ENPP3_HUMAN
ID ENPP3_HUMAN Reviewed; 875 AA.
AC O14638; Q5JTL3;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 3;
DE Short=E-NPP 3;
DE Short=NPP3 {ECO:0000303|PubMed:29717535};
DE AltName: Full=Phosphodiesterase I beta {ECO:0000303|PubMed:9344668};
DE Short=PD-Ibeta {ECO:0000303|PubMed:9344668};
DE AltName: Full=Phosphodiesterase I/nucleotide pyrophosphatase 3;
DE AltName: CD_antigen=CD203c {ECO:0000303|PubMed:11342463, ECO:0000303|PubMed:29717535};
DE Includes:
DE RecName: Full=Alkaline phosphodiesterase I;
DE EC=3.1.4.1 {ECO:0000269|PubMed:11342463};
DE Includes:
DE RecName: Full=Nucleotide pyrophosphatase;
DE Short=NPPase;
DE EC=3.6.1.9 {ECO:0000269|PubMed:29717535};
DE AltName: Full=Nucleotide diphosphatase {ECO:0000305};
GN Name=ENPP3; Synonyms=PDNP3 {ECO:0000303|PubMed:9344668};
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 TISSUE SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=9344668; DOI=10.1006/geno.1997.4949;
RA Piao J.-H., Goding J.W., Nakamura H., Sano K.;
RT "Molecular cloning and chromosomal localization of PD-Ibeta (PDNP3), a new
RT member of the human phosphodiesterase I genes.";
RL Genomics 45:412-415(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endometrium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 393-405, IDENTIFICATION AS CD203C, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=11342463; DOI=10.1182/blood.v97.10.3303;
RA Buehring H.J., Seiffert M., Giesert C., Marxer A., Kanz L., Valent P.,
RA Sano K.;
RT "The basophil activation marker defined by antibody 97A6 is identical to
RT the ectonucleotide pyrophosphatase/phosphodiesterase 3.";
RL Blood 97:3303-3305(2001).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15072822; DOI=10.1016/j.canlet.2003.11.002;
RA Yano Y., Hayashi Y., Sano K., Nagano H., Nakaji M., Seo Y., Ninomiya T.,
RA Yoon S., Yokozaki H., Kasuga M.;
RT "Expression and localization of ecto-nucleotide
RT pyrophosphatase/phosphodiesterase I-1 (E-NPP1/PC-1) and -3 (E-
RT NPP3/CD203c/PD-Ibeta/B10/gp130(RB13-6)) in inflammatory and neoplastic bile
RT duct diseases.";
RL Cancer Lett. 207:139-147(2004).
RN [7]
RP INDUCTION, AND POSSIBLE APPLICATION IN ALLERGY DIAGNOSIS.
RX PubMed=15031605; DOI=10.1159/000077351;
RA Buehring H.J., Streble A., Valent P.;
RT "The basophil-specific ectoenzyme E-NPP3 (CD203c) as a marker for cell
RT activation and allergy diagnosis.";
RL Int. Arch. Allergy Immunol. 133:317-329(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 48-875 IN COMPLEX WITH ZINC AND
RP ATP ANALOG, CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP COFACTOR, ACTIVE SITE, SUBUNIT, MUTAGENESIS OF THR-179; LYS-204; ASN-227;
RP GLU-275 AND ALA-336, GLYCOSYLATION AT ASN-236; ASN-279; ASN-290; ASN-426;
RP ASN-533; ASN-582; ASN-594; ASN-687; ASN-699 AND ASN-789, AND DISULFIDE
RP BOND.
RX PubMed=29717535; DOI=10.1111/febs.14489;
RA Gorelik A., Randriamihaja A., Illes K., Nagar B.;
RT "Structural basis for nucleotide recognition by the ectoenzyme CD203c.";
RL FEBS J. 285:2481-2494(2018).
