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Q9UM07 (PADI4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein-arginine deiminase type-4

EC=3.5.3.15
Alternative name(s):
HL-60 PAD
Peptidylarginine deiminase IV
Protein-arginine deiminase type IV
Gene names
Name:PADI4
Synonyms:PADI5, PDI5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length663 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1. Ref.8 Ref.9 Ref.11 Ref.12 Ref.15 Ref.17

Catalytic activity

Protein L-arginine + H2O = protein L-citrulline + NH3. Ref.15 Ref.17

Cofactor

Binds 5 calcium ions per subunit. Ref.10 Ref.15 Ref.16

Enzyme regulation

Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family (Ref.16). Incorporation of a carboxylate ortho to the backbone amide of Cl-amidine results in inhibitors with increased specificity for PADI4: N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) (Ref.18). Strongly and specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of the family are not inhibited (Ref.19). Ref.16 Ref.18 Ref.19

Subcellular location

Cytoplasm. Nucleus. Cytoplasmic granule. Note: Cytoplasmic granules of eosinophils and neutrophils. Ref.6 Ref.10

Tissue specificity

Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes. Ref.6

Post-translational modification

Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.

Involvement in disease

Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
Note: The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (Ref.7). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (Ref.17). Ref.7

Sequence similarities

Belongs to the protein arginine deiminase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.055 mM for fibrinogen Ref.10

KM=0.064 mM for filaggrin

Vmax=33.2 µmol/h/mg enzyme toward fibrinogen

Vmax=8.0 µmol/h/mg enzyme toward filaggrin

pH dependence:

Optimum pH is 6.5-9.0.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandCalcium
Metal-binding
   Molecular functionChromatin regulator
Hydrolase
   PTMCitrullination
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein modification process

Traceable author statement Ref.1. Source: ProtInc

chromatin modification

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin remodeling

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-R26 citrullination

Inferred from direct assay Ref.8Ref.15. Source: UniProtKB

histone citrullination

Inferred from direct assay Ref.8Ref.15. Source: UniProtKB

nucleosome assembly

Inferred from sequence or structural similarity. Source: UniProtKB

protein citrullination

Inferred from direct assay PubMed 21584310. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

stem cell maintenance

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionarginine deiminase activity

Inferred from direct assay PubMed 21584310. Source: UniProtKB

calcium ion binding

Inferred from direct assay Ref.15. Source: UniProtKB

protein-arginine deiminase activity

Inferred from direct assay Ref.8Ref.15. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 663663Protein-arginine deiminase type-4
PRO_0000220033

Sites

Active site3501 Ref.14
Active site4711 Ref.14
Active site4731 Ref.14
Active site6451 Ref.14
Metal binding1531Calcium 1
Metal binding1551Calcium 1
Metal binding1551Calcium 2
Metal binding1571Calcium 1
Metal binding1571Calcium 2
Metal binding1651Calcium 1
Metal binding1651Calcium 3; via carbonyl oxygen
Metal binding1681Calcium 3
Metal binding1701Calcium 3; via carbonyl oxygen
Metal binding1761Calcium 1
Metal binding1791Calcium 1
Metal binding1791Calcium 2
Metal binding3491Calcium 4
Metal binding3511Calcium 5
Metal binding3531Calcium 4
Metal binding3691Calcium 5
Metal binding3701Calcium 5; via carbonyl oxygen
Metal binding3731Calcium 5
Metal binding3881Calcium 2
Metal binding4071Calcium 4; via carbonyl oxygen
Metal binding4101Calcium 4; via carbonyl oxygen
Metal binding4111Calcium 4
Binding site3461TDFA Inhibitor
Binding site3691TDFA Inhibitor
Binding site3741Substrate
Binding site3741TDFA Inhibitor
Binding site4711TDFA Inhibitor
Binding site4731TDFA Inhibitor
Binding site6391Substrate; via carbonyl oxygen
Binding site6451TDFA Inhibitor

Amino acid modifications

Modified residue2051Citrulline
Modified residue2121Citrulline
Modified residue2181Citrulline
Modified residue3721Citrulline
Modified residue3741Citrulline
Modified residue3831Citrulline

