ID PADI2_HUMAN Reviewed; 665 AA. AC Q9Y2J8; Q96DA7; Q9UPN2; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 24-JAN-2024, entry version 177. DE RecName: Full=Protein-arginine deiminase type-2; DE EC=3.5.3.15 {ECO:0000269|PubMed:12392711, ECO:0000269|PubMed:25621824, ECO:0000269|PubMed:30044909}; DE AltName: Full=PAD-H19; DE AltName: Full=Peptidylarginine deiminase II {ECO:0000303|PubMed:12392711}; DE AltName: Full=Protein-arginine deiminase type II; GN Name=PADI2; Synonyms=KIAA0994, PAD2, PDI2; 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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, COFACTOR, AND TISSUE SPECIFICITY. RC TISSUE=Skin; RX PubMed=12392711; DOI=10.1016/s0003-9861(02)00516-7; RA Ishigami A., Ohsawa T., Asaga H., Akiyama K., Kuramoto M., Maruyama N.; RT "Human peptidylarginine deiminase type II: molecular cloning, gene RT organization, and expression in human skin."; RL Arch. Biochem. Biophys. 407:25-31(2002). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=15087120; DOI=10.1016/j.gene.2003.12.038; RA Chavanas S., Mechin M.-C., Takahara H., Kawada A., Nachat R., Serre G., RA Simon M.; RT "Comparative analysis of the mouse and human peptidylarginine deiminase RT gene clusters reveals highly conserved non-coding segments and a new human RT gene, PADI6."; RL Gene 330:19-27(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Pancreas; 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 [6] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30044909; DOI=10.1021/acschembio.8b00578; RA Nemmara V.V., Tilvawala R., Salinger A.J., Miller L., Nguyen S.H., RA Weerapana E., Thompson P.R.; RT "Citrullination Inactivates Nicotinamide- N-methyltransferase."; RL ACS Chem. Biol. 13:2663-2672(2018). RN [7] {ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N2N} RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) IN COMPLEX WITH CALCIUM, FUNCTION, RP CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, ACTIVE SITE, AND MUTAGENESIS OF RP ASP-123; ASP-125; ASP-166; ASP-169; ASP-177; TRP-348; GLN-350; GLU-354; RP ASP-370; ARG-373; ASP-374; ASP-389; GLU-412 AND CYS-647. RX PubMed=25621824; DOI=10.1021/cb500933j; RA Slade D.J., Fang P., Dreyton C.J., Zhang Y., Fuhrmann J., Rempel D., RA Bax B.D., Coonrod S.A., Lewis H.D., Guo M., Gross M.L., Thompson P.R.; RT "Protein arginine deiminase 2 binds calcium in an ordered fashion: RT implications for inhibitor design."; RL ACS Chem. Biol. 10:1043-1053(2015). CC -!- FUNCTION: Catalyzes the deimination of arginine residues of proteins. CC {ECO:0000269|PubMed:12392711, ECO:0000269|PubMed:25621824, CC ECO:0000269|PubMed:30044909}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-arginyl-[protein] = L-citrullyl-[protein] + NH4(+); CC Xref=Rhea:RHEA:18089, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:10588, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29965, CC ChEBI:CHEBI:83397; EC=3.5.3.15; CC Evidence={ECO:0000269|PubMed:12392711, ECO:0000269|PubMed:25621824, CC ECO:0000269|PubMed:30044909}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:12392711, ECO:0000269|PubMed:25621824}; CC Note=Binding of Ca(2+) triggers a conformation change that is essential CC for catalytic activity. {ECO:0000269|PubMed:25621824}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25621824}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12392711}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y2J8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y2J8-2; Sequence=VSP_056385; CC -!- TISSUE SPECIFICITY: Detected in keratinocytes in epidermis (at protein CC level). {ECO:0000269|PubMed:12392711}. CC -!- SIMILARITY: Belongs to the protein arginine deiminase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76838.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; AB030176; BAA82557.1; -; mRNA. DR EMBL; AJ549502; CAE47740.1; -; Genomic_DNA. DR EMBL; AB023211; BAA76838.1; ALT_INIT; mRNA. DR EMBL; AL049569; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009701; AAH09701.1; -; mRNA. DR CCDS; CCDS177.1; -. [Q9Y2J8-1] DR RefSeq; NP_031391.2; NM_007365.2. [Q9Y2J8-1] DR PDB; 4N20; X-ray; 1.66 A; A=1-665. DR PDB; 4N22; X-ray; 1.89 A; A=1-665. DR PDB; 4N24; X-ray; 1.97 A; A=1-665. DR PDB; 4N25; X-ray; 1.93 A; A=1-665. DR PDB; 4N26; X-ray; 1.94 A; A=1-665. DR PDB; 4N28; X-ray; 1.88 A; A=1-665. DR PDB; 4N2A; X-ray; 1.70 A; A=1-665. DR PDB; 4N2B; X-ray; 1.69 A; A=1-665. DR PDB; 4N2C; X-ray; 3.02 A; A=1-665. DR PDB; 4N2D; X-ray; 2.00 A; A=1-665. DR PDB; 4N2E; X-ray; 1.86 A; A=1-665. DR PDB; 4N2F; X-ray; 1.80 A; A=1-665. DR PDB; 4N2G; X-ray; 1.85 A; A=1-665. DR PDB; 4N2H; X-ray; 1.81 A; A=1-665. DR PDB; 4N2I; X-ray; 1.90 A; A=1-665. DR PDB; 4N2K; X-ray; 1.57 A; A=1-665. DR PDB; 4N2L; X-ray; 2.10 A; A=1-665. DR PDB; 4N2M; X-ray; 1.60 