UFL1_MACFA
ID UFL1_MACFA Reviewed; 793 AA.
AC Q4R367;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 53.
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};
GN Name=UFL1 {ECO:0000250|UniProtKB:O94874};
GN ORFNames=QtsA-19276 {ECO:0000303|Ref.1};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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). 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: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 -!- 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}.
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DR EMBL; AB179400; BAE02451.1; -; mRNA.
DR RefSeq; NP_001270418.1; NM_001283489.1.
DR AlphaFoldDB; Q4R367; -.
DR STRING; 9541.XP_005552381.1; -.
DR GeneID; 101867065; -.
DR CTD; 23376; -.
DR eggNOG; KOG2235; Eukaryota.
DR OrthoDB; 289380at2759; -.
DR Proteomes; UP000233100; Unplaced.
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:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0061666; F:UFM1 ligase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
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; 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:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
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..793
FT /note="E3 UFM1-protein ligase 1"
FT /id="PRO_0000328123"
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 407..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..684
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000250|UniProtKB:B2GV24"
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 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"
SQ SEQUENCE 793 AA; 89484 MW; 1C9AD9CF29A45C2F CRC64;
MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT LDGKEYITPA
QISKEMRDEL HVRGGRVNIV DLQQVINVDL IHIENRIGDI IKSEKHVQLV LGQLIDENYL
DRLAEEVNDK LQESGQVTIS ELCKTYDLPG NFLTQALTQR LGRIISGHID LDNRGVIFTE
AFVARHKARI RGLFSAITRP TAVNSLISKY GFQEQLLYSV LEELVNSGRL RGTVVGGRQD
KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VSYIKKRYKT TQLLFLKAAC
VGQGLVDQVE ASVEEAISSG TWVDIAPLLP TSLSVEDAAI LLQQVMRAFS KQASAVVFSD
TVVVSEKFIN DCTELFRELM HQKAEKEMKN NPVHLITEED LKQISTLESV STSKKDKKDE
RRRKATEGSG SVRGGGGGNA REYKIRKVKK KGRKDDDSDD ETQSSHTGKK KPEISFMFQD
EIEDFLRKHI QDAPEEFISE LAEYLIKPLN KTYLEVVRSV FMSSTTSASG TGRKRTIKDL
QEEVSNLYNN IRLFEKGMKF FADDTQAALT KHLLKSVCTD ITNLIFNFLA SDLMMAVDDP
AAITSEIRKK ILSKLSEETK VALTKLHNSL NEKSIEDFIS CLDSAAEACD IMVKRGDKKR
ERQILFQHRQ ALAEQLKVTE DPALILHLTS VLLFQFSTHT MLHAPGRCVP QIIAFLNSKI
PEDQHALLVK YQGLVVKQLV SQNKKTGQGD YPLNNELGKE QEDVANTRKE LQELSSSIKD
LVLKSRKSSV TEE
