ID   MMP8_HUMAN              Reviewed;         467 AA.
AC   P22894; Q45F99;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1991, sequence version 1.
DT   27-MAR-2024, entry version 217.
DE   RecName: Full=Neutrophil collagenase;
DE            EC=3.4.24.34;
DE   AltName: Full=Matrix metalloproteinase-8;
DE            Short=MMP-8;
DE   AltName: Full=PMNL collagenase;
DE            Short=PMNL-CL;
DE   Flags: Precursor;
GN   Name=MMP8; Synonyms=CLG1;
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], AND PROTEIN SEQUENCE OF 314-337; 347-363 AND
RP   424-441.
RC   TISSUE=Neutrophil;
RX   PubMed=2164002; DOI=10.1016/s0021-9258(19)38413-3;
RA   Hasty K.A., Pourmotabbed T.F., Goldberg G.I., Thompson J.P., Spinella D.G.,
RA   Stevens R.M., Mainardi C.L.;
RT   "Human neutrophil collagenase. A distinct gene product with homology to
RT   other matrix metalloproteinases.";
RL   J. Biol. Chem. 265:11421-11424(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-3; ILE-32; GLU-87;
RP   GLU-154; VAL-193; TYR-246; ALA-436 AND THR-460.
RG   NIEHS SNPs program;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
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   [4]
RP   PROTEIN SEQUENCE OF 21-140, AND VARIANT ILE-32.
RC   TISSUE=Neutrophil;
RX   PubMed=2159879; DOI=10.1111/j.1432-1033.1990.tb15489.x;
RA   Knaeuper V., Kraemer S., Reinke H., Tschesche H.;
RT   "Characterization and activation of procollagenase from human
RT   polymorphonuclear leucocytes. N-terminal sequence determination of the
RT   proenzyme and various proteolytically activated forms.";
RL   Eur. J. Biochem. 189:295-300(1990).
RN   [5]
RP   PROTEIN SEQUENCE OF 21-103.
RC   TISSUE=Neutrophil;
RX   PubMed=1662606; DOI=10.1111/j.1432-1033.1991.tb16494.x;
RA   Blaeser J., Knaeuper V., Osthues A., Reinke H., Tschesche H.;
RT   "Mercurial activation of human polymorphonuclear leucocyte
RT   procollagenase.";
RL   Eur. J. Biochem. 202:1223-1230(1991).
RN   [6]
RP   PROTEIN SEQUENCE OF 85-120, AND CHARACTERIZATION.
RC   TISSUE=Neutrophil;
RX   PubMed=2176876; DOI=10.1021/bi00499a008;
RA   Mallya S.K., Mookthiar K.A., Gao Y., Brew K., Dioszegi M.,
RA   Birkedal-Hansen H., van Wart H.E.;
RT   "Characterization of 58-kilodalton human neutrophil collagenase: comparison
RT   with human fibroblast collagenase.";
RL   Biochemistry 29:10628-10634(1990).
RN   [7]
RP   PARTIAL PROTEIN SEQUENCE.
RX   PubMed=2169256;
RA   Knaeuper V., Kraemer S., Reinke H., Tschesche H.;
RT   "Partial amino acid sequence of human PMN leukocyte procollagenase.";
RL   Biol. Chem. Hoppe-Seyler 371:295-304(1990).
RN   [8]
RP   ERRATUM OF PUBMED:2169256.
RX   PubMed=2169766; DOI=10.1515/bchm3.1990.371.2.733;
RA   Knaeuper V., Kraemer S., Reinke H., Tschesche H.;
RL   Biol. Chem. Hoppe-Seyler 371:733-733(1990).
RN   [9]
RP   CYSTEINE-SWITCH MECHANISM.
RC   TISSUE=Neutrophil;
RX   PubMed=1330697; DOI=10.1016/0014-5793(92)81184-n;
RA   Blaeser J., Triebel S., Reinke H., Tschesche H.;
RT   "Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL
RT   procollagenase gives evidence of a cysteine-switch mechanism.";
RL   FEBS Lett. 313:59-61(1992).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-262.
RX   PubMed=8137810; DOI=10.1002/j.1460-2075.1994.tb06378.x;
RA   Bode W., Reinemer P., Huber R., Klein T., Schnierer S., Tschesche H.;
RT   "The X-ray crystal structure of the catalytic domain of human neutrophil
RT   collagenase inhibited by a substrate analogue reveals the essentials for
RT   catalysis and specificity.";
RL   EMBO J. 13:1263-1269(1994).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 100-262.
