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FLASH GENE

Symbol

PPM1A

contributors: mct - updated : 30-05-2016

HGNC name	protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform
HGNC id	9275

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	53.34 kb     6 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_021003 6 splicing 8210 NP_066283 42.3 382 - 2003 12514180 encoding the same isoform as the one encoded by variant 3 6 exons NM_177951 4 splicing 4334 NP_808820 35.8 324 in brain 2003 12514180 4 exons containing an extra segment within the 5' UTR and having a different 3' region, which includes a part of the coding region as compared to variant 1 NM_177952 6 splicing 8175 NP_808821 - 455 - 2003 12514180 6 exons differing in the 5' UTR compared to variant 1 encoding the same isoform than variant 1

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         Digestive liver         Endocrine neuroendocrine pituitary     predominantly   pancreas         Hearing/Equilibrium ear       highly Lymphoid/Immune lymph node       moderately Nervous nerve       moderately Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone     moderately Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a catalytic domain

secondary structure

a catalytic domain composed of a central beta sandwich that binds 2 manganese ions, which is surrounded by alpha helices

mono polymer

monomer

HOMOLOGY

interspecies	ortholog to rattus Ppm1a (99pc)
	ortholog to murine Ppm1a (98.2pc)

Homologene

FAMILY	PP2C family of Ser/Thr protein phosphatases
	metal-dependent serine/threonine protein phosphatase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	acting as a negative regulator of cell stress response pathways
	negatively regulating the activities of MAP kinases and MAP kinase kinases
	inhibiting the activation of p38 and JNK kinase cascades induced by environmental stresses
	playing an important role in the regulation of receptors and channels
	directly dephosphorylating Smad2 and Smad3 to limit their activation which plays a critical role in terminating TGFbeta signaling
	involved in positive regulation of I-kappaB kinase/NF-kappaB cascade
	inhibiting cell growth
	activating the p53 pathway
	might contribute to secretory cell function
	PPM1A and PPM1B play an important role in the termination of TNF-mediated NF-kappaB activation through dephosphorylating and inactivating IKBKB
	phosphatase which dephosphorylates and inactivates a broad range of substrates, including TGFB1, MAP kinases, MAPK14 and JNK kinase cascades, and is involved in tumor suppression
	plays a critical role in the regulation of normal placentation by inhibiting trophoblast migration and invasion
	critical role of PPM1A in maximizing exporter activity of RANBP3 for efficient termination of canonical TGFB1 signalling
	plays a role in the differentiation and survival processes of nerve cells
	might have an important role in oocyte maturation
	represses HIV-1 gene expression by inhibiting CDK9 T-loop phosphorylation, thus reducing the amount of active CDK9 available for recruitment to the viral LTR
	N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells

CELLULAR PROCESS	cell cycle, progression
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

text	involved in cell cycle control

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Mg2+ (2 ions per subunit)
	Mn2+ (2 ions per subunit)

protein	GRM3 (C terminal cytoplasmic tail)
	PPM1A and PPM1B, are IKBKB phosphatases
	regulates the nuclear export of SMAD2/3 through targeting nuclear exporter RANBP3
	directly interacted with and dephosphorylated RANBP3 at Ser 58
	nuclear envelope-localized mechanism of inactivating TGFB1 signaling in which LEMD3 competes with transcription factors for binding to SMAD2 and SMAD3 and facilitates their dephosphorylation by PPM1A
	TRIM52 was a fibrosis promoter in hepatic fibrosis in vitro, likely through PPM1A-mediated TGB1/Smad pathway

cell & other

REGULATION

Other

N-myristoylated and this modification is essential for its ability to dephosphorylate the alpha subunit of AMPK in cells

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in hydatidiform moles compared with that during normal pregnancy

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS