-like kinases-dependent synthesis and proteolysis of CDKN1A
	activates the essential nonsense-mediated mRNA decay (NMD) factor UPF1
	is a large kinase essential to nonsense-mediated mRNA decay (NMD) that phosphorylates UPF1, which seems to be the definitive signal triggering mRNA decay
	SMG1 and MAP3K14 function as critical repressors of Smac mimetic compounds-mediated apoptosis by potentially converging on the regulation of CFLAR metabolism
	activates TPp53 in response to DNA double-strand breaks independent of the RNA surveillance proteins UPF1 or UPF2
	plays a central role in the process of stress granule formation
	role in nonsense-mediated decay as well as suggested roles in the DNA damage response, resistance to oxidative stress, regulation of hypoxic responses, and apoptosis
	participates likely in the regulation of inflammation and cancer development, and is a cancer susceptibility gene that may play a role in the pathogenesis of both lung and hematopoietic cancers

CELLULAR PROCESS	cell life, antiapoptosis
	nucleotide, repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

other

signaling

mRNA catabolic process

a component

component of a post-splicing multiprotein NMD complex with UPF1, UPF2/RENT2, EST1A (SMG5/7a), EST1B/SMG5 and UPF3 (UPF3A or UPF3B)

INTERACTION

DNA

RNA

small molecule	metal binding,
	Mn2+
	Mg2+

protein	binding to lambda-iota protein kinase C
	interacting with PRKCI
	associated with TELO2 that is a highly conserved regulator of PIKK stability
	SMG8 binding to the SMG1:SMG9 complex specifically down-regulates the kinase activity of SMG1 on UPF1 without contacting the catalytic domain
	MARVELD1 promotes the dissociation of SMG1 from UPF1, resulting in the repression of serine phosphorylation of UPF1
	SMG8 is involved in the recruitment of inactive SMG1 to the SURF complex
	SMG1C (a complex containing SMG1, SMG8, and SMG9) contributes to regulate NMD by recruiting UPF1 and UPF2 to distinct sites in the vicinity of the kinase domain
	UPF1 is recruited to the SMG1 kinase domain and C-terminal insertion domain, inducing an opening of the head domain that provides access to the active site
	SMG8 and SMG9 act, in addition to serving as a scaffold for the interaction between SMG1 and UPF1, to negatively regulate SMG1 kinase activity and maintain UPF1 in the unphosphorylated (inactive) form within the SURF complex

cell & other

REGULATION

inhibited by

caffeine, LY294002 and wortmannin

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

essential for mouse embryogenesis such that Smg1 loss is lethal at embryonic day 8.5