Overview
| Uniprot ID | Q05086 |
|---|
| Protein Name | Ubiquitin-protein ligase E3A |
|---|
| Gene Name | UBE3A |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 123 |
KGARIDFKDVTYLTE |
| 89 |
LCDPHPSKKGASSAY |
Function
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24273172, PubMed:24728990, PubMed:30020076). Several substrates have been identified including the BMAL1, ARC, LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B (PubMed:10373495, PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24728990, PubMed:30020076). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins (PubMed:19233847). Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation (PubMed:24728990). Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation (PubMed:16772533). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (By similarity). Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (By similarity). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533)
Protein Sequence
10
MEKLHQCYWK
20
SGEPQSDDIE
30
ASRMKRAAAK
40
HLIERYYHQL
50
TEGCGNEACT
60
NEFCASCPTF
70
LRMDNNAAAI
80
KALELYKINA
90
KLCDPHPSKK
100
GASSAYLENS
110
KGAPNNSCSE
120
IKMNKKGARI
130
DFKDVTYLTE
140
EKVYEILELC
150
REREDYSPLI
160
RVIGRVFSSA
170
EALVQSFRKV
180
KQHTKEELKS
190
LQAKDEDKDE
200
DEKEKAACSA
210
AAMEEDSEAS
220
SSRIGDSSQG
230
DNNLQKLGPD
240
DVSVDIDAIR
250
RVYTRLLSNE
260
KIETAFLNAL
270
VYLSPNVECD
280
LTYHNVYSRD
290
PNYLNLFIIV
300
MENRNLHSPE
310
YLEMALPLFC
320
KAMSKLPLAA
330
QGKLIRLWSK
340
YNADQIRRMM
350
ETFQQLITYK
360
VISNEFNSRN
370
LVNDDDAIVA
380
ASKCLKMVYY
390
ANVVGGEVDT
400
NHNEEDDEEP
410
IPESSELTLQ
420
ELLGEERRNK
430
KGPRVDPLET
440
ELGVKTLDCR
450
KPLIPFEEFI
460
NEPLNEVLEM
470
DKDYTFFKVE
480
TENKFSFMTC
490
PFILNAVTKN
500
LGLYYDNRIR
510
MYSERRITVL
520
YSLVQGQQLN
530
PYLRLKVRRD
540
HIIDDALVRL
550
EMIAMENPAD
560
LKKQLYVEFE
570
GEQGVDEGGV
580
SKEFFQLVVE
590
EIFNPDIGMF
600
TYDESTKLFW
610
FNPSSFETEG
620
QFTLIGIVLG
630
LAIYNNCILD
640
VHFPMVVYRK
650
LMGKKGTFRD
660
LGDSHPVLYQ
670
SLKDLLEYEG
680
NVEDDMMITF
690
QISQTDLFGN
700
PMMYDLKENG
710
DKIPITNENR
720
KEFVNLYSDY
730
ILNKSVEKQF
740
KAFRRGFHMV
750
TNESPLKYLF
760
RPEEIELLIC
770
GSRNLDFQAL
780
EETTEYDGGY
790
TRDSVLIREF
800
WEIVHSFTDE
810
QKRLFLQFTT
820
GTDRAPVGGL
830
GKLKMIIAKN
840
GPDTERLPTS
850
HTCFNVLLLP
860
EYSSKEKLKE
870
RLLKAITYAK
GFGML
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0098978 |
glutamatergic synapse |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0099524 |
postsynaptic cytosol |
| Cellular Component |
GO:0000502 |
proteasome complex |
| Cellular Component |
GO:0008021 |
synaptic vesicle |
| Molecular Function |
GO:0003713 |
transcription coactivator activity |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0007420 |
brain development |
| Biological Process |
GO:1904262 |
negative regulation of TORC1 signaling |
| Biological Process |
GO:1905528 |
positive regulation of Golgi lumen acidification |
| Biological Process |
GO:0031398 |
positive regulation of protein ubiquitination |
| Biological Process |
GO:0050847 |
progesterone receptor signaling pathway |
| Biological Process |
GO:0043161 |
proteasome-mediated ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0051865 |
protein autoubiquitination |
| Biological Process |
GO:0070936 |
protein K48-linked ubiquitination |
| Biological Process |
GO:0000209 |
protein polyubiquitination |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0042752 |
regulation of circadian rhythm |
| Biological Process |
GO:0048167 |
regulation of synaptic plasticity |
| Biological Process |
GO:2000058 |
regulation of ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0032570 |
response to progesterone |
| Biological Process |
GO:0048511 |
rhythmic process |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.