ISK5_HUMAN
ID ISK5_HUMAN Reviewed; 1064 AA.
AC Q9NQ38; A8MYE8; B7WPB7; D6REN5; O75770; Q3LX95; Q3LX96; Q3LX97; Q96PP2;
AC Q96PP3;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Serine protease inhibitor Kazal-type 5;
DE AltName: Full=Lympho-epithelial Kazal-type-related inhibitor;
DE Short=LEKTI;
DE Contains:
DE RecName: Full=Hemofiltrate peptide HF6478;
DE Contains:
DE RecName: Full=Hemofiltrate peptide HF7665;
DE Flags: Precursor;
GN Name=SPINK5;
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] (ISOFORMS F-L), PARTIAL PROTEIN SEQUENCE,
RP VARIANTS ARG-267; VAL-335; ASN-368; GLU-420 AND GLN-711, FUNCTION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Epithelium;
RX PubMed=10419450; DOI=10.1074/jbc.274.31.21499;
RA Maegert H.-J., Staendker L., Kreutzmann P., Zucht H.-D., Reinecke M.,
RA Sommerhoff C.P., Fritz H., Forssmann W.-G.;
RT "LEKTI, a novel 15-domain type of human serine proteinase inhibitor.";
RL J. Biol. Chem. 274:21499-21502(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN NETHERTON SYNDROME, AND
RP VARIANTS ARG-267 AND ASN-368.
RX PubMed=10835624; DOI=10.1038/75977;
RA Chavanas S., Bodemer C., Rochat A., Hamel-Teillac D., Ali M., Irvine A.D.,
RA Bonafe J.-L., Wilkinson J., Taieb A., Barrandon Y., Harper J.I.,
RA de Prost Y., Hovnanian A.;
RT "Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton
RT syndrome.";
RL Nat. Genet. 25:141-142(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SHORT; F-L AND LONG), ALTERNATIVE
RP SPLICING, AND VARIANTS ARG-267; VAL-335; ASN-368; GLU-420 AND GLN-711.
RC TISSUE=Keratinocyte;
RX PubMed=16374478; DOI=10.1038/sj.jid.5700015;
RA Tartaglia-Polcini A., Bonnart C., Micheloni A., Cianfarani F., Andre A.,
RA Zambruno G., Hovnanian A., D'Alessio M.;
RT "SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI
RT isoforms derived from alternative pre-mRNA processing.";
RL J. Invest. Dermatol. 126:315-324(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 202-222 AND 266-294.
RX PubMed=11511292; DOI=10.1046/j.1523-1747.2001.01389.x;
RA Sprecher E., Chavanas S., DiGiovanna J.J., Amin S., Nielsen K.,
RA Prendiville J.S., Silverman R., Esterly N.B., Spraker M.K., Guelig E.,
RA de Luna M.L., Williams M.L., Buehler B., Siegfried E.C., Van Maldergem L.,
RA Pfendner E., Bale S.J., Uitto J., Hovnanian A., Richard G.;
RT "The spectrum of pathogenic mutations in SPINK5 in 19 families with
RT Netherton syndrome: implications for mutation detection and first case of
RT prenatal diagnosis.";
RL J. Invest. Dermatol. 117:179-187(2001).
RN [6]
RP PROTEIN SEQUENCE OF 490-507.
RC TISSUE=Foreskin keratinocyte;
RX PubMed=11594460; DOI=10.1023/a:1010902815953;
RA Ahmed A., Kandola P., Ziada G., Parenteau N.;
RT "Purification and partial amino acid sequence of proteins from human
RT epidermal keratinocyte conditioned medium.";
RL J. Protein Chem. 20:273-278(2001).
RN [7]
RP FUNCTION, CLEAVAGE BY FURIN, AND INHIBITION OF KLK5; KLK7 AND KLK14.
RX PubMed=17596512; DOI=10.1091/mbc.e07-02-0124;
RA Deraison C., Bonnart C., Lopez F., Besson C., Robinson R., Jayakumar A.,
RA Wagberg F., Brattsand M., Hachem J.P., Leonardsson G., Hovnanian A.;
RT "LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control
RT desquamation through a pH-dependent interaction.";
RL Mol. Biol. Cell 18:3607-3619(2007).
