MYRF1_CAEEL
ID MYRF1_CAEEL Reviewed; 931 AA.
AC G5EFI7;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Myelin regulatory factor homolog 1 {ECO:0000303|PubMed:28441531};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q9Y2G1};
DE AltName: Full=Polyglutamine-repeat protein 47 {ECO:0000303|PubMed:21989027};
DE Contains:
DE RecName: Full=Myelin regulatory factor homolog 1, N-terminal {ECO:0000305};
DE Contains:
DE RecName: Full=Myelin regulatory factor homolog 1, C-terminal {ECO:0000305};
GN Name=myrf-1 {ECO:0000303|PubMed:28441531, ECO:0000312|WormBase:F59B10.1};
GN Synonyms=pqn-47 {ECO:0000303|PubMed:21989027,
GN ECO:0000312|WormBase:F59B10.1};
GN ORFNames=F59B10.1 {ECO:0000312|WormBase:F59B10.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=21989027; DOI=10.1016/j.ydbio.2011.09.025;
RA Russel S., Frand A.R., Ruvkun G.;
RT "Regulation of the C. elegans molt by pqn-47.";
RL Dev. Biol. 360:297-309(2011).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYRF-2, TISSUE
RP SPECIFICITY, DISRUPTION PHENOTYPE, PROTEOLYTIC PROCESSING, AND MUTAGENESIS
RP OF GLY-274 AND SER-483.
RX PubMed=28441531; DOI=10.1016/j.devcel.2017.03.022;
RA Meng J., Ma X., Tao H., Jin X., Witvliet D., Mitchell J., Zhu M.,
RA Dong M.Q., Zhen M., Jin Y., Qi Y.B.;
RT "Myrf ER-bound transcription factors drive C. elegans synaptic plasticity
RT via cleavage-dependent nuclear translocation.";
RL Dev. Cell 41:180-194(2017).
RN [4]
RP FUNCTION, INTERACTION WITH PAN-1, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND MUTAGENESIS OF 483-SER--SER-931; SER-483; LYS-488;
RP 657-GLY--SER-931; 701-GLY--SER-931 AND 791-ILE--SER-931.
RX PubMed=33950834; DOI=10.7554/elife.67628;
RA Xia S.L., Li M., Chen B., Wang C., Yan Y.H., Dong M.Q., Qi Y.B.;
RT "The LRR-TM protein PAN-1 interacts with MYRF to promote its nuclear
RT translocation in synaptic remodeling.";
RL Elife 10:0-0(2021).
CC -!- FUNCTION: [Myelin regulatory factor homolog 1]: Constitutes a precursor
CC of the transcription factor (PubMed:28441531). Mediates the
CC autocatalytic cleavage that releases the Myelin regulatory factor
CC homolog 1, N-terminal component that specifically activates
CC transcription of genes involved in synaptic rewiring during nervous
CC system maturation (PubMed:28441531). {ECO:0000269|PubMed:28441531}.
CC -!- FUNCTION: [Myelin regulatory factor homolog 1, C-terminal]: Membrane-
CC bound part that has no transcription factor activity and remains
CC attached to the endoplasmic reticulum membrane following cleavage.
CC {ECO:0000250|UniProtKB:Q9Y2G1}.
CC -!- FUNCTION: [Myelin regulatory factor homolog 1, N-terminal]:
CC Transcription factor that specifically activates expression of genes
CC involved in synaptic rewiring during nervous system maturation
CC (PubMed:28441531). Specifically required for dorsal D (DD) GABAergic
CC motor neurons synaptic rewiring (PubMed:28441531, PubMed:33950834).
CC Acts in complex with myrf-2 paralog (PubMed:28441531).
CC {ECO:0000269|PubMed:28441531, ECO:0000269|PubMed:33950834}.
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with myrf-2
CC (PubMed:28441531). Interacts (via C-terminus) with pan-1 (via LRR
CC regions); the interaction promotes the role of myrf-1 in the synaptic
CC remodeling of DD GABAergic motor neurons at the cell membrane
CC (PubMed:33950834). {ECO:0000250|UniProtKB:Q9Y2G1,
CC ECO:0000269|PubMed:28441531, ECO:0000269|PubMed:33950834}.
