ELNE_HUMAN
ID ELNE_HUMAN Reviewed; 267 AA.
AC P08246; P09649; Q6B0D9; Q6LDP5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Neutrophil elastase;
DE EC=3.4.21.37;
DE AltName: Full=Bone marrow serine protease;
DE AltName: Full=Elastase-2;
DE AltName: Full=Human leukocyte elastase;
DE Short=HLE;
DE AltName: Full=Medullasin;
DE AltName: Full=PMN elastase;
DE Flags: Precursor;
GN Name=ELANE; Synonyms=ELA2;
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 [GENOMIC DNA].
RX PubMed=3479752; DOI=10.1093/nar/15.22.9601;
RA Nakamura H., Okano K., Aoki Y., Shimizu H., Naruto M.;
RT "Nucleotide sequence of human bone marrow serine protease (medullasin)
RT gene.";
RL Nucleic Acids Res. 15:9601-9601(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2902087; DOI=10.1016/s0021-9258(18)68099-8;
RA Takahashi H., Nukiwa T., Yoshimura K., Quick C.D., States D.J.,
RA Holmes M.D., Whang-Peng J., Knutsen T., Crystal R.G.;
RT "Structure of the human neutrophil elastase gene.";
RL J. Biol. Chem. 263:14739-14747(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2775493; DOI=10.1515/bchm3.1989.370.2.737;
RA Farley D., Travis J., Salvesen G.;
RT "The human neutrophil elastase gene. Analysis of the nucleotide sequence
RT reveals three distinct classes of repetitive DNA.";
RL Biol. Chem. Hoppe-Seyler 370:737-744(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2322278; DOI=10.1016/0006-291x(90)90668-d;
RA Okano K., Aoki Y., Shimizu H., Naruto M.;
RT "Functional expression of human leukocyte elastase (HLE)/medullasin in
RT eukaryotic cells.";
RL Biochem. Biophys. Res. Commun. 167:1326-1332(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-219; LEU-257 AND
RP LEU-262.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-267.
RX PubMed=2822677; DOI=10.1093/oxfordjournals.jbchem.a122024;
RA Okano K., Aoki Y., Sakurai T., Kajitani M., Kanai S., Shimazu T.,
RA Shimizu H., Naruto M.;
RT "Molecular cloning of complementary DNA for human medullasin: an
RT inflammatory serine protease in bone marrow cells.";
RL J. Biochem. 102:13-16(1987).
RN [8]
RP PROTEIN SEQUENCE OF 30-247, AND GLYCOSYLATION AT ASN-124 AND ASN-173.
RX PubMed=3550808; DOI=10.1073/pnas.84.8.2228;
RA Sinha S., Watorek W., Karr S., Giles J., Bode W., Travis J.;
RT "Primary structure of human neutrophil elastase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:2228-2232(1987).
RN [9]
RP PRELIMINARY PROTEIN SEQUENCE OF 30-103.
RA Travis J., Giles P.J., Porcelli L., Reilly C.F., Baugh R., Powers J.;
RT "Human leucocyte elastase and cathepsin G: structural and functional
RT characteristics.";
RL (In) Evered D., Whelan J. (eds.);
RL Protein degradation in health and disease, Ciba Foundation Symposium,
RL pp.75:51-68, Excerpta Medica, Amsterdam and Oxford (1980).
RN [10]
RP PROTEIN SEQUENCE OF 30-49.
RX PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N.,
RA Seeger M., Nathan C.F.;
RT "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN [11]
RP PROTEIN SEQUENCE OF 30-49.
RC TISSUE=Neutrophil;
RX PubMed=7897245; DOI=10.1016/0022-1759(94)00295-8;
RA Gaskin G., Kendal H., Coulthart A., Turner N., Pusey C.D.;
RT "Use of proteinase 3 purified by reverse phase HPLC to detect
RT autoantibodies in systemic vasculitis.";
RL J. Immunol. Methods 180:25-33(1995).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-267.
RX PubMed=3422232; DOI=10.1016/s0021-9258(18)69241-5;
RA Takahashi H., Nukiwa T., Basset P., Cystal R.G.;
RT "Myelomonocytic cell lineage expression of the neutrophil elastase gene.";
RL J. Biol. Chem. 263:2543-2547(1988).
RN [13]
RP PROTEIN SEQUENCE OF 122-129, AND GLYCOSYLATION AT ASN-124.
RX PubMed=26274980; DOI=10.3390/biom5031832;
RA Loke I., Packer N.H., Thaysen-Andersen M.;
RT "Complementary LC-MS/MS-Based N-Glycan, N-Glycopeptide, and Intact N-
RT Glycoprotein Profiling Reveals Unconventional Asn71-Glycosylation of Human
RT Neutrophil Cathepsin G.";
RL Biomolecules 5:1832-1854(2015).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 123-267.
RX PubMed=2462434;
RA Farley D., Salvesen G.S., Travis J.;
RT "Molecular cloning of human neutrophil elastase.";
RL Biol. Chem. Hoppe-Seyler 369:3-7(1988).
RN [15]
RP PROTEIN SEQUENCE OF 262-267.