A; A=1-665. DR PDB; 4N2N; X-ray; 1.80 A; A=1-665. DR PDBsum; 4N20; -. DR PDBsum; 4N22; -. DR PDBsum; 4N24; -. DR PDBsum; 4N25; -. DR PDBsum; 4N26; -. DR PDBsum; 4N28; -. DR PDBsum; 4N2A; -. DR PDBsum; 4N2B; -. DR PDBsum; 4N2C; -. DR PDBsum; 4N2D; -. DR PDBsum; 4N2E; -. DR PDBsum; 4N2F; -. DR PDBsum; 4N2G; -. DR PDBsum; 4N2H; -. DR PDBsum; 4N2I; -. DR PDBsum; 4N2K; -. DR PDBsum; 4N2L; -. DR PDBsum; 4N2M; -. DR PDBsum; 4N2N; -. DR AlphaFoldDB; Q9Y2J8; -. DR SMR; Q9Y2J8; -. DR BioGRID; 116404; 5. DR IntAct; Q9Y2J8; 2. DR STRING; 9606.ENSP00000364635; -. DR BindingDB; Q9Y2J8; -. DR ChEMBL; CHEMBL1909487; -. DR DrugBank; DB00155; Citrulline. DR iPTMnet; Q9Y2J8; -. DR PhosphoSitePlus; Q9Y2J8; -. DR BioMuta; PADI2; -. DR DMDM; 7531171; -. DR EPD; Q9Y2J8; -. DR jPOST; Q9Y2J8; -. DR MassIVE; Q9Y2J8; -. DR MaxQB; Q9Y2J8; -. DR PaxDb; 9606-ENSP00000364635; -. DR PeptideAtlas; Q9Y2J8; -. DR ProteomicsDB; 76266; -. DR ProteomicsDB; 85817; -. [Q9Y2J8-1] DR Antibodypedia; 29317; 307 antibodies from 28 providers. DR DNASU; 11240; -. DR Ensembl; ENST00000375481.1; ENSP00000364630.1; ENSG00000117115.13. [Q9Y2J8-2] DR Ensembl; ENST00000375486.9; ENSP00000364635.4; ENSG00000117115.13. [Q9Y2J8-1] DR Ensembl; ENST00000707396.1; ENSP00000516860.1; ENSG00000291387.1. [Q9Y2J8-1] DR Ensembl; ENST00000707399.1; ENSP00000516861.1; ENSG00000291387.1. [Q9Y2J8-2] DR GeneID; 11240; -. DR KEGG; hsa:11240; -. DR MANE-Select; ENST00000375486.9; ENSP00000364635.4; NM_007365.3; NP_031391.2. DR UCSC; uc001baf.4; human. [Q9Y2J8-1] DR AGR; HGNC:18341; -. DR CTD; 11240; -. DR DisGeNET; 11240; -. DR GeneCards; PADI2; -. DR HGNC; HGNC:18341; PADI2. DR HPA; ENSG00000117115; Tissue enhanced (brain, skeletal muscle, tongue). DR MIM; 607935; gene. DR neXtProt; NX_Q9Y2J8; -. DR OpenTargets; ENSG00000117115; -. DR PharmGKB; PA32900; -. DR VEuPathDB; HostDB:ENSG00000117115; -. DR eggNOG; ENOG502QVJA; Eukaryota. DR GeneTree; ENSGT00940000153217; -. DR HOGENOM; CLU_021911_0_0_1; -. DR InParanoid; Q9Y2J8; -. DR OMA; ENHYFQR; -. DR OrthoDB; 3956477at2759; -. DR PhylomeDB; Q9Y2J8; -. DR TreeFam; TF331952; -. DR BioCyc; MetaCyc:HS04094-MONOMER; -. DR BRENDA; 3.5.3.15; 2681. DR BRENDA; 3.5.3.6; 2681. DR PathwayCommons; Q9Y2J8; -. DR Reactome; R-HSA-3247509; Chromatin modifying enzymes. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; Q9Y2J8; -. DR BioGRID-ORCS; 11240; 11 hits in 1155 CRISPR screens. DR ChiTaRS; PADI2; human. DR GeneWiki; PADI2; -. DR GenomeRNAi; 11240; -. DR Pharos; Q9Y2J8; Tchem. DR PRO; PR:Q9Y2J8; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y2J8; Protein. DR Bgee; ENSG00000117115; Expressed in medial globus pallidus and 181 other cell types or tissues. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0140794; F:histone arginine deiminase activity; IBA:GO_Central. DR GO; GO:0140798; F:histone H3R26 arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0030331; F:nuclear estrogen receptor binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0004668; F:protein-arginine deiminase activity; IDA:UniProtKB. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central. DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0070100; P:negative regulation of chemokine-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:1901624; P:negative regulation of lymphocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IMP:UniProtKB. DR CDD; cd04214; PAD_N; 1. DR Gene3D; 2.60.40.1700; Protein-arginine deiminase, central domain; 1. DR Gene3D; 2.60.40.1860; Protein-arginine deiminase, N-terminal domain; 1. DR InterPro; IPR008972; Cupredoxin. DR InterPro; IPR004303; PAD. DR InterPro; IPR013530; PAD_C. DR InterPro; IPR036556; PAD_central_sf. DR InterPro; IPR013732; PAD_N. DR InterPro; IPR038685; PAD_N_sf. DR InterPro; IPR013733; Prot_Arg_deaminase_cen_dom. DR PANTHER; PTHR10837; PEPTIDYLARGININE DEIMINASE; 1. DR PANTHER; PTHR10837:SF12; PROTEIN-ARGININE DEIMINASE TYPE-2; 1. DR Pfam; PF03068; PAD; 1. DR Pfam; PF08527; PAD_M; 1. DR Pfam; PF08526; PAD_N; 1. DR PIRSF; PIRSF001247; Protein-arginine_deiminase; 1. DR SUPFAM; SSF49503; Cupredoxins; 1. DR SUPFAM; SSF55909; Pentein; 1. DR SUPFAM; SSF110083; Peptidylarginine deiminase Pad4, middle domain; 1. DR Genevisible; Q9Y2J8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cytoplasm; Hydrolase; KW Metal-binding; Reference proteome. FT CHAIN 1..665 FT /note="Protein-arginine deiminase type-2" FT /id="PRO_0000220026" FT ACT_SITE 647 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:25621824" FT BINDING 123 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, FT ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N25, FT ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2F, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2H, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2M, ECO:0007744|PDB:4N2N" FT