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UniProtKB - O43464 (HTRA2_HUMAN)

Entry version 218 (10 Feb 2021)
Sequence version 2 (01 May 2000)
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Protein

Serine protease HTRA2, mitochondrial

Gene

HTRA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

  • Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues. EC:3.4.21.108

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei198Charge relay system1 Publication1
Active sitei228Charge relay system1 Publication1
Active sitei306Charge relay system1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processApoptosis

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		3.4.21.108, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O43464

SIGNOR Signaling Network Open Resource

More...SIGNORi		O43464

Protein family/group databases

MEROPS protease database

More...MEROPSi		S01.278

MoonDB Database of extreme multifunctional and moonlighting proteins

More...MoonDBi		O43464, Predicted

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Serine protease HTRA2, mitochondrial (EC:3.4.21.108)
Alternative name(s):
High temperature requirement protein A2
Short name:
HtrA2
Omi stress-regulated endoprotease
Serine protease 25
Serine proteinase OMI
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HTRA2
Synonyms:OMI, PRSS25
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:14348, HTRA2

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		606441, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O43464

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000115317.11

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei105 – 125HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Membrane, Mitochondrion

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

3-methylglutaconic aciduria 8 (MGCA8)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_077960243 – 244LP → PS in MGCA8; loss of protein expression. 1 PublicationCorresponds to variant dbSNP:rs1057519082Ensembl.2
Natural variantiVAR_077961404R → Q in MGCA8; may lead to skipping of exon 7 and the resultant protein may be truncated; loss of protein expression in patient cells homozygous for the mutation. 1 PublicationCorresponds to variant dbSNP:rs767006508Ensembl.1
Parkinson disease 13 (PARK13)2 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046135404R → W in PARK13. 1 PublicationCorresponds to variant dbSNP:rs1380794702Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi134A → M: Loss of interaction with XIAP. Loss of inhibition of XIAP activity. 1 Publication1
Mutagenesisi306S → A: Loss of protease activity. 1 Publication1

Keywords - Diseasei

Disease variant, Epilepsy, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNET

More...DisGeNETi		27429

MalaCards human disease database

More...MalaCardsi		HTRA2
MIMi168600, phenotype
610297, phenotype
617248, phenotype

Open Targets

More...OpenTargetsi		ENSG00000115317

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		505208, 3-methylglutaconic aciduria type 8
2828, Young-onset Parkinson disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA33836

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O43464, Tbio

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		HTRA2

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a transit peptide.<p><a href='/help/transit' target='_top'>More...</a></p>Transit peptidei1 – 31MitochondrionAdd BLAST31
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000002694532 – 1331 PublicationAdd BLAST102
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000026946134 – 458Serine protease HTRA2, mitochondrialAdd BLAST325

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autoproteolytically activated.

Keywords - PTMi

Autocatalytic cleavage, Zymogen

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		O43464

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O43464

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O43464

MaxQB - The MaxQuant DataBase

More...MaxQBi		O43464

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O43464

PeptideAtlas

More...PeptideAtlasi		O43464

PRoteomics IDEntifications database

More...PRIDEi		O43464

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		48958 [O43464-1]
48959 [O43464-2]
48960 [O43464-3]
48961 [O43464-4]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		O43464-2 [O43464-2]

2D gel databases

USC-OGP 2-DE database

More...OGPi		O43464

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O43464

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O43464

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000115317, Expressed in liver and 234 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O43464, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O43464, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000115317, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotrimer.

Interacts with MXI2.

Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4.

Interacts with BIRC6/bruce.

4 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

O43464
With#Exp.IntAct
ANKRD13D - isoform 2 [Q6ZTN6-2]3EBI-517086,EBI-25840993
ARNT2 [Q86TN1]3EBI-517086,EBI-25844820
ASB3 - isoform 3 [Q9Y575-3]3EBI-517086,EBI-14199987
ASB9 - isoform 3 [Q96DX5-3]3EBI-517086,EBI-25843552
ASIC4 - isoform 3 [Q96FT7-4]3EBI-517086,EBI-9089489
BIRC7 [Q96CA5]2EBI-517086,EBI-517623
CENPV [Q7Z7K6]3EBI-517086,EBI-1210604
CRYAA2 [A0A140G945]3EBI-517086,EBI-25838900
DCAF8 - isoform 2 [Q5TAQ9-2]3EBI-517086,EBI-25842815
EIF3F [O00303]3EBI-517086,EBI-711990
ENKUR [Q8TC29]3EBI-517086,EBI-9246952
ERCC8 - isoform 2 [Q13216-2]3EBI-517086,EBI-16466949
HAUS7 [Q99871]3EBI-517086,EBI-395719
ID2 [Q02363]3EBI-517086,EBI-713450
IFT20 - isoform 2 [Q8IY31-2]3EBI-517086,EBI-11742277
KCTD17 [Q8N5Z5]3EBI-517086,EBI-743960
KLC3 [Q6P597]3EBI-517086,EBI-1643885
KLF3 [P57682]3EBI-517086,EBI-8472267
KLHL20 [Q9Y2M5]3EBI-517086,EBI-714379
KRT19 [P08727]3EBI-517086,EBI-742756
KRT33B [Q14525]3EBI-517086,EBI-1049638
LONRF2 [Q1L5Z9]3EBI-517086,EBI-2510853
MAP3K5 [Q99683]3EBI-517086,EBI-476263
MARCHF10 [Q8NA82]3EBI-517086,EBI-2341554
MPND [Q8N594]3EBI-517086,EBI-2512452
MYLIP [Q8WY64]3EBI-517086,EBI-6952711
NDUFA13 [Q9P0J0]6EBI-517086,EBI-372742
NEUROD1 [Q13562]3EBI-517086,EBI-3908303
NVL - isoform 5 [O15381-5]3EBI-517086,EBI-18577082
OTUB1 [Q96FW1]3EBI-517086,EBI-1058491
OTUD7B - isoform 2 [Q6GQQ9-2]3EBI-517086,EBI-25830200
OTULINL [Q9NUU6]3EBI-517086,EBI-6916492
PATZ1 - isoform 4 [Q9HBE1-4]3EBI-517086,EBI-11022007
PCMTD2 [Q9NV79]3EBI-517086,EBI-6309018
PHOX2A [O14813]3EBI-517086,EBI-25844430
PIAS1 [O75925]3EBI-517086,EBI-629434
PIH1D2 [Q8WWB5]3EBI-517086,EBI-10232538
PPP1R16B [Q96T49]3EBI-517086,EBI-10293968
PPP1R21 - isoform 5 [Q6ZMI0-5]3EBI-517086,EBI-25835994
PSMC3 [P17980]3EBI-517086,EBI-359720
RBM11 [P57052]3EBI-517086,EBI-741332
RNF138 [Q8WVD3]3EBI-517086,EBI-749039
RNF183 [Q96D59]3EBI-517086,EBI-743938
RUSF1 [Q96GQ5]3EBI-517086,EBI-8636004
RYBP [Q8N488]3EBI-517086,EBI-752324
SAMD3 - isoform 2 [Q8N6K7-2]3EBI-517086,EBI-11528848
SH3GLB2 [Q9NR46]3EBI-517086,EBI-749607
SMARCD1 [Q96GM5]3EBI-517086,EBI-358489
SMN2 - isoform SMN-delta7 [Q16637-3]3EBI-517086,EBI-395447
SOCS4 [Q8WXH5]3EBI-517086,EBI-3942425
TASOR2 [Q5VWN6]3EBI-517086,EBI-745958
TEN1 [Q86WV5]3EBI-517086,EBI-2562799
TNFSF15 [O95150]3EBI-517086,EBI-16355546
TTC19 [Q6DKK2]3EBI-517086,EBI-948354
USH1G [Q495M9]3EBI-517086,EBI-8601749
USP2 - isoform 3 [O75604-3]3EBI-517086,EBI-10696113
VPS37A [Q8NEZ2]3EBI-517086,EBI-2850578
WTAP - isoform 2 [Q15007-2]3EBI-517086,EBI-25840023
WWP2 [O00308]3EBI-517086,EBI-743923
XIAP [P98170]20EBI-517086,EBI-517127
ZBTB25 [P24278]3EBI-517086,EBI-739899
ZNF232 [Q9UNY5]3EBI-517086,EBI-749023
ZNF444 - isoform 2 [Q8N0Y2-2]3EBI-517086,EBI-12010736
ZNF500 [O60304]3EBI-517086,EBI-18234077
ZSCAN9 [O15535]3EBI-517086,EBI-751531
Q86V283EBI-517086,EBI-10259496
CSN2 [P02666] from Bos taurus.7EBI-517086,EBI-5260183
Ripk1 [Q60855] from Mus musculus.2EBI-517086,EBI-529119