RN [8]
RP FUNCTION, AND INHIBITION OF CASP14.
RX PubMed=20533828; DOI=10.1021/pr1003467;
RA Bennett K., Callard R., Heywood W., Harper J., Jayakumar A., Clayman G.L.,
RA Di W.L., Mills K.;
RT "New role for LEKTI in skin barrier formation: label-free quantitative
RT proteomic identification of caspase 14 as a novel target for the protease
RT inhibitor LEKTI.";
RL J. Proteome Res. 9:4289-4294(2010).
RN [9]
RP STRUCTURE BY NMR OF 23-77 AND 356-423.
RX PubMed=12684009; DOI=10.1016/s0022-2836(03)00245-6;
RA Lauber T., Schulz A., Schweimer K., Adermann K., Marx U.C.;
RT "Homologous proteins with different folds: the three-dimensional structures
RT of domains 1 and 6 of the multiple Kazal-type inhibitor LEKTI.";
RL J. Mol. Biol. 328:205-219(2003).
RN [10]
RP STRUCTURE BY NMR OF 989-1064.
RX PubMed=15366933; DOI=10.1021/bi0492399;
RA Tidow H., Lauber T., Vitzithum K., Sommerhoff C.P., Rosch P., Marx U.C.;
RT "The solution structure of a chimeric LEKTI domain reveals a chameleon
RT sequence.";
RL Biochemistry 43:11238-11247(2004).
RN [11]
RP VARIANT GLU-420.
RX PubMed=11544479; DOI=10.1038/ng728;
RA Walley A.J., Chavanas S., Moffatt M.F., Esnouf R.M., Ubhi B., Lawrence R.,
RA Wong K., Abecasis G.R., Jones E.Y., Harper J.I., Hovnanian A.,
RA Cookson W.O.C.M.;
RT "Gene polymorphism in Netherton and common atopic disease.";
RL Nat. Genet. 29:175-178(2001).
CC -!- FUNCTION: Serine protease inhibitor, probably important for the anti-
CC inflammatory and/or antimicrobial protection of mucous epithelia.
CC Contribute to the integrity and protective barrier function of the skin
CC by regulating the activity of defense-activating and desquamation-
CC involved proteases. Inhibits KLK5, it's major target, in a pH-dependent
CC manner. Inhibits KLK7, KLK14 CASP14, and trypsin.
CC {ECO:0000269|PubMed:10419450, ECO:0000269|PubMed:17596512,
CC ECO:0000269|PubMed:20533828}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=f-l;
CC IsoId=Q9NQ38-1; Sequence=Displayed;
CC Name=short;
CC IsoId=Q9NQ38-2; Sequence=VSP_040019, VSP_040021;
CC Name=long;
CC IsoId=Q9NQ38-3; Sequence=VSP_040020;
CC -!- TISSUE SPECIFICITY: Highly expressed in the thymus and stratum corneum.
CC Also found in the oral mucosa, parathyroid gland, Bartholin's glands,
CC tonsils, and vaginal epithelium. Very low levels are detected in lung,
CC kidney, and prostate. {ECO:0000269|PubMed:10419450}.
CC -!- DOMAIN: Contains at least one active inhibitory domain for trypsin
CC (domain 6).
CC -!- PTM: Proteolytically processed by furin in individual domains (D1, D5,
CC D6, D8 through D11, and D9 through D15) exhibiting various inhibitory
CC potentials for multiple proteases. {ECO:0000269|PubMed:17596512}.
CC -!- DISEASE: Netherton syndrome (NETH) [MIM:256500]: An autosomal recessive
CC congenital ichthyosis associated with hair shaft abnormalities and
CC anomalies of the immune system. Typical features are ichthyosis
CC linearis circumflexa, ichthyosiform erythroderma, trichorrhexis
CC invaginata (bamboo hair), atopic dermatitis, and hayfever. High
CC postnatal mortality is due to failure to thrive, infections and
CC hypernatremic dehydration. {ECO:0000269|PubMed:10835624}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=SPINK5base; Note=SPINK5 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/SPINK5base/";
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DR EMBL; AJ228139; CAB40839.1; -; mRNA.
