Q4FZB7 · KMT5B_HUMAN
- ProteinHistone-lysine N-methyltransferase KMT5B
- GeneKMT5B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids885 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869).
H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity).
Plays a role in myogenesis by regulating the expression of target genes, such as EID3 (PubMed:23720823).
Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273).
May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).
Catalytic activity
- N6-methyl-L-lysyl20-[histone H4] + S-adenosyl-L-methionine = H+ + N6,N6-dimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
RHEA-COMP:15555 CHEBI:61929 Position: 20+ CHEBI:59789 = CHEBI:15378 + RHEA-COMP:15556 CHEBI:61976 Position: 20+ CHEBI:57856 - N6,N6-dimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-methionine = H+ + N6,N6,N6-trimethyl-L-lysyl20-[histone H4] + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
3.4 μM | H4K20me0 | |||||
1.7 μM | H4K20me1 | |||||
0.3 μM | nucleosome |
pH Dependence
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 98 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 203-206 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: YSSE | ||||||
Binding site | 210 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 257 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 272-273 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: NH | ||||||
Binding site | 275 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 319 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 320 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 321 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 324 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | condensed chromosome, centromeric region | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | chromatin binding | |
Molecular Function | histone H4 methyltransferase activity | |
Molecular Function | histone H4K20 methyltransferase activity | |
Molecular Function | histone H4K20 monomethyltransferase activity | |
Molecular Function | histone H4K20me methyltransferase activity | |
Molecular Function | histone methyltransferase activity | |
Molecular Function | metal ion binding | |
Molecular Function | S-adenosyl-L-methionine binding | |
Biological Process | DNA repair | |
Biological Process | methylation | |
Biological Process | muscle organ development | |
Biological Process | positive regulation of double-strand break repair via nonhomologous end joining | |
Biological Process | positive regulation of isotype switching |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameHistone-lysine N-methyltransferase KMT5B
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ4FZB7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Intellectual developmental disorder, autosomal dominant 51 (MRD51)
- Note
- DescriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
- See alsoMIM:617788
Natural variants in MRD51
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081278 | 187-885 | missing | in MRD51 | |
VAR_080549 | 264 | W>S | in MRD51; uncertain significance; dbSNP:rs1555028104 | |
VAR_080550 | 513 | A>V | in MRD51; uncertain significance; dbSNP:rs377163167 | |
VAR_080551 | 540 | R>Q | in MRD51; uncertain significance; dbSNP:rs565603169 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_047765 | 9 | in dbSNP:rs2512606 | |||
Sequence: N → I | ||||||
Natural variant | VAR_081278 | 187-885 | in MRD51 | |||
Sequence: Missing | ||||||
Mutagenesis | 229 | Km for H4K20me1rise to 17 uM. 8-fold decrease in catalytic efficiency. | ||||
Sequence: G → F | ||||||
Mutagenesis | 229 | Abolishes histone methyltransferase activity (H4-K20 specific). | ||||
Sequence: G → Y | ||||||
