UFL1_BOVIN
ID UFL1_BOVIN Reviewed; 792 AA.
AC A1A4I9;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=E3 UFM1-protein ligase 1 {ECO:0000305};
DE EC=2.3.2.- {ECO:0000250|UniProtKB:O94874};
DE AltName: Full=E3 UFM1-protein transferase 1 {ECO:0000303|PubMed:31721015};
GN Name=UFL1 {ECO:0000303|PubMed:31721015};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=31721015; DOI=10.1007/s12192-019-01033-8;
RA Kuang M., Li L., Li C., Wang G.;
RT "Protective effects of UFL1 against endoplasmic reticulum stress-induced
RT autophagy in bovine mammary epithelial cells.";
RL Cell Stress Chaperones 24:1115-1125(2019).
RN [3]
RP FUNCTION.
RX PubMed=31078114; DOI=10.1016/j.molimm.2019.04.023;
RA Li C., Wang X., Kuang M., Li L., Wang Y., Yang F., Wang G.;
RT "UFL1 modulates NLRP3 inflammasome activation and protects against
RT pyroptosis in LPS-stimulated bovine mammary epithelial cells.";
RL Mol. Immunol. 112:1-9(2019).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=30881595; DOI=10.1155/2019/6505373;
RA Li C., Li L., Chen K., Wang Y., Yang F., Wang G.;
RT "UFL1 alleviates lipopolysaccharide-induced cell damage and inflammation
RT via regulation of the TLR4/NF-kappaB pathway in bovine mammary epithelial
RT cells.";
RL Oxid. Med. Cell. Longev. 2019:6505373-6505373(2019).
RN [5]
RP FUNCTION.
RX PubMed=32050508; DOI=10.3390/biom10020260;
RA Wang X., Li C., Wang Y., Li L., Han Z., Wang G.;
RT "UFL1 alleviates LPS-induced apoptosis by regulating the nF-kappaB
RT signaling pathway in bovine ovarian granulosa cells.";
RL Biomolecules 10:0-0(2020).
CC -!- FUNCTION: E3 protein ligase that mediates ufmylation, the covalent
CC attachment of the ubiquitin-like modifier UFM1 to lysine residues on
CC target proteins, and which plays a key role in reticulophagy (also
CC called ER-phagy) induced in response to endoplasmic reticulum stress
CC (By similarity). In response to endoplasmic reticulum stress, recruited
CC to the endoplasmic reticulum membrane by DDRGK1, and mediates
CC ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting
CC reticulophagy of endoplasmic reticulum sheets (By similarity).
CC Ufmylation-dependent reticulophagy inhibits the unfolded protein
CC response (UPR) via ERN1/IRE1-alpha (By similarity). Ufmylation in
CC response to endoplasmic reticulum stress is essential for processes
CC such as hematopoiesis, blood vessel morphogenesis or inflammatory
CC response (PubMed:30881595). Regulates inflammation in response to
CC endoplasmic reticulum stress by promoting reticulophagy, leading to
CC inhibit the activity of the NF-kappa-B transcription factor
CC (PubMed:31721015, PubMed:31078114, PubMed:30881595, PubMed:32050508).
CC Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these
CC modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as
CC substrate adapters for ufmylation, it is uncertain whether ufmylation
CC of these proteins is a collateral effect or is required for ufmylation
CC (By similarity). Catalyzes ufmylation of various subunits of the
CC ribosomal complex or associated components, such as RPS3/uS3,
CC RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By similarity). Anchors
CC CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus
CC which allows expression of the CCND1 cyclin and progression of cells
CC through the G1/S transition (By similarity). Also involved in the
CC response to DNA damage: recruited to double-strand break sites
CC following DNA damage and mediates monoufmylation of histone H4 (By
CC similarity). Catalyzes ufmylation of TRIP4, thereby playing a role in
CC nuclear receptor-mediated transcription (By similarity). Required for
CC hematopoietic stem cell function and hematopoiesis. Required for
CC cardiac homeostasis (By similarity). {ECO:0000250|UniProtKB:O94874,
CC ECO:0000250|UniProtKB:Q8CCJ3, ECO:0000269|PubMed:30881595,
CC ECO:0000269|PubMed:31078114, ECO:0000269|PubMed:31721015,
CC ECO:0000269|PubMed:32050508}.
CC -!- SUBUNIT: Interacts with DDRGK1 (via PCI domain). Interacts with UFC1.
CC Interacts with RELA. Interacts with TRIP4. Interacts with CDK5RAP3; the
CC interaction is direct. Interacts with NBN; promoting recruitment to
CC double-strand breaks following DNA damage.
CC {ECO:0000250|UniProtKB:O94874}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O94874}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:30881595, ECO:0000269|PubMed:31721015}. Nucleus
CC {ECO:0000269|PubMed:30881595, ECO:0000269|PubMed:31721015}. Chromosome
CC {ECO:0000250|UniProtKB:O94874}. Note=Recruited to double-strand breaks
CC by the MRE11-RAD50-NBN (MRN) complex following DNA damage.
