HTRA1_HUMAN
ID HTRA1_HUMAN Reviewed; 480 AA.
AC Q92743; D3DRE4; Q9UNS5;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Serine protease HTRA1;
DE EC=3.4.21.-;
DE AltName: Full=High-temperature requirement A serine peptidase 1;
DE AltName: Full=L56;
DE AltName: Full=Serine protease 11;
DE Flags: Precursor;
GN Name=HTRA1; Synonyms=HTRA, PRSS11;
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 [MRNA].
RC TISSUE=Placenta;
RX PubMed=8977104; DOI=10.1016/s0014-5793(96)01229-x;
RA Zumbrunn J., Trueb B.;
RT "Primary structure of a putative serine protease specific for IGF-binding
RT proteins.";
RL FEBS Lett. 398:187-192(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Crowl R.M., Luk D., Milnamow M.;
RT "Genomic organization and promoter characterization of the human HTRA
RT (PRSS11) gene.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-480, PROTEIN SEQUENCE OF 33-44, FUNCTION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-328.
RC TISSUE=Cartilage;
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).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15208355; DOI=10.1369/jhc.3a6186.2004;
RA De Luca A., De Falco M., Fedele V., Cobellis L., Mastrogiacomo A.,
RA Laforgia V., Tuduce I.L., Campioni M., Giraldi D., Paggi M.G., Baldi A.;
RT "The serine protease HtrA1 is upregulated in the human placenta during
RT pregnancy.";
RL J. Histochem. Cytochem. 52:885-892(2004).
RN [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16377621; DOI=10.1074/jbc.m500361200;
RA Grau S., Richards P.J., Kerr B., Hughes C., Caterson B., Williams A.S.,
RA Junker U., Jones S.A., Clausen T., Ehrmann M.;
RT "The role of human HtrA1 in arthritic disease.";
RL J. Biol. Chem. 281:6124-6129(2006).
RN [7]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ARMD7.
RX PubMed=17053108; DOI=10.1126/science.1133807;
RA Dewan A., Liu M., Hartman S., Zhang S.S.-M., Liu D.T.L., Zhao C.,
RA Tam P.O.S., Chan W.M., Lam D.S.C., Snyder M., Barnstable C., Pang C.P.,
RA Hoh J.;
RT "HTRA1 promoter polymorphism in wet age-related macular degeneration.";
RL Science 314:989-992(2006).
RN [8]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ARMD7.
RX PubMed=17053109; DOI=10.1126/science.1133811;
RA Yang Z., Camp N.J., Sun H., Tong Z., Gibbs D., Cameron D.J., Chen H.,
RA Zhao Y., Pearson E., Li X., Chien J., DeWan A., Harmon J., Bernstein P.S.,
RA Shridhar V., Zabriskie N.A., Hoh J., Howes K., Zhang K.;
RT "A variant of the HTRA1 gene increases susceptibility to age-related
RT macular degeneration.";
RL Science 314:992-993(2006).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20671064; DOI=10.1158/1541-7786.mcr-09-0473;
RA Campioni M., Severino A., Manente L., Tuduce I.L., Toldo S., Caraglia M.,
RA Crispi S., Ehrmann M., He X., Maguire J., De Falco M., De Luca A.,
RA Shridhar V., Baldi A.;
RT "The serine protease HtrA1 specifically interacts and degrades the tuberous
RT sclerosis complex 2 protein.";
RL Mol. Cancer Res. 8:1248-1260(2010).
RN [10]
RP INVOLVEMENT IN CADASIL2, VARIANTS CADASIL2 ARG-121; SER-123; GLY-133;
RP LEU-166; PRO-173; ARG-284; GLY-284; GLN-285; VAL-286 AND HIS-450, VARIANTS
RP VAL-20 AND GLY-51, AND CHARACTERIZATION OF VARIANTS CADASIL2 ARG-121;
RP LEU-166; PRO-173; ARG-284; GLY-284; GLN-285; VAL-286 AND HIS-450.