Natural variations

Natural variant81R → H.
Corresponds to variant rs35381732 [ dbSNP | Ensembl ].
VAR_053560
Natural variant551G → S Does not catalytic activity. Ref.1 Ref.5 Ref.17
Corresponds to variant rs11203366 [ dbSNP | Ensembl ].
VAR_020639
Natural variant791T → M.
Corresponds to variant rs35809521 [ dbSNP | Ensembl ].
VAR_053561
Natural variant821V → A Does not catalytic activity. Ref.1 Ref.5 Ref.17
Corresponds to variant rs11203367 [ dbSNP | Ensembl ].
VAR_020640
Natural variant891D → N. Ref.20
VAR_027401
Natural variant1021P → T. Ref.20
Corresponds to variant rs34309058 [ dbSNP | Ensembl ].
VAR_027402
Natural variant1121G → A Does not catalytic activity. Ref.1 Ref.5 Ref.17
Corresponds to variant rs874881 [ dbSNP | Ensembl ].
VAR_020641
Natural variant1311R → T. Ref.20
Corresponds to variant rs12733102 [ dbSNP | Ensembl ].
VAR_027403
Natural variant1641M → T.
Corresponds to variant rs11588132 [ dbSNP | Ensembl ].
VAR_027404
Natural variant2601D → N.
Corresponds to variant rs35903413 [ dbSNP | Ensembl ].
VAR_053562
Natural variant2751S → F. Ref.2
Corresponds to variant rs1748020 [ dbSNP | Ensembl ].
VAR_020642

Experimental info

Mutagenesis3461Q → A: Impaired binding of TDFA Inhibitor. Ref.18
Mutagenesis3741R → A: Strongly reduces enzymatic activity. Ref.14 Ref.15 Ref.18
Mutagenesis3741R → Q: Impaired binding of TDFA Inhibitor. Ref.14 Ref.15 Ref.18
Mutagenesis6391R → Q: Impaired binding of TDFA Inhibitor. Ref.18
Mutagenesis6451C → A: Abolishes enzymatic activity. Ref.14
Sequence conflict1491I → V in BAF83196. Ref.3
Sequence conflict2471M → T in BAG37357. Ref.3
Sequence conflict6571K → E in BAF83196. Ref.3

Secondary structure

........................................................................................................................................ 663
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UM07 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 79D7AF7B3D307A3B

FASTA66374,079
        10         20         30         40         50         60 
MAQGTLIRVT PEQPTHAVCV LGTLTQLDIC SSAPEDCTSF SINASPGVVV DIAHGPPAKK 

        70         80         90        100        110        120 
KSTGSSTWPL DPGVEVTLTM KVASGSTGDQ KVQISYYGPK TPPVKALLYL TGVEISLCAD 

       130        140        150        160        170        180 
ITRTGKVKPT RAVKDQRTWT WGPCGQGAIL LVNCDRDNLE SSAMDCEDDE VLDSEDLQDM 

       190        200        210        220        230        240 
SLMTLSTKTP KDFFTNHTLV LHVARSEMDK VRVFQATRGK LSSKCSVVLG PKWPSHYLMV 

       250        260        270        280        290        300 
PGGKHNMDFY VEALAFPDTD FPGLITLTIS LLDTSNLELP EAVVFQDSVV FRVAPWIMTP 

       310        320        330        340        350        360 
NTQPPQEVYA CSIFENEDFL KSVTTLAMKA KCKLTICPEE ENMDDQWMQD EMEIGYIQAP 

       370        380        390        400        410        420 
HKTLPVVFDS PRNRGLKEFP IKRVMGPDFG YVTRGPQTGG ISGLDSFGNL EVSPPVTVRG 

       430        440        450        460        470        480 
KEYPLGRILF GDSCYPSNDS RQMHQALQDF LSAQQVQAPV KLYSDWLSVG HVDEFLSFVP 

       490        500        510        520        530        540 
APDRKGFRLL LASPRSCYKL FQEQQNEGHG EALLFEGIKK KKQQKIKNIL SNKTLREHNS 

       550        560        570        580        590        600 
FVERCIDWNR ELLKRELGLA ESDIIDIPQL FKLKEFSKAE AFFPNMVNML VLGKHLGIPK 

       610        620        630        640        650        660 
PFGPVINGRC CLEEKVCSLL EPLGLQCTFI NDFFTYHIRH GEVHCGTNVR RKPFSFKWWN 