RX PubMed=1859409; DOI=10.1016/0006-291x(91)90135-t;
RA Aoki Y., Hase T.;
RT "The primary structure and elastinolytic activity of medullasin (a serine
RT protease of bone marrow).";
RL Biochem. Biophys. Res. Commun. 178:501-506(1991).
RN [16]
RP FUNCTION IN DEFENSE AGAINST BACTERIA, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10947984; DOI=10.1126/science.289.5482.1185;
RA Belaaouaj A., Kim K.S., Shapiro S.D.;
RT "Degradation of outer membrane protein A in Escherichia coli killing by
RT neutrophil elastase.";
RL Science 289:1185-1188(2000).
RN [17]
RP FUNCTION.
RX PubMed=15140022; DOI=10.1111/j.0906-6705.2004.00145.x;
RA Tralau T., Meyer-Hoffert U., Schroder J.M., Wiedow O.;
RT "Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-
RT dependent neutrophil enzyme release and chemotaxis.";
RL Exp. Dermatol. 13:316-325(2004).
RN [18]
RP INTERACTION WITH NOTCH2NL, AND CHARACTERIZATION OF VARIANT CH GLN-220.
RX PubMed=14673143; DOI=10.1128/mcb.24.1.58-70.2004;
RA Duan Z., Li F.-Q., Wechsler J., Meade-White K., Williams K., Benson K.F.,
RA Horwitz M.;
RT "A novel notch protein, N2N, targeted by neutrophil elastase and implicated
RT in hereditary neutropenia.";
RL Mol. Cell. Biol. 24:58-70(2004).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-88 AND ASN-173.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
RX PubMed=2911584; DOI=10.1073/pnas.86.1.7;
RA Navia M.A., McKeever B.M., Springer J.P., Lin T.-Y., Williams H.R.,
RA Fluder E.M., Dorn C.P., Hoogsteen K.;
RT "Structure of human neutrophil elastase in complex with a peptide
RT chloromethyl ketone inhibitor at 1.84-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:7-11(1989).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=3391280; DOI=10.1016/0014-5793(88)80118-2;
RA Wei A.-Z., Mayr I., Bode W.;
RT "The refined 2.3-A crystal structure of human leukocyte elastase in a
RT complex with a valine chloromethyl ketone inhibitor.";
RL FEBS Lett. 234:367-373(1988).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=3640709; DOI=10.1002/j.1460-2075.1986.tb04521.x;
RA Bode W., Wei A.-Z., Huber R., Meyer E., Travis J., Neumann S.;
RT "X-ray crystal structure of the complex of human leukocyte elastase (PMN
RT elastase) and the third domain of the turkey ovomucoid inhibitor.";
RL EMBO J. 5:2453-2458(1986).
RN [25]
RP VARIANTS CH VAL-61; PHE-206 AND GLN-220.
RX PubMed=10581030; DOI=10.1038/70544;
RA Horwitz M., Benson K.F., Person R.E., Aprikyan A.G., Dale D.C.;
RT "Mutations in ELA2, encoding neutrophil elastase, define a 21-day
RT biological clock in cyclic haematopoiesis.";
RL Nat. Genet. 23:433-436(1999).
RN [26]
RP VARIANTS SCN1 THR-57; THR-60; SER-71; MET-101; LEU-126; LEU-139; VAL-210
RP AND ARG-214, AND VARIANT CH LEU-139.
RX PubMed=11001877;
RA Dale D.C., Person R.E., Bolyard A.A., Aprikyan A.G., Bos C., Bonilla M.A.,
RA Boxer L.A., Kannourakis G., Zeidler C., Welte K., Benson K.F., Horwitz M.;
RT "Mutations in the gene encoding neutrophil elastase in congenital and
RT cyclic neutropenia.";
RL Blood 96:2317-2322(2000).
RN [27]
RP VARIANTS SCN1 TYR-55; GLU-85; PRO-GLN-LEU-123 INS; LEU-126; SER-151;
RP 190-VAL--PHE-199 DEL AND ARG-205.
RX PubMed=11675333; DOI=10.1182/blood.v98.9.2645;
RA Ancliff P.J., Gale R.E., Liesner R., Hann I.M., Linch D.C.;
RT "Mutations in the ELA2 gene encoding neutrophil elastase are present in
RT most patients with sporadic severe congenital neutropenia but only in some
RT patients with the familial form of the disease.";
RL Blood 98:2645-2650(2001).
RN [28]
RP VARIANT SCN1 ARG-71.
RX PubMed=12091371; DOI=10.1182/blood-2002-01-0060;
RA Ancliff P.J., Gale R.E., Watts M.J., Liesner R., Hann I.M., Strobel S.,
RA Linch D.C.;
RT "Paternal mosaicism proves the pathogenic nature of mutations in neutrophil
RT elastase in severe congenital neutropenia.";
RL Blood 100:707-709(2002).
RN [29]
RP VARIANTS SCN1 LEU-42; PRO-47; LEU-53; PRO-81; PRO-84; PRO-121; PRO-127;
RP LEU-139; PRO-152 AND 190-VAL--199-PHE DEL, VARIANTS CH LEU-43; PHE-46;
RP MET-82; LEU-126; LEU-139; 190-VAL--199-PHE DEL AND GLN-220, AND VARIANTS
RP ILE-219 AND LEU-262.
