HTRA2 (HtrA serine peptidase 2)

Gene

• Entrez ID: 27429
• Gene name: HtrA serine peptidase 2
• Gene symbol: HTRA2
• Synonyms: MGCA8, OMI, PARK13, PRSS25
• Chromosome: 2
• Chromosome location: 2p13.1
• Summary: This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT037592	hsa-miR-744-5p	CLASH	23622248
MIRT1057353	hsa-miR-4652-3p	CLIP-seq
MIRT1057354	hsa-miR-4677-3p	CLIP-seq
MIRT1057355	hsa-miR-4679	CLIP-seq
MIRT1057356	hsa-miR-548t	CLIP-seq
MIRT1057357	hsa-miR-1193	CLIP-seq
MIRT1057358	hsa-miR-2392	CLIP-seq
MIRT1057359	hsa-miR-3925-3p	CLIP-seq
MIRT1057360	hsa-miR-4266	CLIP-seq
MIRT1057361	hsa-miR-4426	CLIP-seq
MIRT1057362	hsa-miR-4647	CLIP-seq
MIRT1057363	hsa-miR-4660	CLIP-seq
MIRT1057364	hsa-miR-4662b	CLIP-seq
MIRT1057365	hsa-miR-4695-5p	CLIP-seq
MIRT1057366	hsa-miR-4712-5p	CLIP-seq
MIRT1057367	hsa-miR-4779	CLIP-seq
MIRT1057368	hsa-miR-633	CLIP-seq
MIRT1057369	hsa-miR-646	CLIP-seq
MIRT1057370	hsa-miR-770-5p	CLIP-seq
MIRT1057371	hsa-miR-885-3p	CLIP-seq
MIRT1057355	hsa-miR-4679	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ESR1	Activation	21486948

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IDA	24798695
GO:0004252	Function	Serine-type endopeptidase activity	IMP	10971580, 11967569
GO:0004252	Function	Serine-type endopeptidase activity	TAS	10873535
GO:0005515	Function	Protein binding	IPI	10971580, 11583623, 11602612, 11604410, 11801603, 15200957, 17297443, 19502560, 20125124, 24698088, 25118933, 28642151, 31470122, 32814053
GO:0005634	Component	Nucleus	IDA	10971580, 24798695
GO:0005739	Component	Mitochondrion	IDA	11583623, 11602612
GO:0005739	Component	Mitochondrion	IMP	11604410
GO:0005739	Component	Mitochondrion	TAS	18309324
GO:0005758	Component	Mitochondrial intermembrane space	IDA	15044455
GO:0005783	Component	Endoplasmic reticulum	NAS	10995577
GO:0005789	Component	Endoplasmic reticulum membrane	TAS	10644717
GO:0005829	Component	Cytosol	IDA	11583623, 11602612, 11604410, 24798695
GO:0005856	Component	Cytoskeleton	IDA	24798695
GO:0006508	Process	Proteolysis	IDA	25118933
GO:0006508	Process	Proteolysis	IMP	10971580, 11967569, 24709290
GO:0006508	Process	Proteolysis	TAS	10873535
GO:0006672	Process	Ceramide metabolic process	IEA
GO:0007005	Process	Mitochondrion organization	IEA
GO:0007568	Process	Aging	IEA
GO:0007628	Process	Adult walking behavior	IEA
GO:0008233	Function	Peptidase activity	IDA	11604410, 17266347, 20125124, 25118933
GO:0008233	Function	Peptidase activity	IMP	24709290
GO:0008236	Function	Serine-type peptidase activity	IDA	11583623
GO:0008236	Function	Serine-type peptidase activity	TAS	18309324
GO:0008630	Process	Intrinsic apoptotic signaling pathway in response to DNA damage	IMP	11602612
GO:0009635	Process	Response to herbicide	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	ISS
GO:0010822	Process	Positive regulation of mitochondrion organization	IMP	25118933
GO:0012501	Process	Programmed cell death	IDA	11583623
GO:0016020	Component	Membrane	IDA	24798695
GO:0016540	Process	Protein autoprocessing	TAS	11602612
GO:0019742	Process	Pentacyclic triterpenoid metabolic process	IEA
GO:0030900	Process	Forebrain development	IEA
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0034599	Process	Cellular response to oxidative stress	IMP	24709290
GO:0034599	Process	Cellular response to oxidative stress	NAS	24522549
GO:0034605	Process	Cellular response to heat	IDA	10971580
GO:0035458	Process	Cellular response to interferon-beta	IDA	17297443
GO:0035631	Component	CD40 receptor complex	ISS
GO:0040014	Process	Regulation of multicellular organism growth	IEA
GO:0042802	Function	Identical protein binding	IPI	11967569
GO:0043065	Process	Positive regulation of apoptotic process	IMP	11967569, 20125124
GO:0043065	Process	Positive regulation of apoptotic process	TAS	18221368, 18309324
GO:0043280	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA	11583623, 11604410, 17297443
GO:0043280	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP	11967569
GO:0044257	Process	Cellular protein catabolic process	IDA	17297443
GO:0045786	Process	Negative regulation of cell cycle	TAS	18309324
GO:0048666	Process	Neuron development	IEA
GO:0051082	Function	Unfolded protein binding	NAS	10644717
GO:0071300	Process	Cellular response to retinoic acid	IDA	17297443
GO:0071363	Process	Cellular response to growth factor stimulus	IMP	20125124
GO:0097194	Process	Execution phase of apoptosis	TAS	18309324
GO:1901215	Process	Negative regulation of neuron death	TAS	18221368
GO:1902176	Process	Negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	NAS	18221368
GO:1903146	Process	Regulation of autophagy of mitochondrion	TAS	24522549
GO:1903955	Process	Positive regulation of protein targeting to mitochondrion	HMP	24270810
GO:1904924	Process	Negative regulation of mitophagy in response to mitochondrial depolarization	IEA
GO:1905370	Component	Serine-type endopeptidase complex	IMP	11967569
GO:2001241	Process	Positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	IMP	20125124
GO:2001269	Process	Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IMP	11602612

Other IDs

• MIM: 606441
• HGNC: 14348
• e!Ensembl: ENSG00000115317

Protein

• UniProt ID: O43464
• Protein name: Serine protease HTRA2, mitochondrial (EC 3.4.21.108) (High temperature requirement protein A2) (HtrA2) (Omi stress-regulated endoprotease) (Serine protease 25) (Serine proteinase OMI)
• Protein function: [Isoform 1]: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein (PubMed:10873535). Promotes apoptosis by either relieving the inhibition of BIRC proteins on caspases, leading to an increase in caspase ac
• PDB: 1LCY, 2PZD, 5FHT, 5M3N, 5M3O, 5TNY, 5TNZ, 5TO0, 5TO1, 5WYN, 7VGE, 8AUK, 8E2K
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13365	Trypsin_2	182 → 320		Domain
  PF17820	PDZ_6	392 → 443	PDZ domain	Domain

• Sequence:

  MAAPRAGRGAGWSLRAWRALGGIRWGRRPRLTPDLRALLTSGTSDPRARVTYGTPSLWAR
  LSVGVTEPRACLTSGTPGPRAQLTAVTPDTRTREASENSGTRSRAWLAVALGAGGAVLLL
  LWGGGRGPPAVLAAVPSPPPASPRSQYNFIADVVEKTAPAVVYIEILDRHPFLGREVPIS
  NGSGFVVAADGLIVTNAHVVADRRRVRVRLLSGDTYEAVVTAVDPVADIATLRIQTKEPL
  PTLPLGRSADVRQGEFVVAMGSPFALQNTITSGIVSSAQRPARDLGLPQTNVEYIQTDAA
  IDFGNSGGPLVNLDGEVIGVNTMKVTAGISFAIPSDRLREFLHRGEKKNSSSGISGSQRR
  YIGVMMLTLSPSILAELQLREPSFPDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQM
  VQNAEDVYEAVRTQSQLAVQIRRGRETLTLYVTPEVTE

• Sequence length: 458

Pathways

KEGG:

Apoptosis
Apoptosis - multiple species
Parkinson disease
Pathways of neurodegeneration - multiple diseases

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Cataract	Cataract	rs118203965, rs118203966, rs104893685, rs121908938, rs104894175, rs121909048, rs28937573, rs121909049, rs121909050, rs74315488, rs80358200, rs80358203, rs121434643, rs56141211, rs132630322, rs121917775, rs121917735, rs121917736, rs137853199, rs137853200, rs121917867, rs121917869, rs121913555, rs104893736, rs121909595, rs121909596, rs121909597, rs28931605, rs121909598, rs104893618, rs1695062782, rs74315486, rs74315487, rs74315490, rs74315489, rs745938679, rs1566402656, rs74315439, rs74315441, rs121912973, rs121917823, rs1593332981, rs121917825, rs121917827, rs113994108, rs387906963, rs387906964, rs1240503246, rs387906965, rs387906966, rs750207077, rs387907336, rs387907337, rs387907342, rs140332366, rs397514703, rs398122937, rs398122378, rs398122392, rs398122944, rs137853924, rs398122947, rs397515623, rs397515624, rs397515625, rs397515626, rs398122948, rs587778872, rs398123066, rs587777601, rs370424081, rs786205221, rs786205222, rs864309684, rs864309688, rs864309701, rs864309689, rs864309690, rs864309681, rs864309686, rs864309696, rs864309693, rs864309687, rs864309691, rs864309692, rs864309695, rs864309678, rs864309685, rs864309700, rs864309698, rs864309683, rs864309682, rs864309679, rs111534978, rs864309680, rs864309702, rs864622780, rs756898971, rs869312732, rs775038545, rs878852983, rs1114167312, rs1114167313, rs1114167314, rs1114167315, rs1114167307, rs886041410, rs886041412, rs1057518738, rs1057517926, rs1057518878, rs1057519616, rs12799308, rs1064793935, rs1064797219, rs1085307126, rs1085307127, rs765628635, rs1114167427, rs1114167433, rs1554744860, rs1554743428, rs747093432, rs1411557416, rs1555179713, rs1481963503, rs1555549755, rs1456161420, rs1555547008, rs1555889308, rs1555888762, rs766522434, rs1264025914, rs1553585262, rs1567671947, rs1337897299, rs764945940, rs1307969607, rs949335475, rs1184095219, rs776129797, rs1569203234, rs1567668570, rs749141857, rs764098604, rs1184398243, rs1578956689, rs1568480054, rs1564745688, rs1564722302, rs1564723150, rs1571175950, rs1569602837, rs1576552712, rs1575369255, rs981126461, rs1570403798, rs200557771, rs1477743112, rs1651879427, rs1651881222, rs1651919374, rs2024441691, rs148284531, rs1246080692
Dysautonomia	Dysautonomia	rs111033171, rs137853022, rs28939712, rs754348901, rs749052963, rs1057517169, rs1057516865, rs763445509, rs767527819, rs781333644, rs1239081703, rs1554696574, rs539544212, rs1201626345, rs774890086, rs1554703061, rs1554703613, rs1319053366, rs1554703851, rs868073099, rs926177767, rs376078668, rs1554695299, rs1554696648, rs1554696934, rs1554699327, rs1554691572, rs1554695846, rs1554697001, rs770668926, rs1554698037, rs759412460, rs1554702142, rs765572951, rs1554702880, rs1554703831, rs760774999, rs1554696650, rs757972943, rs1554703874, rs1554703907, rs571348995
Neutropenia	Neutropenia	rs879253882	27696117
Parkinson disease	Parkinsonian Disorders, Autosomal Dominant Juvenile Parkinson Disease, PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE, Young-onset Parkinson disease	rs116074753, rs118203903, rs118203904, rs115735611, rs33939927, rs35801418, rs34805604, rs35870237, rs34995376, rs74315355, rs28940284, rs74315356, rs74315357, rs28940285, rs730880302, rs750664040, rs74315359, rs74315360, rs45539432, rs74315361, rs119451946, rs80356771, rs74500255, rs75822236, rs1141814, rs78973108, rs121908681, rs121908686, rs121908687, rs137853054, rs137853055, rs137853056, rs137853057, rs137853058, rs137853059, rs34424986, rs137853060, rs397518439, rs28938172, rs74315351, rs74315353, rs137853051, rs118192098, rs121917767, rs121918104, rs1589451049, rs104893877, rs104893878, rs283413, rs112176450, rs111290936, rs188286943, rs387906863, rs387906864, rs774631197, rs199935023, rs387906942, rs397514694, rs398122403, rs398122404, rs398122405, rs104886460, rs409652, rs431905511, rs63751392, rs756677845, rs864309527, rs864309650, rs750014782, rs1554391082, rs864622011, rs869312810, rs869312809, rs869312811, rs369100678, rs879253853, rs869320761, rs747506979, rs879255630, rs886039854, rs191486604, rs781442277, rs1060499619, rs751037529, rs55777503, rs768091663, rs34208370, rs1553122929, rs772786691, rs754809877, rs1555907463, rs1557561340, rs781600849, rs141263564, rs1557901552, rs777160388, rs756783990, rs867929413, rs1237637353, rs1005937012, rs755000580, rs747427602, rs1578089802, rs771586218, rs748142049, rs1582953433, rs746646126, rs771529549, rs121918106	26558463

Unknown
Disease name	Disease term	dbSNP ID	References
Abnormal male sexual function	Abnormal male sexual function
Anxiety disorder	Anxiety
Cerebral atrophy	Cerebral atrophy
Cerebral ischemia	Brain Stem Ischemia, Transient, Transient Cerebral Ischemia		15306124
Dementia of frontal lobe	Dementia of frontal lobe type
Dyskinetic syndrome	Dyskinetic syndrome
Female sexual dysfunction	Female sexual dysfunction
Gastroparesis	Gastroparesis
Hallucinations	Hallucinations
Hypoplasia of corpus callosum	Hypoplasia of corpus callosum
Male sexual dysfunction	Male sexual dysfunction
Mental depression	Depressive disorder	rs587778876, rs587778877
Panic disorder	Panic Attacks
Parkinsonian disease	Autosomal Dominant Parkinsonism, Autosomal Recessive Parkinsonism, Familial Juvenile Parkinsonism, Parkinsonism, Juvenile		26558463
Ramsay hunt paralysis syndrome	Ramsay Hunt Paralysis Syndrome		26558463
Respiratory failure	Respiratory Failure
Restless legs syndrome	Restless Legs Syndrome
Social communication disorder	Social Communication Disorder
Transient ischemic attack	Transient Ischemic Attack, Posterior Circulation Transient Ischemic Attack, Carotid Circulation Transient Ischemic Attack, Transient Ischemic Attack, Vertebrobasilar Circulation, Crescendo Transient Ischemic Attacks, Transient Ischemic Attack, Anterior Circulation		15306124