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FLASH GENE

Symbol

HTRA1

contributors: mct/shn/pgu - updated : 26-06-2017

HGNC name	HtrA serine peptidase 1
HGNC id	9476

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	53.38 kb     9 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D10S1679 - D10S1483 - HTRA1 - D10S587 - D10S1213 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002775 9 - 2138 NP_002766 - 480 - 2003 12513693

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 Cardiovascular heart       moderately Digestive liver       highly Endocrine pancreas       lowly Nervous brain       highly Reproductive female system placenta     predominantly Homo sapiens Respiratory lung       lowly Urinary kidney       moderately Visual eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   lowly

cell lineage
cell lines	tumor cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	skeletal elements

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide
	a Kazal-like domain
	a serine protease domain
	a signal sequence for secretion,
	a partial insulin-like growth factor-binding protein-7 domain, serine protease domain resembling classic serine proteases such as trypsin
	one C-terminal PDZ domain

HOMOLOGY

interspecies	ortholog to Htra1, Mus musculus
	ortholog to Htra1, Rattus norvegicus
	ortholog to HTRA1, Pan troglodytes

Homologene

FAMILY	HtrA serine protease family
	peptidase S1B family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus
text	secreted protein
	intracellular HTRA1 was localized to microtubules and to the nucleus

basic FUNCTION	an antagonist of Tgfbeta family proteins
	a candidate tumor suppressor involved in promoting serine-protease-mediated cell death
	potential role as a predictive factor of clinical response to chemotherapy
	a putative role in extracellular matrix homeostasis
	decreases TGFB signaling through its protease activity and might play a pivotal role in human cerebral small-vessel disease
	might likely function as a MAPT protease
	plays a detrimental role in the pathogenesis of intervertebral disc (IVD) degeneration
	promotes IVD degeneration through the proteolytic cleavage of fibronectin and subsequent activation of resident disc cells
	likely a central role for HTRA1 in joint degeneration through its proteolytic actions on ECM components
	HTRA1 and FGF8 may function coordinately in the common FGF signaling pathway
	antagonizes TGFB1 signaling, and plays a key role in the regulation of bone formation
	is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation
	may likely mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes
	HTRA1 and HTRA3 are crucial for trophoblast-decidual cell interaction in the control of trophoblast invasion
	play a modulatory role in metastasis of hepatocellular carcinoma (HCC), and its expression was closely related to EMT, which might be a potential mechanism underlying metastasis of HCC
	HTRA1, HTRA2, HTRA3, HTRA4 function as important modulators of many physiological processes, including maintenance of mitochondrial homeostasis, cell signaling and apoptosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	Bmp4, Gdf5, Tgfbeta 2, Tgfbeta 1 and activin
	decreases TGFB-1 signaling via interaction with proTGF-B1 in the intracellular space (binds to and cleaves the pro-domain of proTGF-beta1 in the ER, resulting in a decreased amount of secreted mature TGF-beta)
	degrades MAPT aggregates and is induced by its substrates
	HTRA1 directly cleaves FGF8 in the extracellular region, and this cleavage results in decreased activation of FGF signaling, which is essential for many physiological processes
	HTRA1 is a novel LRP1 ligand
	decidua-secreted HTRA1 and HTRA3 antagonize HTRA4-mediated trophoblast invasion

cell & other

REGULATION

Other

downregulated in ovarian cancer

ASSOCIATED DISORDERS

corresponding disease(s)

ARMD7 , CARASIL

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       loss of function in tumor cell lines constitutional     --over   mRNA levels are elevated approximately 7-fold in cartilage from individuals with osteoarthritis compared with nonarthritic controls constitutional     --over   in dilated cardiomyopathy constitutional     --over   in osteoarthritic patients and as having the potential to regulate matrix metalloproteinase (MMP) expression in synovial fibroblasts through the generation of fibronectin fragments constitutional     --over   placental HTRA1 is significantly up-regulated in preeclampsia (PE) (significantly increased in early-onset PE, but significantly reduced in late-onset PE)

Susceptibility

to age-macular dgeneration (AMD)

Variant & Polymorphism SNP , other	in the promoter region is a major genetic risk factor for wet AMD
	polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD
	HTRA1 expression is enhanced by AMD specific indel mutation in the promoter region of HTRA1 gene, and this enhanced HTRA1 may be concerned with induce retinal neovascularization , and AMD-associated silent polymorphisms in HTRA1 impair its ability to antagonize IGF1

Candidate gene
Marker	significant increase of serum HTRA1 in early-onset PE suggests that it may be a potential biomarker for the diagnosis of early-onset preeclampsia (PE) at disease presentation
Therapy target
	System Type Disorder Pubmed osteoarticular bone   may represent a novel therapeutic target for the treatment of spinal disc degeneration

ANIMAL & CELL MODELS