DR EMBL; AJ391230; CAB96877.1; -; Genomic_DNA.
DR EMBL; AJ270944; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391231; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391232; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391233; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391234; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391235; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ276579; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391236; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ276580; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391237; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391238; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391239; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391240; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391241; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ276578; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391242; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391243; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391244; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391245; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391246; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391247; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391248; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391249; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391250; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391251; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391252; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391253; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ391254; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; AJ276577; CAB96877.1; JOINED; Genomic_DNA.
DR EMBL; DQ149927; ABA06534.1; -; mRNA.
DR EMBL; DQ149928; ABA06535.1; -; mRNA.
DR EMBL; DQ149929; ABA06536.1; -; mRNA.
DR EMBL; AC008722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF295784; AAK97139.1; -; Genomic_DNA.
DR EMBL; AF295783; AAK97140.1; -; Genomic_DNA.
DR CCDS; CCDS43382.1; -. [Q9NQ38-1]
DR CCDS; CCDS47300.1; -. [Q9NQ38-3]
DR CCDS; CCDS47301.1; -. [Q9NQ38-2]
DR RefSeq; NP_001121170.1; NM_001127698.1. [Q9NQ38-3]
DR RefSeq; NP_001121171.1; NM_001127699.1. [Q9NQ38-2]
DR RefSeq; NP_006837.2; NM_006846.3. [Q9NQ38-1]
DR PDB; 1H0Z; NMR; -; A=356-423.
DR PDB; 1HDL; NMR; -; A=23-77.
DR PDB; 1UUC; NMR; -; A=23-77.
DR PDB; 1UVF; NMR; -; A=989-1047.
DR PDB; 1UVG; NMR; -; A=989-1064.
DR PDB; 5YHN; NMR; -; A=220-288.
DR PDBsum; 1H0Z; -.
DR PDBsum; 1HDL; -.
DR PDBsum; 1UUC; -.
DR PDBsum; 1UVF; -.
DR PDBsum; 1UVG; -.
DR PDBsum; 5YHN; -.
DR AlphaFoldDB; Q9NQ38; -.
DR SMR; Q9NQ38; -.
DR BioGRID; 116196; 15.
DR IntAct; Q9NQ38; 2.
DR STRING; 9606.ENSP00000352936; -.
DR MEROPS; I01.013; -.
DR MEROPS; I01.028; -.
DR MEROPS; I01.029; -.
DR MEROPS; I01.030; -.
DR MEROPS; I01.032; -.
DR MEROPS; I01.044; -.
DR MEROPS; I01.950; -.
DR MEROPS; I01.951; -.
DR MEROPS; I01.953; -.
DR MEROPS; I01.954; -.
DR MEROPS; I01.955; -.
DR MEROPS; I01.957; -.
DR MEROPS; I01.958; -.
DR MEROPS; I01.959; -.
DR MEROPS; I01.960; -.
DR iPTMnet; Q9NQ38; -.
DR PhosphoSitePlus; Q9NQ38; -.
DR BioMuta; SPINK5; -.
DR DMDM; 212276440; -.
DR EPD; Q9NQ38; -.
DR jPOST; Q9NQ38; -.
DR MassIVE; Q9NQ38; -.
DR PaxDb; Q9NQ38; -.
DR PeptideAtlas; Q9NQ38; -.
DR PRIDE; Q9NQ38; -.
DR ProteomicsDB; 82074; -. [Q9NQ38-1]
DR ProteomicsDB; 82075; -. [Q9NQ38-2]
DR ProteomicsDB; 82076; -. [Q9NQ38-3]
DR Antibodypedia; 1727; 191 antibodies from 28 providers.
DR DNASU; 11005; -.
DR Ensembl; ENST00000256084.8; ENSP00000256084.7; ENSG00000133710.16. [Q9NQ38-1]
DR Ensembl; ENST00000359874.7; ENSP00000352936.3; ENSG00000133710.16. [Q9NQ38-3]
DR Ensembl; ENST00000398454.5; ENSP00000381472.1; ENSG00000133710.16. [Q9NQ38-2]
DR GeneID; 11005; -.
