NF2L1_CHICK
ID NF2L1_CHICK Reviewed; 772 AA.
AC Q5ZL67;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Endoplasmic reticulum membrane sensor NFE2L1 {ECO:0000305};
DE AltName: Full=Nuclear factor erythroid 2-related factor 1 {ECO:0000250|UniProtKB:Q14494};
DE Short=NF-E2-related factor 1 {ECO:0000250|UniProtKB:Q14494};
DE Short=NFE2-related factor 1 {ECO:0000250|UniProtKB:Q14494};
DE AltName: Full=Nuclear factor, erythroid derived 2, like 1 {ECO:0000250|UniProtKB:Q14494};
DE Contains:
DE RecName: Full=Transcription factor NRF1 {ECO:0000250|UniProtKB:Q14494};
GN Name=NFE2L1 {ECO:0000250|UniProtKB:Q14494};
GN Synonyms=NRF1 {ECO:0000250|UniProtKB:Q14494};
GN ORFNames=RCJMB04_7g14 {ECO:0000303|PubMed:15642098};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
CC -!- FUNCTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic
CC reticulum membrane sensor that translocates into the nucleus in
CC response to various stresses to act as a transcription factor (By
CC similarity). Constitutes a precursor of the transcription factor NRF1
CC (By similarity). Able to detect various cellular stresses, such as
CC cholesterol excess, oxidative stress or proteasome inhibition (By
CC similarity). In response to stress, it is released from the endoplasmic
CC reticulum membrane following cleavage and translocates into the nucleus
CC to form the transcription factor NRF1 (By similarity). Acts as a key
CC sensor of cholesterol excess: in excess cholesterol conditions, the
CC endoplasmic reticulum membrane form of the protein directly binds
CC cholesterol via its CRAC motif, preventing cleavage and release of the
CC transcription factor NRF1, thereby allowing expression of genes
CC promoting cholesterol removal (By similarity). Involved in proteasome
CC homeostasis: in response to proteasome inhibition, it is released from
CC the endoplasmic reticulum membrane, translocates to the nucleus and
CC activates expression of genes encoding proteasome subunits (By
CC similarity). {ECO:0000250|UniProtKB:Q14494,
CC ECO:0000250|UniProtKB:Q61985}.
CC -!- FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family
CC transcription factor that translocates to the nucleus and regulates
CC expression of target genes in response to various stresses.
CC Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds
CC DNA motifs including the antioxidant response elements (AREs), which
CC regulate expression of genes involved in oxidative stress response.
CC Activates or represses expression of target genes, depending on the
CC context (By similarity). Plays a key role in cholesterol homeostasis by
CC acting as a sensor of cholesterol excess: in low cholesterol
CC conditions, translocates into the nucleus and represses expression of
CC genes involved in defense against cholesterol excess (By similarity).
CC In excess cholesterol conditions, the endoplasmic reticulum membrane
CC form of the protein directly binds cholesterol via its CRAC motif,
CC preventing cleavage and release of the transcription factor NRF1,
CC thereby allowing expression of genes promoting cholesterol removal (By
CC similarity). Critical for redox balance in response to oxidative
CC stress: acts by binding the AREs motifs on promoters and mediating
CC activation of oxidative stress response genes (By similarity). Involved
CC in proteasome homeostasis: in response to proteasome inhibition,
CC mediates the 'bounce-back' of proteasome subunits by translocating into
CC the nucleus and activating expression of genes encoding proteasome
CC subunits (By similarity). {ECO:0000250|UniProtKB:Q14494,
CC ECO:0000250|UniProtKB:Q61985}.
CC -!- SUBUNIT: [Transcription factor NRF1]: Interacts (via the bZIP domain)
CC with small MAF protein (MAFF, MAFG or MAFK); required for binding to
CC antioxidant response elements (AREs) on DNA.
CC {ECO:0000250|UniProtKB:Q14494}.
CC -!- SUBCELLULAR LOCATION: [Endoplasmic reticulum membrane sensor NFE2L1]:
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q14494}; Single-
CC pass type II membrane protein {ECO:0000250|UniProtKB:Q14494}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q14494}; Single-
CC pass type III membrane protein {ECO:0000250|UniProtKB:Q14494}. Note=In
CC normal conditions, probably has a single-pass type II membrane protein
CC topology, with the DNA-binding domain facing the endoplasmic reticulum
CC lumen. Following cellular stress, it is rapidly and efficiently
CC retrotranslocated to the cytosolic side of the membrane, a process
CC dependent on p97/VCP, to have a single-pass type III membrane protein
CC topology with the major part of the protein facing the cytosol.
CC Retrotranslocated proteins are normally rapidly degraded by the
CC proteasome and active species do not accumulate. However,
CC retrotranslocated protein NFE2L1 escapes degradation and is cleaved at
CC Leu-104, releasing the protein from the endoplasmic reticulum membrane
CC and forming the transcription factor NRF1 that translocates into the
CC nucleus. {ECO:0000250|UniProtKB:Q14494}.
CC -!- SUBCELLULAR LOCATION: [Transcription factor NRF1]: Nucleus
CC {ECO:0000250|UniProtKB:Q14494, ECO:0000255|PROSITE-ProRule:PRU00978}.
CC Note=Translocates into the nucleus following cleavage of Endoplasmic
CC reticulum membrane sensor NFE2L1. {ECO:0000250|UniProtKB:Q14494}.