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		118165, 230 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O43464

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		O43464

Protein interaction database and analysis system

More...IntActi		O43464, 116 interactors

Molecular INTeraction database

More...MINTi		O43464

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000258080

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O43464, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O43464

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O43464

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini364 – 445PDZPROSITE-ProRule annotationAdd BLAST82

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni166 – 342Serine proteaseAdd BLAST177

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi134 – 137IAP-binding motif4

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The mature N-terminus is involved in the interaction with XIAP.
The PDZ domain mediates interaction with MXI2.

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the peptidase S1C family.Curated

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1320, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000155108

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_020120_6_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O43464

Identification of Orthologs from Complete Genome Data

More...OMAi		PEPRTCL

Database of Orthologous Groups

More...OrthoDBi		630723at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O43464

TreeFam database of animal gene trees

More...TreeFami		TF323480

Family and domain databases

Database of protein disorder

More...DisProti		DP00315

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.30.42.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR001478, PDZ
IPR041489, PDZ_6
IPR036034, PDZ_sf
IPR009003, Peptidase_S1_PA
IPR001940, Peptidase_S1C

Pfam protein domain database

More...Pfami		View protein in Pfam
PF17820, PDZ_6, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00834, PROTEASES2C

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00228, PDZ, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF50156, SSF50156, 1 hit
SSF50494, SSF50494, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50106, PDZ, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O43464-1) [UniParc]FASTAAdd to basket
Also known as: 13B

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAAPRAGRGA GWSLRAWRAL GGIRWGRRPR LTPDLRALLT SGTSDPRARV 
        60         70         80         90        100
TYGTPSLWAR LSVGVTEPRA CLTSGTPGPR AQLTAVTPDT RTREASENSG 
       110        120        130        140        150
TRSRAWLAVA LGAGGAVLLL LWGGGRGPPA VLAAVPSPPP ASPRSQYNFI 
       160        170        180        190        200
ADVVEKTAPA VVYIEILDRH PFLGREVPIS NGSGFVVAAD GLIVTNAHVV 
       210        220        230        240        250
ADRRRVRVRL LSGDTYEAVV TAVDPVADIA TLRIQTKEPL PTLPLGRSAD 
       260        270        280        290        300
VRQGEFVVAM GSPFALQNTI TSGIVSSAQR PARDLGLPQT NVEYIQTDAA 
       310        320        330        340        350
IDFGNSGGPL VNLDGEVIGV NTMKVTAGIS FAIPSDRLRE FLHRGEKKNS 
       360        370        380        390        400
SSGISGSQRR YIGVMMLTLS PSILAELQLR EPSFPDVQHG VLIHKVILGS 
       410        420        430        440        450
PAHRAGLRPG DVILAIGEQM VQNAEDVYEA VRTQSQLAVQ IRRGRETLTL 

YVTPEVTE
Length:458
Mass (Da):48,841
Last modified:May 1, 2000 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iCEA955A7D0DD8C0D
GO
Isoform 2 (identifier: O43464-2) [UniParc]FASTAAdd to basket
Also known as: D-Omi

The sequence of this isoform differs from the canonical sequence as follows:
     238-302: Missing.
     372-403: Missing.

Show »
Length:361
Mass (Da):38,493
Checksum:iBD0824D4308140D7
GO
Isoform 3 (identifier: O43464-3) [UniParc]FASTAAdd to basket
Also known as: p7

The sequence of this isoform differs from the canonical sequence as follows:
     313-313: L → LARELGAVSLQ
     372-403: Missing.

