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Protein

Serine protease HTRA3

Gene

HTRA3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization (PubMed:21321049, PubMed:22229724).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei191Charge relay system1 Publication1
Active sitei227Charge relay system1 Publication1
Active sitei305Charge relay system2 Publications1

GO - Molecular functioni

  • endopeptidase activity Source: BHF-UCL
  • serine-type endopeptidase activity Source: InterPro
  • serine-type peptidase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170801-MONOMER.

Protein family/group databases

MEROPSiS01.284.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine protease HTRA3 (EC:3.4.21.-)
Alternative name(s):
High-temperature requirement factor A3
Pregnancy-related serine protease
Gene namesi
Name:HTRA3
Synonyms:PRSP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:30406. HTRA3.

Subcellular locationi

  • Secreted 1 Publication

  • Note: Secretion increased during decidualization of endometrial stromal cells.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi305S → A: Abolishes protease activity. Stabilizes the protein. 1 Publication1

Organism-specific databases

DisGeNETi94031.
MalaCardsiHTRA3.
OpenTargetsiENSG00000170801.
PharmGKBiPA134908281.

Polymorphism and mutation databases

BioMutaiHTRA3.
DMDMi21542412.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000002694918 – 453Serine protease HTRA3Add BLAST436

Proteomic databases

MaxQBiP83110.
PaxDbiP83110.
PeptideAtlasiP83110.
PRIDEiP83110.

PTM databases

iPTMnetiP83110.
PhosphoSitePlusiP83110.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in both adult and fetal heart, ovary, uterus placenta, and bladder. In the endometrium, expressed in epithelial glands and the stroma. Also present in leukocytes. Isoform 1 is predominant in heart and skeletal muscle, whereas isoform 2 is predominant in placenta and kidney.3 Publications

Inductioni

Down-regulated in ovarian and endometrial cancers (EC). Decrease of 3.2-fold in endometrial cancer.2 Publications

Gene expression databases

BgeeiENSG00000170801.
CleanExiHS_HTRA3.
GenevisibleiP83110. HS.

Organism-specific databases

HPAiHPA021187.
HPA063810.

Interactioni

Subunit structurei

Homotrimer (PubMed:26110759). Interacts with TGFB1; the interaction inhibits TGFB-mediated signaling. Interacts with BMP4; the interaction inhibits BMP4-mediated signaling. Interacts with TGFB2 and GDF5 (By similarity). Interacts with MYH9.By similarity3 Publications

Protein-protein interaction databases

BioGridi125099. 1 interactor.
IntActiP83110. 2 interactors.
MINTiMINT-4786544.
STRINGi9606.ENSP00000303766.

Structurei

Secondary structure

1453
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi136 – 139Combined sources4
Helixi142 – 150Combined sources9
Helixi151 – 153Combined sources3
Beta strandi154 – 161Combined sources8
Beta strandi166 – 168Combined sources3
Beta strandi171 – 181Combined sources11
Turni182 – 184Combined sources3
Beta strandi185 – 188Combined sources4
Turni190 – 193Combined sources4
Beta strandi203 – 208Combined sources6
Beta strandi214 – 223Combined sources10
Turni224 – 227Combined sources4
Beta strandi228 – 233Combined sources6
Helixi247 – 249Combined sources3
Beta strandi255 – 260Combined sources6
Beta strandi268 – 274Combined sources7
Beta strandi294 – 298Combined sources5
Turni302 – 306Combined sources5
Beta strandi307 – 310Combined sources4
Beta strandi316 – 325Combined sources10
Beta strandi328 – 333Combined sources6
Helixi334 – 342Combined sources9
Beta strandi354 – 356Combined sources3
Beta strandi359 – 363Combined sources5
Helixi366 – 375Combined sources10
Beta strandi384 – 391Combined sources8
Helixi396 – 400Combined sources5
Beta strandi407 – 411Combined sources5
Helixi419 – 428Combined sources10
Beta strandi430 – 438Combined sources9
Beta strandi441 – 447Combined sources7
Beta strandi450 – 452Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P3WX-ray1.70A/B354-453[»]
4RI0X-ray3.27A/B/C130-453[»]
ProteinModelPortaliP83110.
SMRiP83110.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP83110.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 77IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST57
Domaini64 – 128Kazal-likePROSITE-ProRule annotationAdd BLAST65
Domaini359 – 444PDZPROSITE-ProRule annotationAdd BLAST86