BINDING 125 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, FT ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2C, FT ECO:0007744|PDB:4N2D, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2F, ECO:0007744|PDB:4N2G, FT ECO:0007744|PDB:4N2H, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2K, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2M, ECO:0007744|PDB:4N2N" FT BINDING 127 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, FT ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N25, FT ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2D, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2F, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2H, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2K, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2M, FT ECO:0007744|PDB:4N2N" FT BINDING 129 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, FT ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N25, FT ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2D, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2F, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2H, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2K, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2M, FT ECO:0007744|PDB:4N2N" FT BINDING 131 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N20, ECO:0007744|PDB:4N22, FT ECO:0007744|PDB:4N24, ECO:0007744|PDB:4N25, FT ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2D, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2F, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2H, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2K, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2M, FT ECO:0007744|PDB:4N2N" FT BINDING 154 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 156 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 156 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2C, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2G, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2N" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2G, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2N" FT BINDING 158 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N26, ECO:0007744|PDB:4N28, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 166 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 166 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L" FT BINDING 169 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L" FT BINDING 171 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N2A, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L" FT BINDING 177 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2N" FT BINDING 180 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 180 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2C, FT ECO:0007744|PDB:4N2E, ECO:0007744|PDB:4N2G, FT ECO:0007744|PDB:4N2I, ECO:0007744|PDB:4N2L, FT ECO:0007744|PDB:4N2N" FT BINDING 354 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2I" FT BINDING 389 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N25, ECO:0007744|PDB:4N26, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2A, FT ECO:0007744|PDB:4N2B, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2G, ECO:0007744|PDB:4N2I, FT ECO:0007744|PDB:4N2L, ECO:0007744|PDB:4N2N" FT BINDING 408 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I" FT BINDING 411 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I" FT BINDING 412 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:25621824, FT ECO:0007744|PDB:4N28, ECO:0007744|PDB:4N2B, FT ECO:0007744|PDB:4N2C, ECO:0007744|PDB:4N2E, FT ECO:0007744|PDB:4N2I" FT VAR_SEQ 438..665 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056385" FT MUTAGEN 123 FT /note="D->N: Mildly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 125 FT /note="D->A: Mildly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 166 FT /note="D->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 169 FT /note="D->A: Mildly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 177 FT /note="D->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 348 FT /note="W->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 350 FT /note="Q->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 354 FT /note="E->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 370 FT /note="D->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 373 FT /note="R->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 374 FT /note="D->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 389 FT /note="D->A: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 412 FT /note="E->A: Strongly reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT MUTAGEN 647 FT /note="C->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:25621824" FT