UFL1

UniProt ID: O94874
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

UFL1 (E3 UFM1-protein ligase 1; also called Maxer, NLBP, RCAD, KIAA0776) is the E3 ligase of the UFM1 (ufmylation) cascade, which catalyzes covalent attachment of the ubiquitin-like modifier UFM1 to substrate lysines. UFL1 is the catalytic component of the UFM1 ribosome E3 ligase (UREL) complex together with its obligate cofactor DDRGK1/UFBP1 and CDK5RAP3; DDRGK1 tethers the complex to the endoplasmic-reticulum membrane. Acting as a non-canonical scaffold-type E3, UFL1 activates the E2 enzyme UFC1 to transfer UFM1 onto substrates. Its principal physiological substrate is the 60S ribosomal protein RPL26/uL24, where mono-ufmylation of RPL26 on ER-bound ribosomes weakens the junction between post-termination or stalled 60S subunits and SEC61 translocons, promoting release and recycling of the large subunit and supporting ribosome-associated protein quality control. UFL1 also drives reticulophagy (ER-phagy) and the response to ER stress through ufmylation of ER proteins such as CYB5R3 and RPN1, participates in the DNA-damage response (ufmylating histone H4 and MRE11 to promote ATM activation), and ufmylates additional substrates including TP53/p53, PD-L1 and PD-1, contributing to protein stabilization and immune regulation. UFL1 acts mainly at the ER membrane but is also recruited to sites of DNA damage in the nucleus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0071568 UFM1 transferase activity
IBA
GO_REF:0000033
ACCEPT
Summary: UFM1 transferase activity is a near-synonymous description of UFL1's E3 UFM1-ligase activity (transfer of UFM1 to substrate).
Reason: UFL1 is the E3 that mediates UFM1 transfer to substrates; this MF term captures that activity, with GO:0061666 (UFM1 ligase activity) being the most precise E3-step term.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061709 reticulophagy
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: UFL1-mediated ufmylation drives reticulophagy (ER-phagy).
Reason: A genuine downstream process of ER ufmylation; non-core relative to the E3 ligase activity.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Involved in reticulophagy in response to endoplasmic reticulum stress
GO:0005789 endoplasmic reticulum membrane
IBA
GO_REF:0000033
ACCEPT
Summary: UFL1 acts at the ER membrane as part of the DDRGK1-tethered UREL complex.
Reason: ER membrane is the principal site of UFL1 catalytic action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0034976 response to endoplasmic reticulum stress
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: UFL1-mediated ufmylation functions in the ER stress response.
Reason: Valid pathway context; non-core relative to the E3 ligase activity.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Ufmylation in response to endoplasmic reticulum stress
GO:0005634 nucleus
IEA
GO_REF:0000044
ACCEPT
Summary: UFL1 is recruited to the nucleus/sites of DNA damage; nuclear localization is documented experimentally.
Reason: Consistent with UFL1's DNA-damage role at double-strand breaks.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Nucleus
GO:0005694 chromosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UFL1 localizes to chromosomes/sites of double-strand breaks during the DNA-damage response.
Reason: Documented chromatin localization linked to the DNA-damage role; non-core relative to the principal ER-membrane site of action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Chromosome
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044
ACCEPT
Summary: ER membrane localization, the principal compartment of UFL1.
Reason: Correct compartment; corroborated by experimental evidence.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005829 cytosol
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Cytosolic localization, consistent with UFL1's cytoplasm-facing activity.
Reason: Documented cytoplasmic pool; the principal site of action is the ER membrane.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Cytoplasm, cytosol
GO:0061666 UFM1 ligase activity
IEA
GO_REF:0000002
ACCEPT
Summary: UFM1 ligase (E3) activity is the core molecular function of UFL1; this electronic annotation is corroborated by extensive direct experimental evidence.
Reason: UFL1 is the E3 ligase of the ufmylation cascade; this is its core MF.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IEA
GO_REF:0000002
ACCEPT
Summary: UFL1 is the E3 of protein ufmylation.
Reason: Core process annotation for the E3 ligase.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: Binary interactome interaction. Bare protein binding is uninformative.
Reason: Records a real interaction but the term is uninformative; core MF is UFM1 ligase activity.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: BioPlex affinity-purification interactions. Bare protein binding is uninformative.
Reason: Real interactions but uninformative term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781
GO:0005515 protein binding
IPI
PMID:37595036
Mechanistic insights into the roles of the UFM1 E3 ligase co...
KEEP AS NON CORE
Summary: Interactions with UREL-complex partners. Bare term uninformative.
