HTRA1_XENLA
ID HTRA1_XENLA Reviewed; 459 AA.
AC A6YFB5; Q5PPW2;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 63.
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 Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, INDUCTION, AND MUTAGENESIS OF SER-307.
RX PubMed=17681134; DOI=10.1016/j.devcel.2007.07.001;
RA Hou S., Maccarana M., Min T.H., Strate I., Pera E.M.;
RT "The secreted serine protease xHtrA1 stimulates long-range FGF signaling in
RT the early Xenopus embryo.";
RL Dev. Cell 13:226-241(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine protease with a variety of targets, including
CC extracellular matrix proteins and proteoglycans such as biglycan,
CC syndecan-4 and glypican-4. 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. Consequently,
CC facilitates inductive processes in the developing embryo, such as
CC posteriorization, mesoderm induction and neuronal differentiation.
CC Regulates the availability of insulin-like growth factors (IGFs) by
CC cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta
CC family members. Consequently, may regulate many physiological
CC processes. Intracellularly, degrades TSC2, leading to the activation of
CC TSC2 downstream targets. {ECO:0000269|PubMed:17681134}.
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: Cell membrane {ECO:0000250|UniProtKB:Q92743}.
CC Secreted {ECO:0000269|PubMed:17681134}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q92743}. Note=Predominantly secreted. Also found
CC associated with the plasma membrane. {ECO:0000250|UniProtKB:Q92743}.
CC -!- DEVELOPMENTAL STAGE: First detected after midblastula transition.
CC Expression increases during gastrulation and neurulation. Expressed in
CC the blastopore lip at gastrula stage (stage 11), the posterior mesoderm
CC and anterior neural plate after involution (stage 14), the early
CC forebrain and midbrain-hindbrain boundary at the neurula stage (stage
CC 16), and the branchial arch region in tail bud stage embryos (stage
CC 26). {ECO:0000269|PubMed:17681134}.
CC -!- INDUCTION: Up-regulated by FGF4 and FGF8.
CC {ECO:0000269|PubMed:17681134}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH87471.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EF490997; ABR68659.1; -; mRNA.
DR EMBL; BC087471; AAH87471.1; ALT_INIT; mRNA.
DR RefSeq; NP_001088796.2; NM_001095327.2.
DR AlphaFoldDB; A6YFB5; -.
DR SMR; A6YFB5; -.
DR MEROPS; S01.277; -.
DR DNASU; 496061; -.
DR GeneID; 496061; -.
DR KEGG; xla:496061; -.
DR CTD; 496061; -.
DR Xenbase; XB-GENE-865727; htra1.S.
DR OrthoDB; 630723at2759; -.
DR BRENDA; 3.4.21.107; 6725.
DR Proteomes; UP000186698; Chromosome 7S.
DR Bgee; 496061; Expressed in camera-type eye and 18 other tissues.
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; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 Cell membrane; Cytoplasm; Disulfide bond; Growth factor binding; Hydrolase;
KW Membrane; Protease; Reference proteome; Secreted; Serine protease; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..459
FT /note="Serine protease HTRA1"
FT /id="PRO_0000416254"
FT DOMAIN 22..88
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 74..136
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 344..446
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 183..343
FT /note="Serine protease"
FT ACT_SITE 199
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 229
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT ACT_SITE 307
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 148
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 150
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT SITE 257
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000250|UniProtKB:Q92743"
FT DISULFID 89..109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 98..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT MUTAGEN 307
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17681134"
FT CONFLICT 62
FT /note="N -> W (in Ref. 2; AAH87471)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 48991 MW; 8E6CB4EA02BD3FDB CRC64;
MTMLWLAVLL TCGAPAALLP TSGVGCPARC DPSSCSPAPT NCQSGETALR CGCCSVCAAA
ENERCGEGPE DPLCASGLRC VRNGGVTRCQ CPSNQPVCGS DGKTYSSLCR LQAESKAVQG
RGVAAIIPIQ RGDCQQGQKD PDSPRYKYNF IADVVEKIAP AVVHIELFRI LPFFKREVPA
ASGSGFIVSE DGLILTNAHV VTNKHRLKVE RSDGSTYDAQ IIDVDEKADI ALIKIKAKGK
LPVLLLGRSE ELRPGEFVVA IGSPFSLQNT VTTGIVSTAQ RGGKELGLRN SDMDYIQTDA
IINYGNSGGP LVNLDGEVVG INTLKVTAGI SFAIPSDKIR KFMAESHNRQ STGQGTKKKK
YLGIRMMSLS QGKLKELKEQ VKDFPENTSG AYIVEVLPDT PAEEAGLKEG DIIISISGKT
VTSSSEVSEA IKKEGTLQMV IRRGNEDIPI SVTPKEIEF
