Overview
| Uniprot ID | Q9GZZ9 |
|---|
| Protein Name | Ubiquitin-like modifier-activating enzyme 5 |
|---|
| Gene Name | UBA5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 127 |
PHQAGLSKVQAAEHT |
| 42 |
GGRVRIEKMSSEVVD |
Function
E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:15071506, PubMed:18442052, PubMed:20368332, PubMed:25219498, PubMed:26929408, PubMed:27545674, PubMed:27545681, PubMed:27653677, PubMed:30412706, PubMed:30626644, PubMed:34588452). Activates UFM1 by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a UFM1-E1 thioester and free AMP (PubMed:20368332, PubMed:26929408, PubMed:27653677, PubMed:30412706). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:27653677). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (PubMed:27653677, PubMed:34588452). Ufmylation plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:30412706, PubMed:32160526, PubMed:35394863). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity)
Protein Sequence
10
MAESVERLQQ
20
RVQELERELA
30
QERSLQVPRS
40
GDGGGGRVRI
50
EKMSSEVVDS
60
NPYSRLMALK
70
RMGIVSDYEK
80
IRTFAVAIVG
90
VGGVGSVTAE
100
MLTRCGIGKL
110
LLFDYDKVEL
120
ANMNRLFFQP
130
HQAGLSKVQA
140
AEHTLRNINP
150
DVLFEVHNYN
160
ITTVENFQHF
170
MDRISNGGLE
180
EGKPVDLVLS
190
CVDNFEARMT
200
INTACNELGQ
210
TWMESGVSEN
220
AVSGHIQLII
230
PGESACFACA
240
PPLVVAANID
250
EKTLKREGVC
260
AASLPTTMGV
270
VAGILVQNVL
280
KFLLNFGTVS
290
FYLGYNAMQD
300
FFPTMSMKPN
310
PQCDDRNCRK
320
QQEEYKKKVA
330
ALPKQEVIQE
340
EEEIIHEDNE
350
WGIELVSEVS
360
EEELKNFSGP
370
VPDLPEGITV
380
AYTIPKKQED
390
SVTELTVEDS
400
GESLEDLMAK
MKNM
Gene Ontology
| Classification |
GO ID |
Description |
| Molecular Function |
GO:0071566 |
UFM1 activating enzyme activity |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005789 |
endoplasmic reticulum membrane |
| Cellular Component |
GO:0005794 |
Golgi apparatus |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0042803 |
protein homodimerization activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0030218 |
erythrocyte differentiation |
| Biological Process |
GO:0030219 |
megakaryocyte differentiation |
| Biological Process |
GO:0050905 |
neuromuscular process |
| Biological Process |
GO:1990592 |
protein K69-linked ufmylation |
| Biological Process |
GO:0071569 |
protein ufmylation |
| Biological Process |
GO:0033146 |
regulation of intracellular estrogen receptor signaling pathway |
| Biological Process |
GO:0032649 |
regulation of type II interferon production |
| Biological Process |
GO:0034976 |
response to endoplasmic reticulum stress |
| Biological Process |
GO:0061709 |
reticulophagy |
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.