Reason: Real cascade interactions; non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:37595036
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
KEEP AS NON CORE
Summary: Multimodal cell-maps interaction. Bare protein binding is uninformative.
Reason: Real interaction record but uninformative term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054
GO:0005737 cytoplasm
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Cytoplasmic localization (electronic).
Reason: Documented cytoplasmic pool; principal site is the ER membrane.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Cytoplasm, cytosol
GO:0010508 positive regulation of autophagy
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: UFL1 promotes autophagy/reticulophagy via ER ufmylation, inferred electronically.
Reason: Plausible downstream process; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Involved in reticulophagy in response to endoplasmic reticulum stress
GO:0030218 erythrocyte differentiation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Role in erythroid/hematopoietic differentiation inferred by similarity.
Reason: Plausible by orthology; downstream developmental role, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Required for hematopoietic stem cell function and hematopoiesis
GO:0034976 response to endoplasmic reticulum stress
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: ER stress response (electronic), corroborated experimentally.
Reason: Valid pathway context; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Ufmylation in response to endoplasmic reticulum stress
GO:0043005 neuron projection
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Neuron-projection localization inferred electronically from the ortholog.
Reason: Electronically inferred; peripheral to the core ER-membrane site of action.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0043005 neuron projection cellular_component
GO:0050868 negative regulation of T cell activation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: UFL1 negatively regulates T-cell activation via ufmylation/stabilization of PD-1, inferred electronically and shown experimentally.
Reason: Documented immune-regulatory role; downstream, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1
GO:0060218 hematopoietic stem cell differentiation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Role in hematopoietic stem cell function inferred by similarity.
Reason: Plausible by orthology; downstream developmental role, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Required for hematopoietic stem cell function and hematopoiesis
GO:0050821 protein stabilization
IDA
PMID:32807901
UFMylation maintains tumour suppressor p53 stability by anta...
KEEP AS NON CORE
Summary: UFL1-mediated ufmylation of TP53/p53 stabilizes it by antagonizing its ubiquitination.
Reason: A documented substrate-specific stabilization effect; downstream of the E3 activity, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Mediates ufmylation of TP53/p53, promoting its stability
GO:0005783 endoplasmic reticulum
IDA
GO_REF:0000052
ACCEPT
Summary: Direct (HPA) ER localization.
Reason: IDA-supported ER localization consistent with site of action.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005783 endoplasmic reticulum cellular_component ECO:0000314 IDA GO_REF:0000052
GO:0005694 chromosome
EXP
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: UFL1 localizes to chromatin/double-strand-break sites during the DNA-damage response (histone H4 ufmylation/ATM activation).
Reason: Documented DNA-damage-associated localization; non-core relative to the principal ER-membrane site.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
recruited to double-strand break sites following DNA damage
GO:0005789 endoplasmic reticulum membrane
EXP
PMID:20018847
A novel type of E3 ligase for the Ufm1 conjugation system.
ACCEPT
Summary: Experimental ER membrane localization from the paper identifying UFL1 as the UFM1 E3 ligase.
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane
EXP
PMID:20164180
A novel LZAP-binding protein, NLBP, inhibits cell invasion.
ACCEPT
Summary: Experimental ER membrane localization (NLBP/UFL1).
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane
EXP
PMID:20228063
A novel C53/LZAP-interacting protein regulates stability of ...
ACCEPT
Summary: Experimental ER membrane localization (RCAD/UFL1).
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0071569 protein ufmylation
IDA
PMID:36121123
A non-canonical scaffold-type E3 ligase complex mediates pro...
ACCEPT
Summary: UFL1 is the E3 mediating ufmylation in the scaffold-type complex.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:1990234 transferase complex
IPI
PMID:36121123
A non-canonical scaffold-type E3 ligase complex mediates pro...
ACCEPT
Summary: UFL1 is the catalytic component of the UREL transferase complex.
Reason: UFL1 is a bona fide subunit of the UFM1 E3 ligase (transferase) complex.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Catalytic component of the UFM1 ribosome E3 ligase (UREL) complex
GO:0005783 endoplasmic reticulum
IDA
PMID:37795761
UFMylation of HRD1 regulates endoplasmic reticulum homeostas...
ACCEPT
Summary: UFL1 acts at the ER (HRD1 ufmylation study).
Reason: Direct evidence for the site of action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006974 DNA damage response
IDA
PMID:32807901
UFMylation maintains tumour suppressor p53 stability by anta...
KEEP AS NON CORE
Summary: UFL1 participates in the DNA-damage response (p53 stabilization context).
Reason: A genuine but downstream role of UFL1's ufmylation activity; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Also involved in the response to DNA damage
GO:0061666 UFM1 ligase activity
IDA
PMID:32807901
UFMylation maintains tumour suppressor p53 stability by anta...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of p53).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061666 UFM1 ligase activity
IDA
PMID:35753586
P4HB UFMylation regulates mitochondrial function and oxidati...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of P4HB).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061666 UFM1 ligase activity
IDA
PMID:37795761
UFMylation of HRD1 regulates endoplasmic reticulum homeostas...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of HRD1/SYVN1).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IDA
PMID:32807901
UFMylation maintains tumour suppressor p53 stability by anta...
ACCEPT
Summary: UFL1 ufmylates p53.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Mediates ufmylation of TP53/p53, promoting its stability
GO:0071569 protein ufmylation
IDA
PMID:35753586
P4HB UFMylation regulates mitochondrial function and oxidati...
ACCEPT
Summary: UFL1 ufmylates P4HB.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IDA
PMID:37795761
UFMylation of HRD1 regulates endoplasmic reticulum homeostas...
ACCEPT
Summary: UFL1 ufmylates HRD1/SYVN1.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SYVN1/HRD1
GO:0002841 negative regulation of T cell mediated immune response to tumor cell
IDA
PMID:38377992
UFL1 ablation in T cells suppresses PD-1 UFMylation to enhan...
KEEP AS NON CORE
Summary: UFL1 ufmylates/stabilizes PD-1, suppressing anti-tumor T-cell immunity.
Reason: A documented immune-regulatory role downstream of the E3 activity; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1
GO:0050821 protein stabilization
IDA
PMID:38377992
UFL1 ablation in T cells suppresses PD-1 UFMylation to enhan...
KEEP AS NON CORE
Summary: UFL1 ufmylation stabilizes PD-1.
Reason: Substrate-specific stabilization downstream of the E3 activity; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
mediating ufmylation and stabilization of PDCD1/PD-1
GO:0050868 negative regulation of T cell activation
IDA
PMID:38377992
UFL1 ablation in T cells suppresses PD-1 UFMylation to enhan...
KEEP AS NON CORE
Summary: UFL1 negatively regulates T-cell activation via PD-1 ufmylation.
Reason: Documented immune-regulatory role; downstream, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Acts as a negative regulator of T-cell activation by mediating ufmylation and stabilization of PDCD1/PD-1
GO:0061666 UFM1 ligase activity
IDA
PMID:36893266
Dysregulation of PD-L1 by UFMylation imparts tumor immune ev...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of PD-L1/CD274).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
CD274/PD-L1
GO:0061666 UFM1 ligase activity
IDA
PMID:38377992
UFL1 ablation in T cells suppresses PD-1 UFMylation to enhan...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of PD-1/PDCD1).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
PDCD1/PD-1
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:36543799
The UFM1 system regulates ER-phagy through the ufmylation of...
ACCEPT
Summary: UFL1 acts at the ER membrane within UREL (CYB5R3/ER-phagy study).
Reason: Direct evidence for the site of action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0045732 positive regulation of protein catabolic process
IDA
PMID:36543799
The UFM1 system regulates ER-phagy through the ufmylation of...
KEEP AS NON CORE
Summary: UFL1-mediated ufmylation promotes lysosomal degradation of ufmylated ER proteins (reticulophagy).
Reason: Downstream consequence of ER ufmylation; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
thereby promoting lysosomal degradation of ufmylated proteins
GO:0061666 UFM1 ligase activity
IDA
PMID:36543799
The UFM1 system regulates ER-phagy through the ufmylation of...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of CYB5R3).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061666 UFM1 ligase activity
IMP
PMID:37036982
RPL26/uL24 UFMylation is essential for ribosome-associated q...
ACCEPT
Summary: Functional evidence for UFL1 UFM1 ligase activity in ER ribosome-associated quality control (RPL26 ufmylation).
Reason: Direct functional support for the core E3 ligase activity.
Supporting Evidence:
PMID:37036982
RQC-dependent degradation of ER-APs strictly requires conjugation of the
GO:0061666 UFM1 ligase activity
IDA
PMID:37595036
Mechanistic insights into the roles of the UFM1 E3 ligase co...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity in the mechanistic UREL study.
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IDA
PMID:36543799
The UFM1 system regulates ER-phagy through the ufmylation of...
ACCEPT
Summary: UFL1 ufmylates CYB5R3.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IMP