CC -!- INTERACTION:
CC G5EFI7; D9PTN5: myrf-2; NbExp=2; IntAct=EBI-6731843, EBI-6727439;
CC -!- SUBCELLULAR LOCATION: [Myelin regulatory factor homolog 1]: Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:28441531}; Single-pass membrane
CC protein {ECO:0000255}. Nucleus {ECO:0000269|PubMed:33950834}. Apical
CC cell membrane {ECO:0000269|PubMed:33950834}; Single-pass membrane
CC protein {ECO:0000255}. Note=In early L1 larvae, localizes to the cell
CC membrane of the pharynx, epidermis, and neurons, but is not enriched in
CC the nucleus or cytoplasm of these cell types (PubMed:33950834). Later
CC in the L1 larval stage, accumulates in the nucleus of the pharynx,
CC epidermis, and neurons (PubMed:33950834).
CC {ECO:0000269|PubMed:33950834}.
CC -!- SUBCELLULAR LOCATION: [Myelin regulatory factor homolog 1, N-terminal]:
CC Endoplasmic reticulum membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}. Nucleus {ECO:0000269|PubMed:28441531}. Cytoplasm
CC {ECO:0000269|PubMed:28441531}. Apical cell membrane
CC {ECO:0000269|PubMed:33950834}. Note=Translocates from the cytoplasm to
CC the nucleus upon autocatalytic cleavage (PubMed:28441531). In early L1
CC larvae, localizes to the cell membrane of the pharynx, epidermis, and
CC neurons, but is not enriched in the nucleus or cytoplasm of these cell
CC types (PubMed:33950834). Cell membrane localization is promoted by pan-
CC 1 (PubMed:33950834). Later in the L1 larval stage, accumulates in the
CC nucleus of the pharynx, epidermis, and neurons (PubMed:33950834).
CC {ECO:0000269|PubMed:28441531, ECO:0000269|PubMed:33950834}.
CC -!- SUBCELLULAR LOCATION: [Myelin regulatory factor homolog 1, C-terminal]:
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:28441531}; Single-
CC pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed in many tissues, including
CC neuronal, muscle and epidermal stem cells (PubMed:21989027). In
CC neurons, expressed in dorsal D (DD) GABAergic motor neurons
CC (PubMed:28441531). {ECO:0000269|PubMed:21989027,
CC ECO:0000269|PubMed:28441531}.
CC -!- DEVELOPMENTAL STAGE: [Myelin regulatory factor homolog 1]: In early L1
CC larvae, expressed in the pharynx, epidermis, and neurons.
CC {ECO:0000269|PubMed:33950834}.
CC -!- DEVELOPMENTAL STAGE: [Myelin regulatory factor homolog 1, N-terminal]:
CC In early L1 larvae, expressed in the pharynx, epidermis, and neurons.
CC {ECO:0000269|PubMed:33950834}.
CC -!- DOMAIN: Myelin regulatory factor: The peptidase S74 domain, also named
CC Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular
CC Chaperone Domain (ICD), has protease activity and mediates
CC autocatalytic processing of the protein to generate the Myelin
CC regulatory factor, N-terminal active transcription factor and the
CC Myelin regulatory factor, C-terminal components.
CC {ECO:0000250|UniProtKB:Q9Y2G1}.
CC -!- PTM: Myelin regulatory factor: Follows autocatalytic cleavage via the
CC peptidase S74 domain. Autoprocessing is apparently constitutive and is
CC essential for transcriptional activity. {ECO:0000305|PubMed:28441531}.
CC -!- DISRUPTION PHENOTYPE: Worms show normal dorsal D (DD) GABAergic motor
CC neurons rewiring but show larval lethality. Worms lacking both myrf-1
CC and myrf-2 display defective DD neurons rewiring.
CC {ECO:0000269|PubMed:28441531}.
CC -!- SIMILARITY: Belongs to the MRF 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; BX284602; CAA88602.3; -; Genomic_DNA.
