ID PADI4_HUMAN Reviewed; 663 AA. AC Q9UM07; A8K392; B2RBW0; Q5VTZ8; Q70SX4; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 24-JAN-2024, entry version 200. DE RecName: Full=Protein-arginine deiminase type-4; DE EC=3.5.3.15 {ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:21245532}; DE AltName: Full=HL-60 PAD; DE AltName: Full=Peptidylarginine deiminase IV; DE AltName: Full=Protein-arginine deiminase type IV; GN Name=PADI4; Synonyms=PAD4, PADI5, PDI5; 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 VARIANTS SER-55; ALA-82 AND ALA-112. RX PubMed=10488123; DOI=10.1074/jbc.274.39.27786; RA Nakashima K., Hagiwara T., Ishigami A., Nagata S., Asaga H., Kuramoto M., RA Senshu T., Yamada M.; RT "Molecular characterization of peptidylarginine deiminase in HL-60 cells RT induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3)."; RL J. Biol. Chem. 274:27786-27792(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-275. 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]. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). 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], AND VARIANTS SER-55; ALA-82 AND RP ALA-112. RC TISSUE=Pancreas, and Spleen; 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 TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=11435484; RA Asaga H., Nakashima K., Senshu T., Ishigami A., Yamada M.; RT "Immunocytochemical localization of peptidylarginine deiminase in human RT eosinophils and neutrophils."; RL J. Leukoc. Biol. 70:46-51(2001). RN [7] RP INVOLVEMENT IN RA. RX PubMed=12833157; DOI=10.1038/ng1206; RA Suzuki A., Yamada R., Chang X., Tokuhiro S., Sawada T., Suzuki M., RA Nagasaki M., Nakayama-Hamada M., Kawaida R., Ono M., Ohtsuki M., RA Furukawa H., Yoshino S., Yukioka M., Tohma S., Matsubara T., Wakitani S., RA Teshima R., Nishioka Y., Sekine A., Iida A., Takahashi A., Tsunoda T., RA Nakamura Y., Yamamoto K.; RT "Functional haplotypes of PADI4, encoding citrullinating enzyme RT peptidylarginine deiminase 4, are associated with rheumatoid arthritis."; RL Nat. Genet. 34:395-402(2003). RN [8] RP FUNCTION. RX PubMed=15339660; DOI=10.1016/j.cell.2004.08.020; RA Cuthbert G.L., Daujat S., Snowden A.W., Erdjument-Bromage H., Hagiwara T., RA Yamada M., Schneider R., Gregory P.D., Tempst P., Bannister A.J., RA Kouzarides T.; RT "Histone deimination antagonizes arginine methylation."; RL Cell 118:545-553(2004). RN [9] RP FUNCTION. RX PubMed=15345777; DOI=10.1126/science.1101400; RA Wang Y., Wysocka J., Sayegh J., Lee Y.-H., Perlin J.R., Leonelli L., RA Sonbuchner L.S., McDonald C.H., Cook R.G., Dou Y., Roeder R.G., Clarke S., RA Stallcup M.R., Allis C.D., Coonrod S.A.; RT "Human PAD4 regulates histone arginine methylation levels via RT demethylimination."; RL Science 306:279-283(2004). RN [10] RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR. RX PubMed=15629448; DOI=10.1016/j.bbrc.2004.11.152; RA Nakayama-Hamada M., Suzuki A., Kubota K., Takazawa T., Ohsaka M., RA Kawaida R., Ono M., Kasuya A., Furukawa H., Yamada R., Yamamoto K.; RT "Comparison of enzymatic properties between hPADI2 and hPADI4."; RL Biochem. Biophys. Res. Commun. 327:192-200(2005). RN [11] RP FUNCTION IN CITRULLINATION OF EP300. RX PubMed=15731352; DOI=10.1073/pnas.0407159102; RA Lee Y.-H., Coonrod S.A., Kraus W.L., Jelinek M.A., Stallcup M.R.; RT "Regulation of coactivator complex assembly and function by protein RT arginine methylation and demethylimination."; RL Proc. Natl. Acad. Sci. U.S.A. 102:3611-3616(2005). RN [12] RP FUNCTION. RX PubMed=18209087; DOI=10.4049/jimmunol.180.3.1895; RA Neeli I., Khan S.N., Radic M.; RT "Histone deimination as a response to inflammatory stimuli in RT neutrophils."; RL J. Immunol. 180:1895-1902(2008). RN [13] RP CITRULLINATION AT ARG-205; ARG-212; ARG-218; ARG-372; ARG-374 AND ARG-383. RX PubMed=20201080; DOI=10.1002/art.27439; RA Andrade F., Darrah E., Gucek M., Cole R.N., Rosen A., Zhu X.; RT "Autocitrullination of human peptidyl arginine deiminase type 4 regulates RT protein citrullination during cell activation."; RL Arthritis Rheum. 62:1630-1640(2010). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CALCIUM AND HISTONE RP H3 N-TERMINUS, X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH RP CALCIUM AND HISTONE H4 N-TERMINUS, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN RP COMPLEX WITH CALCIUM AND BENZOYL-ARGININE AMIDE, ACTIVE SITE, AND RP MUTAGENESIS OF ARG-374 AND CYS-645. RX PubMed=15247907; DOI=10.1038/nsmb799; RA Arita K., Hashimoto H., Shimizu T., Nakashima K., Yamada M., Sato M.; RT "Structural basis for Ca(2+)-induced activation of human PAD4."; RL Nat. Struct. Mol. Biol. 11:777-783(2004). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH CALCIUM AND HISTONE RP H3 AND H4 N-TERMINUS, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF ARG-374. RX PubMed=16567635; DOI=10.1073/pnas.0509639103; RA Arita K., Shimizu T., Hashimoto H., Hidaka Y., Yamada M., Sato M.; RT "Structural basis for histone N-terminal recognition by human RT peptidylarginine deiminase 4."; RL Proc. Natl. Acad. Sci. U.S.A. 103:5291-5296(2006). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALCIUM, COFACTOR, RP AND ACTIVITY REGULATION. RX PubMed=17002273; DOI=10.1021/bi061180d; RA Luo Y., Arita K., Bhatia M., Knuckley B., Lee Y.H., Stallcup M.R., Sato M., RA Thompson P.R.; RT "Inhibitors and inactivators of protein arginine deiminase 4: functional RT and structural characterization."; RL Biochemistry 45:11727-11736(2006). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, AND RP CHARACTERIZATION OF VARIANTS SER-55; ALA-82 AND ALA-112. RX PubMed=21245532; DOI=10.1107/s0907444910051711; RA Horikoshi N., Tachiwana H., Saito K., Osakabe A., Sato M., Yamada M., RA Akashi S., Nishimura Y., Kagawa W., Kurumizaka H.; RT "Structural and biochemical analyses of the human PAD4 variant encoded by a RT functional haplotype gene."; RL Acta Crystallogr. D 67:112-118(2011). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITOR, ACTIVITY RP REGULATION, AND MUTAGENESIS OF GLN-346; ARG-374 AND ARG-639. RX PubMed=21882827; DOI=10.1021/jm2008985; RA Causey C.P., Jones J.E., Slack J.L., Kamei D., Jones L.E., Subramanian V., RA Knuckley B., Ebrahimi P., Chumanevich A.A., Luo Y., Hashimoto H., Sato M., RA Hofseth L.J., Thompson P.R.; RT "The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1- RT iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2- RT Carboxyl)benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl- RT amidine) as second generation protein arginine deiminase (PAD) RT inhibitors."; RL J. Med. Chem. 54:6919-6935(2011). RN [19] {ECO:0007744|PDB:4DKT} RP X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) IN COMPLEX WITH TDFA, AND ACTIVITY RP REGULATION. RX PubMed=22004374; DOI=10.1021/cb200258q; RA Jones J.E., Slack J.L., Fang P., Zhang X., Subramanian V., Causey C.P., RA Coonrod S.A., Guo M., Thompson P.R.; RT "Synthesis and screening of a haloacetamidine containing library to RT identify PAD4 selective inhibitors."; RL ACS Chem. Biol. 7:160-165(2012). RN [20] RP VARIANTS ASN-89; THR-102 AND THR-131. RX PubMed=15338034; DOI=10.1007/s00109-004-0584-6; RA Hoppe B., Heymann G.A., Tolou F., Kiesewetter H., Doerner T., Salama A.; RT "High variability of peptidylarginine deiminase 4 (PADI4) in a healthy RT white population: characterization of six new variants of PADI4 exons 2-4 RT by a novel haplotype-specific sequencing-based approach."; RL J. Mol. Med. 82:762-767(2004). CC -!