PMID:37036982
RPL26/uL24 UFMylation is essential for ribosome-associated q...
ACCEPT
Summary: UFL1 required for RPL26 ufmylation in ER-RQC.
Reason: Functional evidence for the core process.
Supporting Evidence:
PMID:37036982
UFMylation of translocon-bound 60S subunits modulates the RTJ
GO:0071569 protein ufmylation
IDA
PMID:37595036
Mechanistic insights into the roles of the UFM1 E3 ligase co...
ACCEPT
Summary: UFL1 mediates ufmylation in the mechanistic UREL study.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0072344 rescue of stalled cytosolic ribosome
IMP
PMID:37036982
RPL26/uL24 UFMylation is essential for ribosome-associated q...
ACCEPT
Summary: UFL1, via RPL26 ufmylation, contributes to release/recycling of stalled 60S ribosomes at the ER, supporting ribosome-associated quality control. This is the major biological process of UFL1.
Reason: A core physiological role of UFL1 ufmylation - ribosome recycling/RQC at the ER-translocon junction.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome
GO:0072344 rescue of stalled cytosolic ribosome
IDA
PMID:37595036
Mechanistic insights into the roles of the UFM1 E3 ligase co...
ACCEPT
Summary: UFL1 contributes to ribosome recycling/RQC via RPL26 ufmylation.
Reason: Core physiological role of UFL1 ufmylation.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome
GO:0140501 positive regulation of reticulophagy
IDA
PMID:36543799
The UFM1 system regulates ER-phagy through the ufmylation of...
KEEP AS NON CORE
Summary: UFL1-mediated ufmylation positively regulates reticulophagy.
Reason: Valid downstream process; non-core relative to the E3 activity.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Involved in reticulophagy in response to endoplasmic reticulum stress
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:38383785
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ...
ACCEPT
Summary: UFL1 acts at the ER membrane within the UREL-60S complex.
Reason: Direct structural evidence for the site of action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:38383789
The UFM1 E3 ligase recognizes and releases 60S ribosomes fro...
ACCEPT
Summary: UFL1 acts at the ER membrane within the UREL-60S complex.
Reason: Direct structural evidence for the site of action.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0032790 ribosome disassembly
IDA
PMID:38383785
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ...
KEEP AS NON CORE
Summary: UFL1-mediated RPL26 ufmylation promotes release/dissociation of 60S from the ER translocon.
Reason: Genuine role in 60S release/recycling; captured as downstream process, non-core relative to the E3 MF.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
promoting release and recycling of the large ribosomal subunit
GO:0032790 ribosome disassembly
IDA
PMID:38383789
The UFM1 E3 ligase recognizes and releases 60S ribosomes fro...
KEEP AS NON CORE
Summary: UFL1-mediated RPL26 ufmylation promotes 60S release from the ER translocon.
Reason: Genuine role in 60S release/recycling; downstream process, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
promoting release and recycling of the large ribosomal subunit
GO:0061666 UFM1 ligase activity
IDA
PMID:30626644
Ribosomal protein RPL26 is the principal target of UFMylatio...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (RPL26 is the principal target).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
PMID:30626644
Ribosomal protein RPL26 is the principal target of UFMylation
GO:0061666 UFM1 ligase activity
IDA
PMID:36121123
A non-canonical scaffold-type E3 ligase complex mediates pro...
ACCEPT
Summary: UFL1 acts as a non-canonical scaffold-type E3, activating UFC1 to transfer UFM1.
Reason: Direct mechanistic support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061666 UFM1 ligase activity
IDA
PMID:38383785
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ...
ACCEPT
Summary: Structural/functional evidence for UFL1 E3 ligase activity within the UREL-60S complex.
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061666 UFM1 ligase activity
IDA
PMID:38383789
The UFM1 E3 ligase recognizes and releases 60S ribosomes fro...
ACCEPT
Summary: Structural evidence for UFL1 E3 ligase activity in the UREL-60S complex.
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
PMID:38383789
the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26
GO:0071569 protein ufmylation
IDA
PMID:30626644
Ribosomal protein RPL26 is the principal target of UFMylatio...
ACCEPT
Summary: UFL1 mediates ufmylation; RPL26 is the principal target.
Reason: Direct evidence for the core process.
Supporting Evidence:
PMID:30626644
Ribosomal protein RPL26 is the principal target of UFMylation
GO:0071569 protein ufmylation
IDA
PMID:38383785
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ...
ACCEPT
Summary: UFL1 mediates RPL26 ufmylation in the UREL-60S complex.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0071569 protein ufmylation
IDA
PMID:38383789
The UFM1 E3 ligase recognizes and releases 60S ribosomes fro...
ACCEPT
Summary: UFL1 mediates RPL26 ufmylation in the UREL-60S complex.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0072344 rescue of stalled cytosolic ribosome
