Overview
| Uniprot ID | Q8N371 |
|---|
| Protein Name | Bifunctional peptidase and arginyl-hydroxylase JMJD5 |
|---|
| Gene Name | KDM8 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 167 |
PEQPCTKKARADHGL |
Function
Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase (PubMed:28847961, PubMed:28982940, PubMed:29459673, PubMed:29563586). Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation (PubMed:28847961, PubMed:28982940, PubMed:29459673). Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity (PubMed:28847961, PubMed:29459673). Upon DNA damage, cleaves the N-terminal tail of histone H3 at monomethylated lysine residues, preferably at monomethylated 'Lys-9' (H3K9me1). The histone variant H3F3A is the major target for cleavage (PubMed:28982940). Additionally, acts as a Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (R)-stereospecific hydroxylation at C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but the biological significance of this activity remains to be established (PubMed:29563586). Regulates mitosis through different mechanisms: Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1. Possibly together with RCCD1, is involved in proper mitotic spindle organization and chromosome segregation (PubMed:24981860). Negatively regulates cell cycle repressor CDKN1A/p21, which controls G1/S phase transition (PubMed:24740926). Required for G2/M phase cell cycle progression. Regulates expression of CCNA1/cyclin-A1, leading to cancer cell proliferation (PubMed:20457893). Also, plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability involved in epithelial to mesenchymal transition (PubMed:28455245). Regulates the circadian gene expression in the liver (By similarity). Represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a catalytically-independent manner (PubMed:30500822). Negatively regulates the protein stability and function of CRY1; required for AMPK-FBXL3-induced CRY1 degradation (PubMed:30500822)
Protein Sequence
10
MAGDTHCPAE
20
PLAREGTLWE
30
ALRALLPHSK
40
EDLKLDLGEK
50
VERSVVTLLQ
60
RATELFYEGR
70
RDECLQSSEV
80
ILDYSWEKLN
90
TGTWQDVDKD
100
WRRVYAIGCL
110
LKALCLCQAP
120
EDANTVAAAL
130
RVCDMGLLMG
140
AAILGDILLK
150
VAAILQTHLP
160
GKRPARGSLP
170
EQPCTKKARA
180
DHGLIPDVKL
190
EKTVPRLHRP
200
SLQHFREQFL
210
VPGRPVILKG
220
VADHWPCMQK
230
WSLEYIQEIA
240
GCRTVPVEVG
250
SRYTDEEWSQ
260
TLMTVNEFIS
270
KYIVNEPRDV
280
GYLAQHQLFD
290
QIPELKQDIS
300
IPDYCSLGDG
310
EEEEITINAW
320
FGPQGTISPL
330
HQDPQQNFLV
340
QVMGRKYIRL
350
YSPQESGALY
360
PHDTHLLHNT
370
SQVDVENPDL
380
EKFPKFAKAP
390
FLSCILSPGE
400
ILFIPVKYWH
410
YVRALDLSFS
VSFWWS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005694 |
chromosome |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0004177 |
aminopeptidase activity |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0004175 |
endopeptidase activity |
| Molecular Function |
GO:0051864 |
histone H3K36 demethylase activity |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0002039 |
p53 binding |
| Molecular Function |
GO:0106157 |
peptidyl-arginine 3-dioxygenase activity |
| Biological Process |
GO:0032922 |
circadian regulation of gene expression |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0000086 |
G2/M transition of mitotic cell cycle |
| Biological Process |
GO:0045892 |
negative regulation of DNA-templated transcription |
| Biological Process |
GO:0030961 |
peptidyl-arginine hydroxylation |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:0031648 |
protein destabilization |
| Biological Process |
GO:0006508 |
proteolysis |
Reference
PMID: N/A