RX   PubMed=8307185; DOI=10.1016/0014-5793(94)80370-6;
RA   Reinemer P., Grams F., Huber R., Kleine T., Schnierer S., Piper M.,
RA   Tschesche H., Bode W.;
RT   "Structural implications for the role of the N-terminus in the
RT   'superactivation' of collagenases. A crystallographic study.";
RL   FEBS Lett. 338:227-233(1994).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 100-262.
RX   PubMed=7656015; DOI=10.1038/nsb0294-119;
RA   Stams T., Spurlino J.C., Smith D.L., Wahl R.C., Ho T.F., Qoronfleh M.W.,
RA   Banks T.M., Rubin B.;
RT   "Structure of human neutrophil collagenase reveals large S1' specificity
RT   pocket.";
RL   Nat. Struct. Biol. 1:119-123(1994).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 100-262.
RX   PubMed=9249047; DOI=10.1111/j.1432-1033.1997.00356.x;
RA   Betz M., Huxley P., Davies S.J., Mushtaq Y., Pieper M., Tschesche H.,
RA   Bode W., Gomis-Rueth F.-X.;
RT   "1.8-A crystal structure of the catalytic domain of human neutrophil
RT   collagenase (matrix metalloproteinase-8) complexed with a peptidomimetic
RT   hydroxamate primed-side inhibitor with a distinct selectivity profile.";
RL   Eur. J. Biochem. 247:356-363(1997).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 105-262.
RX   PubMed=9655333; DOI=10.1002/pro.5560070605;
RA   Brandstetter H., Engh R.A., von Roedern E.G., Moroder L., Huber R.,
RA   Bode W., Grams F.;
RT   "Structure of malonic acid-based inhibitors bound to human neutrophil
RT   collagenase. A new binding mode explains apparently anomalous data.";
RL   Protein Sci. 7:1303-1309(1998).
CC   -!- FUNCTION: Can degrade fibrillar type I, II, and III collagens.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Cleavage of interstitial collagens in the triple helical
CC         domain. Unlike EC 3.4.24.7, this enzyme cleaves type III collagen
CC         more slowly than type I.; EC=3.4.24.34;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC       Note=Binds 3 Ca(2+) ions per subunit.;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 2 Zn(2+) ions per subunit.;
CC   -!- ACTIVITY REGULATION: Cannot be activated without removal of the
CC       activation peptide.
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic granule. Secreted, extracellular
CC       space, extracellular matrix {ECO:0000305}. Note=Stored in intracellular
CC       granules.
CC   -!- TISSUE SPECIFICITY: Neutrophils.
CC   -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC       binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC       dissociation of the cysteine from the zinc ion upon the activation-
CC       peptide release activates the enzyme.
CC   -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/mmp8/";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J05556; AAA88021.1; -; mRNA.
DR   EMBL; DQ141306; AAZ38714.1; -; Genomic_DNA.
DR   EMBL; BC074988; AAH74988.1; -; mRNA.
DR   EMBL; BC074989; AAH74989.1; -; mRNA.
DR   CCDS; CCDS8320.1; -.
DR   PIR; A37073; KCHUN.
DR   RefSeq; NP_001291370.1; NM_001304441.1.
DR   RefSeq; NP_001291371.1; NM_001304442.1.
DR   RefSeq; NP_002415.1; NM_002424.2.
DR   PDB; 1A85; X-ray; 2.00 A; A=105-262.
DR   PDB; 1A86; X-ray; 2.00 A; A=105-262.
DR   PDB; 1BZS; X-ray; 1.70 A; A=99-262.
DR   PDB; 1I73; X-ray; 1.40 A; A=100-262.
DR   PDB; 1I76; X-ray; 1.20 A; A=100-262.
DR   PDB; 1JAN; X-ray; 2.50 A; A=99-262.
DR   PDB; 1JAO; X-ray; 2.40 A; A=100-262.
DR   PDB; 1JAP; X-ray; 1.82 A; A=100-262.
DR   PDB; 1JAQ; X-ray; 2.40 A; A=100-262.
DR   PDB; 1JH1; X-ray; 2.70 A; A=105-262.
DR   PDB; 1JJ9; X-ray; 2.00 A; A=100-262.
DR   PDB; 1KBC; X-ray; 1.80 A; A/B=99-262.
DR   PDB; 1MMB; X-ray; 2.10 A; A=100-262.
DR   PDB; 1MNC; X-ray; 2.10 A; A=101-263.
DR   PDB; 1ZP5; X-ray; 1.80 A; A=100-262.