IDA
PMID:38383785
UFM1 E3 ligase promotes recycling of 60S ribosomal subunits ...
ACCEPT
Summary: UFL1, via RPL26 ufmylation, contributes to release/recycling of stalled 60S ribosomes at the ER.
Reason: Core physiological role of UFL1 ufmylation (ribosome recycling/RQC).
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome
GO:0072344 rescue of stalled cytosolic ribosome
IDA
PMID:38383789
The UFM1 E3 ligase recognizes and releases 60S ribosomes fro...
ACCEPT
Summary: UFL1, via RPL26 ufmylation, contributes to release/recycling of stalled 60S ribosomes from the ER translocon.
Reason: Core physiological role of UFL1 ufmylation (ribosome recycling/RQC).
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
promoting release and recycling of the large ribosomal subunit
GO:0006974 DNA damage response
IDA
PMID:30783677
MRE11 UFMylation promotes ATM activation.
KEEP AS NON CORE
Summary: UFL1 ufmylates MRE11 to promote ATM activation in the DNA-damage response.
Reason: A genuine but downstream role of UFL1's ufmylation activity; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
mediates monoufmylation of histone H4 and ufmylation of MRE11
GO:0061666 UFM1 ligase activity
IDA
PMID:30783677
MRE11 UFMylation promotes ATM activation.
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (ufmylation of MRE11).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
ufmylation of MRE11
GO:0005741 mitochondrial outer membrane
IDA
PMID:20164180
A novel LZAP-binding protein, NLBP, inhibits cell invasion.
MARK AS OVER ANNOTATED
Summary: A reported mitochondrial-outer-membrane localization; UFL1's principal and best-supported site of action is the ER membrane, and this localization is not central to its function.
Reason: An isolated localization claim at odds with the extensive evidence for ER-membrane action; likely peripheral or context-specific.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005741 mitochondrial outer membrane cellular_component ECO:0000314 IDA PMID:20164180
GO:0000077 DNA damage checkpoint signaling
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: UFL1 promotes ATM activation (a DNA-damage checkpoint kinase) via histone H4 ufmylation.
Reason: A documented downstream signaling role of UFL1 ufmylation; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
mediates monoufmylation of histone H4
GO:0005515 protein binding
IPI
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: Interaction with NBN/UFC1 in the histone H4 ufmylation/ATM study. Bare term uninformative.
Reason: Real interactions (including cascade partner UFC1); non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:30886146
GO:0005515 protein binding
IPI
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
KEEP AS NON CORE
Summary: Interaction with DDRGK1 in the ER-phagy screen. Bare term uninformative.
Reason: Real cascade interaction; non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32160526
GO:0005634 nucleus
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
ACCEPT
Summary: Direct nuclear localization during the DNA-damage response.
Reason: Direct evidence for nuclear localization linked to UFL1's DNA-damage role.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Nucleus
GO:0005737 cytoplasm
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: Direct cytoplasmic localization.
Reason: Documented cytoplasmic pool; principal site is the ER membrane.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Cytoplasm, cytosol
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
ACCEPT
Summary: ER membrane localization from the ER-phagy screen.
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0010508 positive regulation of autophagy
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Positive regulation of autophagy/reticulophagy transferred from ortholog.
Reason: Plausible by orthology; downstream process, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Involved in reticulophagy in response to endoplasmic reticulum stress
GO:0019901 protein kinase binding
IPI
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: UFL1 binds the protein kinase ATM (and is phosphorylated by it) in the DNA-damage response.
Reason: A real, specific protein-kinase interaction underlying the DNA-damage role; informative but non-core relative to the E3 ligase activity.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Phosphorylated at Ser-462 by ATM
GO:0030218 erythrocyte differentiation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Erythroid differentiation role transferred from ortholog.
Reason: Plausible by orthology; downstream developmental role, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Required for hematopoietic stem cell function and hematopoiesis
GO:0034976 response to endoplasmic reticulum stress
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
KEEP AS NON CORE
Summary: UFL1 functions in the ER stress response.
Reason: Valid pathway context; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Ufmylation in response to endoplasmic reticulum stress
GO:0035861 site of double-strand break
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
KEEP AS NON CORE
Summary: UFL1 is recruited to double-strand-break sites during the DNA-damage response.
