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FLASH GENE

Symbol

PLOD2

contributors: mct/npt/pgu - updated : 01-03-2017

HGNC name	procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2
HGNC id	9082

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	92.06 kb     20 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	TGFB1 induces a SP1- and SMAD3-dependent recruitment of histone modifying enzymes to the PLOD2 promoter other than the currently known TGFB1 downstream co-activators and epigenetic modifications

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_182943 20 splicing 4072 NP_891988 - 758 ubiquitous, overexpressed in scleroderma fibroblasts 2009 19110540 LH2B thought to play a pivotal role in fibrosis by directing the collagen cross-link pattern exerts a bimodal function on collagen synthesis in dermal fibroblasts NM_000935 19 splicing 4009 NP_000926 84.7 737 restricted to kidney, liver, spleen, placenta 2009 19110540 LH2A a spliced out exon

EXPRESSION

Type

widely

constitutive of

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   vessel aorta       Endocrine pancreas       highly Nervous meninges         Skin/Tegument skin

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide
	a C terminal lysyl hydroxylaselase domain

mono polymer

homomer , dimer

HOMOLOGY

interspecies

homolog to murine Plod2

intraspecies

homolog to PLOD3

Homologene

FAMILY

lysyl hydroxylase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum ,rough,smooth

basic FUNCTION	catalyzing the hydroxylation of lysyl residues in collagenous sequences
	extracellular matrix maintenance, playing an important role in fibrotic processes
	collagen telopeptide, bifunctional protein having a potential role in the pathogenesis of fibrosis
	FKBP10, PLOD2 and SERPINH1, acts during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result
	P4HA1, P4HA2, and PLOD2 mediate remodeling of ECM composition, alignment, and mechanical properties in response to hypoxia
	hydroxylates lysine residues in collagen telopeptides and is essential for collagen pyridinoline cross-link formation
	PLOD2 regulated by HIF1A is a potential regulator of peritoneal dissemination of gastric cancer
	promotes cell invasiveness and migration in GC (gastric cancer) under hypoxia and lead to peritoneal dissemination of GC

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

FKBP10 forms complexes with PLOD2 splice variants LH2A and LH2B but not with PLOD1 and PLOD3

INTERACTION

DNA

RNA

small molecule	metal binding,
	iron, ascorbate

protein	interaction with PITX2 (reduced PITX2 expression could decrease PLOD2 expression and hence facilitate ovarian ECM degradation, leading to hypothyroidism associated reproductive disorders)
	RBFOX2 plays an integral role in the regulation of PLOD2 splicing
	RBFOX2, RBFOX1
	HIF1A activates expression of genes encoding collagen prolyl (P4HA1 and P4HA2) and lysyl (PLOD2) hydroxylases
	regulated by HIF1A and mediates extracellular matrix remodeling, alignment, and mechanical properties

cell & other

REGULATION

Other

regulated by PITX2 (homeodomain transcription factor, which regulates PLOD2 gene in brain tissue, transactivates gonadotropin genes in pituitary and plays a substantial role in cell growth and proliferation in different tissues)

ASSOCIATED DISORDERS

corresponding disease(s)

BRKS2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   fibrotic process in isoform b tumoral     --over   in glioblastoma with poor prognosis

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS