UFL1_RAT
ID UFL1_RAT Reviewed; 793 AA.
AC B2GV24;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 92.
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:0000305};
DE AltName: Full=Multiple alpha-helix protein located at ER {ECO:0000303|PubMed:20531390};
DE AltName: Full=Regulator of C53/LZAP and DDRGK1 {ECO:0000303|PubMed:20228063};
GN Name=Ufl1 {ECO:0000312|RGD:1309308};
GN Synonyms=Maxer {ECO:0000303|PubMed:20531390},
GN Rcad {ECO:0000303|PubMed:20228063};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP INTERACTION WITH CDK5RAP3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=20531390; DOI=10.1038/emboj.2010.116;
RA Shiwaku H., Yoshimura N., Tamura T., Sone M., Ogishima S., Watase K.,
RA Tagawa K., Okazawa H.;
RT "Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman
RT glia contributes to non-cell-autonomous toxicity.";
RL EMBO J. 29:2446-2460(2010).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=20228063; DOI=10.1074/jbc.m110.110619;
RA Wu J., Lei G., Mei M., Tang Y., Li H.;
RT "A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and
RT DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB
RT signaling.";
RL J. Biol. Chem. 285:15126-15136(2010).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 In response to endoplasmic reticulum stress, recruited to the
CC endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of
CC proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy
CC of endoplasmic reticulum sheets. Ufmylation-dependent reticulophagy
CC inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha.
CC Ufmylation in response to endoplasmic reticulum stress is essential for
CC processes such as hematopoiesis, blood vessel morphogenesis or
CC inflammatory response (By similarity). Regulates inflammation in
CC response to endoplasmic reticulum stress by promoting reticulophagy,
CC leading to inhibit the activity of the NF-kappa-B transcription factor
CC (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role
CC of these modifications is however unclear: as both DDRGK1 and CDK5RAP3
CC act as substrate adapters for ufmylation, it is uncertain whether
CC ufmylation of these proteins is a collateral effect or is required for
CC ufmylation (By similarity). Catalyzes ufmylation of various subunits of
CC the 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. Also involved in the response to DNA
CC damage: recruited to double-strand break sites following DNA damage and
CC mediates monoufmylation of histone H4. Catalyzes ufmylation of TRIP4,
CC thereby playing a role in nuclear receptor-mediated transcription (By
CC similarity). Required for hematopoietic stem cell function and
CC hematopoiesis. Required for cardiac homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:A1A4I9, ECO:0000250|UniProtKB:O94874,
CC ECO:0000250|UniProtKB:Q8CCJ3}.
CC -!- SUBUNIT: Interacts with DDRGK1 (via PCI domain) (By similarity).
CC Interacts with UFC1 (By similarity). Interacts with RELA (By
CC similarity). Interacts with TRIP4 (By similarity). Interacts with
CC CDK5RAP3; the interaction is direct (PubMed:20531390). Interacts with
CC NBN; promoting recruitment to double-strand breaks following DNA damage
CC (By similarity). {ECO:0000250|UniProtKB:O94874,
CC ECO:0000269|PubMed:20531390}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:20531390}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O94874}. Nucleus {ECO:0000250|UniProtKB:O94874}.
CC Chromosome {ECO:0000250|UniProtKB:O94874}. Note=Recruited to double-
CC strand breaks by the MRE11-RAD50-NBN (MRN) complex following DNA
CC damage. {ECO:0000250|UniProtKB:O94874}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with expression detected in
CC brain, skeletal muscle, lung, heart, gall bladder, liver, small
CC intestine, pancreas, spleen and kidney (at protein level)
CC (PubMed:20228063). At 8 weeks after birth, high expression in the
CC Purkinje cell layer of the cerebellum (PubMed:20531390).
CC {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:20531390}.
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 -!- PTM: Phosphorylated at Ser-462 by ATM, enhancing protein ligase
CC activity and promoting ATM activation in a positive feedback loop.
CC {ECO:0000250|UniProtKB:O94874}.
CC -!- SIMILARITY: Belongs to the UFL1 family. {ECO:0000305}.
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DR EMBL; BC166498; AAI66498.1; -; mRNA.