DR   PDB; 1ZS0; X-ray; 1.56 A; A=100-262.
DR   PDB; 1ZVX; X-ray; 1.87 A; A=100-262.
DR   PDB; 2OY2; X-ray; 1.50 A; A/F=105-262.
DR   PDB; 2OY4; X-ray; 1.70 A; A/F=105-262.
DR   PDB; 3DNG; X-ray; 2.00 A; A/B=100-262.
DR   PDB; 3DPE; X-ray; 1.60 A; A=100-262.
DR   PDB; 3DPF; X-ray; 2.10 A; A/B=100-262.
DR   PDB; 3TT4; X-ray; 1.88 A; A=104-262.
DR   PDB; 4QKZ; X-ray; 1.20 A; A=100-262.
DR   PDB; 5H8X; X-ray; 1.30 A; A=100-262.
DR   PDBsum; 1A85; -.
DR   PDBsum; 1A86; -.
DR   PDBsum; 1BZS; -.
DR   PDBsum; 1I73; -.
DR   PDBsum; 1I76; -.
DR   PDBsum; 1JAN; -.
DR   PDBsum; 1JAO; -.
DR   PDBsum; 1JAP; -.
DR   PDBsum; 1JAQ; -.
DR   PDBsum; 1JH1; -.
DR   PDBsum; 1JJ9; -.
DR   PDBsum; 1KBC; -.
DR   PDBsum; 1MMB; -.
DR   PDBsum; 1MNC; -.
DR   PDBsum; 1ZP5; -.
DR   PDBsum; 1ZS0; -.
DR   PDBsum; 1ZVX; -.
DR   PDBsum; 2OY2; -.
DR   PDBsum; 2OY4; -.
DR   PDBsum; 3DNG; -.
DR   PDBsum; 3DPE; -.
DR   PDBsum; 3DPF; -.
DR   PDBsum; 3TT4; -.
DR   PDBsum; 4QKZ; -.
DR   PDBsum; 5H8X; -.
DR   AlphaFoldDB; P22894; -.
DR   SMR; P22894; -.
DR   BioGRID; 110460; 21.
DR   STRING; 9606.ENSP00000236826; -.
DR   BindingDB; P22894; -.
DR   ChEMBL; CHEMBL4588; -.
DR   DrugBank; DB07772; (1R)-1-{[(4'-methoxy-1,1'-biphenyl-4-yl)sulfonyl]amino}-2-methylpropylphosphonic acid.
DR   DrugBank; DB07713; (1S)-1-{[(4'-methoxy-1,1'-biphenyl-4-yl)sulfonyl]amino}-2-methylpropylphosphonic acid.
DR   DrugBank; DB07397; (5S)-5-(2-amino-2-oxoethyl)-4-oxo-N-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]-3,4,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidine-2-carboxamide.
DR   DrugBank; DB02326; 1-Hydroxyamine-2-Isobutylmalonic Acid.
DR   DrugBank; DB03207; 2-(Biphenyl-4-Sulfonyl)-1,2,3,4-Tetrahydro-Isoquinoline-3-Carboxylic Acid.
DR   DrugBank; DB02953; 2-Thiomethyl-3-Phenylpropanoic Acid.
DR   DrugBank; DB08476; 3-AMINO-AZACYCLOTRIDECAN-2-ONE.
DR   DrugBank; DB07900; 3-FORMYL-2-HYDROXY-5-METHYL-HEXANOIC ACID HYDROXYAMIDE.
DR   DrugBank; DB03622; 5-[4-(2-Hydroxyethyl)-1-piperidinyl]-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione.
DR   DrugBank; DB03880; Batimastat.
DR   DrugBank; DB08028; BUT-3-ENYL-[5-(4-CHLORO-PHENYL)-3,6-DIHYDRO-[1,3,4]THIADIAZIN-2-YLIDENE]-AMINE.
DR   DrugBank; DB03636; Glycinamide.
DR   DrugBank; DB00786; Marimastat.
DR   DrugBank; DB08403; METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID.
DR   DrugBank; DB06971; N-{2-[(4'-CYANO-1,1'-BIPHENYL-4-YL)OXY]ETHYL}-N'-HYDROXY-N-METHYLUREA.
DR   DrugCentral; P22894; -.
DR   GuidetoPHARMACOLOGY; 1632; -.
DR   MEROPS; M10.002; -.
DR   GlyCosmos; P22894; 5 sites, No reported glycans.
DR   GlyGen; P22894; 5 sites.