Mutagenesis | 251 | Abolishes histone methyltransferase activity (H4-K20 specific). | ||||
Sequence: S → A | ||||||
Natural variant | VAR_080549 | 264 | in MRD51; uncertain significance; dbSNP:rs1555028104 | |||
Sequence: W → S | ||||||
Mutagenesis | 264 | Abolishes histone methyltransferase activity (H4-K20 specific). | ||||
Sequence: W → A | ||||||
Mutagenesis | 281 | Abolishes histone methyltransferase activity (H4-K20 specific). | ||||
Sequence: F → A | ||||||
Mutagenesis | 311 | Km for H4K20me1rise to 8.5 uM. 3-fold decrease in catalytic efficiency. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_080550 | 513 | in MRD51; uncertain significance; dbSNP:rs377163167 | |||
Sequence: A → V | ||||||
Natural variant | VAR_080551 | 540 | in MRD51; uncertain significance; dbSNP:rs565603169 | |||
Sequence: R → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 937 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000281787 | 1-885 | UniProt | Histone-lysine N-methyltransferase KMT5B | |||
Sequence: MKWLGESKNMVVNGRRNGGKLSNDHQQNQSKLQHTGKDTLKAGKNAVERRSNRCNGNSGFEGQSRYVPSSGMSAKELCENDDLATSLVLDPYLGFQTHKMNTSAFPSRSSRHFSKSDSFSHNNPVRFRPIKGRQEELKEVIERFKKDEHLEKAFKCLTSGEWARHYFLNKNKMQEKLFKEHVFIYLRMFATDSGFEILPCNRYSSEQNGAKIVATKEWKRNDKIELLVGCIAELSEIEENMLLRHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVSTGRDTACVKALRDIEPGEEISCYYGDGFFGENNEFCECYTCERRGTGAFKSRVGLPAPAPVINSKYGLRETDKRLNRLKKLGDSSKNSDSQSVSSNTDADTTQEKNNATSNRKSSVGVKKNSKSRTLTRQSMSRIPASSNSTSSKLTHINNSRVPKKLKKPAKPLLSKIKLRNHCKRLEQKNASRKLEMGNLVLKEPKVVLYKNLPIKKDKEPEGPAQAAVASGCLTRHAAREHRQNPVRGAHSQGESSPCTYITRRSVRTRTNLKEASDIKLEPNTLNGYKSSVTEPCPDSGEQLQPAPVLQEEELAHETAQKGEAKCHKSDTGMSKKKSRQGKLVKQFAKIEESTPVHDSPGKDDAVPDLMGPHSDQGEHSGTVGVPVSYTDCAPSPVGCSVVTSDSFKTKDSFRTAKSKKKRRITRYDAQLILENNSGIPKLTLRRRHDSSSKTNDQENDGMNSSKISIKLSKDHDNDNNLYVAKLNNGFNSGSGSSSTKLKIQLKRDEENRGSYTEGLHENGVCCSDPLSLLESRMEVDDYSQYEEESTDDSSSSEGDEEEDDYDDDFEDDFIPLPPAKRLRLIVGKDSIDIDISSRRREDQSLRLNA | |||||||
Modified residue (large scale data) | 378 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 532 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 555 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 630 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 635 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts (via C-terminus) with FRG1
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q4FZB7 | TSPYL2 Q9H2G4 | 3 | EBI-1047962, EBI-947459 | |
XENO | Q4FZB7-1 | Ncoa2 Q61026 | 4 | EBI-15746366, EBI-688662 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-62 | Disordered | ||||
Sequence: MKWLGESKNMVVNGRRNGGKLSNDHQQNQSKLQHTGKDTLKAGKNAVERRSNRCNGNSGFEG | ||||||
Compositional bias | 19-36 | Polar residues | ||||
Sequence: GKLSNDHQQNQSKLQHTG | ||||||
Domain | 193-308 | SET | ||||
Sequence: SGFEILPCNRYSSEQNGAKIVATKEWKRNDKIELLVGCIAELSEIEENMLLRHGENDFSVMYSTRKNCAQLWLGPAAFINHDCRPNCKFVSTGRDTACVKALRDIEPGEEISCYYG | ||||||
Region | 363-444 | Disordered | ||||
Sequence: KLGDSSKNSDSQSVSSNTDADTTQEKNNATSNRKSSVGVKKNSKSRTLTRQSMSRIPASSNSTSSKLTHINNSRVPKKLKKP | ||||||
Compositional bias | 368-434 | Polar residues | ||||
Sequence: SKNSDSQSVSSNTDADTTQEKNNATSNRKSSVGVKKNSKSRTLTRQSMSRIPASSNSTSSKLTHINN | ||||||
Compositional bias | 590-613 | Basic and acidic residues | ||||
Sequence: LAHETAQKGEAKCHKSDTGMSKKK | ||||||
Region | 590-655 | Disordered | ||||
Sequence: LAHETAQKGEAKCHKSDTGMSKKKSRQGKLVKQFAKIEESTPVHDSPGKDDAVPDLMGPHSDQGEH | ||||||
Region | 716-740 | Disordered | ||||
Sequence: PKLTLRRRHDSSSKTNDQENDGMNS | ||||||
Compositional bias | 717-731 | Basic and acidic residues | ||||
Sequence: KLTLRRRHDSSSKTN | ||||||
Region | 816-850 | Disordered | ||||
Sequence: DDYSQYEEESTDDSSSSEGDEEEDDYDDDFEDDFI | ||||||
Compositional bias | 820-848 | Acidic residues | ||||
