HTRA3_RAT
ID HTRA3_RAT Reviewed; 459 AA.
AC D3ZA76; D3ZLW3;
DT 13-JUN-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 75.
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 Flags: Precursor;
GN Name=Htra3; Synonyms=Prsp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=19415717; DOI=10.1002/jez.b.21288;
RA Bowden M., Drummond A.E., Salamonsen L.A., Findlay J.K., Nie G.;
RT "Evolutionary conservation of mammalian HTRA3 and its developmental
RT regulation in the rat ovary.";
RL J. Exp. Zool. B Mol. Dev. Evol. 312:701-713(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
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 (By similarity). 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:0000250|UniProtKB:Q9D236}.
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with TGFB1; the
CC interaction inhibits TGFB-mediated signaling. Interacts with BMP4; the
CC interaction inhibits BMP4-mediated signaling. Interacts with TGFB2,
CC GDF5 and MYH9 (By similarity). {ECO:0000250|UniProtKB:P83110,
CC ECO:0000250|UniProtKB:Q9D236}.
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=2;
CC Name=1;
CC IsoId=D3ZA76-1; Sequence=Displayed;
CC Name=2;
CC IsoId=D3ZA76-2; Sequence=VSP_043827, VSP_043828;
CC -!- TISSUE SPECIFICITY: Expressed in the ovary, essentially in granulosa
CC cells in a follicle-stage specific manner. Highest levels found in
CC large luteinizing granulosa cells. {ECO:0000269|PubMed:19415717}.
CC -!- DEVELOPMENTAL STAGE: In the developing ovary, high expression,
CC especially of the longer isoform, at 12 days of age after birth.
CC Expression restricted to the interstitial cells surrounding the
CC follicles. Levels are further increased during ovarian maturation.
CC {ECO:0000269|PubMed:19415717}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR RefSeq; NP_001257956.1; NM_001271027.1. [D3ZA76-1]
DR RefSeq; XP_017454804.1; XM_017599315.1. [D3ZA76-2]
DR AlphaFoldDB; D3ZA76; -.
DR SMR; D3ZA76; -.
DR STRING; 10116.ENSRNOP00000010852; -.
DR PaxDb; D3ZA76; -.
DR Ensembl; ENSRNOT00000010852; ENSRNOP00000010852; ENSRNOG00000008182. [D3ZA76-1]
DR Ensembl; ENSRNOT00000103981; ENSRNOP00000093047; ENSRNOG00000008182. [D3ZA76-2]
DR GeneID; 360959; -.
DR KEGG; rno:360959; -.
DR CTD; 94031; -.
DR RGD; 1308120; Htra3.
DR eggNOG; ENOG502QT3F; Eukaryota.
DR GeneTree; ENSGT00940000159570; -.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; D3ZA76; -.
DR OMA; NDTDAFP; -.
DR OrthoDB; 630723at2759; -.
DR TreeFam; TF323480; -.
DR PRO; PR:D3ZA76; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000008182; Expressed in heart and 19 other tissues.
DR Genevisible; D3ZA76; RN.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008236; F:serine-type peptidase activity; ISS:UniProtKB.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS: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 2: Evidence at transcript 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_0000417598"
FT DOMAIN 27..90
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..346
FT /note="Serine protease"
FT /evidence="ECO:0000250"
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 357..363
FT /note="DWKKRFI -> ALSRALH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19415717"
FT /id="VSP_043827"
FT VAR_SEQ 364..459
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19415717"
FT /id="VSP_043828"
SQ SEQUENCE 459 AA; 49257 MW; BFD7DDD34305C818 CRC64;
MQARALLPAT LATLATLAVS VLAREPPAAP CPARCDVSRC PSPRCPGGYV PDLCNCCLVC
AASEGEPCGR PLDSPCGDSL ECVRGVCRCR WTHTVCGTDG HTYADVCALQ AASRRALQIS
GTPVRQLQKG ACPSGLHQLT SPRYKFNFIA DVVEKIAPAV VHIELFLRHP LFGRNVPLSS
GSGFIMSEAG LIVTNAHVVS SSNTASGRQQ LKVQLQNGDA YEATIQDIDK KSDIATILIH
PNKKLPVLLL GHSADLRPGE FVVAIGSPFA LQNTVTTGIV STAQRDGKEL GLRDSDMDYI
QTDAIINYGN SGGPLVNLDG EVIGINTLKV AAGISFAIPS DRITRFLSEF QDKHVKDWKK
RFIGIRMRTI TPSLVEELKT ANPDFPAVSS GIYVQEVVPN SPSQRGGIQD GDIIVKVNGR
PLVDSSELQE AVLNESSLLL EVRRGNDDLL FSIMPEVVM