CC -!- FUNCTION: Hydrolase that metabolizes extracellular nucleotides,
CC including ATP, GTP, UTP and CTP (PubMed:29717535). Limits mast cell and
CC basophil responses during inflammation and during the chronic phases of
CC allergic responses by eliminating the extracellular ATP that functions
CC as signaling molecule and activates basophils and mast cells and
CC induces the release of inflammatory cytokines. Metabolizes
CC extracellular ATP in the lumen of the small intestine, and thereby
CC prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic
CC cells (By similarity). Has also alkaline phosphodiesterase activity
CC (PubMed:11342463). {ECO:0000250|UniProtKB:Q6DYE8,
CC ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:29717535}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolytically removes 5'-nucleotides successively from the
CC 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.;
CC EC=3.1.4.1; Evidence={ECO:0000269|PubMed:11342463};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:29717535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-
CC deoxyribonucleoside 5'-phosphate + diphosphate + H(+);
CC Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9;
CC Evidence={ECO:0000269|PubMed:29717535};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:29717535};
CC Note=Binds 2 zinc ions per subunit. {ECO:0000269|PubMed:29717535};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=61.5 uM for ATP;
CC KM=120.3 uM for UTP;
CC KM=120.2 uM for CTP;
CC KM=123.7 uM for GTP;
CC -!- SUBUNIT: Monomer and homodimer. {ECO:0000269|PubMed:29717535}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11342463};
CC Single-pass type II membrane protein {ECO:0000305}. Apical cell
CC membrane {ECO:0000269|PubMed:15072822}; Single-pass type II membrane
CC protein {ECO:0000305}. Secreted {ECO:0000269|PubMed:15072822}.
CC Note=Detected at the cell surface of basophils (PubMed:11342463).
CC Detected at the apical plasma membrane of bile duct cells
CC (PubMed:15072822). Located to the apical surface in intestinal and
CC kidney epithelial cells. Secreted in serum, and in lumen of epithelial
CC cells. {ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:15072822}.
CC -!- TISSUE SPECIFICITY: Detected on bile ducts in liver, and in blood serum
CC (at protein level) (PubMed:15072822). Detected in prostate and uterus
CC (PubMed:9344668). Detected on basophils, but not neutrophils
CC (PubMed:11342463). {ECO:0000269|PubMed:11342463,
CC ECO:0000269|PubMed:15072822, ECO:0000269|PubMed:9344668}.
CC -!- INDUCTION: Up-regulated by stimulation by allergen or by cross-linking
CC with IgE. The IgE-mediated activation is enhanced by tetradecanoyl
CC phorbol acetate (TPA), a stimulator of the PKC pathway, and inhibited
CC by the P13 kinase inhibitors, LY294002 and wortmannin. Up-regulated in
CC invasive bile duct cancers. {ECO:0000269|PubMed:15031605}.
CC -!- PTM: N-glycosylated. N-glycosylation is necessary for normal transport
CC to the cell membrane, but is not the apical targeting signal.
CC {ECO:0000250|UniProtKB:P97675}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD05192.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF005632; AAC51813.1; -; mRNA.
DR EMBL; EF560735; ABQ59045.1; -; mRNA.
DR EMBL; AC005587; AAD05192.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL121575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48045.1; -; Genomic_DNA.
DR CCDS; CCDS5148.1; -.
DR RefSeq; NP_005012.2; NM_005021.4.
DR PDB; 6C01; X-ray; 2.30 A; A/B=48-875.
DR PDB; 6C02; X-ray; 1.94 A; A/B=48-875.
DR PDBsum; 6C01; -.
DR PDBsum; 6C02; -.
DR AlphaFoldDB; O14638; -.
DR SMR; O14638; -.
DR BioGRID; 111195; 17.
DR IntAct; O14638; 3.
DR MINT; O14638; -.
DR STRING; 9606.ENSP00000406261; -.
DR BindingDB; O14638; -.
DR ChEMBL; CHEMBL5580; -.
DR GlyGen; O14638; 13 sites.
DR iPTMnet; O14638; -.
DR PhosphoSitePlus; O14638; -.
DR BioMuta; ENPP3; -.
DR jPOST; O14638; -.
DR MassIVE; O14638; -.
DR MaxQB; O14638; -.
DR PaxDb; O14638; -.
DR PeptideAtlas; O14638; -.
DR PRIDE; O14638; -.
DR ProteomicsDB; 48132; -.
DR Antibodypedia; 32905; 480 antibodies from 36 providers.
DR DNASU; 5169; -.
DR Ensembl; ENST00000357639.8; ENSP00000350265.3; ENSG00000154269.15.
DR Ensembl; ENST00000414305.5; ENSP00000406261.1; ENSG00000154269.15.
DR GeneID; 5169; -.
DR KEGG; hsa:5169; -.
