KDM8
entrez
79831
canonical
uniprot
Q8N371
canonical
ensembl
ENSG00000155666
resolver
ensp
ENSP00000286096
resolver
ensp
ENSP00000398410
resolver
ensp
ENSP00000539468
resolver
ensp
ENSP00000539469
resolver
ensp
ENSP00000675003
resolver
genesymbol
JMJD5
resolver
genesymbol
KDM8
resolver
genesymbol_syn
JMJD5
resolver
hgnc
HGNC:25840
resolver
uniprot
A0A0S2Z5P8
resolver
uniprot
A0A0S2Z5T1
resolver
uniprot
B4DLU9
resolver
uniprot
Q6VAK5
resolver
uniprot
Q9H8B1
resolver
uniprot_entry
A0A0S2Z5P8_HUMAN
resolver
uniprot_entry
A0A0S2Z5T1_HUMAN
resolver
uniprot_entry
KDM8_HUMAN
resolver
uniprot_sec
B4DLU9
resolver
uniprot_sec
Q6VAK5
resolver
uniprot_sec
Q9H8B1
resolver
amino_acid_sequence
MAGDTHCPAEPLAREGTLWEALRALLPHSKEDLKLDLGEKVERSVVTLLQRATELFYEGRRDECLQSSEVILDYSWEKLNTGTWQDVDKDWRRVYAIGCLLKALCLCQAPEDANTVAAALRVCDMGLLMGAAILGDILLKVAAILQTHLPGKRPARGSLPEQPCTKKARADHGLIPDVKLEKTVPRLHRPSLQHFREQFLVPGRPVILKGVADHWPCMQKWSLEYIQEIAGCRTVPVEVGSRYTDEEWSQTLMTVNEFISKYIVNEPRDVGYLAQHQLFDQIPELKQDISIPDYCSLGDGEEEEITINAWFGPQGTISPLHQDPQQNFLVQVMGRKYIRLYSPQESGALYPHDTHLLHNTSQVDVENPDLEKFPKFAKAPFLSCILSPGEILFIPVKYWHYVRALDLSFSVSFWWS
uniprot
proteins
ec_number
1.14.11.73
uniprot
proteins
ec_number
3.4.-.-
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q9CXT6, ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:24740926, ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28455245, ECO:0000269|PubMed:28847961, ECO:0000269|PubMed:28982940, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000269|PubMed:30500822}.
uniprot
proteins
mass_dalton
47270
uniprot
proteins
mutagenesis
MUTAGEN 1..182; /note="Missing: No effect on L-arginyl 3-hydroxylase activity toward RPS6."; /evidence="ECO:0000269|PubMed:29563586"; MUTAGEN 238; /note="E->A: Loss of L-arginyl 3-hydroxylase activity toward RPS6."; /evidence="ECO:0000269|PubMed:29563586"; MUTAGEN 243; /note="Y->A: Loss of L-arginyl 3-hydroxylase activity toward RPS6."; /evidence="ECO:0000269|PubMed:29563586"; MUTAGEN 275; /note="Q->A: Loss of L-arginyl 3-hydroxylase activity toward RPS6. Loss of peptidase activity toward methylated histones."; /evidence="ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586"; MUTAGEN 310; /note="W->A: Loss of L-arginyl 3-hydroxylase activity toward RPS6."; /evidence="ECO:0000269|PubMed:29563586"; MUTAGEN 321..323; /note="HQD->AQA: Fails to cleave H3C1."; /evidence="ECO:0000269|PubMed:28982940"; MUTAGEN 321; /note="H->A: Loss of H3K36me2 demethylase activity."; /evidence="ECO:0000269|PubMed:20457893"; MUTAGEN 321; /note="H->A: Loss of L-arginyl 3-hydroxylase activity toward RPS6. Loss of peptidase activity toward methylated histones; when associated with A-323 and A-400. No effect on its regulatory function on the circadian clock or CRY1 stability."; /evidence="ECO:0000269|PubMed:28847961, ECO:0000269|PubMed:29563586, ECO:0000269|PubMed:30500822"; MUTAGEN 323; /note="D->A: Loss of peptidase activity toward methylated histones; when associated with A-321 and A-400."; /evidence="ECO:0000269|PubMed:28847961"; MUTAGEN 335..336; /note="RK->AA: Loss of interaction with H3C1. Fails to cleave H3C1."; /evidence="ECO:0000269|PubMed:28982940"; MUTAGEN 336; /note="K->E: Loss of peptidase activity toward methylated histones."; /evidence="ECO:0000269|PubMed:29459673"; MUTAGEN 356; /note="L->A: Reduces L-arginyl 3-hydroxylase activity toward RPS6 substrate."; /evidence="ECO:0000269|PubMed:29563586"; MUTAGEN 398..400; /note="YWH->AAA: Fails to cleave H3C1."; /evidence="ECO:0000269|PubMed:28982940"; MUTAGEN 400; /note="H->A: Loss of peptidase activity toward methylated histones; when associated with A-321 and A-323."; /evidence="ECO:0000269|PubMed:28847961"; MUTAGEN 414; /note="W->A: Reduces L-arginyl 3-hydroxylase activity toward RPS6."; /evidence="ECO:0000269|PubMed:29563586
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
20457893
uniprot
proteins
pubmed
22851697
uniprot
proteins
pubmed
24100311
uniprot
proteins
pubmed
24740926
uniprot
proteins
pubmed
24981860
uniprot
proteins
pubmed
28455245
uniprot
proteins
pubmed
28847961
uniprot
proteins
pubmed
28982940
uniprot
proteins
pubmed
29459673
uniprot
proteins
pubmed
29563586
uniprot
proteins
pubmed
30500822
uniprot
proteins
sequence_length
416
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:28982940}. Chromosome {ECO:0000269|PubMed:24981860}. Note=Colocalizes with trimethylated 'Lys-9' of histone H3 (H3K9me3). {ECO:0000269|PubMed:24981860}.
uniprot
proteins