CONFLICT 661 FT /note="W -> L (in Ref. 1; BAA82557)" FT /evidence="ECO:0000305" FT STRAND 4..6 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 11..13 FT /evidence="ECO:0007829|PDB:4N2B" FT STRAND 15..20 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 24..27 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 30..33 FT /evidence="ECO:0007829|PDB:4N20" FT STRAND 39..44 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 49..54 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 57..61 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 75..80 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:4N2C" FT STRAND 91..98 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 106..121 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:4N2K" FT TURN 135..138 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 149..151 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:4N2A" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:4N2B" FT HELIX 175..178 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 181..193 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 198..203 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 220..222 FT /evidence="ECO:0007829|PDB:4N2M" FT STRAND 226..231 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 236..239 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 243..254 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 264..274 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 283..294 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 306..312 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 318..329 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 334..338 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 340..343 FT /evidence="ECO:0007829|PDB:4N2C" FT HELIX 348..351 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 353..360 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 363..370 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 375..377 FT /evidence="ECO:0007829|PDB:4N2N" FT HELIX 383..386 FT /evidence="ECO:0007829|PDB:4N2M" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 398..400 FT /evidence="ECO:0007829|PDB:4N2B" FT HELIX 404..406 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 408..410 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 411..413 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 422..424 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 429..433 FT /evidence="ECO:0007829|PDB:4N2K" FT TURN 436..439 FT /evidence="ECO:0007829|PDB:4N2B" FT HELIX 445..453 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 467..469 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 472..474 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 476..480 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 487..493 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 494..506 FT /evidence="ECO:0007829|PDB:4N2K" FT TURN 507..511 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 513..515 FT /evidence="ECO:0007829|PDB:4N2K" FT TURN 519..521 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 522..524 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 528..532 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 535..559 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 563..565 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 566..570 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 573..575 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 581..585 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 592..594 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 597..601 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 613..622 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 623..625 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 628..632 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 636..638 FT /evidence="ECO:0007829|PDB:4N2K" FT STRAND 648..653 FT /evidence="ECO:0007829|PDB:4N2K" FT HELIX 660..662 FT /evidence="ECO:0007829|PDB:4N2K" SQ SEQUENCE 665 AA; 75564 MW; 8D417A87A02D6839 CRC64; MLRERTVRLQ YGSRVEAVYV LGTYLWTDVY SAAPAGAQTF SLKHSEHVWV EVVRDGEAEE VATNGKQRWL LSPSTTLRVT MSQASTEASS DKVTVNYYDE EGSIPIDQAG LFLTAIEISL DVDADRDGVV EKNNPKKASW TWGPEGQGAI LLVNCDRETP WLPKEDCRDE KVYSKEDLKD MSQMILRTKG PDRLPAGYEI VLYISMSDSD KVGVFYVENP FFGQRYIHIL GRRKLYHVVK YTGGSAELLF FVEGLCFPDE GFSGLVSIHV SLLEYMAQDI PLTPIFTDTV IFRIAPWIMT PNILPPVSVF VCCMKDNYLF LKEVKNLVEK TNCELKVCFQ YLNRGDRWIQ DEIEFGYIEA PHKGFPVVLD SPRDGNLKDF PVKELLGPDF GYVTREPLFE SVTSLDSFGN LEVSPPVTVN GKTYPLGRIL IGSSFPLSGG RRMTKVVRDF LKAQQVQAPV ELYSDWLTVG HVDEFMSFVP IPGTKKFLLL MASTSACYKL FREKQKDGHG EAIMFKGLGG MSSKRITINK ILSNESLVQE NLYFQRCLDW NRDILKKELG LTEQDIIDLP ALFKMDEDHR ARAFFPNMVN MIVLDKDLGI PKPFGPQVEE ECCLEMHVRG LLEPLGLECT FIDDISAYHK FLGEVHCGTN VRRKPFTFKW WHMVP //