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FLASH GENE

Symbol

ID4

contributors: SGE - updated : 06-09-2015

HGNC name	inhibitor of DNA binding 4, dominant negative helix-loop-helix protein
HGNC id	5363

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	3.30 kb     3 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_001546 3 - 2389 NP_001537 16.6 161 - Pagliuca (1995)

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 Cardiovascular heart       moderately Digestive liver       moderately Endocrine pancreas       highly   thyroid       highly Nervous brain       highly Reproductive male system prostate     moderately Respiratory lung       highly Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal     Nervous central

cell lineage
cell lines	in some nervous system tumor cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	fetal tissue

PROTEIN

PHYSICAL PROPERTIES		basic
STRUCTURE

motifs/domains

basic helix-loop-helix (bHLH) motif, lacking the DNA binding basic domain

conjugated

PhosphoP

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to murine Id4 (98.1pc)
	homolog to rattus Id4 (95.7pc)

Homologene

FAMILY	basic-helix-loop-helix (BHLH) family of transcription factor
	inhibitor of DNA-binding (ID) family

CATEGORY

regulatory , tumor suppressor , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	antagonist of MyoD activity or creatine kinase enhancer
	may play an important suppressive role in tumor progression, and its silencing by hypermethylation may increase the risk of regional lymph node metastasis
	promotes osteoblast differentiation by releasing HES1 from HES1-HES2 complexes, thus stabilizing RUNX2 (a key molecule differentiation) (Tokuzawa 2010)
	inhibiting binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins (Pagliuca 1995)
	tumor suppressor in normal breast tissue and epigenetically silenced during cancer development, indicating increased risk for tumor relapse (Noetzel 2008)
	decreased MMP2 expression by a direct inhibitory interaction with TWIST1, a basic helix-loop-helix transcription factor known to increase MMP2 expression

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA	binding to and stabilizing mRNAs encoding pro-angiogenic factors IL8 and GRO-alpha (Fontemaggi 2009)

small molecule

protein	PRMT5 is required for maintaining the methylation status of CpG islands of ID2 and ID4 leading to gene silencing during glial cell differentiation
	KCNK10 hyperpolarizes IB4 binding C-nociceptors and limits pathological spontaneous pain

cell & other

REGULATION

repressed by

ZBTB18, repressing ID1, ID2, ID3, ID4 genes during corticogenesis

Other	regulated by BRCA1
	down-regulated by CDC42 through an epigenetic mechanism (Gomez Del Pulzar 2008)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         by promoter hypermethylation in acute myeloid leukemia tumoral     --other   dysregulated in breast and ovarian carcinomas with BRCA1 tumoral     --low   in breast cancer by aberrant hypermethylation of the promoter region, increasing risk of lymph node metastasis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	ID4 could be efficacious for identifying previously unrecognized human spermatogonial subpopulations in conjunction with other putative human stem cell markers
Therapy target	ID4 methylation could serve as a prognostic biomarker in breast cancer (Noetzel 2008)
	may be a therapeutic target in myelodysplastic syndrome (MDS) (Wang 2010)

ANIMAL & CELL MODELS