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Overview

Uniprot IDQ5M7A4
Protein NameUbiquitin-like modifier-activating enzyme 5
Gene NameUba5
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
40 CGRTRIQKMSDEVVD

Function

E1-like enzyme which specifically catalyzes the first step in ufmylation. 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. Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer. Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding. Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism. Ufmylation plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (By similarity). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity)

Protein Sequence

10 MAESVERLLQ 20 RVEELEQELA 30 RERSRRIAGD 40 GHCGRTRIQK 50 MSDEVVDSNP 60 YSRLMALKRM 70 GVVSDYEKIR 80 TYAVAIVGVG 90 GVGSVTAEML 100 TRCGIGKLLL 110 FDYDKVELAN 120 MNRLFFQPYQ 130 AGMSKVQAAE 140 HTLRSINPDV 150 LFEVHNYNIT 160 TVEHFEHFMN 170 RISNGGLEEG 180 QPVDLVLSCV 190 DNFEARMAIN 200 TACNELGQTW 210 MESGVSENAV 220 SGHIQLMVPG 230 ESACFACAPP 240 LVVASNIDEK 250 TLKREGVCAA 260 SLPTTMGVVA 270 GILVQNVLKF 280 LLKFGTVSFY 290 LGYNAMQDFF 300 PTMFMKPNPQ 310 CDDKNCRKQQ 320 EEYKKRAPAQ 330 PTQETAPQEE 340 EEVVHEDNEW 350 GIELVSEVSE 360 EELKNSSGPV 370 PTLPEGITVA 380 YTVPKKREDS 390 VSEVTVEDSG 400 ESLEDLMARM KKM

Gene Ontology

Classification GO ID Description
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:0071566 UFM1 activating enzyme 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] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.