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Protein

Serine protease HTRA3

Gene

Htra3

Organism
Mus musculus (Mouse)
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 (PubMed:15206957). 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 (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei197 – 1971Charge relay systemBy similarity
Active sitei233 – 2331Charge relay systemBy similarity
Active sitei311 – 3111Charge relay systemBy similarity

GO - Molecular functioni

GO - Biological processi

  • negative regulation of BMP signaling pathway Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • proteolysis Source: UniProtKB
  • regulation of cell growth Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

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
Toll-associated serine protease
Gene namesi
Name:Htra3
Synonyms:Prsp, Tasp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1925808. Htra3.

Subcellular locationi

  • Secreted By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi311 – 3111S → A: Abolishes protease activity. No inhibition of BMP4-mediated signaling. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 459436Serine protease HTRA3PRO_0000026950Add
BLAST

Proteomic databases

MaxQBiQ9D236.
PaxDbiQ9D236.
PRIDEiQ9D236.

PTM databases

iPTMnetiQ9D236.
PhosphoSiteiQ9D236.

Expressioni

Tissue specificityi

Highest level of isoform 1 in maternal part of the placenta, moderate level in heart, testis and ovary, low level in muscle and lung. High expression found in granulosa cells of the ovary. Expressed in bone matrix, particularly in articular chondrocytes. Very low level of isoform 2 expressed in placenta. Expressed in the bone matrix, particularly in articular chondrocytes.3 Publications

Developmental stagei

First expressed at E9.5. Levels then increase until E14.5 after which they remain high until newborn. First detected in the eye at E10.5 and then expressed in tissues associated with skeletal tissue. At E12.5 expressed in the vertebral rudiments in the tail region and, in the developing eye, in lens epithelium. At adulthood, expression found in the ganglion cell layer and the inner nuclear layer of the retina. In the developing heart at E16.5, expressed in the endocardial cushion. In the trachea at this stage, in outer layers and in the aorta, in adventitia.2 Publications

Inductioni

Up-regulated during early pregnancy coinciding with placentation. Also up-regulated in joint cartilage affected by arthritis.2 Publications

Gene expression databases

BgeeiQ9D236.
CleanExiMM_HTRA3.
ExpressionAtlasiQ9D236. baseline and differential.
GenevisibleiQ9D236. MM.

Interactioni

Subunit structurei

Homotrimer (By similarity). Interacts with MYH9 (By similarity). Interacts with TGFB1; the interaction inhibits TGFB-mediated signaling. Interacts with BMP4; the interaction inhibits BMP4-mediated signaling. Interacts with TGFB2 and GDF5.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000084910.

Structurei

3D structure databases

ProteinModelPortaliQ9D236.
SMRiQ9D236. Positions 31-131, 136-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 8357IGFBP N-terminalPROSITE-ProRule annotationAdd
BLAST
Domaini76 – 13459Kazal-likePROSITE-ProRule annotationAdd
BLAST
Domaini365 – 45086PDZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni181 – 347167Serine proteaseAdd
BLAST

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.
InParanoidiQ9D236.
KOiK08785.
OMAiCESGHLQ.
OrthoDBiEOG7V1FR7.
PhylomeDBiQ9D236.
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9D236-3) [UniParc]FASTAAdd to basket

Also known as: A, Long

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
MQARALLPAT LAILATLAVL ALAREPPAAP CPARCDVSRC PSPRCPGGYV
60 70 80 90 100
PDLCNCCLVC AASEGEPCGR PLDSPCGDSL ECVRGVCRCR WTHTVCGTDG
110 120 130 140 150
HTYADVCALQ AASRRALQVS GTPVRQLQKG ACPSGLHQLT SPRYKFNFIA
160 170 180 190 200
DVVEKIAPAV VHIELFLRHP LFGRNVPLSS GSGFIMSEAG LIVTNAHVVS
210 220 230 240 250
SSSTASGRQQ LKVQLQNGDA YEATIQDIDK KSDIATIVIH PKKKLPVLLL
260 270 280 290 300
GHSADLRPGE FVVAIGSPFA LQNTVTTGIV STAQRDGKEL GLRDSDMDYI
310 320 330 340 350
QTDAIINYGN SGGPLVNLDG EVIGINTLKV AAGISFAIPS DRITRFLSEF
360 370 380 390 400
QNKHVKDWKK RFIGIRMRTI TPSLVEELKA ANPDFPAVSS GIYVQEVVPN
410 420 430 440 450
SPSQRGGIQD GDIIVKVNGR PLADSSELQE AVLNESSLLL EVRRGNDDLL

FSIIPEVVM
Length:459
Mass (Da):49,149
Last modified:May 2, 2006 - v3
Checksum:iE13C6042DC4AFF64
GO
Isoform 2 (identifier: Q9D236-4) [UniParc]FASTAAdd to basket

Also known as: B, Short

The sequence of this isoform differs from the canonical sequence as follows:
     357-363: DWKKRFI → ALSPALH
     364-459: Missing.