RX PubMed=14962902; DOI=10.1182/blood-2003-10-3518;
RA Bellanne-Chantelot C., Clauin S., Leblanc T., Cassinat B.,
RA Rodrigues-Lima F., Beaufils S., Vaury C., Barkaoui M., Fenneteau O.,
RA Maier-Redelsperger M., Chomienne C., Donadieu J.;
RT "Mutations in the ELA2 gene correlate with more severe expression of
RT neutropenia: a study of 81 patients from the French Neutropenia Register.";
RL Blood 103:4119-4125(2004).
RN [30]
RP VARIANTS SCN1 LEU-98 AND LEU-101, AND CHARACTERIZATION OF VARIANTS SCN1
RP LEU-98 AND LEU-101.
RX PubMed=17436313; DOI=10.1002/humu.20529;
RA Salipante S.J., Benson K.F., Luty J., Hadavi V., Kariminejad R.,
RA Kariminejad M.H., Rezaei N., Horwitz M.S.;
RT "Double de novo mutations of ELA2 in cyclic and severe congenital
RT neutropenia.";
RL Hum. Mutat. 28:874-881(2007).
RN [31]
RP VARIANT SCN1 VAL-57.
RX PubMed=18946670; DOI=10.1007/s00277-008-0629-y;
RA Lee S.T., Yoon H.S., Kim H.J., Lee J.H., Park J.H., Kim S.H., Seo J.J.,
RA Im H.J.;
RT "A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe
RT congenital neutropenia.";
RL Ann. Hematol. 88:593-595(2009).
RN [32]
RP VARIANTS SCN1 ARG-44; CYS-46; TYR-53; ARG-85; ARG-203 AND CYS-203.
RX PubMed=19036076; DOI=10.1111/j.1365-2141.2008.07493.x;
RA Smith B.N., Ancliff P.J., Pizzey A., Khwaja A., Linch D.C., Gale R.E.;
RT "Homozygous HAX1 mutations in severe congenital neutropenia patients with
RT sporadic disease: a novel mutation in two unrelated British kindreds.";
RL Br. J. Haematol. 144:762-770(2009).
RN [33]
RP VARIANTS SCN1 LEU-42; PRO-81; MET-101 AND LEU-126.
RX PubMed=19415009; DOI=10.1097/mph.0b013e3181984dbe;
RA Shiohara M., Shigemura T., Saito S., Tanaka M., Yanagisawa R.,
RA Sakashita K., Asada H., Ishii E., Koike K., Chin M., Kobayashi M.,
RA Koike K.;
RT "Ela2 mutations and clinical manifestations in familial congenital
RT neutropenia.";
RL J. Pediatr. Hematol. Oncol. 31:319-324(2009).
RN [34]
RP VARIANTS SCN1 VAL-25 AND THR-166.
RX PubMed=20220065; DOI=10.3324/haematol.2009.017665;
RA Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M.,
RA Welte K.;
RT "Digenic mutations in severe congenital neutropenia.";
RL Haematologica 95:1207-1210(2010).
RN [35]
RP VARIANTS SCN1 PRO-59 AND GLU-235.
RX PubMed=19927291; DOI=10.1002/pbc.22350;
RA Fioredda F., Calvillo M., Lanciotti M., Lanza T., Giunti L., Castagnola E.,
RA Lorenzi I., Tonelli R., Ghezzi P., Dufour C.;
RT "Pegfilgrastim in children with severe congenital neutropenia.";
RL Pediatr. Blood Cancer 54:465-467(2010).
RN [36]
RP VARIANT SCN1 SER-57.
RX PubMed=20803142; DOI=10.1007/s00277-010-1056-4;
RA van de Vosse E., Verhard E.M., Tool A.J., de Visser A.W., Kuijpers T.W.,
RA Hiemstra P.S., van Dissel J.T.;
RT "Severe congenital neutropenia in a multigenerational family with a novel
RT neutrophil elastase (ELANE) mutation.";
RL Ann. Hematol. 90:151-158(2011).
RN [37]
RP VARIANTS SCN1 THR-131; PRO-152; GLY-235 AND 190-VAL--199-PHE DEL.
RX PubMed=21425445; DOI=10.1002/pbc.23104;
RA Kurnikova M., Maschan M., Dinova E., Shagina I., Finogenova N.,
RA Mamedova E., Polovtseva T., Shagin D., Shcherbina A.;
RT "Four novel ELANE mutations in patients with congenital neutropenia.";
RL Pediatr. Blood Cancer 57:332-335(2011).
RN [38]
RP VARIANTS SCN1 VAL-25; LEU-42; LEU-43; GLU-45; PHE-46; ARG-47; PRO-49;
RP SER-55; ARG-56; SER-57; THR-57; VAL-57; PRO-59; 60-ILE-ALA-61 DELINS ARG;
RP THR-60; VAL-61; VAL-65 DEL; 66-MET--HIS-70 DEL; TRP-67; ARG-71; PHE-71;
RP TYR-71; GLY-72; GLY-80; PRO-81; MET-82; PRO-84; GLU-85; LEU-98; MET-98;
RP LEU-101; MET-101; LEU-103; PRO-103; ASN-120; PHE-120; SER-120; PRO-121;
RP HIS-123; ILE-124; LEU-126; ASP-127; THR-131; ASP-136; ARG-139; LEU-139;
RP PHE-151; TRP-151; TYR-151; PRO-152; ASP-153; PRO-153; ARG-156; CYS-156;
RP THR-166; ARG-203; ARG-205; SER-206; GLY-208; ARG-214; GLU-214; GLN-220;
RP PRO-233; GLU-235 AND GLY-235, VARIANTS CH LEU-45; VAL-61; PRO-81; LEU-97;
RP ASN-104; PHE-120; LEU-126; LEU-139; HIS-143; 190-VAL--199-PHE DEL; CYS-203;
RP ILE-209; TRP-210 AND GLN-220, AND VARIANTS VAL-118; ARG-125; MET-135;
RP ILE-219 AND LEU-257.