DR MANE-Select; ENST00000357639.8; ENSP00000350265.3; NM_005021.5; NP_005012.2.
DR UCSC; uc003qcu.5; human.
DR CTD; 5169; -.
DR DisGeNET; 5169; -.
DR GeneCards; ENPP3; -.
DR HGNC; HGNC:3358; ENPP3.
DR HPA; ENSG00000154269; Tissue enhanced (cervix, intestine).
DR MIM; 602182; gene.
DR neXtProt; NX_O14638; -.
DR OpenTargets; ENSG00000154269; -.
DR PharmGKB; PA27793; -.
DR VEuPathDB; HostDB:ENSG00000154269; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000159640; -.
DR HOGENOM; CLU_012256_0_1_1; -.
DR InParanoid; O14638; -.
DR OMA; CETDLLH; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; O14638; -.
DR TreeFam; TF330032; -.
DR BRENDA; 3.6.1.9; 2681.
DR PathwayCommons; O14638; -.
DR Reactome; R-HSA-199220; Vitamin B5 (pantothenate) metabolism.
DR SABIO-RK; O14638; -.
DR SignaLink; O14638; -.
DR BioGRID-ORCS; 5169; 23 hits in 1081 CRISPR screens.
DR ChiTaRS; ENPP3; human.
DR GeneWiki; ENPP3; -.
DR GenomeRNAi; 5169; -.
DR Pharos; O14638; Tchem.
DR PRO; PR:O14638; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O14638; protein.
DR Bgee; ENSG00000154269; Expressed in jejunal mucosa and 126 other tissues.
DR ExpressionAtlas; O14638; baseline and differential.
DR Genevisible; O14638; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0047429; F:nucleoside-triphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0004528; F:phosphodiesterase I activity; IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; IDA:UniProtKB.
DR GO; GO:0002276; P:basophil activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0033007; P:negative regulation of mast cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IDA:BHF-UCL.
DR GO; GO:0055062; P:phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; IDA:BHF-UCL.
DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; IMP:UniProtKB.
DR Gene3D; 3.40.570.10; -; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR020821; Extracellular_endonuc_su_A.
DR InterPro; IPR044925; His-Me_finger_sf.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR Pfam; PF01223; Endonuclease_NS; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR Pfam; PF01033; Somatomedin_B; 2.
DR SMART; SM00892; Endonuclease_NS; 1.
DR SMART; SM00477; NUC; 1.
DR SMART; SM00201; SO; 2.
DR SUPFAM; SSF53649; SSF53649; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
DR SUPFAM; SSF90188; SSF90188; 2.
DR PROSITE; PS00524; SMB_1; 2.
DR PROSITE; PS50958; SMB_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Repeat; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..875
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 3"
FT /id="PRO_0000188570"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..875
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 50..93
FT /note="SMB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 94..138
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT REGION 140..510
FT /note="Phosphodiesterase"
FT REGION 605..875
FT /note="Nuclease"
FT MOTIF 78..80
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 205
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:29717535"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT BINDING 289
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT BINDING 325
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 329
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 483
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 752
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 754
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 756
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 758
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT BINDING 760
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 582
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01"
FT CARBOHYD 594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01"
FT CARBOHYD 687
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:29717535"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT CARBOHYD 789
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C02"
FT DISULFID 54..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 58..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 69..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 75..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 98..115
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 103..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 113..126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 119..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 144..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 152..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 380..478
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 429..818
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 562..623
FT /evidence="ECO:0000269|PubMed:29717535,
FT ECO:0007744|PDB:6C01, ECO:0007744|PDB:6C02"
FT DISULFID 575..679
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 577..664
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT DISULFID 787..797
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350,
FT ECO:0000269|PubMed:29717535, ECO:0007744|PDB:6C01,
FT ECO:0007744|PDB:6C02"
FT VARIANT 620
FT /note="V -> M (in dbSNP:rs9321309)"
FT /id="VAR_018516"
FT VARIANT 744
FT /note="N -> H (in dbSNP:rs36094194)"
FT /id="VAR_046538"
FT VARIANT 786
FT /note="S -> N (in dbSNP:rs17601580)"
FT /id="VAR_031253"
FT MUTAGEN 179
FT /note="T->C: Causes the formation of covalently linked
FT homodimers in solution; when associated with C-336."
