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IID00379
 UniprotQ03164
ProteinHistone-lysine N-methyltransferase 2A
GeneKMT2A
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
3969
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 6-25 Hetero dimer : IID00404Complex
 Evidence X-RAY 3u85 B Reference
       Region 3u85 B 6-13 order
       Region 3u85 B 14-25 disorder
 Evidence X-RAY 4gq6 B Reference
       Region 4gq6 B 6-15 order
Seq 6-16,24-39,103-153 Hetero trimer : IID00404Complex,IID00408Complex
 Evidence X-RAY 3u88 N Reference
       Region 3u88 N 6-16 order
       Region 3u88 N 24-39 order
       Region 3u88 N 103-134 order
       Region 3u88 N 135-153 disorder
 Evidence X-RAY 3u88 M Reference
       Region 3u88 M 6-16 order
       Region 3u88 M 24-39 order
       Region 3u88 M 103-135 order
       Region 3u88 M 136-153 disorder
Seq 110-160 Monomer : IID00408Complex
 Evidence NMR 2mtn A Reference
       Region 2mtn A 110-121 disorder
       Region 2mtn A 122-154 order
       Region 2mtn A 122-126 high_rmsd
       Region 2mtn A 135-145 high_rmsd
       Region 2mtn A 154-155 high_rmsd
       Region 2mtn A 155-160 disorder
Seq 140-160 Hetero dimer : IID00408Complex
 Evidence NMR 2msr A Reference
       Region 2msr A 140-160 order
Seq 1143-1214 Monomer :
 Evidence X-RAY 4nw3 A Reference
       Region 4nw3 A 1147-1149 disorder
       Region 4nw3 A 1150-1200 order
       Region 4nw3 A 1201-1204 disorder
 Evidence NMR 2kkf A Reference
       Region 2kkf A 1147-1203 order
       Region 2kkf A 1147-1149 high_rmsd
       Region 2kkf A 1202-1203 high_rmsd
 Evidence NMR 2jyi A Reference
       Region 2jyi A 1147-1203 order
       Region 2jyi A 1147-1150 high_rmsd
       Region 2jyi A 1201-1203 high_rmsd
 Evidence NMR 2j2s A Reference
       Region 2j2s A 1143-1214 order
       Region 2j2s A 1143-1148 high_rmsd
       Region 2j2s A 1204-1214 high_rmsd
Seq 1564-1628 Monomer :
 Evidence NMR 2kyu A Reference
       Region 2kyu A 1564-1628 order
       Region 2kyu A 1564-1565 high_rmsd
       Region 2kyu A 1628-1628 high_rmsd
Seq 1566-1665,1703-1784 Monomer :
 Evidence X-RAY 3lqh A Reference
       Region 3lqh A 1566-1664 order
       Region 3lqh A 1665-1665 disorder
       Region 3lqh A 1703-1703 disorder
       Region 3lqh A 1704-1778 order
       Region 3lqh A 1779-1784 disorder
Seq 1566-1665,1703-1784 Hetero dimer : IID00062Complex
 Evidence X-RAY 3lqj B Reference
       Region 3lqj B 1566-1663 order
       Region 3lqj B 1664-1665 disorder
       Region 3lqj B 1703-1778 order
       Region 3lqj B 1779-1784 disorder
 Evidence X-RAY 3lqj A Reference
       Region 3lqj A 1566-1664 order
       Region 3lqj A 1665-1665 disorder
       Region 3lqj A 1703-1779 order
       Region 3lqj A 1780-1784 disorder
 Evidence X-RAY 3lqi C Reference
       Region 3lqi C 1566-1663 order
       Region 3lqi C 1664-1665 disorder
       Region 3lqi C 1703-1784 order
 Evidence X-RAY 3lqi B Reference
       Region 3lqi B 1566-1665 order
       Region 3lqi B 1703-1703 disorder
       Region 3lqi B 1704-1779 order
       Region 3lqi B 1780-1784 disorder
 Evidence X-RAY 3lqi A Reference
       Region 3lqi A 1566-1665 order
       Region 3lqi A 1703-1703 disorder
       Region 3lqi A 1704-1778 order