DR   iPTMnet; P22894; -.
DR   PhosphoSitePlus; P22894; -.
DR   BioMuta; MMP8; -.
DR   DMDM; 116862; -.
DR   jPOST; P22894; -.
DR   MassIVE; P22894; -.
DR   PaxDb; 9606-ENSP00000236826; -.
DR   PeptideAtlas; P22894; -.
DR   PRIDE; P22894; -.
DR   ProteomicsDB; 54047; -.
DR   TopDownProteomics; P22894; -.
DR   Antibodypedia; 18018; 710 antibodies from 40 providers.
DR   DNASU; 4317; -.
DR   Ensembl; ENST00000236826.8; ENSP00000236826.3; ENSG00000118113.12.
DR   GeneID; 4317; -.
DR   KEGG; hsa:4317; -.
DR   MANE-Select; ENST00000236826.8; ENSP00000236826.3; NM_002424.3; NP_002415.1.
DR   UCSC; uc001phe.2; human.
DR   AGR; HGNC:7175; -.
DR   CTD; 4317; -.
DR   DisGeNET; 4317; -.
DR   GeneCards; MMP8; -.
DR   HGNC; HGNC:7175; MMP8.
DR   HPA; ENSG00000118113; Tissue enriched (bone).
DR   MalaCards; MMP8; -.
DR   MIM; 120355; gene.
DR   neXtProt; NX_P22894; -.
DR   OpenTargets; ENSG00000118113; -.
DR   PharmGKB; PA30888; -.
DR   VEuPathDB; HostDB:ENSG00000118113; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   GeneTree; ENSGT00940000161871; -.
DR   InParanoid; P22894; -.
DR   OMA; SNLWLNC; -.
DR   OrthoDB; 391167at2759; -.
DR   PhylomeDB; P22894; -.
DR   TreeFam; TF315428; -.
DR   BRENDA; 3.4.24.34; 2681.
DR   PathwayCommons; P22894; -.
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-6798695; Neutrophil degranulation.
DR   SignaLink; P22894; -.
DR   SIGNOR; P22894; -.
DR   BioGRID-ORCS; 4317; 12 hits in 1157 CRISPR screens.
DR   EvolutionaryTrace; P22894; -.
DR   GeneWiki; MMP8; -.
DR   GenomeRNAi; 4317; -.
DR   Pharos; P22894; Tchem.
DR   PRO; PR:P22894; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P22894; Protein.
DR   Bgee; ENSG00000118113; Expressed in trabecular bone tissue and 105 other cell types or tissues.
DR   ExpressionAtlas; P22894; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR   GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR   GO; GO:0004175; F:endopeptidase activity; IMP:ARUK-UCL.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0043120; F:tumor necrosis factor binding; IDA:ARUK-UCL.
DR   GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ARUK-UCL.
DR   GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR   GO; GO:0035987; P:endodermal cell differentiation; IEP:UniProtKB.
DR   GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:1903980; P:positive regulation of microglial cell activation; ISS:ARUK-UCL.
DR   GO; GO:0150078; P:positive regulation of neuroinflammatory response; ISS:ARUK-UCL.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR   GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISS:ARUK-UCL.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR   CDD; cd00094; HX; 1.
DR   CDD; cd04278; ZnMc_MMP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.110.10.10; Hemopexin-like domain; 1.
DR   InterPro; IPR000585; Hemopexin-like_dom.
DR   InterPro; IPR036375; Hemopexin-like_dom_sf.
DR   InterPro; IPR018487; Hemopexin-like_repeat.
DR   InterPro; IPR018486; Hemopexin_CS.
DR   InterPro; IPR033739; M10A_MMP.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001818; Pept_M10_metallopeptidase.
DR   InterPro; IPR021190; Pept_M10A.
DR   InterPro; IPR021158; Pept_M10A_Zn_BS.
DR   InterPro; IPR006026; Peptidase_Metallo.
DR   InterPro; IPR002477; Peptidoglycan-bd-like.
DR   InterPro; IPR036365; PGBD-like_sf.
DR   PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1.
DR   PANTHER; PTHR10201:SF137; NEUTROPHIL COLLAGENASE; 1.
DR   Pfam; PF00045; Hemopexin; 4.
DR   Pfam; PF00413; Peptidase_M10; 1.
DR   Pfam; PF01471; PG_binding_1; 1.
DR   PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR   PRINTS; PR00138; MATRIXIN.
DR   SMART; SM00120; HX; 4.
DR   SMART; SM00235; ZnMc; 1.