Reason: Documented DNA-damage-associated localization; non-core relative to the principal ER-membrane site.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
recruited to double-strand break sites following DNA damage
GO:0043122 regulation of canonical NF-kappaB signal transduction
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: NF-kappaB regulatory role transferred from ortholog (UFL1/DDRGK1 axis).
Reason: Plausible by orthology; downstream signaling role, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0043122 regulation of canonical NF-kappaB signal transduction biological_process ECO:0000250 ISS GO_REF:0000024
GO:0050727 regulation of inflammatory response
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Inflammatory-response regulation transferred from ortholog.
Reason: Plausible by orthology; downstream, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
inflammatory response
GO:0060218 hematopoietic stem cell differentiation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Hematopoietic stem cell differentiation transferred from ortholog.
Reason: Plausible by orthology; downstream developmental role, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Required for hematopoietic stem cell function and hematopoiesis
GO:0061666 UFM1 ligase activity
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity (histone H4 ufmylation).
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
mediates monoufmylation of histone H4
GO:0061666 UFM1 ligase activity
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
ACCEPT
Summary: Direct evidence of UFL1 UFM1 ligase activity in the ER-phagy context.
Reason: Direct support for the core E3 ligase molecular function.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0061709 reticulophagy
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
KEEP AS NON CORE
Summary: UFL1 drives reticulophagy via ER ufmylation.
Reason: Valid downstream process; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Involved in reticulophagy in response to endoplasmic reticulum stress
GO:0071569 protein ufmylation
IDA
PMID:30886146
UFL1 promotes histone H4 ufmylation and ATM activation.
ACCEPT
Summary: UFL1 ufmylates histone H4.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
mediates monoufmylation of histone H4
GO:0071569 protein ufmylation
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
ACCEPT
Summary: UFL1 mediates ufmylation in the ER-phagy context.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:1903895 negative regulation of IRE1-mediated unfolded protein response
IDA
PMID:32160526
A genome-wide ER-phagy screen highlights key roles of mitoch...
KEEP AS NON CORE
Summary: UFL1/UREL-dependent ufmylation negatively regulates the IRE1 arm of the UPR (via DDRGK1-IRE1-alpha).
Reason: Documented signaling role downstream of ufmylation; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Ufmylation-dependent reticulophagy inhibits the unfolded protein response
GO:0061666 UFM1 ligase activity
IDA
PMID:20018847
A novel type of E3 ligase for the Ufm1 conjugation system.
ACCEPT
Summary: The founding paper identifying UFL1 as the E3 ligase of the UFM1 system, with catalytic activity demonstrated.
Reason: Original direct demonstration of the core E3 UFM1 ligase activity.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0032991 protein-containing complex
IDA
PMID:20531390
Suppression of the novel ER protein Maxer by mutant ataxin-1...
KEEP AS NON CORE
Summary: UFL1 (Maxer) is part of an ER protein complex; more specifically the UREL complex.
Reason: A generic complex-membership term; the specific and informative term is the UREL transferase complex.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0032991 protein-containing complex cellular_component ECO:0000314 IDA PMID:20531390
GO:0001649 osteoblast differentiation
HDA
PMID:16210410
Differential expression profiling of membrane proteins by qu...
KEEP AS NON CORE
Summary: From a membrane-proteomics differentiation study; an HDA association not central to UFL1's defined function.
Reason: High-throughput association of uncertain functional relevance; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0001649 osteoblast differentiation biological_process ECO:0007005 HDA PMID:16210410
GO:0016020 membrane
HDA
PMID:16210410
Differential expression profiling of membrane proteins by qu...
KEEP AS NON CORE
Summary: Membrane association from proteomics; consistent with UFL1's ER-membrane localization but non-specific.
Reason: Generic membrane term; the specific compartment is the ER membrane.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:1990592 protein K69-linked ufmylation
IDA
PMID:25219498
Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat...
KEEP AS NON CORE
Summary: UFL1 mediates ufmylation including K69-linked UFM1 chains.
Reason: Specific chain-linkage sub-aspect of ufmylation; narrow process annotation.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:1990592 protein K69-linked ufmylation biological_process ECO:0000314 IDA PMID:25219498
GO:0005515 protein binding
IPI
PMID:20228063
A novel C53/LZAP-interacting protein regulates stability of ...
KEEP AS NON CORE
Summary: Interaction with CDK5RAP3/DDRGK1 (RCAD study). Bare term uninformative.