RX PubMed=23463630; DOI=10.1002/humu.22308;
RA Germeshausen M., Deerberg S., Peter Y., Reimer C., Kratz C.P.,
RA Ballmaier M.;
RT "The spectrum of ELANE mutations and their implications in severe
RT congenital and cyclic neutropenia.";
RL Hum. Mutat. 34:905-914(2013).
CC -!- FUNCTION: Modifies the functions of natural killer cells, monocytes and
CC granulocytes. Inhibits C5a-dependent neutrophil enzyme release and
CC chemotaxis (PubMed:15140022). Capable of killing E.coli but not
CC S.aureus in vitro; digests outer membrane protein A (ompA) in E.coli
CC and K.pneumoniae (PubMed:10947984). {ECO:0000269|PubMed:10947984,
CC ECO:0000269|PubMed:15140022}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins, including elastin. Preferential
CC cleavage: Val-|-Xaa > Ala-|-Xaa.; EC=3.4.21.37;
CC -!- SUBUNIT: Interacts with NOTCH2NL. {ECO:0000269|PubMed:14673143}.
CC -!- INTERACTION:
CC P08246; Q07563: Col17a1; Xeno; NbExp=2; IntAct=EBI-986345, EBI-6251005;
CC P08246; P0DTC2: S; Xeno; NbExp=2; IntAct=EBI-986345, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:10947984}. Note=Localized in phagolysosomes
CC following ingestion of E.coli by neutrophils.
CC {ECO:0000269|PubMed:10947984}.
CC -!- TISSUE SPECIFICITY: Bone marrow cells. Neutrophil (PubMed:10947984).
CC {ECO:0000269|PubMed:10947984}.
CC -!- DISEASE: Cyclic haematopoiesis (CH) [MIM:162800]: Autosomal dominant
CC disease in which blood-cell production from the bone marrow oscillates
CC with 21-day periodicity. Circulating neutrophils vary between almost
CC normal numbers and zero. During intervals of neutropenia, affected
CC individuals are at risk for opportunistic infection. Monocytes,
CC platelets, lymphocytes and reticulocytes also cycle with the same
CC frequency. {ECO:0000269|PubMed:10581030, ECO:0000269|PubMed:11001877,
CC ECO:0000269|PubMed:14673143, ECO:0000269|PubMed:14962902,
CC ECO:0000269|PubMed:23463630}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neutropenia, severe congenital 1, autosomal dominant (SCN1)
CC [MIM:202700]: A disorder of hematopoiesis characterized by maturation
CC arrest of granulopoiesis at the level of promyelocytes with peripheral
CC blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of
CC severe bacterial infections. {ECO:0000269|PubMed:11001877,
CC ECO:0000269|PubMed:11675333, ECO:0000269|PubMed:12091371,
CC ECO:0000269|PubMed:14962902, ECO:0000269|PubMed:17436313,
CC ECO:0000269|PubMed:18946670, ECO:0000269|PubMed:19036076,
CC ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:19927291,
CC ECO:0000269|PubMed:20220065, ECO:0000269|PubMed:20803142,
CC ECO:0000269|PubMed:21425445, ECO:0000269|PubMed:23463630}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA29300.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=CCHMC molecular genetics laboratory mutation
CC database; Note=ELA2 elastase, neutrophil expressed (ELANE);
CC URL="https://databases.lovd.nl/shared/genes/ELANE";
CC -!- WEB RESOURCE: Name=ELA2base; Note=ELA2 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/ELA2base/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ela2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Elastase entry;
CC URL="https://en.wikipedia.org/wiki/Elastase";
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DR EMBL; Y00477; CAA68537.1; -; Genomic_DNA.
DR EMBL; M20203; AAA36359.1; -; Genomic_DNA.
DR EMBL; M20199; AAA36359.1; JOINED; Genomic_DNA.
DR EMBL; M20200; AAA36359.1; JOINED; Genomic_DNA.
DR EMBL; M20201; AAA36359.1; JOINED; Genomic_DNA.
DR EMBL; M34379; AAA36173.1; -; mRNA.
DR EMBL; AY596461; AAS89303.1; -; Genomic_DNA.
DR EMBL; BC074816; AAH74816.1; -; mRNA.
DR EMBL; BC074817; AAH74817.1; -; mRNA.
DR EMBL; D00187; BAA00128.1; -; mRNA.
DR EMBL; X05875; CAA29299.1; -; mRNA.
DR EMBL; X05875; CAA29300.1; ALT_INIT; mRNA.