RX PubMed=26063658; DOI=10.1093/brain/awv155;
RA Verdura E., Herve D., Scharrer E., del Mar Amador M., Guyant-Marechal L.,
RA Philippi A., Corlobe A., Bergametti F., Gazal S., Prieto-Morin C.,
RA Beaufort N., Le Bail B., Viakhireva I., Dichgans M., Chabriat H.,
RA Haffner C., Tournier-Lasserve E.;
RT "Heterozygous HTRA1 mutations are associated with autosomal dominant
RT cerebral small vessel disease.";
RL Brain 138:2347-2358(2015).
RN [11]
RP STRUCTURE BY NMR OF 367-480.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ-domain of human protease HTRA 1 precursor.";
RL Submitted (APR-2008) to the PDB data bank.
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 158-480, HOMOTRIMERIZATION,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-328, SITE, AND ACTIVE SITE.
RX PubMed=21297635; DOI=10.1038/nsmb.2013;
RA Truebestein L., Tennstaedt A., Monig T., Krojer T., Canellas F., Kaiser M.,
RA Clausen T., Ehrmann M.;
RT "Substrate-induced remodeling of the active site regulates human HTRA1
RT activity.";
RL Nat. Struct. Mol. Biol. 18:386-388(2011).
RN [13]
RP VARIANTS CARASIL THR-252 AND MET-297, AND CHARACTERIZATION OF VARIANTS
RP CARASIL THR-252 AND MET-297.
RX PubMed=19387015; DOI=10.1056/nejmoa0801560;
RA Hara K., Shiga A., Fukutake T., Nozaki H., Miyashita A., Yokoseki A.,
RA Kawata H., Koyama A., Arima K., Takahashi T., Ikeda M., Shiota H.,
RA Tamura M., Shimoe Y., Hirayama M., Arisato T., Yanagawa S., Tanaka A.,
RA Nakano I., Ikeda S., Yoshida Y., Yamamoto T., Ikeuchi T., Kuwano R.,
RA Nishizawa M., Tsuji S., Onodera O.;
RT "Association of HTRA1 mutations and familial ischemic cerebral small-vessel
RT disease.";
RL N. Engl. J. Med. 360:1729-1739(2009).
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.
CC {ECO:0000269|PubMed:16377621, ECO:0000269|PubMed:20671064,
CC ECO:0000269|PubMed:9852107}.
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 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q92743; Q92743: HTRA1; NbExp=7; IntAct=EBI-352256, EBI-352256;
CC Q92743; P83105: HTRA4; NbExp=5; IntAct=EBI-352256, EBI-21776319;
CC Q92743; P10636-8: MAPT; NbExp=6; IntAct=EBI-352256, EBI-366233;
CC Q92743; P14174: MIF; NbExp=3; IntAct=EBI-352256, EBI-372712;
CC Q92743; PRO_0000035842 [P07996]: THBS1; NbExp=2; IntAct=EBI-352256, EBI-13915509;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21297635}.
CC Secreted {ECO:0000269|PubMed:15208355, ECO:0000269|PubMed:9852107}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:15208355,
CC ECO:0000269|PubMed:20671064}. Note=Predominantly secreted
CC (PubMed:15208355). Also found associated with the plasma membrane
CC (PubMed:21297635). {ECO:0000269|PubMed:15208355,
CC ECO:0000269|PubMed:21297635}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with strongest expression in
CC placenta (at protein level). Secreted by synovial fibroblasts. Up-
CC regulated in osteoarthritis and rheumatoid arthritis synovial fluids
CC and cartilage as compared with non-arthritic (at protein level).
CC {ECO:0000269|PubMed:15208355, ECO:0000269|PubMed:16377621,
CC ECO:0000269|PubMed:9852107}.
CC -!- DEVELOPMENTAL STAGE: In the placenta, in the first trimester of
CC gestation, low expression in the cells surrounding villi both in the
CC inner layer of the cytotrophoblast and in the outer layer of the
CC syncytiotrophoblast (at protein level). In the third trimester of
CC gestation, very strong expression in the outer layer forming the
CC syncytiotrophoblast and lower in the cytotrophoblast (at protein
CC level). {ECO:0000269|PubMed:15208355}.
