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Protein

Serine protease HTRA3

Gene

Htra3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Active sitei197Charge relay systemBy similarity1
Active sitei233Charge relay systemBy similarity1
Active sitei311Charge relay systemBy similarity1

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

Keywordsi

Molecular functionHydrolase, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1925808 Htra3

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi311S → A: Abolishes protease activity. No inhibition of BMP4-mediated signaling. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002695024 – 459Serine protease HTRA3Add BLAST436

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi87 ↔ 107PROSITE-ProRule annotation
Disulfide bondi96 ↔ 132PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiQ9D236
PaxDbiQ9D236
PeptideAtlasiQ9D236
PRIDEiQ9D236

PTM databases

iPTMnetiQ9D236
PhosphoSitePlusiQ9D236

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

BgeeiENSMUSG00000029096
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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000084910

Structurei

3D structure databases

ProteinModelPortaliQ9D236
SMRiQ9D236
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 83IGFBP N-terminalPROSITE-ProRule annotationAdd BLAST57
Domaini76 – 134Kazal-likePROSITE-ProRule annotationAdd BLAST59
Domaini365 – 450PDZPROSITE-ProRule annotationAdd BLAST86

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni181 – 347Serine proteaseAdd BLAST167

Sequence similaritiesi

Belongs to the peptidase S1C family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG1320 Eukaryota
COG0265 LUCA
GeneTreeiENSGT00510000046315
HOGENOMiHOG000223641
HOVERGENiHBG052044
InParanoidiQ9D236
KOiK08785
OMAiTDGHTYA
OrthoDBiEOG091G0LXR
PhylomeDBiQ9D236
TreeFamiTF323480

Family and domain databases

InterProiView protein in InterPro
IPR009030 Growth_fac_rcpt_cys_sf
IPR000867 IGFBP-like
IPR002350 Kazal_dom
IPR036058 Kazal_dom_sf
IPR001478 PDZ
IPR036034 PDZ_sf
IPR009003 Peptidase_S1_PA
IPR001940 Peptidase_S1C
PfamiView protein in Pfam
PF00219 IGFBP, 1 hit
PF07648 Kazal_2, 1 hit
PF13180 PDZ_2, 1 hit
PRINTSiPR00834 PROTEASES2C
SMARTiView protein in SMART
SM00121 IB, 1 hit
SM00280 KAZAL, 1 hit
SM00228 PDZ, 1 hit
SUPFAMiSSF100895 SSF100895, 1 hit
SSF50156 SSF50156, 1 hit
SSF50494 SSF50494, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS51323 IGFBP_N_2, 1 hit
PS51465 KAZAL_2, 1 hit
PS50106 PDZ, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti286D → T in AAK70226 (Ref. 2) Curated1
Sequence conflicti440L → AA in AAK70226 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_018127266 – 278GSPFA…TVTTG → ESPLCPAEHRDKC in isoform 3. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_018128357 – 363DWKKRFI → ALSPALH in isoform 2. 1 Publication7
Alternative sequenceiVSP_018129364 – 459Missing in isoform 2. 1 PublicationAdd BLAST96

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

Similar proteinsi

Entry informationi

Entry nameiHTRA3_MOUSE
AccessioniPrimary (citable) accession number: Q9D236
Secondary accession number(s): B2RRV0, Q6WLC5, Q6YDR0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 2, 2006
Last modified: May 23, 2018
This is version 143 of the entry and version 3 of the sequence. See 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

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