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FLASH GENE

Symbol

ING4

contributors: mct/pgu - updated : 21-06-2017

HGNC name	inhibitor of growth family, member 4
HGNC id	19423

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	12p13.31      Physical location : 6.759.704 - 6.772.308
Synonym name	brain my036 protein
	candidate tumor suppressor p33 ING1 homolog
	inhibitor of growth protein 4
Synonym symbol(s)	p29ING4, my036, MGC12557

DNA

TYPE	functioning gene
STRUCTURE	12.87 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016162 8 - 1458 NP_057246 28.4 248 - PMID: 17325660, PMID: 16973615 encodes the longer isoform variant 2 - - 1993 isoform 2 - 47 - Gunduz contains an additional exon within the coding region, which leads to a frameshift has a distinct and shorter C-terminus NM_001127582 8 - 1461 NP_001121054 28.5 249 - PMID: 17325660 NM_001127583 8 - 1452 NP_001121055 28.2 246 - PMID: 17325660, PMID: 16973615 lack the full NLS, resulting in increased cytoplasmic localization NM_001127585 7 - 1389 NP_001121057 25.6 225 - PMID: 17325660 NM_001127586 7 - 1313 NP_001121058 - 179 - PMID: 17325660 NM_001127584 8 - 1449 NP_001121056 28.1 245 - PMID: 17325660, PMID: 16973615 lack the full NLS, resulting in increased cytoplasmic localization played dominant-negative roles in the induction of p21(WAF1) promoter activation

EXPRESSION

Type

widely

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 digestive mouth gingiva       Endocrine neuroendocrine pituitary     highly Lymphoid/Immune tonsils       highly Nervous brain forebrain cerebral lobe frontal     nerve       highly Reproductive female system ovary     highly Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a conserved C-terminal plant homeodomain-like zinc finger
	in the middle region, a potential bipartite nuclear localization signal (NLS), could be involved in the binding to TP53

HOMOLOGY

interspecies	ortholog to rattus ing4_predicted
	ortholog to murine Ing4

Homologene

FAMILY

inhibitor of growth (ING) family of chromatin-modifying proteins

CATEGORY

tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,nucleus,nucleolus
text	nucleolar accumulation of ING4 prolongs its half-life, but lack of nucleolar targeting potentially increases ING4 degradation

basic FUNCTION	involved in regulating brain tumour growth and angiogenesis
	involved in negative regulation of transcription, DNA-dependent
	play an important role in cell cycle, transcription and oncogenesis
	potential role in lung fibrogenesis because its down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease
	may specifically regulate the activity of NF-kappaB molecules that are bound to target gene promoters
	may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression
	role in regulating NF-KB–mediated innate immunity
	play important roles in regulating apoptosis, cell cycle progress, cell migration, and invasion
	non-histone protein whose citrullination impacts regulation of gene expression

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

subunit of the MYST2-PHF17-MEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	NFKB1 to repress NFKB1 responsive genes
	with TP53 and enhancing its activity as a trancription factor (the binding of ING4 to TP53 is necessary for the function of ING4)
	interacts with methylated histone H3 and with the MYST2-PHF17-MEAF6 histone acetyltransferase complex
	ING4-MYST2 association is required for cells to progress properly through the DNA synthesis (S) phase of the cell cycle
	downstream target of BRMS1 in regulating tumor angiogenesis
	Epstein-Barr virus (EBV)-encoded EBNA3C significantly suppresses both the ING4- and ING5-mediated regulation of TP53 transcriptional activity in a dose-dependent manner
	binding of PADI4 to ING4 stabilizes ING4 and protects it from rapid degradation (protein binding occurs through the IgG-like domains of PADI4 and the PHD finger of ING4)
	ING4 acts as an E3 ubiquitin ligase to induce ubiquitination of RELA and degradation, which is critical to terminate NFKB activation
	RAS downregulated thymine-DNA glycosylase (TDG), a DNA demethylation enzyme, by inhibiting the interaction of transcription activator ING4 with TDG promoter

cell & other

REGULATION

induced by	BRMS1 (its expression was induced by BRMS1, a metastasis suppressor that inhibits melanoma angiogenesis through inhibiting NFKB activity and IL6 level as well)(

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in breast cancer tumoral     --low   in glioma tissues, and the extent of reduction correlated with the progression from lower to higher grades of tumors tumoral     --low   in head and neck squamous cell carcinomas

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer skin   restoration of ING4 function offers a potential new strategy for the treatment of human melanoma

ANIMAL & CELL MODELS