DR   SUPFAM; SSF50923; Hemopexin-like domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF47090; PGBD-like; 1.
DR   PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR   PROSITE; PS00024; HEMOPEXIN; 1.
DR   PROSITE; PS51642; HEMOPEXIN_2; 4.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; P22894; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Collagen degradation; Direct protein sequencing;
KW   Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase;
KW   Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW   Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000269|PubMed:1662606,
FT                   ECO:0000269|PubMed:2159879"
FT   PROPEP          21..100
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028744"
FT   CHAIN           101..467
FT                   /note="Neutrophil collagenase"
FT                   /id="PRO_0000028745"
FT   REPEAT          276..325
FT                   /note="Hemopexin 1"
FT   REPEAT          326..372
FT                   /note="Hemopexin 2"
FT   REPEAT          374..420
FT                   /note="Hemopexin 3"
FT   REPEAT          421..464
FT                   /note="Hemopexin 4"
FT   MOTIF           89..96
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        218
FT   BINDING         91
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /note="in inhibited form"
FT   BINDING         157
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         167
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         174
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         175
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         177
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         179
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         189
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         191
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         193
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         195
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         197
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         200
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         217
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         221
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         227
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:8137810"
FT   BINDING         286
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         378
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         425
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        54
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305"
FT   CARBOHYD        73
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305"
FT   CARBOHYD        112
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   CARBOHYD        204
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        279..464
FT                   /evidence="ECO:0000305"
FT   VARIANT         3
FT                   /note="S -> C (in dbSNP:rs17099450)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025036"
FT   VARIANT         32
FT                   /note="T -> I (in dbSNP:rs3765620)"
FT                   /evidence="ECO:0000269|PubMed:2159879, ECO:0000269|Ref.2"
FT                   /id="VAR_025037"
FT   VARIANT         87
FT                   /note="K -> E (in dbSNP:rs1940475)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_006730"
FT   VARIANT         154
FT                   /note="G -> E (in dbSNP:rs35056226)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025038"
FT   VARIANT         193
FT                   /note="D -> V (in dbSNP:rs34428739)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025039"
FT   VARIANT         246
FT                   /note="N -> Y (in dbSNP:rs35243553)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025040"
FT   VARIANT         436
FT                   /note="V -> A (in dbSNP:rs34009635)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025041"
FT   VARIANT         460
FT                   /note="K -> T (in dbSNP:rs35866072)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_025042"
FT   CONFLICT        40
FT                   /note="F -> I (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        48
FT                   /note="Y -> V (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          107..109
FT                   /evidence="ECO:0007829|PDB:1MNC"
FT   STRAND          111..117
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          122..124
FT                   /evidence="ECO:0007829|PDB:1JAQ"
FT   HELIX           126..141
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          147..150
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          157..163
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          168..170
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          175..178
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          181..183
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          186..188
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   TURN            189..192
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          194..197
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          203..208
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   HELIX           211..223
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          236..238
FT                   /evidence="ECO:0007829|PDB:1I76"
FT   STRAND          244..246
FT                   /evidence="ECO:0007829|PDB:1ZP5"
FT   HELIX           251..261
FT                   /evidence="ECO:0007829|PDB:1I76"
SQ   SEQUENCE   467 AA;  53412 MW;  4D4602A53AD7F8BC CRC64;
     MFSLKTLPFL LLLHVQISKA FPVSSKEKNT KTVQDYLEKF YQLPSNQYQS TRKNGTNVIV
     EKLKEMQRFF GLNVTGKPNE ETLDMMKKPR CGVPDSGGFM LTPGNPKWER TNLTYRIRNY
     TPQLSEAEVE RAIKDAFELW SVASPLIFTR ISQGEADINI AFYQRDHGDN SPFDGPNGIL
     AHAFQPGQGI GGDAHFDAEE TWTNTSANYN LFLVAAHEFG HSLGLAHSSD PGALMYPNYA
     FRETSNYSLP QDDIDGIQAI YGLSSNPIQP TGPSTPKPCD PSLTFDAITT LRGEILFFKD
     RYFWRRHPQL QRVEMNFISL FWPSLPTGIQ AAYEDFDRDL IFLFKGNQYW ALSGYDILQG
     YPKDISNYGF PSSVQAIDAA VFYRSKTYFF VNDQFWRYDN QRQFMEPGYP KSISGAFPGI
     ESKVDAVFQQ EHFFHVFSGP RYYAFDLIAQ RVTRVARGNK WLNCRYG
//