DR KEGG; hsa:11005; -.
DR MANE-Select; ENST00000256084.8; ENSP00000256084.7; NM_006846.4; NP_006837.2.
DR UCSC; uc003low.2; human. [Q9NQ38-1]
DR CTD; 11005; -.
DR DisGeNET; 11005; -.
DR GeneCards; SPINK5; -.
DR HGNC; HGNC:15464; SPINK5.
DR HPA; ENSG00000133710; Tissue enhanced (esophagus, lymphoid tissue, skin, vagina).
DR MalaCards; SPINK5; -.
DR MIM; 256500; phenotype.
DR MIM; 605010; gene.
DR neXtProt; NX_Q9NQ38; -.
DR OpenTargets; ENSG00000133710; -.
DR Orphanet; 634; Netherton syndrome.
DR PharmGKB; PA37962; -.
DR VEuPathDB; HostDB:ENSG00000133710; -.
DR eggNOG; KOG3649; Eukaryota.
DR GeneTree; ENSGT00510000048608; -.
DR InParanoid; Q9NQ38; -.
DR OMA; NAKDQCR; -.
DR OrthoDB; 1283825at2759; -.
DR PhylomeDB; Q9NQ38; -.
DR TreeFam; TF336724; -.
DR PathwayCommons; Q9NQ38; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SABIO-RK; Q9NQ38; -.
DR SignaLink; Q9NQ38; -.
DR BioGRID-ORCS; 11005; 15 hits in 1066 CRISPR screens.
DR ChiTaRS; SPINK5; human.
DR EvolutionaryTrace; Q9NQ38; -.
DR GeneWiki; LEKTI; -.
DR GenomeRNAi; 11005; -.
DR Pharos; Q9NQ38; Tbio.
DR PRO; PR:Q9NQ38; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9NQ38; protein.
DR Bgee; ENSG00000133710; Expressed in tongue squamous epithelium and 127 other tissues.
DR ExpressionAtlas; Q9NQ38; baseline and differential.
DR Genevisible; Q9NQ38; HS.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0097209; C:epidermal lamellar body; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IBA:GO_Central.
DR GO; GO:0009913; P:epidermal cell differentiation; IDA:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; TAS:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; TAS:UniProtKB.
DR GO; GO:0035315; P:hair cell differentiation; TAS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; TAS:UniProtKB.
DR GO; GO:0002787; P:negative regulation of antibacterial peptide production; IEA:Ensembl.
DR GO; GO:0050777; P:negative regulation of immune response; TAS:UniProtKB.
DR GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:1902572; P:negative regulation of serine-type peptidase activity; IBA:GO_Central.
DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0045580; P:regulation of T cell differentiation; TAS:UniProtKB.
DR GO; GO:0051884; P:regulation of timing of anagen; TAS:UniProtKB.
DR InterPro; IPR002350; Kazal_dom.
DR InterPro; IPR036058; Kazal_dom_sf.
DR Pfam; PF00050; Kazal_1; 11.
DR SMART; SM00280; KAZAL; 14.
DR SUPFAM; SSF100895; SSF100895; 15.
DR PROSITE; PS00282; KAZAL_1; 2.