DR EMBL; J03545; AAA52378.1; -; mRNA.
DR EMBL; M27783; AAA35792.1; -; mRNA.
DR CCDS; CCDS12045.1; -.
DR PIR; A31976; ELHUL.
DR RefSeq; NP_001963.1; NM_001972.3.
DR RefSeq; XP_011526077.1; XM_011527775.1.
DR RefSeq; XP_011526078.1; XM_011527776.1.
DR PDB; 1B0F; X-ray; 3.00 A; A=30-247.
DR PDB; 1H1B; X-ray; 2.00 A; A/B=30-247.
DR PDB; 1HNE; X-ray; 1.84 A; E=30-247.
DR PDB; 1PPF; X-ray; 1.80 A; E=30-247.
DR PDB; 1PPG; X-ray; 2.30 A; E=30-247.
DR PDB; 2RG3; X-ray; 1.80 A; A=30-247.
DR PDB; 2Z7F; X-ray; 1.70 A; E=30-247.
DR PDB; 3Q76; X-ray; 1.86 A; A/B=30-247.
DR PDB; 3Q77; X-ray; 2.00 A; A=30-247.
DR PDB; 4NZL; X-ray; 1.85 A; A=30-247.
DR PDB; 4WVP; X-ray; 1.63 A; E=30-247.
DR PDB; 5A09; X-ray; 1.81 A; A=30-247.
DR PDB; 5A0A; X-ray; 1.78 A; E=30-247.
DR PDB; 5A0B; X-ray; 2.23 A; A=30-247.
DR PDB; 5A0C; X-ray; 2.10 A; A/B=30-247.
DR PDB; 5A8X; X-ray; 2.23 A; A=30-247.
DR PDB; 5A8Y; X-ray; 1.90 A; A=30-247.
DR PDB; 5A8Z; X-ray; 2.00 A; A=30-247.
DR PDB; 5ABW; X-ray; 1.60 A; A=30-247.
DR PDB; 6E69; X-ray; 2.33 A; A/B/C/D=30-247.
DR PDB; 6F5M; X-ray; 2.70 A; A/B=30-247.
DR PDB; 6SMA; X-ray; 2.59 A; A/B/C=30-247.
DR PDB; 7CBK; X-ray; 2.70 A; B/D=1-267.
DR PDBsum; 1B0F; -.
DR PDBsum; 1H1B; -.
DR PDBsum; 1HNE; -.
DR PDBsum; 1PPF; -.
DR PDBsum; 1PPG; -.
DR PDBsum; 2RG3; -.
DR PDBsum; 2Z7F; -.
DR PDBsum; 3Q76; -.
DR PDBsum; 3Q77; -.
DR PDBsum; 4NZL; -.
DR PDBsum; 4WVP; -.
DR PDBsum; 5A09; -.
DR PDBsum; 5A0A; -.
DR PDBsum; 5A0B; -.
DR PDBsum; 5A0C; -.
DR PDBsum; 5A8X; -.
DR PDBsum; 5A8Y; -.
DR PDBsum; 5A8Z; -.
DR PDBsum; 5ABW; -.
DR PDBsum; 6E69; -.
DR PDBsum; 6F5M; -.
DR PDBsum; 6SMA; -.
DR PDBsum; 7CBK; -.
DR AlphaFoldDB; P08246; -.
DR SMR; P08246; -.
DR BioGRID; 108306; 36.
DR CORUM; P08246; -.
DR IntAct; P08246; 11.
DR MINT; P08246; -.
DR STRING; 9606.ENSP00000466090; -.
DR BindingDB; P08246; -.
DR ChEMBL; CHEMBL248; -.
DR DrugBank; DB00058; Alpha-1-proteinase inhibitor.
DR DrugBank; DB05161; Elafin.
DR DrugBank; DB00099; Filgrastim.
DR DrugBank; DB03925; Freselestat.
DR DrugBank; DB02341; Mdl 101,146.
DR DrugBank; DB00019; Pegfilgrastim.
DR DrugCentral; P08246; -.
DR GuidetoPHARMACOLOGY; 2358; -.
DR MEROPS; S01.131; -.
DR GlyConnect; 1564; 3 N-Linked glycans (2 sites).
DR GlyGen; P08246; 3 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; P08246; -.
DR PhosphoSitePlus; P08246; -.
DR BioMuta; ELANE; -.
DR DMDM; 119292; -.
DR jPOST; P08246; -.
DR MassIVE; P08246; -.
DR PaxDb; P08246; -.
DR PeptideAtlas; P08246; -.
DR PRIDE; P08246; -.
DR ProteomicsDB; 52099; -.
DR ABCD; P08246; 2 sequenced antibodies.
DR Antibodypedia; 4209; 711 antibodies from 42 providers.
DR DNASU; 1991; -.
DR Ensembl; ENST00000263621.2; ENSP00000263621.1; ENSG00000197561.7.
DR Ensembl; ENST00000590230.5; ENSP00000466090.1; ENSG00000197561.7.
DR Ensembl; ENST00000615489.1; ENSP00000480128.1; ENSG00000277571.2.
DR Ensembl; ENST00000632488.1; ENSP00000488075.1; ENSG00000277571.2.
DR GeneID; 1991; -.