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 340Serine proteaseAdd BLAST166

Sequence similaritiesi

Belongs to the peptidase S1C family.Curated
Contains 1 IGFBP N-terminal domain.PROSITE-ProRule annotation
Contains 1 Kazal-like domain.PROSITE-ProRule annotation
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiP83110.
KOiK08785.
OMAiCRWSHAV.
OrthoDBiEOG091G0LXR.
PhylomeDBiP83110.
TreeFamiTF323480.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR000867. IGFBP-like.
IPR002350. Kazal_dom.
IPR001478. PDZ.
IPR009003. Peptidase_S1_PA.
IPR001940. Peptidase_S1C.
[Graphical view]
PfamiPF00219. IGFBP. 1 hit.
PF07648. Kazal_2. 1 hit.
PF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSiPR00834. PROTEASES2C.
SMARTiSM00121. IB. 1 hit.
SM00280. KAZAL. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS51323. IGFBP_N_2. 1 hit.
PS51465. KAZAL_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P83110-1) [UniParc]FASTAAdd to basket
Also known as: Long, pL

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
MQARALLLAA LAALALAREP PAAPCPARCD VSRCPSPRCP GGYVPDLCNC
60 70 80 90 100
CLVCAASEGE PCGGPLDSPC GESLECVRGL CRCRWSHAVC GTDGHTYANV
110 120 130 140 150
CALQAASRRA LQLSGTPVRQ LQKGACPLGL HQLSSPRYKF NFIADVVEKI
160 170 180 190 200
APAVVHIELF LRHPLFGRNV PLSSGSGFIM SEAGLIITNA HVVSSNSAAP
210 220 230 240 250
GRQQLKVQLQ NGDSYEATIK DIDKKSDIAT IKIHPKKKLP VLLLGHSADL
260 270 280 290 300
RPGEFVVAIG SPFALQNTVT TGIVSTAQRE GRELGLRDSD MDYIQTDAII
310 320 330 340 350
NYGNSGGPLV NLDGEVIGIN TLKVTAGISF AIPSDRITRF LTEFQDKQIK
360 370 380 390 400
DWKKRFIGIR MRTITPSLVD ELKASNPDFP EVSSGIYVQE VAPNSPSQRG
410 420 430 440 450
GIQDGDIIVK VNGRPLVDSS ELQEAVLTES PLLLEVRRGN DDLLFSIAPE

VVM
Length:453
Mass (Da):48,608
Last modified:June 20, 2002 - v2
Checksum:i3046FCDA1AB24FA6
GO
Isoform 2 (identifier: P83110-2) [UniParc]FASTAAdd to basket
Also known as: Short, pS

The sequence of this isoform differs from the canonical sequence as follows:
     351-357: DWKKRFI → APSLAVH
     358-453: Missing.

Show »
Length:357
Mass (Da):37,940
Checksum:i8A62D2B9823BC420
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012570351 – 357DWKKRFI → APSLAVH in isoform 2. 1 Publication7
Alternative sequenceiVSP_012571358 – 453Missing in isoform 2. 1 PublicationAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY280665 mRNA. Translation: AAP42282.1.
AY280666 mRNA. Translation: AAP42283.1.
AY040094 mRNA. Translation: AAK71475.2.
AC113611 Genomic DNA. No translation available.
BC034390 mRNA. Translation: AAH34390.1.
BC035717 mRNA. Translation: AAH35717.1.
CCDSiCCDS3400.1. [P83110-1]
CCDS75105.1. [P83110-2]
RefSeqiNP_001284488.1. NM_001297559.1. [P83110-2]
NP_444272.1. NM_053044.4. [P83110-1]
UniGeneiHs.479119.

