HTRA4_HUMAN
ID HTRA4_HUMAN Reviewed; 476 AA.
AC P83105; Q542Z4; Q6PF13;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Serine protease HTRA4;
DE EC=3.4.21.-;
DE AltName: Full=High-temperature requirement factor A4;
DE Flags: Precursor;
GN Name=HTRA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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).
RN [4]
RP IDENTIFICATION.
RA Southan C.;
RL Submitted (AUG-2001) to UniProtKB.
CC -!- FUNCTION: Serine protease. {ECO:0000305}.
CC -!- INTERACTION:
CC P83105; P55210: CASP7; NbExp=6; IntAct=EBI-21776319, EBI-523958;
CC P83105; Q92743: HTRA1; NbExp=5; IntAct=EBI-21776319, EBI-352256;
CC P83105; P83110: HTRA3; NbExp=5; IntAct=EBI-21776319, EBI-2867394;
CC P83105; P83105: HTRA4; NbExp=3; IntAct=EBI-21776319, EBI-21776319;
CC P83105; P17987: TCP1; NbExp=7; IntAct=EBI-21776319, EBI-356553;
CC P83105; P98170: XIAP; NbExp=11; IntAct=EBI-21776319, EBI-517127;
CC P83105; P02666: CSN2; Xeno; NbExp=5; IntAct=EBI-21776319, EBI-5260183;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
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DR EMBL; AK075205; BAC11470.1; -; mRNA.
DR EMBL; AC108863; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057765; AAH57765.1; -; mRNA.
DR CCDS; CCDS6110.1; -.
DR RefSeq; NP_710159.1; NM_153692.3.
DR AlphaFoldDB; P83105; -.
DR SMR; P83105; -.
DR BioGRID; 128450; 184.
DR IntAct; P83105; 184.
DR STRING; 9606.ENSP00000305919; -.
DR MEROPS; S01.285; -.
DR iPTMnet; P83105; -.
DR PhosphoSitePlus; P83105; -.
DR BioMuta; HTRA4; -.
DR DMDM; 17366421; -.
DR jPOST; P83105; -.
DR MassIVE; P83105; -.
DR PaxDb; P83105; -.
DR PeptideAtlas; P83105; -.
DR PRIDE; P83105; -.
DR ProteomicsDB; 57730; -.
DR Antibodypedia; 23738; 109 antibodies from 19 providers.
DR DNASU; 203100; -.
DR Ensembl; ENST00000302495.5; ENSP00000305919.4; ENSG00000169495.5.
DR GeneID; 203100; -.
DR KEGG; hsa:203100; -.
DR MANE-Select; ENST00000302495.5; ENSP00000305919.4; NM_153692.4; NP_710159.1.
DR UCSC; uc003xmj.4; human.
DR CTD; 203100; -.
DR DisGeNET; 203100; -.
DR GeneCards; HTRA4; -.
DR HGNC; HGNC:26909; HTRA4.
DR HPA; ENSG00000169495; Tissue enriched (placenta).
DR MIM; 610700; gene.
DR neXtProt; NX_P83105; -.
DR OpenTargets; ENSG00000169495; -.
DR PharmGKB; PA134862039; -.
DR VEuPathDB; HostDB:ENSG00000169495; -.
DR eggNOG; ENOG502RMZV; Eukaryota.
DR GeneTree; ENSGT00940000160760; -.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; P83105; -.
DR OMA; NQQWIEV; -.
DR OrthoDB; 630723at2759; -.
DR PhylomeDB; P83105; -.
DR TreeFam; TF323480; -.
DR BRENDA; 3.4.21.107; 2681.
DR PathwayCommons; P83105; -.
DR SignaLink; P83105; -.
DR BioGRID-ORCS; 203100; 11 hits in 1070 CRISPR screens.
DR GenomeRNAi; 203100; -.
DR Pharos; P83105; Tbio.
DR PRO; PR:P83105; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P83105; protein.
DR Bgee; ENSG00000169495; Expressed in decidua and 82 other tissues.
DR Genevisible; P83105; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
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; IDA:BHF-UCL.
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; 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; PF13180; PDZ_2; 1.
DR PRINTS; PR00834; PROTEASES2C.
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 Disulfide bond; Hydrolase; Protease; Reference proteome; Secreted;
KW Serine protease; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..476
FT /note="Serine protease HTRA4"
FT /id="PRO_0000026951"
FT DOMAIN 36..99
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 88..154
FT /note="Kazal-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 383..474
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 202..362
FT /note="Serine protease"
FT ACT_SITE 218
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 248
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT ACT_SITE 326
FT /note="Charge relay system"
FT /evidence="ECO:0000255"
FT DISULFID 108..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 116..152
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT CONFLICT 416
FT /note="V -> F (in Ref. 2; AAH57765)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 50979 MW; D458FFFAB4AF4328 CRC64;
MIRPQLRTAG LGRCLLPGLL LLLVPVLWAG AEKLHTQPSC PAVCQPTRCP ALPTCALGTT
PVFDLCRCCR VCPAAEREVC GGAQGQPCAP GLQCLQPLRP GFPSTCGCPT LGGAVCGSDR
RTYPSMCALR AENRAARRLG KVPAVPVQWG NCGDTGTRSA GPLRRNYNFI AAVVEKVAPS
VVHVQLWGRL LHGSRLVPVY SGSGFIVSED GLIITNAHVV RNQQWIEVVL QNGARYEAVV
KDIDLKLDLA VIKIESNAEL PVLMLGRSSD LRAGEFVVAL GSPFSLQNTA TAGIVSTKQR
GGKELGMKDS DMDYVQIDAT INYGNSGGPL VNLDGDVIGV NSLRVTDGIS FAIPSDRVRQ
FLAEYHEHQM KGKAFSNKKY LGLQMLSLTV PLSEELKMHY PDFPDVSSGV YVCKVVEGTA
AQSSGLRDHD VIVNINGKPI TTTTDVVKAL DSDSLSMAVL RGKDNLLLTV IPETIN