- FUNCTION: Catalyzes the citrullination/deimination of arginine residues CC of proteins such as histones, thereby playing a key role in histone CC code and regulation of stem cell maintenance (PubMed:15339660, CC PubMed:15345777, PubMed:16567635, PubMed:21245532). Citrullinates CC histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg- CC 8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, CC respectively) and histone H4 at 'Arg-3' (to form H4R3ci) CC (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). CC Acts as a key regulator of stem cell maintenance by mediating CC citrullination of histone H1: citrullination of 'Arg-54' of histone H1 CC (H1R54ci) results in H1 displacement from chromatin and global CC chromatin decondensation, thereby promoting pluripotency and stem cell CC maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, CC PubMed:21245532). Promotes profound chromatin decondensation during the CC innate immune response to infection in neutrophils by mediating CC formation of H1R54ci (PubMed:18209087). Required for the formation of CC neutrophil extracellular traps (NETs); NETs are mainly composed of DNA CC fibers and are released by neutrophils to bind pathogens during CC inflammation (By similarity). Citrullination of histone H3 prevents CC their methylation by CARM1 and HRMT1L2/PRMT1 and represses CC transcription (PubMed:15345777). Citrullinates EP300/P300 at 'Arg- CC 2142', which favors its interaction with NCOA2/GRIP1 (PubMed:15731352). CC {ECO:0000250|UniProtKB:Q9Z183, ECO:0000269|PubMed:15339660, CC ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15731352, CC ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:18209087, CC ECO:0000269|PubMed:21245532}. 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:16567635, ECO:0000269|PubMed:21245532}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:15629448, ECO:0000269|PubMed:16567635, CC ECO:0000269|PubMed:17002273}; CC Note=Binds 5 Ca(2+) ions per subunit. {ECO:0000269|PubMed:15629448, CC ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273}; CC -!- ACTIVITY REGULATION: Strongly Inhibited by F-amidine and N-alpha- CC benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). CC These inhibitors are however not specific to PADI4 and also inhibit CC other members of the family (PubMed:17002273). Incorporation of a CC carboxylate ortho to the backbone amide of Cl-amidine results in CC inhibitors with increased specificity for PADI4: N-alpha-(2- CC carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F- CC amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)- CC L-ornithine amide (o-Cl-amidine) (PubMed:21882827). Strongly and CC specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of CC the family are not inhibited (PubMed:22004374). CC {ECO:0000269|PubMed:17002273, ECO:0000269|PubMed:21882827, CC ECO:0000269|PubMed:22004374}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.055 mM for fibrinogen {ECO:0000269|PubMed:15629448}; CC KM=0.064 mM for filaggrin {ECO:0000269|PubMed:15629448}; CC Vmax=33.2 umol/h/mg enzyme toward fibrinogen CC {ECO:0000269|PubMed:15629448}; CC Vmax=8 umol/h/mg enzyme toward filaggrin CC {ECO:0000269|PubMed:15629448}; CC pH dependence: CC Optimum pH is 6.5-9.0. {ECO:0000269|PubMed:15629448}; CC -!- INTERACTION: CC Q9UM07; P09525: ANXA4; NbExp=8; IntAct=EBI-1042511, EBI-2556852; CC Q9UM07; P78424: POU6F2; NbExp=3; IntAct=EBI-1042511, EBI-12029004; CC Q9UM07; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-1042511, EBI-492476; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15629448}. Nucleus CC {ECO:0000269|PubMed:15629448}. Cytoplasmic granule CC {ECO:0000269|PubMed:11435484}. Note=Cytoplasmic granules of eosinophils CC and neutrophils. {ECO:0000269|PubMed:11435484}. CC -!- TISSUE SPECIFICITY: Expressed in eosinophils and neutrophils, not CC expressed in peripheral monocytes or lymphocytes. CC {ECO:0000269|PubMed:11435484}. CC -!- PTM: Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme. CC {ECO:0000269|PubMed:20201080}. CC -!- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory CC disease with autoimmune features and a complex genetic component. It CC primarily affects the joints and is characterized by inflammatory CC changes in the synovial membranes and articular structures, widespread CC fibrinoid degeneration of the collagen fibers in mesenchymal tissues, CC and by atrophy and rarefaction of bony structures. CC {ECO:0000269|PubMed:12833157}. Note=The gene represented in this entry CC may be involved in disease pathogenesis. The association to rheumatoid CC arthritis was initially thought to result from increased citrullination CC of target proteins (PubMed:12833157). However, variants that have been CC associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not CC affect the catalytic activity or the citrullination activity of PADI4, CC suggesting that these variants may affect the mRNA stability rather CC than the protein (PubMed:21245532). {ECO:0000269|PubMed:12833157, CC ECO:0000269|PubMed:21245532}. CC -!- SIMILARITY: Belongs to the protein arginine deiminase family. CC {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; AB017919; BAA84542.1; -; mRNA. DR EMBL; AJ549502; CAE47743.1; -; Genomic_DNA. DR EMBL; AK290507; BAF83196.1; -; mRNA. DR EMBL; AK314839; BAG37357.1; -; mRNA. DR EMBL; AC004824; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590644; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025718; AAH25718.1; -; mRNA. DR CCDS; CCDS180.1; -. DR RefSeq; NP_036519.2; NM_012387.2. DR PDB; 1WD8; X-ray; 2.80 A; A=1-663. DR PDB; 1WD9; X-ray; 2.60 A; A=1-663. DR PDB; 1WDA; X-ray; 2.30 A; A=1-663. DR PDB; 2DEW; X-ray; 2.10 A; X=1-663. DR PDB; 2DEX; X-ray; 2.10 A; X=1-663. DR PDB; 2DEY; X-ray; 2.25 A; X=1-663. DR PDB; 2DW5; X-ray; 2.30 A; A=1-663. DR PDB; 3APM; X-ray; 2.50 A; A=1-663. DR PDB; 3APN; X-ray; 2.70 A; A=1-663. DR PDB; 3B1T; X-ray; 2.50 A; A=1-663. DR PDB; 3B1U; X-ray; 2.10 A; A=1-663. DR PDB; 4DKT; X-ray; 2.98 A; A=1-663. DR PDB; 4X8C; X-ray; 3.10 A; A=1-663. DR PDB; 4X8G; X-ray; 3.29 A; A=1-663. DR PDB; 5N0M; X-ray; 2.18 A; A=1-663. DR PDB; 5N0Y; X-ray; 2.23 A; A=1-663. DR PDB; 5N0Z; X-ray; 2.52 A; A=1-663. DR PDB; 5N1B; X-ray; 2.90 A; A=1-663. DR PDB; 8GOD; X-ray; 2.88 A; A=1-663. DR PDBsum; 1WD8; -. DR PDBsum; 1WD9; -. DR PDBsum; 1WDA; -. DR PDBsum; 2DEW; -. DR PDBsum; 2DEX; -. DR PDBsum; 2DEY; -. DR PDBsum; 2DW5; -. DR PDBsum; 3APM; -. DR PDBsum; 3APN; -. DR PDBsum; 3B1T; -. DR PDBsum; 3B1U; -. DR PDBsum; 4DKT; -. DR PDBsum; 4X8C; -. DR PDBsum; 4X8G; -. DR PDBsum; 5N0M; -. DR PDBsum; 5N0Y; -. DR PDBsum; 5N0Z; -. DR PDBsum; 5N1B; -. DR PDBsum; 8GOD; -. DR AlphaFoldDB; Q9UM07; -. DR SMR; Q9UM07; -. DR BioGRID; 117111; 33. DR DIP; DIP-50397N; -. DR IntAct; Q9UM07; 11. DR MINT; Q9UM07; -. DR STRING; 9606.ENSP00000364597; -. DR BindingDB; Q9UM07; -. DR ChEMBL; CHEMBL6111; -. DR DrugBank; DB00207; Azithromycin. DR DrugBank; DB09093; Chlortetracycline. DR DrugBank; DB00155; Citrulline. DR DrugBank; DB07449; N-[(1S)-1-(aminocarbonyl)-4-(ethanimidoylamino)butyl]benzamide. DR DrugBank; DB01082; Streptomycin. DR DrugBank; DB00759; Tetracycline. DR DrugCentral; Q9UM07; -. DR GuidetoPHARMACOLOGY; 2877; -. DR GlyGen; Q9UM07; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UM07; -. DR PhosphoSitePlus; Q9UM07; -. DR BioMuta; PADI4; -. DR DMDM; 296439260; -. DR jPOST; Q9UM07; -. DR MassIVE; Q9UM07; -. DR MaxQB; Q9UM07; -. DR PaxDb; 9606-ENSP00000364597; -. DR PeptideAtlas; Q9UM07; -. DR PRIDE; Q9UM07; -. DR ProteomicsDB; 85166; -. DR Pumba; Q9UM07; -. DR ABCD; Q9UM07; 10 sequenced antibodies. DR Antibodypedia; 1465; 578 antibodies from 38 providers. DR DNASU; 23569; -. DR Ensembl; ENST00000375448.4; ENSP00000364597.4; ENSG00000159339.13. DR Ensembl; ENST00000628229.1; ENSP00000487021.1; ENSG00000280908.2. DR GeneID; 23569; -. DR KEGG; hsa:23569; -. DR MANE-Select; ENST00000375448.4; ENSP00000364597.4; NM_012387.3; NP_036519.2. DR UCSC; uc001baj.3; human. DR AGR; HGNC:18368; -. DR CTD; 23569; -. DR DisGeNET; 23569; -. DR GeneCards; PADI4; -. DR