DR PROSITE; PS51465; KAZAL_2; 14.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hypotrichosis; Ichthyosis;
KW Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1064
FT /note="Serine protease inhibitor Kazal-type 5"
FT /id="PRO_0000016572"
FT PEPTIDE 23..77
FT /note="Hemofiltrate peptide HF6478"
FT /id="PRO_0000016573"
FT PEPTIDE 356..423
FT /note="Hemofiltrate peptide HF7665"
FT /id="PRO_0000016574"
FT DOMAIN 28..66
FT /note="Kazal-like 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 91..153
FT /note="Kazal-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 155..216
FT /note="Kazal-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 219..285
FT /note="Kazal-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 291..352
FT /note="Kazal-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 361..423
FT /note="Kazal-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 431..489
FT /note="Kazal-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 490..551
FT /note="Kazal-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 561..622
FT /note="Kazal-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 626..688
FT /note="Kazal-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 701..757
FT /note="Kazal-like 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 768..830
FT /note="Kazal-like 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 843..905
FT /note="Kazal-like 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 910..971
FT /note="Kazal-like 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DOMAIN 987..1048
FT /note="Kazal-like 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT REGION 676..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..775
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 967..987
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1041..1064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..690
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 46..47
FT /note="Reactive bond"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 30..66
FT DISULFID 44..63
FT DISULFID 97..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 111..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 119..151
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 161..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 175..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 225..261
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 239..258
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 297..333
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 311..330
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 367..403
FT DISULFID 381..400
FT DISULFID 437..473
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 451..470
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 496..532
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 510..529
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 567..603
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 581..600
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 632..668
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 646..665
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 707..743
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 721..740
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 774..810
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 788..807
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 849..885
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 863..882
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 916..952
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 930..949
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798"
FT DISULFID 993..1028
FT DISULFID 1006..1025
FT DISULFID 1014..1046
FT VAR_SEQ 914..916
FT /note="DEC -> VIY (in isoform short)"
FT /evidence="ECO:0000303|PubMed:16374478"
FT /id="VSP_040019"
FT VAR_SEQ 914
FT /note="D -> DQCRQVQNEAEDAKFRQPGRSLASVARMSTD (in isoform
FT long)"
FT /evidence="ECO:0000303|PubMed:16374478"
FT /id="VSP_040020"
FT VAR_SEQ 917..1064
FT /note="Missing (in isoform short)"
FT /evidence="ECO:0000303|PubMed:16374478"