MVP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3)."
Nakashima K., Hagiwara T., Ishigami A., Nagata S., Asaga H., Kuramoto M., Senshu T., Yamada M.
J. Biol. Chem. 274:27786-27792(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-55; ALA-82 AND ALA-112.
[2]"Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6."
Chavanas S., Mechin M.-C., Takahara H., Kawada A., Nachat R., Serre G., Simon M.
Gene 330:19-27(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-275.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-55; ALA-82 AND ALA-112.
Tissue: Pancreas and Spleen.
[6]"Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils."
Asaga H., Nakashima K., Senshu T., Ishigami A., Yamada M.
J. Leukoc. Biol. 70:46-51(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]"Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis."
Suzuki A., Yamada R., Chang X., Tokuhiro S., Sawada T., Suzuki M., Nagasaki M., Nakayama-Hamada M., Kawaida R., Ono M., Ohtsuki M., Furukawa H., Yoshino S., Yukioka M., Tohma S., Matsubara T., Wakitani S., Teshima R. expand/collapse author list , Nishioka Y., Sekine A., Iida A., Takahashi A., Tsunoda T., Nakamura Y., Yamamoto K.
Nat. Genet. 34:395-402(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN RA.
[8]"Histone deimination antagonizes arginine methylation."
Cuthbert G.L., Daujat S., Snowden A.W., Erdjument-Bromage H., Hagiwara T., Yamada M., Schneider R., Gregory P.D., Tempst P., Bannister A.J., Kouzarides T.
Cell 118:545-553(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Human PAD4 regulates histone arginine methylation levels via demethylimination."
Wang Y., Wysocka J., Sayegh J., Lee Y.-H., Perlin J.R., Leonelli L., Sonbuchner L.S., McDonald C.H., Cook R.G., Dou Y., Roeder R.G., Clarke S., Stallcup M.R., Allis C.D., Coonrod S.A.
Science 306:279-283(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Comparison of enzymatic properties between hPADI2 and hPADI4."
Nakayama-Hamada M., Suzuki A., Kubota K., Takazawa T., Ohsaka M., Kawaida R., Ono M., Kasuya A., Furukawa H., Yamada R., Yamamoto K.
Biochem. Biophys. Res. Commun. 327:192-200(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
[11]"Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination."
Lee Y.-H., Coonrod S.A., Kraus W.L., Jelinek M.A., Stallcup M.R.
Proc. Natl. Acad. Sci. U.S.A. 102:3611-3616(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CITRULLINATION OF EP300.
[12]"Histone deimination as a response to inflammatory stimuli in neutrophils."
Neeli I., Khan S.N., Radic M.
J. Immunol. 180:1895-1902(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation."
Andrade F., Darrah E., Gucek M., Cole R.N., Rosen A., Zhu X.
Arthritis Rheum. 62:1630-1640(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CITRULLINATION AT ARG-205; ARG-212; ARG-218; ARG-372; ARG-374 AND ARG-383.
[14]"Structural basis for Ca(2+)-induced activation of human PAD4."
Arita K., Hashimoto H., Shimizu T., Nakashima K., Yamada M., Sato M.
Nat. Struct. Mol. Biol. 11:777-783(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH CALCIUM AND HISTONE H3 N-TERMINUS, X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH CALCIUM AND HISTONE H4 N-TERMINUS, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALCIUM AND BENZOYL-ARGININE AMIDE, ACTIVE SITE, MUTAGENESIS OF ARG-374 AND CYS-645.
[15]"Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4."
Arita K., Shimizu T., Hashimoto H., Hidaka Y., Yamada M., Sato M.
Proc. Natl. Acad. Sci. U.S.A. 103:5291-5296(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH CALCIUM AND HISTONE H3 AND H4 N-TERMINUS, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-374.
[16]"Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization."
Luo Y., Arita K., Bhatia M., Knuckley B., Lee Y.H., Stallcup M.R., Sato M., Thompson P.R.
Biochemistry 45:11727-11736(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALCIUM, COFACTOR, ENZYME REGULATION.
[17]"Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene."
Horikoshi N., Tachiwana H., Saito K., Osakabe A., Sato M., Yamada M., Akashi S., Nishimura Y., Kagawa W., Kurumizaka H.
Acta Crystallogr. D 67:112-118(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANTS SER-55; ALA-82 AND ALA-112.
[18]"The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-Carboxyl)benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors."
Causey C.P., Jones J.E., Slack J.L., Kamei D., Jones L.E., Subramanian V., Knuckley B., Ebrahimi P., Chumanevich A.A., Luo Y., Hashimoto H., Sato M., Hofseth L.J., Thompson P.R.
J. Med. Chem. 54:6919-6935(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITOR, ENZYME REGULATION, MUTAGENESIS OF GLN-346; ARG-374 AND ARG-639.
[19]"Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors."
Jones J.E., Slack J.L., Fang P., Zhang X., Subramanian V., Causey C.P., Coonrod S.A., Guo M., Thompson P.R.
ACS Chem. Biol. 7:160-165(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.98 ANGSTROMS) IN COMPLEX WITH TDFA, ENZYME REGULATION.
[20]"High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach."
Hoppe B., Heymann G.A., Tolou F., Kiesewetter H., Doerner T., Salama A.
J. Mol. Med. 82:762-767(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASN-89; THR-102 AND THR-131.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB017919 mRNA. Translation: BAA84542.1.
AJ549502 Genomic DNA. Translation: CAE47743.1.
AK290507 mRNA. Translation: BAF83196.1.
AK314839 mRNA. Translation: BAG37357.1.
AL590644, AC004824 Genomic DNA. Translation: CAH73167.1.
BC025718 mRNA. Translation: AAH25718.1.
RefSeqNP_036519.2. NM_012387.2.
UniGeneHs.522969.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WD8X-ray2.80A1-663[»]
1WD9X-ray2.60A1-663[»]
1WDAX-ray2.30A1-663[»]
2DEWX-ray2.10X1-663[»]
2DEXX-ray2.10X1-663[»]
2DEYX-ray2.25X1-663[»]
2DW5X-ray2.30A1-663[»]
3APMX-ray2.50A1-663[»]
3APNX-ray2.70A1-663[»]
3B1TX-ray2.50A1-663[»]
3B1UX-ray2.10A1-663[»]
4DKTX-ray2.98A1-663[»]
DisProtDP00321.
ProteinModelPortalQ9UM07.
SMRQ9UM07. Positions 2-663.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117111. 9 interactions.
STRING9606.ENSP00000364597.