Genome annotation databases

EnsembliENST00000307358; ENSP00000303766; ENSG00000170801. [P83110-1]
ENST00000382512; ENSP00000371952; ENSG00000170801. [P83110-2]
GeneIDi94031.
KEGGihsa:94031.
UCSCiuc003gkz.4. human. [P83110-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY280665 mRNA. Translation: AAP42282.1.
AY280666 mRNA. Translation: AAP42283.1.
AY040094 mRNA. Translation: AAK71475.2.
AC113611 Genomic DNA. No translation available.
BC034390 mRNA. Translation: AAH34390.1.
BC035717 mRNA. Translation: AAH35717.1.
CCDSiCCDS3400.1. [P83110-1]
CCDS75105.1. [P83110-2]
RefSeqiNP_001284488.1. NM_001297559.1. [P83110-2]
NP_444272.1. NM_053044.4. [P83110-1]
UniGeneiHs.479119.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P3WX-ray1.70A/B354-453[»]
4RI0X-ray3.27A/B/C130-453[»]
ProteinModelPortaliP83110.
SMRiP83110.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125099. 1 interactor.
IntActiP83110. 2 interactors.
MINTiMINT-4786544.
STRINGi9606.ENSP00000303766.

Protein family/group databases

MEROPSiS01.284.

PTM databases

iPTMnetiP83110.
PhosphoSitePlusiP83110.

Polymorphism and mutation databases

BioMutaiHTRA3.
DMDMi21542412.

Proteomic databases

MaxQBiP83110.
PaxDbiP83110.
PeptideAtlasiP83110.
PRIDEiP83110.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307358; ENSP00000303766; ENSG00000170801. [P83110-1]
ENST00000382512; ENSP00000371952; ENSG00000170801. [P83110-2]
GeneIDi94031.
KEGGihsa:94031.
UCSCiuc003gkz.4. human. [P83110-1]

Organism-specific databases

CTDi94031.
DisGeNETi94031.
GeneCardsiHTRA3.
HGNCiHGNC:30406. HTRA3.
HPAiHPA021187.
HPA063810.
MalaCardsiHTRA3.
MIMi608785. gene.
neXtProtiNX_P83110.
OpenTargetsiENSG00000170801.
PharmGKBiPA134908281.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiP83110.
KOiK08785.
OMAiCRWSHAV.
OrthoDBiEOG091G0LXR.
PhylomeDBiP83110.
TreeFamiTF323480.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170801-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP83110.
GenomeRNAii94031.
PROiP83110.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170801.
CleanExiHS_HTRA3.
GenevisibleiP83110. HS.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
InterProiIPR009030. Growth_fac_rcpt_.
IPR000867. IGFBP-like.
IPR002350. Kazal_dom.
IPR001478. PDZ.
IPR009003. Peptidase_S1_PA.
IPR001940. Peptidase_S1C.
[Graphical view]
PfamiPF00219. IGFBP. 1 hit.
PF07648. Kazal_2. 1 hit.
PF13180. PDZ_2. 1 hit.
[Graphical view]
PRINTSiPR00834. PROTEASES2C.
SMARTiSM00121. IB. 1 hit.
SM00280. KAZAL. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF57184. SSF57184. 1 hit.
PROSITEiPS51323. IGFBP_N_2. 1 hit.
PS51465. KAZAL_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHTRA3_HUMAN
AccessioniPrimary (citable) accession number: P83110
Secondary accession number(s): Q7Z7A2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: June 20, 2002
Last modified: November 2, 2016
This is version 139 of the entry and version 2 of the sequence. [Complete history]
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  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. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.