Show »
Length:363
Mass (Da):38,510
Checksum:iF8454CF274FE007B
GO
Isoform 3 (identifier: Q9D236-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     266-278: GSPFALQNTVTTG → ESPLCPAEHRDKC

Show »
Length:459
Mass (Da):49,342
Checksum:i3886D70109328C82
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti286 – 2861D → T in AAK70226 (Ref. 2) Curated
Sequence conflicti440 – 4401L → AA in AAK70226 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei266 – 27813GSPFA…TVTTG → ESPLCPAEHRDKC in isoform 3. 1 PublicationVSP_018127Add
BLAST
Alternative sequencei357 – 3637DWKKRFI → ALSPALH in isoform 2. 1 PublicationVSP_018128
Alternative sequencei364 – 45996Missing in isoform 2. 1 PublicationVSP_018129Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY156509 mRNA. Translation: AAO17289.1.
AY280664 mRNA. Translation: AAQ16583.1.
AY037300 mRNA. Translation: AAK70226.1.
BC138587 mRNA. Translation: AAI38588.1.
BC138588 mRNA. Translation: AAI38589.1.
CCDSiCCDS19233.1. [Q9D236-3]
CCDS39071.1. [Q9D236-4]
RefSeqiNP_001036080.1. NM_001042615.2. [Q9D236-4]
NP_084403.2. NM_030127.3. [Q9D236-3]
UniGeneiMm.274255.

Genome annotation databases

EnsembliENSMUST00000087629; ENSMUSP00000084910; ENSMUSG00000029096. [Q9D236-3]
ENSMUST00000114233; ENSMUSP00000109871; ENSMUSG00000029096. [Q9D236-4]
GeneIDi78558.
KEGGimmu:78558.
UCSCiuc008xea.2. mouse. [Q9D236-3]
uc008xeb.2. mouse. [Q9D236-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY156509 mRNA. Translation: AAO17289.1.
AY280664 mRNA. Translation: AAQ16583.1.
AY037300 mRNA. Translation: AAK70226.1.
BC138587 mRNA. Translation: AAI38588.1.
BC138588 mRNA. Translation: AAI38589.1.
CCDSiCCDS19233.1. [Q9D236-3]
CCDS39071.1. [Q9D236-4]
RefSeqiNP_001036080.1. NM_001042615.2. [Q9D236-4]
NP_084403.2. NM_030127.3. [Q9D236-3]
UniGeneiMm.274255.

3D structure databases

ProteinModelPortaliQ9D236.
SMRiQ9D236. Positions 31-131, 136-459.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000084910.

Protein family/group databases

MEROPSiS01.284.

PTM databases

iPTMnetiQ9D236.
PhosphoSiteiQ9D236.

Proteomic databases

MaxQBiQ9D236.
PaxDbiQ9D236.
PRIDEiQ9D236.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000087629; ENSMUSP00000084910; ENSMUSG00000029096. [Q9D236-3]
ENSMUST00000114233; ENSMUSP00000109871; ENSMUSG00000029096. [Q9D236-4]
GeneIDi78558.
KEGGimmu:78558.
UCSCiuc008xea.2. mouse. [Q9D236-3]
uc008xeb.2. mouse. [Q9D236-4]

Organism-specific databases

CTDi94031.
MGIiMGI:1925808. Htra3.

Phylogenomic databases

eggNOGiKOG1320. Eukaryota.
COG0265. LUCA.
GeneTreeiENSGT00510000046315.
HOGENOMiHOG000223641.
HOVERGENiHBG052044.
InParanoidiQ9D236.
KOiK08785.
OMAiCESGHLQ.
OrthoDBiEOG7V1FR7.
PhylomeDBiQ9D236.
TreeFamiTF323480.

Miscellaneous databases

NextBioi349087.
PROiQ9D236.
SOURCEiSearch...

Gene expression databases

BgeeiQ9D236.
CleanExiMM_HTRA3.
ExpressionAtlasiQ9D236. baseline and differential.
GenevisibleiQ9D236. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "A novel serine protease of the mammalian HtrA family is up-regulated in mouse uterus coinciding with placentation."
    Nie G.Y., Li Y., Minoura H., Batten L., Ooi G.T., Findlay J.K., Salamonsen L.A.
    Mol. Hum. Reprod. 9:279-290(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INDUCTION.
    Strain: SWR/J.
    Tissue: Placenta.
  2. "TASP, a novel mammalian serine protease."
    Matsuguchi T., Yoshikai Y.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY.
    Strain: BALB/cJ.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  4. "Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling."
    Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.
    Dev. Growth Differ. 46:257-274(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYMATIC ACTIVITY, DEVELOPMENTAL STAGE, INDUCTION, TISSUE SPECIFICITY, INTERACTION WITH TGFB1, TGFB2, BMP4 AND GDF5, MUTAGENESIS OF SER-311.
  5. "HtrA3, a serine protease possessing an IGF-binding domain, is selectively expressed at the maternal-fetal interface during placentation in the mouse."
    Nie G., Li Y., He H., Findlay J.K., Salamonsen L.A.
    Placenta 27:491-501(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiHTRA3_MOUSE
AccessioniPrimary (citable) accession number: Q9D236
Secondary accession number(s): B2RRV0, Q6WLC5, Q6YDR0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 2, 2006
Last modified: May 11, 2016
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. 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.