MMP8_HUMAN
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 03-AUG-2022, entry version 209.
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/";
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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; 8.
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 GlyGen; P22894; 5 sites.
DR iPTMnet; P22894; -.
DR PhosphoSitePlus; P22894; -.
DR BioMuta; MMP8; -.
DR DMDM; 116862; -.
DR jPOST; P22894; -.
DR MassIVE; P22894; -.
DR PaxDb; P22894; -.
DR PeptideAtlas; P22894; -.
DR PRIDE; P22894; -.
DR ProteomicsDB; 54047; -.
DR TopDownProteomics; P22894; -.
DR Antibodypedia; 18018; 679 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 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; 1075463at2759; -.
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; 11 hits in 1073 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 103 other tissues.
DR ExpressionAtlas; P22894; baseline and differential.
DR Genevisible; P22894; HS.
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:0008270; F:zinc ion binding; TAS:UniProtKB.
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:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISS:ARUK-UCL.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:ARUK-UCL.
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:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:ARUK-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:1903978; P:regulation of microglial cell activation; TAS:ARUK-UCL.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; TAS:ARUK-UCL.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 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; IPR028709; MMP8.
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:SF137; PTHR10201:SF137; 1.
DR Pfam; PF00045; Hemopexin; 3.
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; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
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