CC -!- DOMAIN: The IGFBP N-terminal domain mediates interaction with TSC2
CC substrate.
CC -!- DISEASE: Macular degeneration, age-related, 7 (ARMD7) [MIM:610149]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:17053108,
CC ECO:0000269|PubMed:17053109}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Cerebral arteriopathy, autosomal recessive, with subcortical
CC infarcts and leukoencephalopathy (CARASIL) [MIM:600142]: A
CC cerebrovascular disease characterized by non-hypertensive arteriopathy
CC of cerebral small vessels with subcortical infarcts, alopecia, and
CC spondylosis. Small cerebral arteries show arteriosclerotic changes,
CC fibrous intimal proliferation, and hyaline degeneration with splitting
CC of the intima and/or the internal elastic membrane. Neurologic features
CC include progressive dementia, gait disturbances, extrapyramidal and
CC pyramidal signs, and demyelination of the cerebral white matter with
CC sparing of U fibers. {ECO:0000269|PubMed:19387015}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Cerebral arteriopathy, autosomal dominant, with subcortical
CC infarcts and leukoencephalopathy, 2 (CADASIL2) [MIM:616779]: A
CC cerebrovascular disease characterized by multiple subcortical infarcts,
CC pseudobulbar palsy, dementia, and the presence of granular deposits in
CC small cerebral arteries producing ischemic stroke.
CC {ECO:0000269|PubMed:26063658}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1C family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HTRA1ID41877ch10q26.html";
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DR EMBL; Y07921; CAA69226.1; -; mRNA.
DR EMBL; AF157623; AAD41525.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49312.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49313.1; -; Genomic_DNA.
DR EMBL; AF097709; AAC97211.1; -; mRNA.
DR CCDS; CCDS7630.1; -.
DR RefSeq; NP_002766.1; NM_002775.4.
DR PDB; 2JOA; NMR; -; A=380-480.
DR PDB; 2YTW; NMR; -; A=370-480.
DR PDB; 3NUM; X-ray; 2.75 A; A=158-480.
DR PDB; 3NWU; X-ray; 3.20 A; A/B/C=158-375.
DR PDB; 3NZI; X-ray; 2.75 A; A=158-480.
DR PDB; 3TJN; X-ray; 3.00 A; A/B/D=161-367.
DR PDB; 3TJO; X-ray; 2.30 A; A/B/D=161-370.
DR PDB; 3TJQ; X-ray; 2.00 A; A=35-156.
DR PDB; 6Z0E; X-ray; 2.60 A; A/B=161-375.
DR PDB; 6Z0X; X-ray; 3.10 A; A/B/C=161-375.
DR PDB; 6Z0Y; X-ray; 2.20 A; A/B/C=161-375.
DR PDBsum; 2JOA; -.
DR PDBsum; 2YTW; -.
DR PDBsum; 3NUM; -.
DR PDBsum; 3NWU; -.
DR PDBsum; 3NZI; -.
DR PDBsum; 3TJN; -.
DR PDBsum; 3TJO; -.
DR PDBsum; 3TJQ; -.
DR PDBsum; 6Z0E; -.
DR PDBsum; 6Z0X; -.
DR PDBsum; 6Z0Y; -.
DR AlphaFoldDB; Q92743; -.
DR BMRB; Q92743; -.
DR SMR; Q92743; -.
DR BioGRID; 111635; 40.
DR DIP; DIP-33195N; -.
DR IntAct; Q92743; 44.
DR MINT; Q92743; -.
DR STRING; 9606.ENSP00000357980; -.
DR BindingDB; Q92743; -.
DR ChEMBL; CHEMBL4523419; -.
DR GuidetoPHARMACOLOGY; 3194; -.
DR MEROPS; S01.277; -.
DR iPTMnet; Q92743; -.
DR PhosphoSitePlus; Q92743; -.
DR BioMuta; HTRA1; -.
DR DMDM; 18202620; -.
DR EPD; Q92743; -.
DR jPOST; Q92743; -.
DR MassIVE; Q92743; -.
DR PaxDb; Q92743; -.
DR PeptideAtlas; Q92743; -.
