PADI2_HUMAN
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 03-AUG-2022, entry version 169.
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};
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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; 1.
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; Q9Y2J8; -.
DR PeptideAtlas; Q9Y2J8; -.
DR PRIDE; Q9Y2J8; -.
DR ProteomicsDB; 76266; -.
DR ProteomicsDB; 85817; -. [Q9Y2J8-1]
DR Antibodypedia; 29317; 270 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 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 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; DFPIKQL; -.
DR PhylomeDB; Q9Y2J8; -.
DR TreeFam; TF331952; -.
DR BioCyc; MetaCyc:HS04094-MON; -.
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; 10 hits in 1076 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 179 other tissues.
DR Genevisible; Q9Y2J8; HS.
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: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:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; IMP:UniProtKB.
DR GO; GO:0036414; P:histone citrullination; IBA:GO_Central.
DR GO; GO:0036413; P:histone H3-R26 citrullination; IDA:UniProtKB.
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 Gene3D; 2.60.40.1700; -; 1.
DR Gene3D; 2.60.40.1860; -; 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; PTHR10837; 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; SSF110083; SSF110083; 1.
DR SUPFAM; SSF49503; SSF49503; 1.
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