Show »
Length:436
Mass (Da):46,382
Checksum:iB48266A8EB7E4EE8
GO
Isoform 4 (identifier: O43464-4) [UniParc]FASTAAdd to basket
Also known as: p4

The sequence of this isoform differs from the canonical sequence as follows:
     314-458: DGEVIGVNTM...TLYVTPEVTE → VSETSFLPRI...FGCPHPLLFV

Show »
Length:377
Mass (Da):39,914
Checksum:i14D0982E08A58FB2
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DG44A0A0C4DG44_HUMAN
Serine protease HTRA2, mitochondria...
HTRA2
423Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07696712W → C1 PublicationCorresponds to variant dbSNP:rs775840965Ensembl.1
Natural variantiVAR_04613472L → P1 PublicationCorresponds to variant dbSNP:rs150047108EnsemblClinVar.1
Natural variantiVAR_076968128P → L1 PublicationCorresponds to variant dbSNP:rs757704467Ensembl.1
Natural variantiVAR_027349141A → S May be a risk factor for Parkinson disease; reduced protease activity. 3 PublicationsCorresponds to variant dbSNP:rs72470544EnsemblClinVar.1
Natural variantiVAR_076969227A → S1 PublicationCorresponds to variant dbSNP:rs375322953Ensembl.1
Natural variantiVAR_077960243 – 244LP → PS in MGCA8; loss of protein expression. 1 PublicationCorresponds to variant dbSNP:rs1057519082Ensembl.2
Natural variantiVAR_027350399G → S May be a risk factor for Parkinson disease; reduced protease activity. 4 PublicationsCorresponds to variant dbSNP:rs72470545Ensembl.1
Natural variantiVAR_077961404R → Q in MGCA8; may lead to skipping of exon 7 and the resultant protein may be truncated; loss of protein expression in patient cells homozygous for the mutation. 1 PublicationCorresponds to variant dbSNP:rs767006508Ensembl.1
Natural variantiVAR_046135404R → W in PARK13. 1 PublicationCorresponds to variant dbSNP:rs1380794702Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_005359238 – 302Missing in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_005360313L → LARELGAVSLQ in isoform 3. 1 Publication1
Alternative sequenceiVSP_005362314 – 458DGEVI…PEVTE → VSETSFLPRIPAPGQCGKGR FPLIQGCLVKFLSSSLLAIS QYPTRSPQHLLVLLFGCPHP LLFV in isoform 4. 1 PublicationAdd BLAST145
Alternative sequenceiVSP_005361372 – 403Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST32

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF020760 mRNA Translation: AAB94569.2
AF141305 mRNA Translation: AAF66596.1
AF141306 mRNA Translation: AAF66597.1
AF141307 mRNA Translation: AAF66598.1
AF184911 mRNA Translation: AAG13126.1
AC006544 Genomic DNA No translation available.
BC000096 mRNA Translation: AAH00096.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS1951.1 [O43464-1]
CCDS1952.1 [O43464-2]

NCBI Reference Sequences

More...RefSeqi		NP_001308656.1, NM_001321727.1 [O43464-3]
NP_037379.1, NM_013247.4 [O43464-1]
NP_659540.1, NM_145074.2 [O43464-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000258080; ENSP00000258080; ENSG00000115317 [O43464-1]
ENST00000352222; ENSP00000312893; ENSG00000115317 [O43464-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		27429

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:27429

UCSC genome browser

More...UCSCi		uc002smi.2, human [O43464-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020760 mRNA Translation: AAB94569.2
AF141305 mRNA Translation: AAF66596.1
AF141306 mRNA Translation: AAF66597.1
AF141307 mRNA Translation: AAF66598.1
AF184911 mRNA Translation: AAG13126.1
AC006544 Genomic DNA No translation available.
BC000096 mRNA Translation: AAH00096.1
CCDSiCCDS1951.1 [O43464-1]
CCDS1952.1 [O43464-2]
RefSeqiNP_001308656.1, NM_001321727.1 [O43464-3]
NP_037379.1, NM_013247.4 [O43464-1]
NP_659540.1, NM_145074.2 [O43464-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LCYX-ray2.00A134-458[»]
2PZDX-ray2.75A/B359-458[»]
5FHTX-ray1.95A134-458[»]
5M3NX-ray1.65A134-458[»]
5M3OX-ray1.70A134-458[»]
5TNYX-ray1.70A134-458[»]
5TNZX-ray1.75A134-458[»]
5TO0X-ray1.90A134-458[»]
5TO1X-ray1.69A134-458[»]
5WYNX-ray2.05A134-458[»]
SMRiO43464
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi118165, 230 interactors
CORUMiO43464
ELMiO43464
IntActiO43464, 116 interactors
MINTiO43464
STRINGi9606.ENSP00000258080