DR KEGG; hsa:1991; -.
DR MANE-Select; ENST00000263621.2; ENSP00000263621.1; NM_001972.4; NP_001963.1.
DR UCSC; uc002lqb.4; human.
DR CTD; 1991; -.
DR DisGeNET; 1991; -.
DR GeneCards; ELANE; -.
DR GeneReviews; ELANE; -.
DR HGNC; HGNC:3309; ELANE.
DR HPA; ENSG00000197561; Tissue enriched (bone).
DR MalaCards; ELANE; -.
DR MIM; 130130; gene.
DR MIM; 162800; phenotype.
DR MIM; 202700; phenotype.
DR neXtProt; NX_P08246; -.
DR OpenTargets; ENSG00000197561; -.
DR Orphanet; 486; Autosomal dominant severe congenital neutropenia.
DR Orphanet; 2686; Cyclic neutropenia.
DR PharmGKB; PA27735; -.
DR VEuPathDB; HostDB:ENSG00000197561; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01030000234528; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; P08246; -.
DR OMA; RRRVNVC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P08246; -.
DR BRENDA; 3.4.21.37; 2681.
DR PathwayCommons; P08246; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SABIO-RK; P08246; -.
DR SignaLink; P08246; -.
DR SIGNOR; P08246; -.
DR BioGRID-ORCS; 1991; 18 hits in 1072 CRISPR screens.
DR ChiTaRS; ELANE; human.
DR EvolutionaryTrace; P08246; -.
DR GeneWiki; Neutrophil_elastase; -.
DR GenomeRNAi; 1991; -.
DR Pharos; P08246; Tclin.
DR PRO; PR:P08246; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P08246; protein.
DR Bgee; ENSG00000197561; Expressed in bone marrow and 85 other tissues.
DR Genevisible; P08246; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; EXP:Reactome.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
DR GO; GO:0002438; P:acute inflammatory response to antigenic stimulus; IBA:GO_Central.
DR GO; GO:0002812; P:biosynthetic process of antibacterial peptides active against Gram-negative bacteria; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; NAS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProtKB.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0032682; P:negative regulation of chemokine production; IDA:UniProtKB.
DR GO; GO:0050922; P:negative regulation of chemotaxis; NAS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; NAS:UniProtKB.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0070947; P:neutrophil-mediated killing of fungus; IEA:Ensembl.
DR GO; GO:0070945; P:neutrophil-mediated killing of gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0050778; P:positive regulation of immune response; IEA:Ensembl.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; NAS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; NAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; TAS:Reactome.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0001878; P:response to yeast; IEA:Ensembl.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasmic vesicle; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW Reference proteome; Serine protease; Signal; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..29
FT /evidence="ECO:0000269|PubMed:2501794,
FT ECO:0000269|PubMed:3550808, ECO:0000269|PubMed:7897245"
FT /id="PRO_0000027703"
FT CHAIN 30..267
FT /note="Neutrophil elastase"
FT /id="PRO_0000027704"
FT DOMAIN 30..247
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 70
FT /note="Charge relay system"
FT ACT_SITE 117
FT /note="Charge relay system"
FT ACT_SITE 202
FT /note="Charge relay system"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26274980,
FT ECO:0000269|PubMed:3550808"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:3550808"
FT DISULFID 55..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:3550808"
FT DISULFID 151..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:3550808"
FT DISULFID 181..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:3550808"
FT DISULFID 198..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274,
FT ECO:0000269|PubMed:3550808"
FT VARIANT 25
FT /note="A -> V (in SCN1; dbSNP:rs1396230082)"
FT /evidence="ECO:0000269|PubMed:20220065,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_064512"
FT VARIANT 42
FT /note="P -> L (in SCN1)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:23463630"
FT /id="VAR_070696"
FT VARIANT 43
FT /note="F -> L (in SCN1 and CH)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070697"
FT VARIANT 44
FT /note="M -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:19036076"
FT /id="VAR_070698"
FT VARIANT 45
FT /note="V -> E (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070699"
FT VARIANT 45
FT /note="V -> L (in CH)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070700"
FT VARIANT 46
FT /note="S -> C (in SCN1)"
FT /evidence="ECO:0000269|PubMed:19036076"
FT /id="VAR_070701"
FT VARIANT 46
FT /note="S -> F (in CH and SCN1; dbSNP:rs878855320)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070702"
FT VARIANT 47
FT /note="L -> P (in SCN1; dbSNP:rs878855319)"
FT /evidence="ECO:0000269|PubMed:14962902"
FT /id="VAR_070703"
FT VARIANT 47
FT /note="L -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070704"
FT VARIANT 49
FT /note="L -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070705"
FT VARIANT 53
FT /note="H -> L (in SCN1)"
FT /evidence="ECO:0000269|PubMed:14962902"
FT /id="VAR_070706"
FT VARIANT 53
FT /note="H -> Q (in CH)"
FT /id="VAR_070707"
FT VARIANT 53
FT /note="H -> Y (in SCN1; dbSNP:rs1131691882)"
FT /evidence="ECO:0000269|PubMed:19036076"
FT /id="VAR_070708"
FT VARIANT 55
FT /note="C -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070709"
FT VARIANT 55
FT /note="C -> Y (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11675333"
FT /id="VAR_038609"
FT VARIANT 56
