HTRA1_RAT
ID HTRA1_RAT Reviewed; 480 AA.
AC Q9QZK5;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Serine protease HTRA1;
DE EC=3.4.21.-;
DE AltName: Full=High-temperature requirement A serine peptidase 1;
DE AltName: Full=Serine protease 11;
DE Flags: Precursor;
GN Name=Htra1; Synonyms=Htra, Prss11;
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].
RC STRAIN=Sprague-Dawley; TISSUE=Ovary;
RA Hourvitz A., Hennebold J.D., King G., Negishi H., Erickson G.F., Roby J.A.,
RA Mayo K.E., Adashi E.Y.;
RT "Mouse insulin-like growth factor binding protein 5-directed endopeptidase:
RT structural assessment, evolutionary analysis, ovarian expression, hormonal
RT regulation and cellular localization.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Serine protease with a variety of targets, including
CC extracellular matrix proteins such as fibronectin. HTRA1-generated
CC fibronectin fragments further induce synovial cells to up-regulate MMP1
CC and MMP3 production. May also degrade proteoglycans, such as aggrecan,
CC decorin and fibromodulin. Through cleavage of proteoglycans, may
CC release soluble FGF-glycosaminoglycan complexes that promote the range
CC and intensity of FGF signals in the extracellular space. Regulates the
CC availability of insulin-like growth factors (IGFs) by cleaving IGF-
CC binding proteins. Inhibits signaling mediated by TGF-beta family
CC members. This activity requires the integrity of the catalytic site,
CC although it is unclear whether TGF-beta proteins are themselves
CC degraded. By acting on TGF-beta signaling, may regulate many
CC physiological processes, including retinal angiogenesis and neuronal
CC survival and maturation during development. Intracellularly, degrades
CC TSC2, leading to the activation of TSC2 downstream targets (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms homotrimers. In the presence of substrate, may form
CC higher-order multimers in a PDZ-independent manner. Interacts with TGF-
CC beta family members, including BMP4, TGFB1, TGFB2, activin A and GDF5.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q92743}.
CC Secreted {ECO:0000250|UniProtKB:Q92743}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q92743}. Note=Predominantly secreted. Also found
CC associated with the plasma membrane. {ECO:0000250|UniProtKB:Q92743}.
CC -!- DOMAIN: The IGFBP N-terminal domain mediates interaction with TSC2
CC substrate. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; AF179370; AAD52683.1; -; mRNA.
DR EMBL; CH473956; EDM17131.1; -; Genomic_DNA.
DR EMBL; BC081767; AAH81767.1; -; mRNA.
DR RefSeq; NP_113909.1; NM_031721.1.
DR AlphaFoldDB; Q9QZK5; -.
DR SMR; Q9QZK5; -.
DR BioGRID; 249278; 1.
DR IntAct; Q9QZK5; 3.
DR STRING; 10116.ENSRNOP00000027860; -.
DR MEROPS; S01.277; -.
DR jPOST; Q9QZK5; -.
DR PaxDb; Q9QZK5; -.
DR PRIDE; Q9QZK5; -.
DR GeneID; 65164; -.
DR KEGG; rno:65164; -.
DR UCSC; RGD:69235; rat.
DR CTD; 5654; -.
DR RGD; 69235; Htra1.
DR VEuPathDB; HostDB:ENSRNOG00000020533; -.
DR eggNOG; KOG1320; Eukaryota.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; Q9QZK5; -.
DR OMA; THGWVLE; -.
DR OrthoDB; 630723at2759; -.
DR PhylomeDB; Q9QZK5; -.
DR TreeFam; TF323480; -.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR PRO; PR:Q9QZK5; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000020533; Expressed in ovary and 19 other tissues.
DR Genevisible; Q9QZK5; RN.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019838; F:growth factor binding; IEA:UniProtKB-KW.
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:0060718; P:chorionic trophoblast cell differentiation; ISO:RGD.
DR GO; GO:0097187; P:dentinogenesis; IEP:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IMP:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0001890; P:placenta development; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0012501; P:programmed cell death; IBA:GO_Central.
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 Cell membrane; Cytoplasm; Disulfide bond; Growth factor binding; Hydrolase;
KW Membrane; Protease; Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..480
FT /note="Serine protease HTRA1"
FT /id="PRO_0000416251"
FT DOMAIN 33..100
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 98..157
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 365..467
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 204..364
FT /note="Serine protease"
FT /evidence="ECO:0000250"
FT ACT_SITE 220
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 250
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 328
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 169
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 171
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 278
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT DISULFID 110..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 119..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
SQ SEQUENCE 480 AA; 51330 MW; 37A864C5A8FFC035 CRC64;
MQFLRTALLS LLLLLLAAPS LALPSGISRS APAATVCPEH CDPTRCAPPP TDCEGGRVRD
ACGCCEVCGA LEGAVCGLQE GPCGEGLQCV VPFGVPASAT VRRRAQAGLC VCASSEPVCG
SDAKTYTNLC QLRAASRRSE KLRQPPVIVL QRGACGQGQE DPNSLRHKYN FIADVVEKIA
PAVVHIELYR KLPFSKREVP VASGSGFIVS EDGLIVTNAH VVTNKNRVKV ELKNGATYEA
KIKDVDEKAD IALIKIDHQG KLPVLLLGRS SELRPGEFVV AIGSPFSLQN TVTTGIVSTT
QRGGKELGLR NSDMDYIQTD AIINYGNSGG PLVNLDGEVI GINTLKVTAG ISFAIPSDKI
KKFLTESHDR QAKGKTVTKK KYIGIRMMSL TSSKAKELKD RHRDFPDVIS GAYIIEVIPD
TPAEAGGLKE NDVIISINGQ SVVTANDVSD VIKKENTLNM VVRRGNEDIV ITVVPEEIDP