Protein family/group databases

MEROPSiS01.278
MoonDBiO43464, Predicted

PTM databases

iPTMnetiO43464
PhosphoSitePlusiO43464

Genetic variation databases

BioMutaiHTRA2

2D gel databases

OGPiO43464

Proteomic databases

EPDiO43464
jPOSTiO43464
MassIVEiO43464
MaxQBiO43464
PaxDbiO43464
PeptideAtlasiO43464
PRIDEiO43464
ProteomicsDBi48958 [O43464-1]
48959 [O43464-2]
48960 [O43464-3]
48961 [O43464-4]
TopDownProteomicsiO43464-2 [O43464-2]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		O43464, 1 sequenced antibody

Antibodypedia a portal for validated antibodies

More...Antibodypediai		3554, 740 antibodies

The DNASU plasmid repository

More...DNASUi		27429

Genome annotation databases

EnsembliENST00000258080; ENSP00000258080; ENSG00000115317 [O43464-1]
ENST00000352222; ENSP00000312893; ENSG00000115317 [O43464-2]
GeneIDi27429
KEGGihsa:27429
UCSCiuc002smi.2, human [O43464-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		27429
DisGeNETi27429

GeneCards: human genes, protein and diseases

More...GeneCardsi		HTRA2
HGNCiHGNC:14348, HTRA2
HPAiENSG00000115317, Low tissue specificity
MalaCardsiHTRA2
MIMi168600, phenotype
606441, gene
610297, phenotype
617248, phenotype
neXtProtiNX_O43464
OpenTargetsiENSG00000115317
Orphaneti505208, 3-methylglutaconic aciduria type 8
2828, Young-onset Parkinson disease
PharmGKBiPA33836
VEuPathDBiHostDB:ENSG00000115317.11

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1320, Eukaryota
GeneTreeiENSGT00940000155108
HOGENOMiCLU_020120_6_0_1
InParanoidiO43464
OMAiPEPRTCL
OrthoDBi630723at2759
PhylomeDBiO43464
TreeFamiTF323480

Enzyme and pathway databases

BRENDAi3.4.21.108, 2681
PathwayCommonsiO43464
SIGNORiO43464

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		27429, 79 hits in 878 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		HTRA2, human
EvolutionaryTraceiO43464

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		HtrA_serine_peptidase_2

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		27429
PharosiO43464, Tbio

Protein Ontology

More...PROi		PR:O43464
RNActiO43464, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000115317, Expressed in liver and 234 other tissues
ExpressionAtlasiO43464, baseline and differential
GenevisibleiO43464, HS

Family and domain databases

DisProtiDP00315
Gene3Di2.30.42.10, 1 hit
InterProiView protein in InterPro
IPR001478, PDZ
IPR041489, PDZ_6
IPR036034, PDZ_sf
IPR009003, Peptidase_S1_PA
IPR001940, Peptidase_S1C
PfamiView protein in Pfam
PF17820, PDZ_6, 1 hit
PRINTSiPR00834, PROTEASES2C
SMARTiView protein in SMART
SM00228, PDZ, 1 hit
SUPFAMiSSF50156, SSF50156, 1 hit
SSF50494, SSF50494, 1 hit
PROSITEiView protein in PROSITE
PS50106, PDZ, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHTRA2_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O43464
Secondary accession number(s): Q9HBZ4, Q9P0Y3, Q9P0Y4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: February 10, 2021
This is version 218 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human variants curated from literature reports
    Index of human variants curated from literature reports
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
  5. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  6. Human entries with genetic variants
    List of human entries with genetic variants
  7. Peptidase families
    Classification of peptidase families and list of entries
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