FT /note="G -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070710"
FT VARIANT 57
FT /note="A -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:20803142,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070711"
FT VARIANT 57
FT /note="A -> T (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038610"
FT VARIANT 57
FT /note="A -> V (in SCN1; dbSNP:rs1057520110)"
FT /evidence="ECO:0000269|PubMed:18946670,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070712"
FT VARIANT 59
FT /note="L -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:19927291,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070713"
FT VARIANT 60..61
FT /note="IA -> R"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070714"
FT VARIANT 60
FT /note="I -> T (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038611"
FT VARIANT 61
FT /note="A -> V (in SCN1 and CH; dbSNP:rs137854447)"
FT /evidence="ECO:0000269|PubMed:10581030,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070715"
FT VARIANT 65
FT /note="Missing (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070716"
FT VARIANT 66..70
FT /note="Missing (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070717"
FT VARIANT 67
FT /note="S -> W (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070718"
FT VARIANT 71
FT /note="C -> F (in SCN1; dbSNP:rs878855315)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070719"
FT VARIANT 71
FT /note="C -> R (in SCN1; dbSNP:rs28931611)"
FT /evidence="ECO:0000269|PubMed:12091371,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038612"
FT VARIANT 71
FT /note="C -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11001877"
FT /id="VAR_038613"
FT VARIANT 71
FT /note="C -> Y (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070720"
FT VARIANT 72
FT /note="V -> G (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070721"
FT VARIANT 80
FT /note="V -> G (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070722"
FT VARIANT 81
FT /note="R -> P (in SCN1 and CH)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:23463630"
FT /id="VAR_070723"
FT VARIANT 82
FT /note="V -> M (in SCN1 and CH)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070724"
FT VARIANT 84
FT /note="L -> P (in SCN1; dbSNP:rs1064793108)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070725"
FT VARIANT 85
FT /note="G -> E (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11675333,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038614"
FT VARIANT 85
FT /note="G -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:19036076"
FT /id="VAR_070726"
FT VARIANT 97
FT /note="Q -> L (in CH)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070727"
FT VARIANT 98
FT /note="V -> L (in SCN1; located on the same allele as L-
FT 101; reduces proteolytic enzyme activity by slightly less
FT than half; together with L-101 shows an additive effect
FT with minimal remaining enzyme activity; dbSNP:rs267606781)"
FT /evidence="ECO:0000269|PubMed:17436313,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038615"
FT VARIANT 98
FT /note="V -> M (in SCN1; dbSNP:rs267606781)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070728"
FT VARIANT 101
FT /note="V -> L (in SCN1; located on the same allele as L-98;
FT reduces proteolytic enzyme activity by slightly less than
FT half; together with L-98 shows an additive effect with
FT minimal remaining enzyme activity; dbSNP:rs137854449)"
FT /evidence="ECO:0000269|PubMed:17436313,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038616"
FT VARIANT 101
FT /note="V -> M (in SCN1; dbSNP:rs137854449)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:23463630"
FT /id="VAR_038617"
FT VARIANT 103
FT /note="R -> L (in SCN1; dbSNP:rs745455816)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070729"
FT VARIANT 103
FT /note="R -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070730"
FT VARIANT 104
FT /note="I -> N (in CH)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070731"
FT VARIANT 118
FT /note="I -> V (in dbSNP:rs1382122842)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070732"
FT VARIANT 120
FT /note="I -> F (in SCN1 and CH; dbSNP:rs1131691520)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070733"
FT VARIANT 120
FT /note="I -> N (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070734"
FT VARIANT 120
FT /note="I -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070735"
FT VARIANT 121
FT /note="L -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070736"
FT VARIANT 123
FT /note="L -> H (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070737"
FT VARIANT 123
FT /note="L -> PQL (in SCN1)"
FT /id="VAR_038618"
FT VARIANT 124
FT /note="N -> I (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070738"
FT VARIANT 125
FT /note="G -> R (in dbSNP:rs377698556)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070739"
FT VARIANT 126
FT /note="S -> L (in SCN1 and CH; dbSNP:rs137854450)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:11675333, ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:19415009, ECO:0000269|PubMed:23463630"
FT /id="VAR_038619"
FT VARIANT 127
FT /note="A -> D (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070740"
FT VARIANT 127
FT /note="A -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:14962902"
FT /id="VAR_070741"
FT VARIANT 131
FT /note="A -> T (in SCN1; unknown pathological significance;
FT dbSNP:rs201729066)"
FT /evidence="ECO:0000269|PubMed:21425445,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070742"
FT VARIANT 135