       Region 3lqi A 1779-1784 disorder
Seq 1585-1628 Monomer : Q9UNP9
 Evidence NMR 2ku7 A Reference
       Region 2ku7 A 1585-1602 disorder
       Region 2ku7 A 1585-1600 high_rmsd
       Region 2ku7 A 1603-1619 order
       Region 2ku7 A 1620-1628 disorder
       Region 2ku7 A 1621-1628 high_rmsd
Seq 2840-2858 Hetero dimer : IID00092Complex
 Evidence NMR 2lxs B Reference
       Region 2lxs B 2840-2858 order
       Region 2lxs B 2840-2842 high_rmsd
Seq 2840-2858 Hetero trimer : IID00092Complex,IID00442Complex
 Evidence NMR 2lxt B Reference
       Region 2lxt B 2840-2858 order
       Region 2lxt B 2840-2842 high_rmsd
Seq 2840-2869 Hetero trimer : IID50008Complex
 Evidence NMR 2agh C Reference
       Region 2agh C 2840-2869 order
       Region 2agh C 2840-2842 high_rmsd
       Region 2agh C 2860-2869 high_rmsd
Seq 3755-3771 Hetero dimer : IID00377Complex
 Evidence X-RAY 4esg C Reference
       Region 4esg C 3755-3770 order
       Region 4esg C 3771-3771 disorder
 Evidence X-RAY 4esg D Reference
       Region 4esg D 3755-3770 order
       Region 4esg D 3771-3771 disorder
Seq 3761-3770 Hetero trimer : IID00377Complex
 Evidence X-RAY 3p4f C Reference
       Region 3p4f C 3761-3761 disorder
       Region 3p4f C 3762-3770 order
Seq 3762-3776 Hetero dimer : IID00377Complex
 Evidence X-RAY 3emh B Reference
       Region 3emh B 3764-3769 order
       Region 3emh B 3770-3776 disorder
 Evidence X-RAY 3eg6 C Reference
       Region 3eg6 C 3762-3770 order
       Region 3eg6 C 3771-3773 disorder
Seq 3785-3969 Monomer :
 Evidence X-RAY 2w5y A Reference
       Region 2w5y A 3785-3792 disorder
       Region 2w5y A 3793-3946 order
       Region 2w5y A 3947-3953 disorder
       Region 2w5y A 3954-3969 order
 Evidence X-RAY 5f5e A Reference
       Region 5f5e A 3813-3813 disorder
       Region 5f5e A 3814-3945 order
       Region 5f5e A 3946-3953 disorder
       Region 5f5e A 3954-3969 order
Seq 3785-3969 Hetero dimer : P68433
 Evidence X-RAY 2w5z A Reference
       Region 2w5z A 3785-3789 disorder
       Region 2w5z A 3790-3969 order
Seq 3813-3969 Hetero trimer : IID00387Complex,Q9UBL3
 Evidence X-RAY 5f6l A Reference
       Region 5f6l A 3813-3813 disorder
       Region 5f6l A 3814-3950 order
       Region 5f6l A 3951-3953 disorder
       Region 5f6l A 3954-3969 order
SeqProS verified 13-15 Hetero dimer : IID00404Complex
       Region 4gq6 B 6-15 order
       Region 3u85 B 14-25 disorder
SeqProS verified 1620-1628 The region is disordered in the complex with CyP33 RRM domain. Hetero dimer : IID00062Complex
       Region 3lqi C 1566-1663 order
       Region 3lqj A 1566-1664 order
       Region 3lqj B 1566-1663 order
       Region 2ku7 A 1620-1628 disorder
SeqProS verified 1620-1628 The region is ordered in the free state but disordered in the complex with CyP33 RRM domain. :
       Region 2kyu A 1564-1628 order
       Region 2ku7 A 1620-1628 disorder
SeqProS verified 1620-1628 The region is disordered in the complex with CyP33 RRM domain. :
       Region 3lqh A 1566-1664 order
       Region 2ku7 A 1620-1628 disorder
SeqProS possible 2842-2858 This region is described to be disordered in the absence of CBP KIX domain (PubMed=15738986 ). Hetero trimer : IID00092Complex,IID00442Complex
       Region 2lxt B 2840-2858 order