Reason: Real cascade interactions; non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20228063
GO:0033146 regulation of intracellular estrogen receptor signaling pathway
IDA
PMID:25219498
Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat...
KEEP AS NON CORE
Summary: UFL1 ufmylates TRIP4/ASC1, affecting ERalpha transactivation.
Reason: A specialized signaling role downstream of ufmylation; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription
GO:0005515 protein binding
IPI
PMID:25219498
Modification of ASC1 by UFM1 is crucial for ERΞ± transactivat...
KEEP AS NON CORE
Summary: Interaction with DDRGK1/TRIP4 (ASC1/ufmylation study). Bare term uninformative.
Reason: Real cascade-relevant interactions; non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25219498
GO:0005783 endoplasmic reticulum
IDA
PMID:20531390
Suppression of the novel ER protein Maxer by mutant ataxin-1...
ACCEPT
Summary: ER localization (Maxer/UFL1).
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane
IDA
PMID:20531390
Suppression of the novel ER protein Maxer by mutant ataxin-1...
ACCEPT
Summary: ER membrane localization (Maxer/UFL1).
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0008284 positive regulation of cell population proliferation
IMP
PMID:20531390
Suppression of the novel ER protein Maxer by mutant ataxin-1...
KEEP AS NON CORE
Summary: Effect on cell proliferation in the Maxer study.
Reason: Downstream cellular phenotype; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0008284 positive regulation of cell population proliferation biological_process ECO:0000315 IMP PMID:20531390
GO:0032880 regulation of protein localization
IMP
PMID:20531390
Suppression of the novel ER protein Maxer by mutant ataxin-1...
KEEP AS NON CORE
Summary: UFL1 affects protein localization in the Maxer study.
Reason: Downstream effect; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0032880 regulation of protein localization biological_process ECO:0000315 IMP PMID:20531390
GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
IMP
PMID:20228063
A novel C53/LZAP-interacting protein regulates stability of ...
KEEP AS NON CORE
Summary: UFL1 regulates proteasomal degradation (protects CDK5RAP3/itself from ubiquitination).
Reason: Downstream effect on protein turnover; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Interaction with CDK5RAP3 protects both proteins against ubiquitination and degradation
GO:0034976 response to endoplasmic reticulum stress
IDA
PMID:23152784
Transcriptional regulation of the Ufm1 conjugation system in...
KEEP AS NON CORE
Summary: UFL1 is up-regulated by ER stress (thapsigargin) and functions in ER homeostasis.
Reason: Valid pathway context; non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Up-regulated by thapsigargin
GO:0071569 protein ufmylation
IMP
PMID:23152784
Transcriptional regulation of the Ufm1 conjugation system in...
ACCEPT
Summary: UFL1 is part of the UFM1 conjugation system implicated in ER homeostasis.
Reason: Supports the core process annotation.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation
GO:0005515 protein binding
IPI
PMID:20164180
A novel LZAP-binding protein, NLBP, inhibits cell invasion.
KEEP AS NON CORE
Summary: Interaction with CDK5RAP3/LZAP and RELA (NLBP study). Bare term uninformative.
Reason: Real interactions (including cascade partner CDK5RAP3); non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20164180
GO:0031397 negative regulation of protein ubiquitination
IDA
PMID:20164180
A novel LZAP-binding protein, NLBP, inhibits cell invasion.
KEEP AS NON CORE
Summary: UFL1 (NLBP) interaction with CDK5RAP3 protects against ubiquitination/degradation.
Reason: A documented effect on partner stability; downstream, non-core.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Interaction with CDK5RAP3 protects both proteins against ubiquitination and degradation
GO:0005737 cytoplasm
IDA
PMID:20164180
A novel LZAP-binding protein, NLBP, inhibits cell invasion.
KEEP AS NON CORE
Summary: Cytoplasmic localization (NLBP/UFL1).
Reason: Documented cytoplasmic pool; principal site is the ER membrane.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
Cytoplasm, cytosol
GO:0005515 protein binding
IPI
PMID:20018847
A novel type of E3 ligase for the Ufm1 conjugation system.
KEEP AS NON CORE
Summary: Interaction with DDRGK1 and UFC1 in the founding UFM1 E3 ligase paper. Bare term uninformative.
Reason: Real cascade interactions; non-core under generic term.
Supporting Evidence:
file:human/UFL1/UFL1-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:20018847
GO:0005783 endoplasmic reticulum
IDA
PMID:20018847
A novel type of E3 ligase for the Ufm1 conjugation system.
ACCEPT
Summary: ER localization from the founding UFM1 E3 ligase paper.
Reason: Direct evidence for the principal compartment.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0071569 protein ufmylation
IDA
PMID:20018847
A novel type of E3 ligase for the Ufm1 conjugation system.
ACCEPT
Summary: Founding demonstration that UFL1 is the E3 of ufmylation.
Reason: Direct evidence for the core process.
Supporting Evidence:
file:human/UFL1/UFL1-uniprot.txt
E3 protein ligase that mediates ufmylation

