HTRA1_BOVIN
ID HTRA1_BOVIN Reviewed; 487 AA.
AC F1N152; O97658;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 118-487.
RC TISSUE=Lung;
RX PubMed=9852107; DOI=10.1074/jbc.273.51.34406;
RA Hu S.I., Carozza M., Klein M., Nantermet P., Luk D., Crowl R.M.;
RT "Human HtrA, an evolutionarily conserved serine protease identified as a
RT differentially expressed gene product in osteoarthritic cartilage.";
RL J. Biol. Chem. 273:34406-34412(1998).
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; DAAA02059453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02059454; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF097707; AAC95151.1; -; mRNA.
DR RefSeq; NP_001269011.1; NM_001282082.1.
DR AlphaFoldDB; F1N152; -.
DR BMRB; F1N152; -.
DR SMR; F1N152; -.
DR STRING; 9913.ENSBTAP00000011042; -.
DR PaxDb; F1N152; -.
DR PRIDE; F1N152; -.
DR GeneID; 282326; -.
DR KEGG; bta:282326; -.
DR CTD; 5654; -.
DR eggNOG; KOG1320; Eukaryota.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; F1N152; -.
DR OrthoDB; 630723at2759; -.
DR TreeFam; TF323480; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
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:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0012501; P:programmed cell death; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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..29
FT /evidence="ECO:0000255"
FT CHAIN 30..487
FT /note="Serine protease HTRA1"
FT /id="PRO_0000416250"
FT DOMAIN 40..104
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 105..164
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 372..474
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 211..371
FT /note="Serine protease"
FT /evidence="ECO:0000250"
FT ACT_SITE 227
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 257
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 335
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 176
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 178
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 285
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT DISULFID 117..137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 126..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
SQ SEQUENCE 487 AA; 51907 MW; A10711589D444E58 CRC64;
MQPPRAPFLP PPTPPLLLLL LLLAAPASAQ PARAGRSAPG AAGCPERCDP ARCAPPPGSC
EGGRVRDACG CCEVCGAPEG AECGLQEGPC GEGLQCVVPF GVPASATVRR RAQSGLCVCA
SNEPVCGSDA KTYTNLCQLR AASRRSERLH QPPVIVLQRG ACGQGQEDPN SLRHKYNFIA
DVVEKIAPAV VHIELFRKLP FSKREVPVAS GSGFIVSEDG LIVTNAHVVT NKHRVKVELK
NGATYEAKIK DVDEKADIAL IKIDHQGKLP VLLLGRSSEL RPGEFVVAIG SPFSLQNTVT
TGIVSTTQRG GKELGLRNSD MDYIQTDAII NYGNSGGPLV NLDGEVIGIN TLKVTAGISF
AIPSDKIKKF LTESHDRQAK GKAITKKKYI GIRMMSLTPS KAKELKDRHR DFPDVLSGAY
IIEVIPDTPA EAGGLKENDV IISINGQSVV SANDVSDVIK KESTLNMVVR RGNEDIMITV
IPEEIDP