FT /id="VSP_040021"
FT VARIANT 267
FT /note="Q -> R (in dbSNP:rs6892205)"
FT /evidence="ECO:0000269|PubMed:10419450,
FT ECO:0000269|PubMed:10835624, ECO:0000269|PubMed:16374478"
FT /id="VAR_047115"
FT VARIANT 335
FT /note="A -> V (in dbSNP:rs34482796)"
FT /evidence="ECO:0000269|PubMed:10419450,
FT ECO:0000269|PubMed:16374478"
FT /id="VAR_061337"
FT VARIANT 368
FT /note="S -> N (in dbSNP:rs2303063)"
FT /evidence="ECO:0000269|PubMed:10419450,
FT ECO:0000269|PubMed:10835624, ECO:0000269|PubMed:16374478"
FT /id="VAR_047116"
FT VARIANT 386
FT /note="D -> N (in dbSNP:rs2303064)"
FT /id="VAR_047117"
FT VARIANT 395
FT /note="V -> M (in dbSNP:rs17775319)"
FT /id="VAR_047118"
FT VARIANT 420
FT /note="K -> E (in dbSNP:rs2303067)"
FT /evidence="ECO:0000269|PubMed:10419450,
FT ECO:0000269|PubMed:11544479, ECO:0000269|PubMed:16374478"
FT /id="VAR_015537"
FT VARIANT 441
FT /note="R -> H (in dbSNP:rs34393923)"
FT /id="VAR_047119"
FT VARIANT 588
FT /note="I -> M (in dbSNP:rs35877540)"
FT /id="VAR_047120"
FT VARIANT 711
FT /note="R -> Q (in dbSNP:rs3777134)"
FT /evidence="ECO:0000269|PubMed:10419450,
FT ECO:0000269|PubMed:16374478"
FT /id="VAR_047121"
FT VARIANT 825
FT /note="E -> D (in dbSNP:rs2303070)"
FT /id="VAR_047122"
FT VARIANT 887
FT /note="S -> R (in dbSNP:rs28408445)"
FT /id="VAR_047123"
FT VARIANT 969
FT /note="K -> E (in dbSNP:rs3188691)"
FT /id="VAR_047124"
FT VARIANT 972
FT /note="H -> R (in dbSNP:rs17705005)"
FT /id="VAR_047125"
FT CONFLICT 19..27
FT /note="DAASKNEDQ -> GQCEKDSLS (in Ref. 2; CAB96877)"
FT /evidence="ECO:0000305"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:1HDL"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:1HDL"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:1HDL"
FT HELIX 48..52
FT /evidence="ECO:0007829|PDB:1HDL"
FT HELIX 54..76
FT /evidence="ECO:0007829|PDB:1HDL"
FT HELIX 221..230
FT /evidence="ECO:0007829|PDB:5YHN"
FT HELIX 258..273
FT /evidence="ECO:0007829|PDB:5YHN"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:5YHN"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:5YHN"
FT TURN 283..286
FT /evidence="ECO:0007829|PDB:5YHN"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:1H0Z"
FT HELIX 367..370
FT /evidence="ECO:0007829|PDB:1H0Z"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:1H0Z"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:1H0Z"
FT HELIX 399..413
FT /evidence="ECO:0007829|PDB:1H0Z"
FT HELIX 990..993
FT /evidence="ECO:0007829|PDB:1UVF"
FT TURN 1000..1002
FT /evidence="ECO:0007829|PDB:1UVF"
FT STRAND 1013..1015
FT /evidence="ECO:0007829|PDB:1UVF"
FT TURN 1016..1018
FT /evidence="ECO:0007829|PDB:1UVF"
FT STRAND 1019..1024
FT /evidence="ECO:0007829|PDB:1UVF"
FT HELIX 1025..1034
FT /evidence="ECO:0007829|PDB:1UVF"
FT STRAND 1040..1045
FT /evidence="ECO:0007829|PDB:1UVF"
FT HELIX 1047..1049
FT /evidence="ECO:0007829|PDB:1UVG"
FT HELIX 1055..1058
FT /evidence="ECO:0007829|PDB:1UVG"
SQ SEQUENCE 1064 AA; 120714 MW; 6CBEF39BB9E6D75D CRC64;
MKIATVSVLL PLALCLIQDA ASKNEDQEMC HEFQAFMKNG KLFCPQDKKF FQSLDGIMFI
NKCATCKMIL EKEAKSQKRA RHLARAPKAT APTELNCDDF KKGERDGDFI CPDYYEAVCG
TDGKTYDNRC ALCAENAKTG SQIGVKSEGE CKSSNPEQDV CSAFRPFVRD GRLGCTREND
PVLGPDGKTH GNKCAMCAEL FLKEAENAKR EGETRIRRNA EKDFCKEYEK QVRNGRLFCT
RESDPVRGPD GRMHGNKCAL CAEIFKQRFS EENSKTDQNL GKAEEKTKVK REIVKLCSQY
QNQAKNGILF CTRENDPIRG PDGKMHGNLC SMCQAYFQAE NEEKKKAEAR ARNKRESGKA
TSYAELCSEY RKLVRNGKLA CTRENDPIQG PDGKVHGNTC SMCEVFFQAE EEEKKKKEGK
SRNKRQSKST ASFEELCSEY RKSRKNGRLF CTRENDPIQG PDGKMHGNTC SMCEAFFQQE
ERARAKAKRE AAKEICSEFR DQVRNGTLIC TREHNPVRGP DGKMHGNKCA MCASVFKLEE
EEKKNDKEEK GKVEAEKVKR EAVQELCSEY RHYVRNGRLP CTRENDPIEG LDGKIHGNTC
SMCEAFFQQE AKEKERAEPR AKVKREAEKE TCDEFRRLLQ NGKLFCTREN DPVRGPDGKT
HGNKCAMCKA VFQKENEERK RKEEEDQRNA AGHGSSGGGG GNTQDECAEY REQMKNGRLS
CTRESDPVRD ADGKSYNNQC TMCKAKLERE AERKNEYSRS RSNGTGSESG KDTCDEFRSQ
MKNGKLICTR ESDPVRGPDG KTHGNKCTMC KEKLEREAAE KKKKEDEDRS NTGERSNTGE
RSNDKEDLCR EFRSMQRNGK LICTRENNPV RGPYGKMHIN KCAMCQSIFD REANERKKKD
EEKSSSKPSN NAKDECSEFR NYIRNNELIC PRENDPVHGA DGKFYTNKCY MCRAVFLTEA
LERAKLQEKP SHVRASQEED SPDSFSSLDS EMCKDYRVLP RIGYLCPKDL KPVCGDDGQT
YNNPCMLCHE NLIRQTNTHI RSTGKCEESS TPGTTAASMP PSDE