Chemistry

BindingDBQ9UM07.
ChEMBLCHEMBL6111.
DrugBankDB00155. L-Citrulline.

PTM databases

PhosphoSiteQ9UM07.

Polymorphism databases

DMDM296439260.

Proteomic databases

PaxDbQ9UM07.
PRIDEQ9UM07.

Protocols and materials databases

DNASU23569.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375448; ENSP00000364597; ENSG00000159339.
GeneID23569.
KEGGhsa:23569.
UCSCuc001baj.2. human.

Organism-specific databases

CTD23569.
GeneCardsGC01P017634.
H-InvDBHIX0000182.
HGNCHGNC:18368. PADI4.
HPAHPA017007.
MIM180300. phenotype.
605347. gene.
neXtProtNX_Q9UM07.
PharmGKBPA32903.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42085.
HOGENOMHOG000220908.
HOVERGENHBG053016.
InParanoidQ9UM07.
KOK01481.
OMAMTLSTKT.
OrthoDBEOG7P5T09.
PhylomeDBQ9UM07.
TreeFamTF331952.

Enzyme and pathway databases

BioCycMetaCyc:HS08389-MONOMER.
BRENDA3.5.3.15. 2681.

Gene expression databases

ArrayExpressQ9UM07.
BgeeQ9UM07.
CleanExHS_PADI4.
GenevestigatorQ9UM07.

Family and domain databases

InterProIPR008972. Cupredoxin.
IPR004303. PAD.
IPR013530. PAD_C.
IPR013732. PAD_N.
IPR013733. Prot_Arg_deaminase_cen_dom.
IPR016296. Protein-arginine_deiminase_sub.
[Graphical view]
PANTHERPTHR10837. PTHR10837. 1 hit.
PfamPF03068. PAD. 1 hit.
PF08527. PAD_M. 1 hit.
PF08526. PAD_N. 1 hit.
[Graphical view]
PIRSFPIRSF001247. Protein-arginine_deiminase. 1 hit.
SUPFAMSSF110083. SSF110083. 1 hit.
SSF49503. SSF49503. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9UM07.
GeneWikiPADI4.
GenomeRNAi23569.
NextBio35463997.
PROQ9UM07.
SOURCESearch...

Entry information

Entry namePADI4_HUMAN
AccessionPrimary (citable) accession number: Q9UM07
Secondary accession number(s): A8K392 expand/collapse secondary AC list , B2RBW0, Q5VTZ8, Q70SX4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM