Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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_section">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 ‘Function’ 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

  • identical protein binding Source: CAFA
  • peptidase activity Source: UniProtKB
  • serine-type endopeptidase activity Source: UniProtKB
  • serine-type peptidase activity Source: UniProtKB
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

<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

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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_manual">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

Eukaryotic Pathogen Database Resources

More...
EuPathDBi
HostDB:ENSG00000115317.11

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

<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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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 mutations 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.
See also OMIM:617248
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:rs767006508EnsemblClinVar.1
Parkinson disease 13 (PARK13)2 Publications
Disease susceptibility is associated with variations 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.
See also OMIM:610297
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046135404R → W in PARK13. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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 mutation, 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

Polymorphism and mutation 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_processing_section">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.<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_processing_section">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

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 human proteome resource

More...
ProteomicsDBi
48958
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

Miscellaneous databases

CutDB - Proteolytic event database

More...
PMAP-CutDBi
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 221 organ(s), highest expression level in liver

CleanEx database of gene expression profiles

More...
CleanExi
HS_HTRA2

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
CAB004004
HPA006602
HPA027366

<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_section">'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_section">'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_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
118165, 72 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, 47 interactors

Molecular INTeraction database

More...
MINTi
O43464

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000258080

<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

Database of protein disorder

More...
DisProti
DP00315

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

More...
ProteinModelPortali
O43464

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

More...
SMRi
O43464

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
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_and_domains_section">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
COG0265 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000155108

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000223641

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG052044

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
O43464

KEGG Orthology (KO)

More...
KOi
K08669

Identification of Orthologs from Complete Genome Data

More...
OMAi
VLVWKVI

Database of Orthologous Groups

More...
OrthoDBi
EOG091G0LXR

Database for complete collections of gene phylogenies

More...
PhylomeDBi
O43464

TreeFam database of animal gene trees

More...
TreeFami
TF323480

Family and domain databases

Integrated resource of protein families, domains and functional sites

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

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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.<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 'canonical' 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 Polymorphism; 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 Polymorphism; may be a risk factor for Parkinson disease; reduced protease activity. 4 PublicationsCorresponds to variant dbSNP:rs72470545EnsemblClinVar.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:rs767006508EnsemblClinVar.1
Natural variantiVAR_046135404R → W in PARK13. 1 Publication1

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. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<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]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.469045
Hs.744841

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, Polymorphism

<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_references_section">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]
UniGeneiHs.469045
Hs.744841

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[»]
DisProtiDP00315
ProteinModelPortaliO43464
SMRiO43464
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118165, 72 interactors
CORUMiO43464
ELMiO43464
IntActiO43464, 47 interactors
MINTiO43464
STRINGi9606.ENSP00000258080

Protein family/group databases

MEROPSiS01.278
MoonDBiO43464 Predicted

PTM databases

iPTMnetiO43464
PhosphoSitePlusiO43464

Polymorphism and mutation databases

BioMutaiHTRA2

2D gel databases

OGPiO43464

Proteomic databases

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

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
27429
Structural Biology KnowledgebaseSearch...

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
EuPathDBiHostDB:ENSG00000115317.11

GeneCards: human genes, protein and diseases

More...
GeneCardsi
HTRA2
HGNCiHGNC:14348 HTRA2
HPAiCAB004004
HPA006602
HPA027366
MalaCardsiHTRA2
MIMi168600 phenotype
606441 gene
610297 phenotype
617248 phenotype
neXtProtiNX_O43464
OpenTargetsiENSG00000115317
Orphaneti505208 3-methylglutaconic aciduria type 8
2828 Young-onset Parkinson disease
PharmGKBiPA33836

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1320 Eukaryota
COG0265 LUCA
GeneTreeiENSGT00940000155108
HOGENOMiHOG000223641
HOVERGENiHBG052044
InParanoidiO43464
KOiK08669
OMAiVLVWKVI
OrthoDBiEOG091G0LXR
PhylomeDBiO43464
TreeFamiTF323480

Enzyme and pathway databases

BRENDAi3.4.21.108 2681
SIGNORiO43464

Miscellaneous databases

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
PMAP-CutDBiO43464

Protein Ontology

More...
PROi
PR:O43464

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000115317 Expressed in 221 organ(s), highest expression level in liver
CleanExiHS_HTRA2
ExpressionAtlasiO43464 baseline and differential
GenevisibleiO43464 HS

Family and domain databases

InterProiView protein in InterPro
IPR001478 PDZ
IPR036034 PDZ_sf
IPR009003 Peptidase_S1_PA
IPR001940 Peptidase_S1C
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...

<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_and_isoforms">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: December 5, 2018
This is version 202 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again