CC {ECO:0000250|UniProtKB:O94874}.
CC -!- INDUCTION: Expressed in response to endoplasmic reticulum stress
CC (PubMed:31721015). By lipopolysaccharide (LPS) (PubMed:30881595).
CC {ECO:0000269|PubMed:30881595, ECO:0000269|PubMed:31721015}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Interaction with CDK5RAP3 protects both proteins against ubiquitination
CC and degradation via the proteasome. {ECO:0000250|UniProtKB:O94874}.
CC -!- SIMILARITY: Belongs to the UFL1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC126563; AAI26564.1; -; mRNA.
DR RefSeq; NP_001073745.1; NM_001080276.2.
DR AlphaFoldDB; A1A4I9; -.
DR STRING; 9913.ENSBTAP00000027202; -.
DR PaxDb; A1A4I9; -.
DR PRIDE; A1A4I9; -.
DR Ensembl; ENSBTAT00000027202; ENSBTAP00000027202; ENSBTAG00000020410.
DR GeneID; 515894; -.
DR KEGG; bta:515894; -.
DR CTD; 23376; -.
DR VEuPathDB; HostDB:ENSBTAG00000020410; -.
DR VGNC; VGNC:36646; UFL1.
DR eggNOG; KOG2235; Eukaryota.
DR GeneTree; ENSGT00390000002112; -.
DR HOGENOM; CLU_012417_1_0_1; -.
DR InParanoid; A1A4I9; -.
DR OMA; NECSATK; -.
DR OrthoDB; 289380at2759; -.
DR TreeFam; TF319116; -.
DR Reactome; R-BTA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000020410; Expressed in spermatocyte and 107 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0061666; F:UFM1 ligase activity; ISS:UniProtKB.
DR GO; GO:0071568; F:UFM1 transferase activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0016570; P:histone modification; ISS:UniProtKB.
DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:1990592; P:protein K69-linked ufmylation; ISS:UniProtKB.
DR GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl.
DR GO; GO:0061709; P:reticulophagy; ISS:UniProtKB.
DR InterPro; IPR018611; Ufl1.
DR PANTHER; PTHR31057; PTHR31057; 1.
DR Pfam; PF09743; E3_UFM1_ligase; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chromosome; Cytoplasm; DNA damage; DNA repair;
KW Endoplasmic reticulum; Membrane; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT CHAIN 2..792
FT /note="E3 UFM1-protein ligase 1"
FT /id="PRO_0000328122"
FT REGION 2..212
FT /note="Required for E3 UFM1-protein ligase activity"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 2..200
FT /note="Mediates interaction with DDRGK1"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 121..250
FT /note="Involved in CDK5RAP3-binding"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 200..400
FT /note="Mediates interaction with TRIP4"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 412..471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..682
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000250|UniProtKB:B2GV24"
FT COMPBIAS 412..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT MOD_RES 433
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8CCJ3"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CCJ3"
SQ SEQUENCE 792 AA; 89383 MW; F24D37AF7C8F5D7D CRC64;
MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT LDGKEYITPA
QISKEMRDEL HVRGGRVNIV DLQQAINVDL THIENRIGDI VKSEKHVQLV LGQLIDENYL
DRLAEEVNDK LQESGQVTIA ELCKTYDLPG NFLTQALTQR LGRIINGHID LDNRGVIFTE
AFVSRHKARI RGLFSAITRP TAVNSLISRY GFQEQLLYSV LEELVNDGRL RGTVVGGRQD
KAVFIPDIYS RTQSTWVDSF LRQNGYLEFD ALSRLGIPDA MSYIKKRYKT TQLLFLKAAC
VGQGLVDQVE ASVEEAISSG TWVDIAPLLP SSLSVEDAAI LLQHVMRALS KQASAVVFSD
TIVVSEKFIN DCTDLFSELM HQKAEKEMKN NPVHLITEED LKQISILESI NTSKKDKKDE
RRRKATEGSG SVRGGGGSNA REYKIKKTKK KGRKDDDSDD ESSHTGKKKP EITFMFQDEI
EDFLRKHLQD APEEFISELA EYLIKPLNKT YLEVVHSVYM SSTSSASGTG RKRTIKDLQE
EVSNLYNNIR LFEKGMKFFT DDTQAALTKH LLKTVCTDIT NLVFNFLASD LMMAVDDPAT
ITSEVRKKIL SKLSEETKVA LTKLHNSLNE KSIEDFLACL DSAAEACDIM LKKGDKKRER
QVLFQHRQAL VEQLKVTEDP ALTLHLTSVL LFQFSTHSML HAPGRCVPQI IAFLSSKIPE
DQHALLVKYQ GLVVKHLVSQ NKKTGQGEDP LSDELDKEQE DIINTTRKEL QELSSSIKDL
VLKSRKSSVT EE
