PADI4_HUMAN
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 03-AUG-2022, entry version 192.
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=8.0 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; Q6LES2: ANXA4; NbExp=8; IntAct=EBI-1042511, EBI-10250835;
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}.
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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 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 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; 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 iPTMnet; Q9UM07; -.
DR PhosphoSitePlus; Q9UM07; -.
DR BioMuta; PADI4; -.
DR DMDM; 296439260; -.
DR jPOST; Q9UM07; -.
DR MassIVE; Q9UM07; -.
DR MaxQB; Q9UM07; -.
DR PaxDb; Q9UM07; -.
DR PeptideAtlas; Q9UM07; -.
DR PRIDE; Q9UM07; -.
DR ProteomicsDB; 85166; -.
DR ABCD; Q9UM07; 10 sequenced antibodies.
DR Antibodypedia; 1465; 528 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 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; RVFQATR; -.
DR OrthoDB; 787070at2759; -.
DR PhylomeDB; Q9UM07; -.
DR TreeFam; TF331952; -.
DR BioCyc; MetaCyc:HS08389-MON; -.
DR BRENDA; 3.5.3.15; 2681.
DR PathwayCommons; Q9UM07; -.
DR Reactome; R-HSA-3247509; Chromatin modifying enzymes.
DR SignaLink; Q9UM07; -.
DR BioGRID-ORCS; 23569; 11 hits in 1084 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 88 other tissues.
DR ExpressionAtlas; Q9UM07; baseline and differential.
DR Genevisible; Q9UM07; HS.
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:0140797; F:histone-arginine deiminase activity (H3-R17 specific); IDA:UniProtKB.
DR GO; GO:0140795; F:histone-arginine deiminase activity (H3-R2 specific); IDA:UniProtKB.
DR GO; GO:0140798; F:histone-arginine deiminase activity (H3-R26 specific); IDA:UniProtKB.
DR GO; GO:0140796; F:histone-arginine deiminase activity (H3-R8 specific); 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:0036414; P:histone citrullination; IDA:UniProtKB.
DR GO; GO:0036413; P:histone H3-R26 citrullination; IDA: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:GO_Central.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR DisProt; DP00321; -.
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; 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 TDFA Inhibitor."
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 TDFA Inhibitor."
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 TDFA Inhibitor."
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