FT /evidence="ECO:0000269|PubMed:29717535"
FT MUTAGEN 204
FT /note="K->A: Strongly decreases affinity for nucleotides
FT and slows their hydrolysis."
FT /evidence="ECO:0000269|PubMed:29717535"
FT MUTAGEN 227
FT /note="N->A: No effect on affinity for nucleotides and
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:29717535"
FT MUTAGEN 275
FT /note="E->A: No effect on substrate specificity. Increases
FT affinity for nucleotides and slows their hydrolysis."
FT /evidence="ECO:0000269|PubMed:29717535"
FT MUTAGEN 336
FT /note="A->C: Causes the formation of covalently linked
FT homodimers in solution; when associated with C-179."
FT /evidence="ECO:0000269|PubMed:29717535"
FT CONFLICT 122
FT /note="R -> K (in Ref. 1; AAC51813)"
FT /evidence="ECO:0000305"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 85..89
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 100..104
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:6C01"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 182..190
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 191..195
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 205..214
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 225..230
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 231..234
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 255..261
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:6C01"
FT HELIX 295..306
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 315..321
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 325..331
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 336..358
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 396..399
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 405..410
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 411..417
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 420..426
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 458..463
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 468..472
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 479..482
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 505..509
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 517..525
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 536..539
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 540..542
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 578..580
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 583..591
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 597..607
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 617..619
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 622..626
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 631..635
FT /evidence="ECO:0007829|PDB:6C02"
FT TURN 636..639
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 640..648
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 679..684
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 689..694
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 696..698
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 700..703
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 704..708
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 711..713
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 714..717
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 719..730
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 732..739
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 742..750
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 756..758
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 762..764
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 778..789
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 801..809
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 815..817
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 824..826
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 828..834
FT /evidence="ECO:0007829|PDB:6C02"
FT HELIX 839..846
FT /evidence="ECO:0007829|PDB:6C02"
FT STRAND 847..849
FT /evidence="ECO:0007829|PDB:6C01"
FT HELIX 858..866
FT /evidence="ECO:0007829|PDB:6C02"
SQ SEQUENCE 875 AA; 100124 MW; 629D2E33B4C45196 CRC64;
MESTLTLATE QPVKKNTLKK YKIACIVLLA LLVIMSLGLG LGLGLRKLEK QGSCRKKCFD
ASFRGLENCR CDVACKDRGD CCWDFEDTCV ESTRIWMCNK FRCGETRLEA SLCSCSDDCL
QRKDCCADYK SVCQGETSWL EENCDTAQQS QCPEGFDLPP VILFSMDGFR AEYLYTWDTL
MPNINKLKTC GIHSKYMRAM YPTKTFPNHY TIVTGLYPES HGIIDNNMYD VNLNKNFSLS
SKEQNNPAWW HGQPMWLTAM YQGLKAATYF WPGSEVAING SFPSIYMPYN GSVPFEERIS
TLLKWLDLPK AERPRFYTMY FEEPDSSGHA GGPVSARVIK ALQVVDHAFG MLMEGLKQRN
LHNCVNIILL ADHGMDQTYC NKMEYMTDYF PRINFFYMYE GPAPRIRAHN IPHDFFSFNS
EEIVRNLSCR KPDQHFKPYL TPDLPKRLHY AKNVRIDKVH LFVDQQWLAV RSKSNTNCGG
GNHGYNNEFR SMEAIFLAHG PSFKEKTEVE PFENIEVYNL MCDLLRIQPA PNNGTHGSLN
HLLKVPFYEP SHAEEVSKFS VCGFANPLPT ESLDCFCPHL QNSTQLEQVN QMLNLTQEEI
TATVKVNLPF GRPRVLQKNV DHCLLYHREY VSGFGKAMRM PMWSSYTVPQ LGDTSPLPPT
VPDCLRADVR VPPSESQKCS FYLADKNITH GFLYPPASNR TSDSQYDALI TSNLVPMYEE
FRKMWDYFHS VLLIKHATER NGVNVVSGPI FDYNYDGHFD APDEITKHLA NTDVPIPTHY
FVVLTSCKNK SHTPENCPGW LDVLPFIIPH RPTNVESCPE GKPEALWVEE RFTAHIARVR
DVELLTGLDF YQDKVQPVSE ILQLKTYLPT FETTI
