PADI4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PADI4_HUMAN
• UniProt AC: Q9UM07
• Protein Name: Protein-arginine deiminase type-4
• Gene Name: PADI4
• Organism: Homo sapiens (Human).
• Sequence Length: 663
• Subcellular Localization: Cytoplasm. Nucleus. Cytoplasmic granule. Cytoplasmic granules of eosinophils and neutrophils.
• Protein Description: 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..
• Protein Sequence: MAQGTLIRVTPEQPTHAVCVLGTLTQLDICSSAPEDCTSFSINASPGVVVDIAHGPPAKKKSTGSSTWPLDPGVEVTLTMKVASGSTGDQKVQISYYGPKTPPVKALLYLTGVEISLCADITRTGKVKPTRAVKDQRTWTWGPCGQGAILLVNCDRDNLESSAMDCEDDEVLDSEDLQDMSLMTLSTKTPKDFFTNHTLVLHVARSEMDKVRVFQATRGKLSSKCSVVLGPKWPSHYLMVPGGKHNMDFYVEALAFPDTDFPGLITLTISLLDTSNLELPEAVVFQDSVVFRVAPWIMTPNTQPPQEVYACSIFENEDFLKSVTTLAMKAKCKLTICPEEENMDDQWMQDEMEIGYIQAPHKTLPVVFDSPRNRGLKEFPIKRVMGPDFGYVTRGPQTGGISGLDSFGNLEVSPPVTVRGKEYPLGRILFGDSCYPSNDSRQMHQALQDFLSAQQVQAPVKLYSDWLSVGHVDEFLSFVPAPDRKGFRLLLASPRSCYKLFQEQQNEGHGEALLFEGIKKKKQQKIKNILSNKTLREHNSFVERCIDWNRELLKRELGLAESDIIDIPQLFKLKEFSKAEAFFPNMVNMLVLGKHLGIPKPFGPVINGRCCLEEKVCSLLEPLGLQCTFINDFFTYHIRHGEVHCGTNVRRKPFSFKWWNMVP

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
63	Phosphorylation	PPAKKKSTGSSTWPL CCCCCCCCCCCCCCC	50.38	-
205	Citrullination	TLVLHVARSEMDKVR EEEEEEEHHHHCCEE	31.87	-
205	Citrullination	TLVLHVARSEMDKVR EEEEEEEHHHHCCEE	31.87	20201080
212	Citrullination	RSEMDKVRVFQATRG HHHHCCEEEEEEECC	29.31	-
212	Citrullination	RSEMDKVRVFQATRG HHHHCCEEEEEEECC	29.31	20201080
217	Phosphorylation	KVRVFQATRGKLSSK CEEEEEEECCCCCCC	29.22	-
218	Citrullination	VRVFQATRGKLSSKC EEEEEEECCCCCCCC	43.17	-
218	Citrullination	VRVFQATRGKLSSKC EEEEEEECCCCCCCC	43.17	20201080
222	Phosphorylation	QATRGKLSSKCSVVL EEECCCCCCCCEEEE	31.10	-
363	Phosphorylation	YIQAPHKTLPVVFDS EEECCCCCCCEEECC	33.01	-
370	Phosphorylation	TLPVVFDSPRNRGLK CCCEEECCCCCCCCC	17.81	24719451
372	Citrullination	PVVFDSPRNRGLKEF CEEECCCCCCCCCCC	49.80	-
372	Citrullination	PVVFDSPRNRGLKEF CEEECCCCCCCCCCC	49.80	20201080
374	Citrullination	VFDSPRNRGLKEFPI EECCCCCCCCCCCCC	53.77	-
374	Citrullination	VFDSPRNRGLKEFPI EECCCCCCCCCCCCC	53.77	20201080
383	Citrullination	LKEFPIKRVMGPDFG CCCCCCCEEECCCCE	25.11	20201080
383	Citrullination	LKEFPIKRVMGPDFG CCCCCCCEEECCCCE	25.11	-
402	Phosphorylation	GPQTGGISGLDSFGN CCCCCCCCCCCCCCC	36.26	-
406	Phosphorylation	GGISGLDSFGNLEVS CCCCCCCCCCCEEEC	39.84	-
493	Phosphorylation	GFRLLLASPRSCYKL CHHEEEECHHHHHHH	22.33	22617229
533	Acetylation	IKNILSNKTLREHNS HHHHHCCHHHHHCHH	45.63	7297023
655	Phosphorylation	NVRRKPFSFKWWNMV CCCCCCCCCCCCCCC	34.15	24719451

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
-	K	Ubiquitination	E3 ubiquitin ligase	SMURF1	Q9HCE7	PMID:20804422

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
372	R	Citrullination	Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.	20201080
374	R	Citrullination	Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.	20201080

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PADI4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HDAC1_HUMAN	HDAC1	physical	19581286
P53_HUMAN	TP53	physical	18505818
HDAC2_HUMAN	HDAC2	physical	20190809
P53_HUMAN	TP53	physical	20190809
NPM_HUMAN	NPM1	physical	19843866
ELK1_HUMAN	ELK1	physical	21655091
ING4_HUMAN	ING4	physical	21454715
A4_HUMAN	APP	physical	21832049

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.