ID HTR1A_DANRE Reviewed; 479 AA.
AC Q6GMI0;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 27-MAR-2024, entry version 121.
DE RecName: Full=Serine protease HTRA1A;
DE EC=3.4.21.-;
DE AltName: Full=High-temperature requirement A serine peptidase 1A;
DE AltName: Full=Serine protease 11;
DE Flags: Precursor;
GN Name=htra1a; Synonyms=htra1, prss11; ORFNames=zgc:92029;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine protease with a variety of targets, including
CC extracellular matrix proteins and proteoglycans. Through cleavage of
CC proteoglycans, may release soluble FGF-glycosaminoglycan complexes that
CC promote the range and intensity of FGF signals in the extracellular
CC space. Regulates the availability of insulin-like growth factors (IGFs)
CC by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-
CC beta family members. Consequently, may regulate many physiological
CC processes. Intracellularly, degrades TSC2, leading to the activation of
CC TSC2 downstream targets (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms homotrimers. In the presence of substrate, may form
CC higher-order multimers in a PDZ-independent manner. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. Cytoplasm, cytosol
CC {ECO:0000250}. Note=Also found associated with the plasma membrane.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; AL773596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX511271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074069; AAH74069.1; -; mRNA.
DR RefSeq; NP_001002219.1; NM_001002219.1.
DR AlphaFoldDB; Q6GMI0; -.
DR SMR; Q6GMI0; -.
DR STRING; 7955.ENSDARP00000048135; -.
DR MEROPS; S01.284; -.
DR PaxDb; 7955-ENSDARP00000048135; -.
DR GeneID; 431766; -.
DR KEGG; dre:431766; -.
DR AGR; ZFIN:ZDB-GENE-040704-64; -.
DR CTD; 431766; -.
DR ZFIN; ZDB-GENE-040704-64; htra1a.
DR eggNOG; KOG1320; Eukaryota.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; Q6GMI0; -.
DR OMA; MFWSLLC; -.
DR OrthoDB; 2159919at2759; -.
DR PhylomeDB; Q6GMI0; -.
DR TreeFam; TF323480; -.
DR PRO; PR:Q6GMI0; -.
DR Proteomes; UP000000437; Alternate scaffold 17.
DR Proteomes; UP000000437; Chromosome 17.
DR Bgee; ENSDARG00000032831; Expressed in swim bladder and 16 other cell types or tissues.
DR ExpressionAtlas; Q6GMI0; baseline and differential.
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: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 GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IMP:ZFIN.
DR CDD; cd00104; KAZAL_FS; 1.
DR CDD; cd00987; PDZ_serine_protease; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 2.40.10.120; -; 1.
DR Gene3D; 3.30.60.30; -; 1.
DR Gene3D; 4.10.40.20; -; 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 PANTHER; PTHR22939; SERINE PROTEASE FAMILY S1C HTRA-RELATED; 1.
DR PANTHER; PTHR22939:SF128; SERINE PROTEASE HTRA1A; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF07648; Kazal_2; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF13365; Trypsin_2; 1.
DR PRINTS; PR00834; PROTEASES2C.
DR SMART; SM00121; IB; 1.
DR SMART; SM00280; KAZAL; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1.
DR SUPFAM; SSF50156; PDZ domain-like; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 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 Cytoplasm; Disulfide bond; Growth factor binding; Hydrolase; Protease;
KW Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..479
FT /note="Serine protease HTRA1A"
FT /id="PRO_0000416252"
FT DOMAIN 27..111
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 96..155
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 364..466
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 203..363
FT /note="Serine protease"
FT ACT_SITE 219
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 249
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 327
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 168
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 170
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 277
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT DISULFID 31..56
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 35..58
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 40..59
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 47..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 70..87
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DISULFID 81..108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
SQ SEQUENCE 479 AA; 51441 MW; EAD01D0A9B258920 CRC64;
MILVTLFCIC ALVTSLQADA RLSKRYVIGG CPSHCDKSMC PTMPKDCSTG QVMDHCNCCL
VCASGEGEAC GGVGKLGDPV CGESLECSVT GGVSYSATVR RRGKQGVCVC KSSDPVCGSD
GVSYRDICEL KRVSNRAQSL QQPPVLFIQR GACGTSLHDN PNSLRYKYNF IADVVEKIAP
AVVHIELYRK MVYSKREMAV ASGSGFVVSD DGLIVTNAHV VANKNRVKVE LKNGASYDAK
IKDVDEKADI ALIKIDLPNK LPVLLLGRSA DLRPGEFVVA IGSPFSLQNT VTTGIVSTTQ
RGGKELGLRN SDMDYIQTDA IINYGNSGGP LVNLDGEVIG INTLKVTAGI SFAIPSDKIR
QFLAESYDRL ARGRGTTKKR YIGVRMMTLT PSLSKELKGR LRDFPDITSG AYVIEVISKT
PAAAGGLKEH DVIISINGQR ISTATDVSAI IKKESSLRVV VRRGNEDIIL TIIPMEIDP
//