HGNC; HGNC:18368; PADI4. DR HPA; ENSG00000159339; Group enriched (bone marrow, lymphoid tissue). DR MIM; 180300; phenotype. DR MIM; 605347; gene. DR neXtProt; NX_Q9UM07; -. DR OpenTargets; ENSG00000159339; -. DR PharmGKB; PA32903; -. DR VEuPathDB; HostDB:ENSG00000159339; -. DR eggNOG; ENOG502QVJA; Eukaryota. DR GeneTree; ENSGT00940000153217; -. DR HOGENOM; CLU_021911_0_0_1; -. DR InParanoid; Q9UM07; -. DR OMA; DQRTWTW; -. DR OrthoDB; 3956477at2759; -. DR PhylomeDB; Q9UM07; -. DR TreeFam; TF331952; -. DR BioCyc; MetaCyc:HS08389-MONOMER; -. DR BRENDA; 3.5.3.15; 2681. DR PathwayCommons; Q9UM07; -. DR Reactome; R-HSA-3247509; Chromatin modifying enzymes. DR SignaLink; Q9UM07; -. DR SIGNOR; Q9UM07; -. DR BioGRID-ORCS; 23569; 11 hits in 1163 CRISPR screens. DR ChiTaRS; PADI4; human. DR EvolutionaryTrace; Q9UM07; -. DR GeneWiki; PADI4; -. DR GenomeRNAi; 23569; -. DR Pharos; Q9UM07; Tchem. DR PRO; PR:Q9UM07; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9UM07; Protein. DR Bgee; ENSG00000159339; Expressed in blood and 89 other cell types or tissues. DR ExpressionAtlas; Q9UM07; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0140794; F:histone arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0140797; F:histone H3R17 arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0140795; F:histone H3R2 arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0140798; F:histone H3R26 arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0140796; F:histone H3R8 arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0004668; F:protein-arginine deiminase activity; IDA:UniProtKB. DR GO; GO:0006325; P:chromatin organization; ISS:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0006334; P:nucleosome assembly; ISS:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB. DR CDD; cd04214; PAD_N; 1. DR DisProt; DP00321; -. 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:SF3; PROTEIN-ARGININE DEIMINASE TYPE-4; 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; Q9UM07; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Chromatin regulator; Citrullination; Cytoplasm; KW Hydrolase; Immunity; Innate immunity; Metal-binding; Nucleus; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..663 FT /note="Protein-arginine deiminase type-4" FT /id="PRO_0000220033" FT ACT_SITE 350 FT /evidence="ECO:0000269|PubMed:15247907" FT ACT_SITE 471 FT /evidence="ECO:0000269|PubMed:15247907" FT ACT_SITE 473 FT /evidence="ECO:0000269|PubMed:15247907" FT ACT_SITE 645 FT /evidence="ECO:0000269|PubMed:15247907" FT BINDING 153 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 155 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 155 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 157 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 157 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 165 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 165 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 168 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 170 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 176 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 349 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 351 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 353 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 369 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 370 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 373 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 374 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:21882827" FT BINDING 388 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 407 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 410 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 411 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:17002273" FT BINDING 639 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:21882827" FT MOD_RES 205 