HTRA3_MOUSE
ID HTRA3_MOUSE Reviewed; 459 AA.
AC Q9D236; B2RRV0; Q6WLC5; Q6YDR0;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Serine protease HTRA3;
DE EC=3.4.21.-;
DE AltName: Full=High-temperature requirement factor A3;
DE AltName: Full=Pregnancy-related serine protease;
DE AltName: Full=Toll-associated serine protease;
DE Flags: Precursor;
GN Name=Htra3; Synonyms=Prsp, Tasp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INDUCTION.
RC STRAIN=SWR/J; TISSUE=Placenta;
RX PubMed=12728021; DOI=10.1093/molehr/gag036;
RA Nie G.Y., Li Y., Minoura H., Batten L., Ooi G.T., Findlay J.K.,
RA Salamonsen L.A.;
RT "A novel serine protease of the mammalian HtrA family is up-regulated in
RT mouse uterus coinciding with placentation.";
RL Mol. Hum. Reprod. 9:279-290(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RA Matsuguchi T., Yoshikai Y.;
RT "TASP, a novel mammalian serine protease.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, ENZYMATIC ACTIVITY, DEVELOPMENTAL STAGE, INDUCTION, TISSUE
RP SPECIFICITY, INTERACTION WITH TGFB1, TGFB2, BMP4 AND GDF5, AND MUTAGENESIS
RP OF SER-311.
RX PubMed=15206957; DOI=10.1111/j.1440-169x.2004.00743.x;
RA Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.;
RT "Developmentally regulated expression of mouse HtrA3 and its role as an
RT inhibitor of TGF-beta signaling.";
RL Dev. Growth Differ. 46:257-274(2004).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15951015; DOI=10.1016/j.placenta.2005.03.009;
RA Nie G., Li Y., He H., Findlay J.K., Salamonsen L.A.;
RT "HtrA3, a serine protease possessing an IGF-binding domain, is selectively
RT expressed at the maternal-fetal interface during placentation in the
RT mouse.";
RL Placenta 27:491-501(2006).
CC -!- FUNCTION: Serine protease that cleaves beta-casein/CSN2 as well as
CC several extracellular matrix (ECM) proteoglycans such as decorin/DCN,
CC biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-
CC beta family proteins possibly indirectly by degradation of these ECM
CC proteoglycans (PubMed:15206957). May act as a tumor suppressor.
CC Negatively regulates, in vitro, trophoblast invasion during placental
CC development and may be involved in the development of the placenta in
CC vivo. May also have a role in ovarian development, granulosa cell
CC differentiation and luteinization (By similarity).
CC {ECO:0000250|UniProtKB:P83110, ECO:0000269|PubMed:15206957}.
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with MYH9 (By
CC similarity). Interacts with TGFB1; the interaction inhibits TGFB-
CC mediated signaling. Interacts with BMP4; the interaction inhibits BMP4-
CC mediated signaling. Interacts with TGFB2 and GDF5.
CC {ECO:0000250|UniProtKB:P83110, ECO:0000269|PubMed:15206957}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P83110}.
CC Note=Secretion increased during decidualization of endometrial stromal
CC cells. {ECO:0000250|UniProtKB:P83110}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=A, Long;
CC IsoId=Q9D236-3; Sequence=Displayed;
CC Name=2; Synonyms=B, Short;
CC IsoId=Q9D236-4; Sequence=VSP_018128, VSP_018129;
CC Name=3;
CC IsoId=Q9D236-1; Sequence=VSP_018127;
CC -!- TISSUE SPECIFICITY: Highest level of isoform 1 in maternal part of the
CC placenta, moderate level in heart, testis and ovary, low level in
CC muscle and lung. High expression found in granulosa cells of the ovary.
CC Expressed in bone matrix, particularly in articular chondrocytes. Very
CC low level of isoform 2 expressed in placenta. Expressed in the bone
CC matrix, particularly in articular chondrocytes.
CC {ECO:0000269|PubMed:15206957, ECO:0000269|PubMed:15951015,
CC ECO:0000269|Ref.2}.
CC -!- DEVELOPMENTAL STAGE: First expressed at 9.5 dpc. Levels then increase
CC until 14.5 dpc after which they remain high until newborn. First
CC detected in the eye at 10.5 dpc and then expressed in tissues
CC associated with skeletal tissue. At 12.5 dpc expressed in the vertebral
CC rudiments in the tail region and, in the developing eye, in lens
CC epithelium. At adulthood, expression found in the ganglion cell layer
CC and the inner nuclear layer of the retina. In the developing heart at
CC 16.5 dpc, expressed in the endocardial cushion. In the trachea at this
CC stage, in outer layers and in the aorta, in adventitia.
CC {ECO:0000269|PubMed:15206957, ECO:0000269|PubMed:15951015}.
CC -!- INDUCTION: Up-regulated during early pregnancy coinciding with
CC placentation. Also up-regulated in joint cartilage affected by
CC arthritis. {ECO:0000269|PubMed:12728021, ECO:0000269|PubMed:15206957}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; AY156509; AAO17289.1; -; mRNA.
DR EMBL; AY280664; AAQ16583.1; -; mRNA.