SeqProS possible 2842-2858 This region is described to be disordered in the absence of CBP KIX domain (PubMed=15738986 ). Hetero dimer : IID00092Complex
       Region 2lxs B 2840-2858 order
SeqProS possible 2842-2858 This region is described to be disordered in the absence of CBP KIX domain (PubMed=15738986 ). Hetero trimer : IID50008Complex
       Region 2agh C 2840-2869 order
SeqProS possible 3762-3770 This region is described to be disordered in the free state. (PubMed=20716525) Hetero dimer : IID00377Complex
       Region 3emh B 3764-3769 order
SeqProS possible 3762-3770 This region is described to be disordered in the free state. (PubMed=20716525) Hetero trimer : IID00377Complex
       Region 3p4f C 3762-3770 order
Seqphosphorylation
    136-136 Phosphoserine; by CK2
    142-142 Phosphoserine; by CK2
    153-153 Phosphoserine
    197-197 Phosphoserine
    518-518 Phosphoserine
    680-680 Phosphoserine
    840-840 Phosphothreonine
    926-926 Phosphoserine
    1056-1056 Phosphoserine
    1837-1837 Phosphoserine
    1845-1845 Phosphothreonine
    1858-1858 Phosphoserine
    2098-2098 Phosphoserine
    2147-2147 Phosphothreonine
    2151-2151 Phosphoserine
    2201-2201 Phosphoserine
    2525-2525 Phosphothreonine
    2611-2611 Phosphoserine
    2796-2796 Phosphoserine
    2955-2955 Phosphoserine
    3036-3036 Phosphoserine
    3372-3372 Phosphothreonine
    3511-3511 Phosphoserine
    3515-3515 Phosphoserine
    3527-3527 Phosphoserine
Seqacetylation
    239-239 N6-acetyllysine
    373-373 N6-acetyllysine
    636-636 N6-acetyllysine
    1130-1130 N6-acetyllysine
    1235-1235 N6-acetyllysine
    2958-2958 N6-acetyllysine
    3462-3462 N6-acetyllysine
 
Prediction
NeProc
Disorder 1-1153,1202-1424,1644-1647,1657-1726,1743-1753,1759-1768,1774-1862,2102-2616,2652-3659,3771-3811
Order 1154-1201,1425-1626,1631-1643,1648-1656,1727-1742,1754-1758,1769-1773,1863-2101,2617-2651,3660-3770,3812-3969
ProS 1-12,29-40,103-135,146-158,178-181,298-312,428-433,584-593,613-621,648-660,699-713,794-797,836-840,1019-1041,1064-1106,1126-1131,1147-1153,1202-1210,1396-1424,1644-1647,1657-1665,1673-1726,1759-1768,1774-1808,1820-1837,1846-1857,2140-2168,2173-2185,2279-2282,2319-2324,2368-2381,2393-2401,2423-2439,2462-2465,2519-2527,2586-2616,2657-2671,2678-2693,2714-2732,2747-2759,2780-2788,2819-2835,2841-2859,2873-2876,2881-2902,2923-2931,2993-2997,3556-3560,3640-3659,3771-3783,3802-3811
Pfam Hmmer
PF02008 1147-1194 1.4e-24
PF00628 1433-1482 3.7e-07
PF00628 1483-1533 3.2e-07
PF00628 1568-1627 4.7e-12
PF05964 2023-2073 3e-19
PF05965 3666-3749 4.1e-36
PF00856 3823-3951 1e-55
SEG 14-29 ,41-104 ,134-144 ,171-185 ,201-221 ,452-491 ,526-537 ,546-577 ,662-676 ,762-790 ,820-841 ,869-895 ,992-1008 ,1207-1243 ,1250-1273 ,1306-1315 ,1320-1344 ,1354-1373 ,1515-1523 ,1817-1851 ,1991-2002 ,2182-2196 ,2283-2302 ,2350-2364 ,2614-2625 ,2649-2660 ,2796-2807 ,2831-2840 ,2863-2885 ,2909-2916 ,3122-3141 ,3171-3182 ,3307-3316 ,3328-3345 ,3348-3357 ,3411-3425 ,3508-3541 ,3574-3583 ,3796-3800
Function
Function in SwissProt
Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145).
Biological Process
See also
Diagram with PDB data
CREB1/CRBBP/KMT2AAllosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core