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT MOD_RES 212 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT MOD_RES 218 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT MOD_RES 372 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT MOD_RES 374 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT MOD_RES 383 FT /note="Citrulline" FT /evidence="ECO:0000269|PubMed:20201080" FT VARIANT 8 FT /note="R -> H (in dbSNP:rs35381732)" FT /id="VAR_053560" FT VARIANT 55 FT /note="G -> S (does not affect catalytic activity; FT dbSNP:rs11203366)" FT /evidence="ECO:0000269|PubMed:10488123, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:21245532" FT /id="VAR_020639" FT VARIANT 79 FT /note="T -> M (in dbSNP:rs35809521)" FT /id="VAR_053561" FT VARIANT 82 FT /note="V -> A (does not affect catalytic activity; FT dbSNP:rs11203367)" FT /evidence="ECO:0000269|PubMed:10488123, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:21245532" FT /id="VAR_020640" FT VARIANT 89 FT /note="D -> N (in dbSNP:rs143187209)" FT /evidence="ECO:0000269|PubMed:15338034" FT /id="VAR_027401" FT VARIANT 102 FT /note="P -> T (in dbSNP:rs34309058)" FT /evidence="ECO:0000269|PubMed:15338034" FT /id="VAR_027402" FT VARIANT 112 FT /note="G -> A (does not affect catalytic activity; FT dbSNP:rs874881)" FT /evidence="ECO:0000269|PubMed:10488123, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:21245532" FT /id="VAR_020641" FT VARIANT 131 FT /note="R -> T (in dbSNP:rs12733102)" FT /evidence="ECO:0000269|PubMed:15338034" FT /id="VAR_027403" FT VARIANT 164 FT /note="M -> T (in dbSNP:rs11588132)" FT /id="VAR_027404" FT VARIANT 260 FT /note="D -> N (in dbSNP:rs35903413)" FT /id="VAR_053562" FT VARIANT 275 FT /note="S -> F (in dbSNP:rs1748020)" FT /evidence="ECO:0000269|PubMed:15087120" FT /id="VAR_020642" FT MUTAGEN 346 FT /note="Q->A: Impaired binding of TDFAInhibitor." FT /evidence="ECO:0000269|PubMed:21882827" FT MUTAGEN 374 FT /note="R->A: Strongly reduces enzymatic activity." FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:21882827" FT MUTAGEN 374 FT /note="R->Q: Impaired binding of TDFAInhibitor." FT /evidence="ECO:0000269|PubMed:15247907, FT ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:21882827" FT MUTAGEN 639 FT /note="R->Q: Impaired binding of TDFAInhibitor." FT /evidence="ECO:0000269|PubMed:21882827" FT MUTAGEN 645 FT /note="C->A: Abolishes enzymatic activity." FT /evidence="ECO:0000269|PubMed:15247907" FT CONFLICT 149 FT /note="I -> V (in Ref. 3; BAF83196)" FT /evidence="ECO:0000305" FT CONFLICT 247 FT /note="M -> T (in Ref. 3; BAG37357)" FT /evidence="ECO:0000305" FT CONFLICT 657 FT /note="K -> E (in Ref. 3; BAF83196)" FT /evidence="ECO:0000305" FT STRAND 4..8 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 11..13 FT /evidence="ECO:0007829|PDB:2DEX" FT STRAND 15..20 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 23..28 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 30..32 FT /evidence="ECO:0007829|PDB:4X8C" FT STRAND 39..44 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 48..51 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 77..82 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:1WD8" FT STRAND 90..98 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 101..118 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:5N0M" FT TURN 133..137 FT /evidence="ECO:0007829|PDB:4X8G" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:3B1U" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 174..179 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 180..189 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 196..202 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 205..207 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 208..210 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 211..215 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 226..230 