DR EMBL; AY037300; AAK70226.1; -; mRNA.
DR EMBL; BC138587; AAI38588.1; -; mRNA.
DR EMBL; BC138588; AAI38589.1; -; mRNA.
DR CCDS; CCDS19233.1; -. [Q9D236-3]
DR CCDS; CCDS39071.1; -. [Q9D236-4]
DR RefSeq; NP_001036080.1; NM_001042615.2. [Q9D236-4]
DR RefSeq; NP_084403.2; NM_030127.3. [Q9D236-3]
DR AlphaFoldDB; Q9D236; -.
DR SMR; Q9D236; -.
DR STRING; 10090.ENSMUSP00000084910; -.
DR MEROPS; S01.284; -.
DR iPTMnet; Q9D236; -.
DR PhosphoSitePlus; Q9D236; -.
DR MaxQB; Q9D236; -.
DR PaxDb; Q9D236; -.
DR PeptideAtlas; Q9D236; -.
DR PRIDE; Q9D236; -.
DR ProteomicsDB; 273200; -. [Q9D236-3]
DR ProteomicsDB; 273201; -. [Q9D236-4]
DR ProteomicsDB; 273202; -. [Q9D236-1]
DR Antibodypedia; 9597; 115 antibodies from 26 providers.
DR DNASU; 78558; -.
DR Ensembl; ENSMUST00000087629; ENSMUSP00000084910; ENSMUSG00000029096. [Q9D236-3]
DR Ensembl; ENSMUST00000114233; ENSMUSP00000109871; ENSMUSG00000029096. [Q9D236-4]
DR GeneID; 78558; -.
DR KEGG; mmu:78558; -.
DR UCSC; uc008xea.2; mouse. [Q9D236-3]
DR UCSC; uc008xeb.2; mouse. [Q9D236-4]
DR CTD; 94031; -.
DR MGI; MGI:1925808; Htra3.
DR VEuPathDB; HostDB:ENSMUSG00000029096; -.
DR eggNOG; ENOG502QT3F; Eukaryota.
DR GeneTree; ENSGT00940000159570; -.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; Q9D236; -.
DR OMA; NDTDAFP; -.
DR OrthoDB; 630723at2759; -.
DR PhylomeDB; Q9D236; -.
DR TreeFam; TF323480; -.
DR BioGRID-ORCS; 78558; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Htra3; mouse.
DR PRO; PR:Q9D236; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9D236; protein.
DR Bgee; ENSMUSG00000029096; Expressed in decidua and 171 other tissues.
DR ExpressionAtlas; Q9D236; baseline and differential.
DR Genevisible; Q9D236; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR001940; Peptidase_S1C.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR PRINTS; PR00834; PROTEASES2C.
DR SMART; SM00121; IB; 1.
DR SMART; SM00280; KAZAL; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF100895; SSF100895; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS51465; KAZAL_2; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Hydrolase; Protease;
KW Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..459
FT /note="Serine protease HTRA3"
FT /id="PRO_0000026950"
FT DOMAIN 27..83
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 76..134
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 365..450
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 181..347
FT /note="Serine protease"
FT ACT_SITE 197
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P83110"
FT ACT_SITE 233
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P83110"
FT ACT_SITE 311
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P83110"
FT DISULFID 87..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 96..132
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT VAR_SEQ 266..278
FT /note="GSPFALQNTVTTG -> ESPLCPAEHRDKC (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_018127"
FT VAR_SEQ 357..363
FT /note="DWKKRFI -> ALSPALH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12728021"
FT /id="VSP_018128"
FT VAR_SEQ 364..459
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12728021"
FT /id="VSP_018129"
FT MUTAGEN 311
FT /note="S->A: Abolishes protease activity. No inhibition of
FT BMP4-mediated signaling."
FT /evidence="ECO:0000269|PubMed:15206957"
FT CONFLICT 286
FT /note="D -> T (in Ref. 2; AAK70226)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="L -> AA (in Ref. 2; AAK70226)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 49149 MW; E13C6042DC4AFF64 CRC64;
MQARALLPAT LAILATLAVL ALAREPPAAP CPARCDVSRC PSPRCPGGYV PDLCNCCLVC
AASEGEPCGR PLDSPCGDSL ECVRGVCRCR WTHTVCGTDG HTYADVCALQ AASRRALQVS
GTPVRQLQKG ACPSGLHQLT SPRYKFNFIA DVVEKIAPAV VHIELFLRHP LFGRNVPLSS
GSGFIMSEAG LIVTNAHVVS SSSTASGRQQ LKVQLQNGDA YEATIQDIDK KSDIATIVIH
PKKKLPVLLL GHSADLRPGE FVVAIGSPFA LQNTVTTGIV STAQRDGKEL GLRDSDMDYI
QTDAIINYGN SGGPLVNLDG EVIGINTLKV AAGISFAIPS DRITRFLSEF QNKHVKDWKK
RFIGIRMRTI TPSLVEELKA ANPDFPAVSS GIYVQEVVPN SPSQRGGIQD GDIIVKVNGR
PLADSSELQE AVLNESSLLL EVRRGNDDLL FSIIPEVVM