CC -!- DOMAIN: The cholesterol recognition/amino acid consensus (CRAC) region
CC directly binds cholesterol, as well as campesterol and 27-
CC hydroxycholesterol. Has much lower affinity for epicholesterol.
CC {ECO:0000250|UniProtKB:Q61985}.
CC -!- PTM: [Endoplasmic reticulum membrane sensor NFE2L1]: Cleaved at Leu-104
CC following retrotranslocation, releasing the protein from the
CC endoplasmic reticulum membrane and forming the transcription factor
CC NRF1 that translocates into the nucleus.
CC {ECO:0000250|UniProtKB:Q14494}.
CC -!- SIMILARITY: Belongs to the bZIP family. CNC subfamily. {ECO:0000305}.
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DR EMBL; AJ719867; CAG31526.1; -; mRNA.
DR RefSeq; NP_001025927.1; NM_001030756.1.
DR AlphaFoldDB; Q5ZL67; -.
DR SMR; Q5ZL67; -.
DR STRING; 9031.ENSGALP00000035379; -.
DR PaxDb; Q5ZL67; -.
DR Ensembl; ENSGALT00000069198; ENSGALP00000050038; ENSGALG00000011937.
DR GeneID; 417987; -.
DR KEGG; gga:417987; -.
DR CTD; 4779; -.
DR VEuPathDB; HostDB:geneid_417987; -.
DR eggNOG; KOG3863; Eukaryota.
DR GeneTree; ENSGT00950000182892; -.
DR HOGENOM; CLU_024173_1_0_1; -.
DR InParanoid; Q5ZL67; -.
DR OMA; LQAMDVN; -.
DR OrthoDB; 1095280at2759; -.
DR PhylomeDB; Q5ZL67; -.
DR PRO; PR:Q5ZL67; -.
DR Proteomes; UP000000539; Chromosome 27.
DR Bgee; ENSGALG00000011937; Expressed in skeletal muscle tissue and 13 other tissues.
DR ExpressionAtlas; Q5ZL67; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0097201; P:negative regulation of transcription from RNA polymerase II promoter in response to stress; ISS:UniProtKB.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; ISS:UniProtKB.
DR GO; GO:1901329; P:regulation of odontoblast differentiation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR029847; NFE2L1.
DR InterPro; IPR008917; TF_DNA-bd_sf.
DR PANTHER; PTHR24411:SF31; PTHR24411:SF31; 1.
DR Pfam; PF03131; bZIP_Maf; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 2: Evidence at transcript level;
KW Activator; Cholesterol metabolism; DNA-binding; Endoplasmic reticulum;
KW Glycoprotein; Lipid metabolism; Lipid-binding; Membrane; Nucleus;
KW Reference proteome; Repressor; Signal-anchor; Steroid metabolism;
KW Sterol metabolism; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..772
FT /note="Endoplasmic reticulum membrane sensor NFE2L1"
FT /id="PRO_0000341948"
FT CHAIN 104..772
FT /note="Transcription factor NRF1"
FT /evidence="ECO:0000250|UniProtKB:Q14494"
FT /id="PRO_0000443106"
FT TRANSMEM 7..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 654..717
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 191..199
FT /note="Cholesterol recognition/amino acid consensus (CRAC)
FT region"
FT /evidence="ECO:0000250|UniProtKB:Q61985"
FT REGION 198..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 656..675
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 682..696
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 761..768
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 198..216
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..613
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 103..104
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q14494"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 574
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 772 AA; 85186 MW; 56387649E95BEDF0 CRC64;
MLSLKKYFTE GLIQFTILLS LIGVRVDVDT YLNSQLPPLR EIILGQSSAY TQTQFHNLRN
TLDGYGIHPK SVDLDYYFTA RRLLNQVRAL DRFQVPTTEV SAWLVHRDPD GSVSGTQPSA
GIALENSGGL QDGTGPDGAV RESGAEQGFG EELEDLGAVA APVNGDLTKE DIDLIDILWR
QDIDLGAGRE IFDYSHRQKE SEVDKELSDG RERGDGWRSA GGQVTNRNLL VDGETGESFP
AQVPGVEDQT ALSLEECLRL LEATFPFGEN SEFPAADVST LSEAVPSESR PAGIQSSLLS
PLLPETESPF DLEQQWQDLM SIMEMQAMEV NNTTAETLYN GTSGDLLTSN YNLAPNTPIN
QNVSLHQASL GSCSQDFSLF SSEIESPSMG GSSALLQLAP DNSTGLNTTF SSTNFSGIFF
PPQLNSTVNE TAGPELPDPL GGLLDEAMLD EISLMDLAIE EGFNPVQASQ LEEEFDSDSG
LSLDSGHSPA SLSSSEASSS SSSSSSSSSS SSSSSSSFSE EGAVGYSSDS ENVDFEEAEG
AVGYQPEYSK FCRMSYQDPS QLHYLPYLEH VGHNHTYNMA PGTLDPEEPK LPSVGKKSSK
EKPSEFLDKQ MSRDEHRARA MKIPFTNDKI INLPVEEFNE LLSKYQLSEA QLSLIRDIRR
RGKNKMAAQN CRKRKLDTIL NLERDVEDLQ RDKSKLLREK VEFLKSIRQM KQKVQNLYQE
VFGRLRDENG QPYSPNQYAL QYASDGSVIL IPRTLADQQA RRQERKQKDR RK
