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FLASH GENE

Symbol

PLAGL1

contributors: mct - updated : 17-02-2016

HGNC name	pleiomorphic adenoma gene-like 1
HGNC id	9046

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	TNDM transient neonatal diabetes mellitus UPD6P chromosome 6 uniparental disomy, paternal
Location	6q24.2      Physical location : 144.261.438 - 144.385.735
Synonym name	rat lot-1 (lost in transformation 1)
	Zac tumor suppressor
	PLAG-like 1
Synonym symbol(s)	LOT1, ZAC1, ZAC, PAL1, MGC126275, MGC126276, DKFZp781P1017

DNA

TYPE	functioning gene
STRUCTURE	124.30 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
text structure	a CpG island overlapping exon 1of PLAGL1/HYMAI is differentially methylated in somatic cells
	independently-regulated P2 promoter, within CpG island , with biallelic expression, having important implications in cancer and neonatal diabetes

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - C6orf56 - PLAGL1 - HYMAI - qter
Authors	Arima (01)
Text	see ST8

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002656 6 splicing 2949 NP_002647 - 411 - 1998 9722527 NM_006718 7 splicing 3411 NP_006709 - 463 - 1998 9722527 NM_001080951 8 - 3284 NP_001074420 - 463 - 1998 9722527 NM_001080952 7 - 3425 NP_001074421 - 463 - 1998 9722527 NM_001080953 7 - 3379 NP_001074422 - 463 - 1998 9722527 NM_001080954 7 - 3778 NP_001074423 - 463 - 1998 9722527 NM_001080955 6 - 2733 NP_001074424 - 411 - 1998 9722527 NM_001080956 6 - 2917 NP_001074425 - 411 - 1998 9722527

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 Cardiovascular heart       highly Homo sapiens Endocrine adrenal gland       highly Reproductive female system placenta     highly Respiratory respiratory tract larynx     highly

cell lineage

cell lines

fluid/secretion

at STAGE

IMPRINTING	maternally
text	ubiquitous, from the paternal allele
	maternally imprinted in neonatal diabetes
	biallelic in peripheral blood leukocytes

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

seven zinc finger motifs C2H2 type

HOMOLOGY

interspecies

homolog to murine Zac1

Homologene

FAMILY

krueppel C2H2-type zinc-finger protein family

CATEGORY

regulatory , transcription factor , tumor suppressor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide
	growth suppressor gene with antiproliferative activity
	may regulate CDKN1C through KCNQ1OT1, forming part of a novel signaling pathway regulating cell growth
	has an essential role in cell number control during retinal development
	transcription factors from the PLAG family of cell cycle progression-related DNA-binding proteins, involved in transcriptional induction of ABCC6 (Ratajewski 2008)
	may be a regulator of cardiomyocyte SLC2A4 expression and glucose uptake (Czubryt 2010)
	maternally imprinted gene and is the first such gene found to be involved in heart development
	plays an essential role in the cardiac gene regulatory network
	is a histone acetylation-regulated suppressor of NFKB, which is induced and implicated in HDAC inhibitor-mediated embryonic carcinoma (EC) cell apoptosis
	might serve as an SP1-like protein that directly interacts with the SP1-responsive element to oligomerize with and/or to coactivate SP1
	its functions are regulated, at least in part, via non-covalent interactions with SUMO1 for the induction of CDKN1A, which is important for the modulation of apoptosis
	is a negative regulator of the acute stimulatory effects of glucose on beta-cells

CELLULAR PROCESS	cell life, cell death/apoptosis
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text

arrest

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with WBSCR22 (WBSCR22 suppressed PLAGL1 expression with histone H3 methylation at Lys(9) in the PLAGL1 promoter)
	might act as a transcriptional repressor via the recruitment of histone deacetylase 1 (HDAC1)
	CDKN1A may be an important factor for the prevention of PLAGL1-induced apoptosis without affecting autophagosome formation
	PLAGL1 interacts with TCF4, and PLAGL1 and TCF4 expression concomitantly increased during neuronal progenitor differentiation
	controls cell cycle arrest function in neuronal progenitors through induction of CDKN1C via TCF4
	transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
	PLAGL1 interacts likely directly with PAX7, which can regulate GPR39 expression by activating PLAGL1

cell & other

REGULATION

Other

regulated by alternative splicing and by impriting

ASSOCIATED DISORDERS

corresponding disease(s)

UPD6P , TNDM

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in breast cancer constitutional germinal mutation   --low   by partial and complete hypomethylation in Beckwith-Wiedemann syndrome (Bliek (2009) tumoral     --low   is a contributing factor in the development of extraskeletal myxoid chondrosarcoma tumors tumoral     --low   with SSTR2, are underexpressed in non-functioning pituitary adenomas (NFPA), compared to somatotropinomas and normal pituitaries

Susceptibility

TNDM

Variant & Polymorphism SNP

Candidate gene	putative candidate for transient neonatal diabetes mellitus (TNDM)
Marker
Therapy target

ANIMAL & CELL MODELS