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 233..238 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 242..253 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 263..273 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:3B1U" FT STRAND 282..293 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 305..310 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 317..329 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 333..336 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 339..342 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 348..350 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 351..359 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 362..369 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 375..377 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 378..383 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 389..393 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 397..399 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 403..405 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 410..412 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 415..418 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 421..423 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 428..432 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 445..453 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 455..457 FT /evidence="ECO:0007829|PDB:2DEX" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 467..469 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 472..474 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 476..480 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:1WD8" FT STRAND 486..493 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 494..506 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 507..511 FT /evidence="ECO:0007829|PDB:5N0M" FT TURN 515..517 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 519..521 FT /evidence="ECO:0007829|PDB:5N0M" FT HELIX 526..531 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 533..557 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 561..563 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 564..568 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 571..573 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 575..577 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 579..583 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 586..588 FT /evidence="ECO:0007829|PDB:4X8C" FT STRAND 590..592 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 595..599 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 607..610 FT /evidence="ECO:0007829|PDB:2DEY" FT HELIX 611..620 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 621..623 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 626..630 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 633..636 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 637..639 FT /evidence="ECO:0007829|PDB:2DEW" FT TURN 643..646 FT /evidence="ECO:0007829|PDB:2DEW" FT STRAND 647..651 FT /evidence="ECO:0007829|PDB:2DEW" FT HELIX 658..660 FT /evidence="ECO:0007829|PDB:2DEW" SQ SEQUENCE 663 AA; 74079 MW; 79D7AF7B3D307A3B CRC64; MAQGTLIRVT PEQPTHAVCV LGTLTQLDIC SSAPEDCTSF SINASPGVVV DIAHGPPAKK KSTGSSTWPL DPGVEVTLTM KVASGSTGDQ KVQISYYGPK TPPVKALLYL TGVEISLCAD ITRTGKVKPT RAVKDQRTWT WGPCGQGAIL LVNCDRDNLE SSAMDCEDDE VLDSEDLQDM SLMTLSTKTP KDFFTNHTLV LHVARSEMDK VRVFQATRGK LSSKCSVVLG PKWPSHYLMV PGGKHNMDFY VEALAFPDTD FPGLITLTIS LLDTSNLELP EAVVFQDSVV FRVAPWIMTP NTQPPQEVYA CSIFENEDFL KSVTTLAMKA KCKLTICPEE ENMDDQWMQD EMEIGYIQAP HKTLPVVFDS PRNRGLKEFP IKRVMGPDFG YVTRGPQTGG ISGLDSFGNL EVSPPVTVRG KEYPLGRILF GDSCYPSNDS RQMHQALQDF LSAQQVQAPV KLYSDWLSVG HVDEFLSFVP APDRKGFRLL LASPRSCYKL FQEQQNEGHG EALLFEGIKK KKQQKIKNIL SNKTLREHNS FVERCIDWNR ELLKRELGLA ESDIIDIPQL FKLKEFSKAE AFFPNMVNML VLGKHLGIPK PFGPVINGRC CLEEKVCSLL EPLGLQCTFI NDFFTYHIRH GEVHCGTNVR RKPFSFKWWN MVP //