Sequence: QYEEESTDDSSSSEGDEEEDDYDDDFEDD |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q4FZB7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length885
- Mass (Da)99,188
- Last updated2019-05-08 v5
- Checksum13B0B6E35F751F48
Q4FZB7-2
- Name2
Q4FZB7-4
- Name3
Computationally mapped potential isoform sequences
There are 12 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J6S5 | C9J6S5_HUMAN | KMT5B | 814 | ||
F8WFA4 | F8WFA4_HUMAN | KMT5B | 159 | ||
C9JP58 | C9JP58_HUMAN | KMT5B | 118 | ||
B5MCB3 | B5MCB3_HUMAN | KMT5B | 402 | ||
C9JFG1 | C9JFG1_HUMAN | KMT5B | 322 | ||
H7BXP2 | H7BXP2_HUMAN | KMT5B | 103 | ||
A0A8V8TQA0 | A0A8V8TQA0_HUMAN | KMT5B | 136 | ||
A0A8V8TQB9 | A0A8V8TQB9_HUMAN | KMT5B | 713 | ||
A0A8V8TQY7 | A0A8V8TQY7_HUMAN | KMT5B | 159 | ||
A0A8V8TR96 | A0A8V8TR96_HUMAN | KMT5B | 106 | ||
A0A8V8TPR6 | A0A8V8TPR6_HUMAN | KMT5B | 75 | ||
B7WNX0 | B7WNX0_HUMAN | KMT5B | 370 |
Sequence caution
Features
Showing features for compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 19-36 | Polar residues | ||||
Sequence: GKLSNDHQQNQSKLQHTG | ||||||
Sequence conflict | 74 | in Ref. 4; AAD34080 | ||||
Sequence: A → P | ||||||
Sequence conflict | 79 | in Ref. 4; AAD34080 | ||||
Sequence: E → G | ||||||
Sequence conflict | 99 | in Ref. 4; AAD34080 | ||||
Sequence: K → Q | ||||||
Sequence conflict | 108 | in Ref. 3; AAG36937 | ||||
Sequence: R → W | ||||||
Sequence conflict | 123 | in Ref. 4; AAD34080 | ||||
Sequence: N → K | ||||||
Sequence conflict | 135 | in Ref. 4; AAD34080 | ||||
Sequence: E → G | ||||||
Alternative sequence | VSP_040034 | 274 | in isoform 3 | |||
Sequence: D → DLINS | ||||||
Alternative sequence | VSP_040035 | 275-885 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 368-434 | Polar residues | ||||
Sequence: SKNSDSQSVSSNTDADTTQEKNNATSNRKSSVGVKKNSKSRTLTRQSMSRIPASSNSTSSKLTHINN | ||||||
Alternative sequence | VSP_024051 | 392-393 | in isoform 2 | |||
Sequence: TS → SK | ||||||
Alternative sequence | VSP_024052 | 394-885 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 469 | in Ref. 5; BAA90905 | ||||
Sequence: K → E | ||||||
Sequence conflict | 483 | in Ref. 5; BAA90905 | ||||
Sequence: V → A | ||||||
Compositional bias | 590-613 | Basic and acidic residues | ||||
Sequence: LAHETAQKGEAKCHKSDTGMSKKK | ||||||
Compositional bias | 717-731 | Basic and acidic residues | ||||
Sequence: KLTLRRRHDSSSKTN | ||||||
Compositional bias | 820-848 | Acidic residues | ||||
Sequence: QYEEESTDDSSSSEGDEEEDDYDDDFEDD |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AP002992 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KC877427 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
KC877429 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC002522 EMBL· GenBank· DDBJ | AAH02522.2 EMBL· GenBank· DDBJ | mRNA | ||
BC012933 EMBL· GenBank· DDBJ | AAH12933.2 EMBL· GenBank· DDBJ | mRNA | ||
BC065287 EMBL· GenBank· DDBJ | AAH65287.1 EMBL· GenBank· DDBJ | mRNA | ||
BC087834 EMBL· GenBank· DDBJ | AAH87834.1 EMBL· GenBank· DDBJ | mRNA | ||
BC098121 EMBL· GenBank· DDBJ | AAH98121.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC099714 EMBL· GenBank· DDBJ | AAH99714.1 EMBL· GenBank· DDBJ | mRNA | ||
BC103498 EMBL· GenBank· DDBJ | AAI03499.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104483 EMBL· GenBank· DDBJ | AAI04484.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AF264782 EMBL· GenBank· DDBJ | AAG36937.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AF151843 EMBL· GenBank· DDBJ | AAD34080.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK000046 EMBL· GenBank· DDBJ | BAA90905.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AL512763 EMBL· GenBank· DDBJ | CAC21680.1 EMBL· GenBank· DDBJ | mRNA |