DR PRIDE; Q92743; -.
DR ProteomicsDB; 75437; -.
DR Antibodypedia; 32265; 263 antibodies from 32 providers.
DR DNASU; 5654; -.
DR Ensembl; ENST00000368984.8; ENSP00000357980.3; ENSG00000166033.13.
DR GeneID; 5654; -.
DR KEGG; hsa:5654; -.
DR MANE-Select; ENST00000368984.8; ENSP00000357980.3; NM_002775.5; NP_002766.1.
DR UCSC; uc001lgj.2; human.
DR CTD; 5654; -.
DR DisGeNET; 5654; -.
DR GeneCards; HTRA1; -.
DR GeneReviews; HTRA1; -.
DR HGNC; HGNC:9476; HTRA1.
DR HPA; ENSG00000166033; Low tissue specificity.
DR MalaCards; HTRA1; -.
DR MIM; 600142; phenotype.
DR MIM; 602194; gene.
DR MIM; 610149; phenotype.
DR MIM; 616779; phenotype.
DR neXtProt; NX_Q92743; -.
DR OpenTargets; ENSG00000166033; -.
DR Orphanet; 199354; Cerebral autosomal recessive arteriopathy-subcortical infarcts-leukoencephalopathy.
DR Orphanet; 482077; HTRA1-related autosomal dominant cerebral small vessel disease.
DR Orphanet; 252128; Malignant peripheral nerve sheath tumor with perineurial differentiation.
DR Orphanet; 252212; Malignant triton tumor.
DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration.
DR PharmGKB; PA33829; -.
DR VEuPathDB; HostDB:ENSG00000166033; -.
DR eggNOG; KOG1320; Eukaryota.
DR GeneTree; ENSGT00940000156955; -.
DR HOGENOM; CLU_020120_6_2_1; -.
DR InParanoid; Q92743; -.
DR OrthoDB; 630723at2759; -.
DR PhylomeDB; Q92743; -.
DR TreeFam; TF323480; -.
DR BRENDA; 3.4.21.107; 2681.
DR BRENDA; 3.4.21.108; 2681.
DR PathwayCommons; Q92743; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR SignaLink; Q92743; -.
DR BioGRID-ORCS; 5654; 16 hits in 1079 CRISPR screens.
DR ChiTaRS; HTRA1; human.
DR EvolutionaryTrace; Q92743; -.
DR GeneWiki; HTRA1; -.
DR GenomeRNAi; 5654; -.
DR Pharos; Q92743; Tchem.
DR PRO; PR:Q92743; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q92743; protein.
DR Bgee; ENSG00000166033; Expressed in tendon of biceps brachii and 202 other tissues.
DR ExpressionAtlas; Q92743; baseline and differential.
DR Genevisible; Q92743; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0019838; F:growth factor binding; IEA:UniProtKB-KW.
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:0008236; F:serine-type peptidase activity; ISS:UniProtKB.
DR GO; GO:0060718; P:chorionic trophoblast cell differentiation; IEA:Ensembl.