FT /note="V -> M (in dbSNP:rs774457980)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070743"
FT VARIANT 136
FT /note="A -> D (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070744"
FT VARIANT 139
FT /note="P -> L (in SCN1 and CH; dbSNP:rs137854448)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:14962902, ECO:0000269|PubMed:23463630"
FT /id="VAR_038620"
FT VARIANT 139
FT /note="P -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070745"
FT VARIANT 143
FT /note="R -> H (in CH; unknown pathological significance;
FT dbSNP:rs200993994)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070746"
FT VARIANT 151
FT /note="C -> F (in SCN1; dbSNP:rs57246956)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070747"
FT VARIANT 151
FT /note="C -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11675333"
FT /id="VAR_038621"
FT VARIANT 151
FT /note="C -> W (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070748"
FT VARIANT 151
FT /note="C -> Y (in SCN1; unknown pathological significance;
FT dbSNP:rs57246956)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070749"
FT VARIANT 152
FT /note="L -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:21425445, ECO:0000269|PubMed:23463630"
FT /id="VAR_070750"
FT VARIANT 153
FT /note="A -> D (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070751"
FT VARIANT 153
FT /note="A -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070752"
FT VARIANT 156
FT /note="W -> C (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070753"
FT VARIANT 156
FT /note="W -> R (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070754"
FT VARIANT 166
FT /note="A -> T (in SCN1; the patient also carries mutation
FT Lys-116 in G6PC3; dbSNP:rs201788817)"
FT /evidence="ECO:0000269|PubMed:20220065,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_064513"
FT VARIANT 190..199
FT /note="Missing (in SCN1 and CH)"
FT /evidence="ECO:0000269|PubMed:11675333"
FT /id="VAR_038622"
FT VARIANT 203
FT /note="G -> C (in SCN1 and CH)"
FT /evidence="ECO:0000269|PubMed:19036076,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070755"
FT VARIANT 203
FT /note="G -> R (in SCN1; dbSNP:rs201139487)"
FT /evidence="ECO:0000269|PubMed:19036076,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070756"
FT VARIANT 205
FT /note="P -> R (in SCN1; dbSNP:rs1555710077)"
FT /evidence="ECO:0000269|PubMed:11675333,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038623"
FT VARIANT 206
FT /note="L -> F (in CH; dbSNP:rs137854446)"
FT /evidence="ECO:0000269|PubMed:10581030"
FT /id="VAR_070757"
FT VARIANT 206
FT /note="L -> S (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070758"
FT VARIANT 208
FT /note="C -> G (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070759"
FT VARIANT 209
FT /note="N -> I (in CH)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070760"
FT VARIANT 210
FT /note="G -> V (in SCN1)"
FT /evidence="ECO:0000269|PubMed:11001877"
FT /id="VAR_038624"
FT VARIANT 210
FT /note="G -> W (in CH)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070761"
FT VARIANT 214
FT /note="G -> E (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070762"
FT VARIANT 214
FT /note="G -> R (in SCN1; dbSNP:rs137854451)"
FT /evidence="ECO:0000269|PubMed:11001877,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_038625"
FT VARIANT 219
FT /note="V -> I (in dbSNP:rs17216656)"
FT /evidence="ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630, ECO:0000269|Ref.5"
FT /id="VAR_019237"
FT VARIANT 220
FT /note="R -> Q (in CH and SCN1; loss of interaction with
FT NOTCH2NL and loss of NOTCH2NL and NOTCH2 proteolytic
FT cleavage; dbSNP:rs137854445)"
FT /evidence="ECO:0000269|PubMed:10581030,
FT ECO:0000269|PubMed:14673143, ECO:0000269|PubMed:14962902,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070763"
FT VARIANT 233
FT /note="A -> P (in SCN1)"
FT /evidence="ECO:0000269|PubMed:23463630"
FT /id="VAR_070764"
FT VARIANT 235
FT /note="V -> E (in SCN1)"
FT /evidence="ECO:0000269|PubMed:19927291,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070765"
FT VARIANT 235
FT /note="V -> G (in SCN1)"
FT /evidence="ECO:0000269|PubMed:21425445,
FT ECO:0000269|PubMed:23463630"
FT /id="VAR_070766"
FT VARIANT 257
FT /note="P -> L (in dbSNP:rs17216663)"
FT /evidence="ECO:0000269|PubMed:23463630, ECO:0000269|Ref.5"
FT /id="VAR_019238"
FT VARIANT 262
FT /note="P -> L (found in patients with severe congenital or
FT cyclic neutropenia; dbSNP:rs17216670)"
FT /evidence="ECO:0000269|PubMed:14962902, ECO:0000269|Ref.5"
FT /id="VAR_019239"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:5ABW"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:6F5M"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 97..106
FT /evidence="ECO:0007829|PDB:5ABW"
FT TURN 111..114
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2Z7F"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4WVP"
FT STRAND 170..177
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 211..218
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:5ABW"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:5ABW"
FT HELIX 235..238
FT /evidence="ECO:0007829|PDB:5ABW"
FT HELIX 239..246
FT /evidence="ECO:0007829|PDB:5ABW"
SQ SEQUENCE 267 AA; 28518 MW; 3F7610DC33CAA4B9 CRC64;
MTLGRRLACL FLACVLPALL LGGTALASEI VGGRRARPHA WPFMVSLQLR GGHFCGATLI
APNFVMSAAH CVANVNVRAV RVVLGAHNLS RREPTRQVFA VQRIFENGYD PVNLLNDIVI
LQLNGSATIN ANVQVAQLPA QGRRLGNGVQ CLAMGWGLLG RNRGIASVLQ ELNVTVVTSL
CRRSNVCTLV RGRQAGVCFG DSGSPLVCNG LIHGIASFVR GGCASGLYPD AFAPVAQFVN
WIDSIIQRSE DNPCPHPRDP DPASRTH