DR RefSeq; NP_001119751.1; NM_001126279.1.
DR AlphaFoldDB; B2GV24; -.
DR SMR; B2GV24; -.
DR IntAct; B2GV24; 2.
DR MINT; B2GV24; -.
DR STRING; 10116.ENSRNOP00000010421; -.
DR iPTMnet; B2GV24; -.
DR PhosphoSitePlus; B2GV24; -.
DR jPOST; B2GV24; -.
DR PaxDb; B2GV24; -.
DR PeptideAtlas; B2GV24; -.
DR PRIDE; B2GV24; -.
DR Ensembl; ENSRNOT00000010421; ENSRNOP00000010421; ENSRNOG00000007831.
DR GeneID; 313115; -.
DR KEGG; rno:313115; -.
DR UCSC; RGD:1309308; rat.
DR CTD; 23376; -.
DR RGD; 1309308; Ufl1.
DR eggNOG; KOG2235; Eukaryota.
DR GeneTree; ENSGT00390000002112; -.
DR HOGENOM; CLU_012417_1_0_1; -.
DR InParanoid; B2GV24; -.
DR OMA; NECSATK; -.
DR OrthoDB; 289380at2759; -.
DR PhylomeDB; B2GV24; -.
DR TreeFam; TF319116; -.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:B2GV24; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000007831; Expressed in pancreas and 20 other tissues.
DR ExpressionAtlas; B2GV24; baseline and differential.
DR Genevisible; B2GV24; RN.
DR GO; GO:0005737; C:cytoplasm; ISS: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; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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:0043066; P:negative regulation of apoptotic process; IMP:ParkinsonsUK-UCL.
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; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:RGD.
DR GO; GO:1990592; P:protein K69-linked ufmylation; ISS:UniProtKB.
DR GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS: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; ISO:RGD.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:1902065; P:response to L-glutamate; ISO:RGD.
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 1: Evidence at protein 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..793
FT /note="E3 UFM1-protein ligase 1"
FT /id="PRO_0000391875"
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 410..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..683
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000269|PubMed:20531390"
FT REGION 742..769
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..473
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..768
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:0007744|PubMed:22673903"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CCJ3"
FT MOD_RES 753
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CCJ3"
SQ SEQUENCE 793 AA; 89585 MW; F99BB2764FD8F7DF CRC64;
MADAWEEIRR LAADFQRAQF AESTQRLSER NCIEIVNKLI SQKQLEVVHT LDGKEYITPA
QISKEMRDEL HVRGGRVNIV DLQQVINVDL THIENRVGDI IKSEKHVQMV LGQLVDENYL
DRLSEEVNDK LQESGQVTVS ELCKTYDLPG DFLTQALTQR LGRIINGHLD LDNRGVIFTE
AFVARHKARI RGLFSAITRP TAVNSLVSKY GFQEQLLYSV LEELVSTGRL RGTVVGGRQD
KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VNYIKKRYKN TPLLFLKATC
VGQGLVDQVE ASVEEAISSG TWVDVSPLLP SSLSVEDAAM LLQQVMRPFG KHASATVFSD
TVVVSEKFIN DCTKLFSERM HQKAEKEMKN NPVHLITEED LKQISILESV NTNKKDKKDE
RRKKATEGSG SVRGGGGGNA REYKIKKVKK KGRKDEDSDD ESQSSHAGKK KPDITFMFQD
EIEGCLRKHI PDAPEEFISE LAEHLIKPLN KMYLEVVRSV FMSSTSASGT GRKRTIKDLQ
EEVSNLYNNI RLFEKGMKYF ADDTQTALTK HLLKTVCTDI TNLMFNFLAS DLMMAVEDPA
TITSDMRKKI LSKLTEETKV ALTKLHNSLN EKSIEDFLSC LDSATEACDI MVKKGDKKRE
RQILFQHRQA LADQLKVTED PALILHLTSV LLFQFSTHSM LHAPGRCVPQ IIAFLHNKIP
EDQHTLLVKY QGLVVKQLVS QNKKSGQGED PSSDDLDKEQ HDVTNTTRKE LQELSLSIKD
LVLKPRKSSV TEE