DR GO; GO:0097187; P:dentinogenesis; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IEA:Ensembl.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Growth factor binding; Hydrolase; Membrane; Protease; Reference proteome;
KW Secreted; Serine protease; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..480
FT /note="Serine protease HTRA1"
FT /id="PRO_0000026943"
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 ACT_SITE 220
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:21297635"
FT ACT_SITE 250
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:21297635"
FT ACT_SITE 328
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:21297635"
FT SITE 169
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000269|PubMed:21297635"
FT SITE 171
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000269|PubMed:21297635"
FT SITE 278
FT /note="Involved in trimer stabilization"
FT /evidence="ECO:0000269|PubMed:21297635"
FT DISULFID 110..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 119..155
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT VARIANT 20
FT /note="A -> V (in dbSNP:rs369149111)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076371"
FT VARIANT 51
FT /note="E -> G"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076372"
FT VARIANT 121
FT /note="S -> R (in CADASIL2)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076373"
FT VARIANT 123
FT /note="A -> S (in CADASIL2)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076374"
FT VARIANT 133
FT /note="R -> G (in CADASIL2)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076375"
FT VARIANT 166
FT /note="R -> L (in CADASIL2; loss of proteolytic activity;
FT dbSNP:rs864622781)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076376"
FT VARIANT 173
FT /note="A -> P (in CADASIL2; loss of proteolytic activity;
FT dbSNP:rs781563777)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076377"
FT VARIANT 252
FT /note="A -> T (in CARASIL; has 21 to 50% normal protease
FT activity; is unable to suppress TGF-beta activity;
FT dbSNP:rs113993968)"
FT /evidence="ECO:0000269|PubMed:19387015"
FT /id="VAR_063148"
FT VARIANT 284
FT /note="S -> G (in CADASIL2; partial loss of proteolytic
FT activity)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076378"
FT VARIANT 284
FT /note="S -> R (in CADASIL2; loss of proteolytic activity;
FT dbSNP:rs864622782)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076379"
FT VARIANT 285
FT /note="P -> Q (in CADASIL2; loss of proteolytic activity)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076380"
FT VARIANT 286
FT /note="F -> V (in CADASIL2; loss of proteolytic activity)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076381"
FT VARIANT 297
FT /note="V -> M (in CARASIL; has 21 to 50% normal protease
FT activity; is unable to suppress TGF-beta activity;
FT dbSNP:rs113993969)"
FT /evidence="ECO:0000269|PubMed:19387015"
FT /id="VAR_063149"
FT VARIANT 450
FT /note="D -> H (in CADASIL2; unknown pathological
FT significance; small decrease, if any, in proteolytic
FT activity; dbSNP:rs772225907)"
FT /evidence="ECO:0000269|PubMed:26063658"
FT /id="VAR_076382"
FT MUTAGEN 328
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:21297635,
FT ECO:0000269|PubMed:9852107"
FT CONFLICT 323
FT /note="I -> T (in Ref. 4; AAC97211)"
FT /evidence="ECO:0000305"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3TJQ"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:3TJQ"
FT HELIX 129..141
FT /evidence="ECO:0007829|PDB:3TJQ"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT HELIX 172..179
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 183..191
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 193..196
FT /evidence="ECO:0007829|PDB:3NZI"
FT STRAND 198..208
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:3NUM"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:3NZI"
FT STRAND 237..246
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:3TJO"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 285..288
FT /evidence="ECO:0007829|PDB:6Z0E"
FT STRAND 292..297
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:3TJN"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:3NZI"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 328..333
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 339..348
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 351..356
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT HELIX 357..369
FT /evidence="ECO:0007829|PDB:6Z0Y"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:2YTW"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:2JOA"
FT HELIX 392..401
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 411..417
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:2JOA"
FT HELIX 422..426
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:2YTW"
FT HELIX 445..454
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 456..464
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 467..473
FT /evidence="ECO:0007829|PDB:2JOA"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:2YTW"
SQ SEQUENCE 480 AA; 51287 MW; CA20A99480FB2330 CRC64;
MQIPRAALLP LLLLLLAAPA SAQLSRAGRS APLAAGCPDR CEPARCPPQP EHCEGGRARD
ACGCCEVCGA PEGAACGLQE GPCGEGLQCV VPFGVPASAT VRRRAQAGLC VCASSEPVCG
SDANTYANLC QLRAASRRSE RLHRPPVIVL QRGACGQGQE DPNSLRHKYN FIADVVEKIA
PAVVHIELFR KLPFSKREVP VASGSGFIVS EDGLIVTNAH VVTNKHRVKV ELKNGATYEA
KIKDVDEKAD IALIKIDHQG KLPVLLLGRS SELRPGEFVV AIGSPFSLQN TVTTGIVSTT
QRGGKELGLR NSDMDYIQTD AIINYGNSGG PLVNLDGEVI GINTLKVTAG ISFAIPSDKI
KKFLTESHDR QAKGKAITKK KYIGIRMMSL TSSKAKELKD RHRDFPDVIS GAYIIEVIPD
TPAEAGGLKE NDVIISINGQ SVVSANDVSD VIKRESTLNM VVRRGNEDIM ITVIPEEIDP