Core Functions

E3 UFM1-protein ligase, the catalytic component of the UFM1 ribosome E3 ligase (UREL) complex (with cofactor DDRGK1 and CDK5RAP3), that acts as a non-canonical scaffold-type E3 to activate the E2 UFC1 and catalyze transfer of UFM1 onto substrate lysines.

Molecular Function:
UFM1 ligase activity
Supporting Evidence:
  • file:human/UFL1/UFL1-uniprot.txt
    E3 protein ligase that mediates ufmylation
  • PMID:30626644
    Ribosomal protein RPL26 is the principal target of UFMylation

Mediates mono-ufmylation of the 60S ribosomal protein RPL26/uL24 on ER-bound ribosomes, weakening the 60S-SEC61 junction to promote release and recycling of post-termination/stalled large ribosomal subunits, thereby supporting ribosome-associated protein quality control at the ER.

Molecular Function:
UFM1 ligase activity
Supporting Evidence:
  • file:human/UFL1/UFL1-uniprot.txt
    plays a key role in ribosome recycling by catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome
  • PMID:37036982
    UFMylation of translocon-bound 60S subunits modulates the RTJ

References

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Suggested Questions for Experts

Q: How is UFL1 substrate selectivity determined across its diverse substrates (RPL26, histone H4, MRE11, p53, PD-1/PD-L1, CYB5R3) - is it driven by DDRGK1/CDK5RAP3 adaptors, localization, or post-translational regulation?

Q: Is the reported mitochondrial-outer-membrane localization of UFL1 a genuine functional pool or carryover from ER-mitochondria contact sites?

Q: How does ATM-mediated phosphorylation of UFL1 at Ser-462 mechanistically enhance its ligase activity in the DNA-damage response?

Suggested Experiments

Experiment: Substrate-trapping or proximity-labeling proteomics of catalytically active versus inactive UFL1 across ER-stress, DNA-damage and basal conditions to define context-dependent substrate repertoires.

Experiment: Reconstitute the UREL-60S complex with purified UFL1/DDRGK1/CDK5RAP3 and UFC1 to measure how each subunit and the ATM-phosphorylation site contribute to RPL26 ufmylation and 60S release from SEC61.

Experiment: Separation-of-function UFL1 alleles tested in ER-RQC reporter, reticulophagy, and DNA-damage (ATM activation) assays to determine whether a single catalytic activity underlies all phenotypes.

πŸ“š Additional Documentation

Notes

(UFL1-notes.md)

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Pn Notes

(UFL1-pn-notes.md)

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πŸ“„ View Raw YAML

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