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histone-lysine N-methyltransferase 2A; lysine N-methyltransferase 2A; ALL-1; CXXC-type zinc finger protein 7; myeloid/lymphoid or mixed-lineage leukemia protein 1; trithorax-like protein; zinc finger protein HRX; contains: MLL cleavage product N320; N-terminal cleavage product of 320 kDa; p320; contains: MLL cleavage product C180; C-terminal cleavage product of 180 kD; p180 (KMT2A, ALL1, CXXC7, HRX, HTRX, MLL, MLL1)

Function: - histone methyltransferase - methylates Lys-4 of histone H3 - histone H3 Lys-4 methylation represents a specific tag for epigenetic transcriptional activation - promotes PPP1R15A-induced apoptosis - interacts with SBF1 & PPP1R15A - component of the MLL complex S-adenosyl-L-methionine + histone L-lysine S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine Structure: - belongs to the histone-lysine methyltransferase family, TRX/MLL subfamily - contains 3 A.T hook DNA-binding domains - contains 1 bromo domain - contains 1 CXXC-type Zn+2 finger - contains 3 PHD-type Zn+2 fingers - contains 1 post-SET domain - contains 1 SET domain Compartment: nucleus Alternative splicing: named isoforms=3 Expression: heart, lung, brain & T- & B-lymphocytes Pathology: - mutations in KMT2A associated with Wiedemann-Steiner syndrome - chromosomal aberrations involving MLL are a cause of acute leukemias translocation t(1;11)(q21;q23) with MLLT11/AF1Q translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21 translocation t(3,11)(q25,q23) with GMPS translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4 insertion ins (5;11)(q31;q13q23) with AFF4/AF5Q31 translocation t(5;11)(q12;q23) with AF5-alpha/CENPK translocation t(6;11)(q27;q23) with MLLT4/AF6 translocation t(9;11)(p22;q23) with MLLT3/AF9 translocation t(10;11)(p11.2;q23) with ABI1 translocation t(10;11)(p12;q23) with MLLT10/AF10 translocation t(11;15)(q23;q14) with CASC5 & ZFYVE19 translocation t(11;17)(q23;q21) with MLLT6/AF17 translocation t(11;19)(q23;p13.3) with ELL translocation t(11;19)(q23;p13.3) with MLLT1/ENL translocation t(11;19)(q23;p23) with GAS7 translocation t(X;11)(q13;q23) with FOXO4/AFX1 translocation t(3;11)(q28;q23) with LPP translocation t(10;11)(q22;q23) with TET1 translocation t(9;11)(q34;q23) with DAB2IP translocation t(4;11)(p12;q23) with FRYL - fusion proteins MLL-MLLT1, MLL-MLLT3 & MLL-ELL interact with PPP1R15A &, on the contrary to unfused MLL, inhibit PPP1R15A- induced apoptosis - chromosomal translocation t(4;11)(q21;q23) involving MLL with SEPT11 may be a cause of chronic neutrophilic leukemia

Related

myeloid/lymphoid, or mixed lineage, leukemia (MLL) gene, TRX1 gene, trithorax homolog, HRX gene or ALL1 gene

General

DNA-binding protein histone N-methyltransferase phosphoprotein proto oncogene protein transcription factor (TF) zinc finger protein

Properties

SIZE: entity length = 3969 aa MW = 432 kD COMPARTMENT: cell nucleus MOTIF: serine-rich region {17-102} MOTIF: serine residue (SEVERAL) glycine-rich region {137-143} Ser phosphorylation site {S153} A+T hook SITE: 169-180 Ser phosphorylation site {S197} A+T hook SITE: 217-227 A+T hook SITE: 301-309 Ser phosphorylation site {S518} proline-rich region SITE: 561-564 MOTIF: proline residue (SEVERAL) proline-rich region SITE: 568-571 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S680} Thr phosphorylation site {T840} Ser phosphorylation site {S926} Ser phosphorylation site {S1056} Zinc finger NAME: Zinc finger SITE: 1147-1195 EFFECTOR-BOUND: Zn+2 breakpoint {1334-1335} breakpoint {1362-1363} MOTIF: breakpoint {1362-1363} breakpoint {1362} breakpoint {1406-1407} Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1431-1482 EFFECTOR-BOUND: Zn+2 MOTIF: breakpoint {1444-1445} breakpoint {1444-1445} Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1479-1533 EFFECTOR-BOUND: Zn+2 Zn finger PHD-type NAME: Zn finger PHD-type SITE: 1566-1627 EFFECTOR-BOUND: Zn+2 Bromo; divergent {1703-1748} Thr phosphorylation site {T1845} Ser phosphorylation site {S1858} FYR N-terminal {2018-2074} Ser phosphorylation site {S2098} Thr phosphorylation site {T2147} Ser phosphorylation site {S2151} Ser phosphorylation site {S2201} Thr phosphorylation site {T2525} proteolytic site {2666-2667} proteolytic site {2718-2719} 9aaTAD {2847-2855} Ser phosphorylation site {S2955} Ser phosphorylation site {S3036} Thr phosphorylation site {T3372} Ser phosphorylation site {S3511} Ser phosphorylation site {S3515} FYR C-terminal {3666-3747} arginine residue {3765} SET domain {3829-3945} MOTIF: binding site SITE: 3839-3839 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 3841-3841 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 3883-3883 FOR-BINDING-OF: S-adenosylmethionine S-adenosyl-L-methionine binding {3906-3907} Zn+2-binding site SITE: 3909-3909 post-SET domain {3953-3969} MOTIF: Zn+2-binding site SITE: 3957-3957 binding site SITE: 3958-3958 FOR-BINDING-OF: S-adenosylmethionine Zn+2-binding site SITE: 3959-3959 Zn+2-binding site SITE: 3964-3964

Database Correlations

OMIM correlations UniProt Q03164 PFAM correlations LOCUS-LINK correlations Kegg hsa:4297 ENZYME 2.1.1.43

References

  1. UniProt :accession Q03164
  2. OMIM :accession 159555
  3. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/MLL.html
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/mll/

Component-of

MLL complex