DR PIR; H88293; H88293.
DR PIR; T22982; T22982.
DR RefSeq; NP_496262.2; NM_063861.4.
DR AlphaFoldDB; G5EFI7; -.
DR SMR; G5EFI7; -.
DR ComplexPortal; CPX-3521; myrf-1-myrf-2 complex.
DR IntAct; G5EFI7; 3.
DR STRING; 6239.F59B10.1; -.
DR EPD; G5EFI7; -.
DR PaxDb; G5EFI7; -.
DR PeptideAtlas; G5EFI7; -.
DR EnsemblMetazoa; F59B10.1.1; F59B10.1.1; WBGene00004134.
DR GeneID; 174614; -.
DR KEGG; cel:CELE_F59B10.1; -.
DR CTD; 174614; -.
DR WormBase; F59B10.1; CE36940; WBGene00004134; myrf-1.
DR eggNOG; KOG3661; Eukaryota.
DR GeneTree; ENSGT00530000063626; -.
DR HOGENOM; CLU_010255_0_0_1; -.
DR InParanoid; G5EFI7; -.
DR OMA; WNPLYDI; -.
DR OrthoDB; 311898at2759; -.
DR PhylomeDB; G5EFI7; -.
DR PRO; PR:G5EFI7; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00004134; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045178; C:basal part of cell; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:WormBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042395; P:ecdysis, collagen and cuticulin-based cuticle; IMP:WormBase.
DR GO; GO:0018996; P:molting cycle, collagen and cuticulin-based cuticle; IGI:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:1904799; P:regulation of neuron remodeling; IDA:UniProtKB.
DR GO; GO:0051963; P:regulation of synapse assembly; IMP:ComplexPortal.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR025719; MYRF_C2.
DR InterPro; IPR026932; MYRF_ICA.
DR InterPro; IPR024061; NDT80_DNA-bd_dom.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR030392; S74_ICA.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF13888; MRF_C2; 1.
DR Pfam; PF13887; MYRF_ICA; 1.
DR Pfam; PF05224; NDT80_PhoG; 1.
DR Pfam; PF13884; Peptidase_S74; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS51688; ICA; 1.
DR PROSITE; PS51517; NDT80; 1.
PE 1: Evidence at protein level;
KW Activator; Autocatalytic cleavage; Cell membrane; Cytoplasm;
KW Differentiation; DNA-binding; Endoplasmic reticulum; Glycoprotein;
KW Hydrolase; Membrane; Nucleus; Protease; Reference proteome; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix.
FT CHAIN 1..931
FT /note="Myelin regulatory factor homolog 1"
FT /id="PRO_0000441325"
FT CHAIN 1..482
FT /note="Myelin regulatory factor homolog 1, N-terminal"
FT /evidence="ECO:0000305|PubMed:28441531"
FT /id="PRO_0000441326"
FT CHAIN 483..931
FT /note="Myelin regulatory factor homolog 1, C-terminal"
FT /evidence="ECO:0000305|PubMed:28441531"
FT /id="PRO_0000441327"
FT TOPO_DOM 1..658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 659..679
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 680..931
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT DOMAIN 483..582
FT /note="Peptidase S74"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01025"
FT DNA_BIND 169..436
FT /note="NDT80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00850"
FT REGION 29..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 482..483
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01025,
FT ECO:0000269|PubMed:28441531"
FT CARBOHYD 797
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 912
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 274
FT /note="G->R: In ju1121; defective dorsal D (DD) GABAergic
FT motor neurons rewiring. Impairs the function of myrf-2 by
FT obstructing its function in the complex formed between
FT myrf-1 and myrf-2."
FT /evidence="ECO:0000269|PubMed:28441531"
FT MUTAGEN 483..931
FT /note="Missing: Lethality at the L2 larval stage. Localizes
FT to the nucleus. Defective synaptic rewiring of DD GABAergic
FT motor neurons."
FT /evidence="ECO:0000269|PubMed:33950834"
FT MUTAGEN 483
FT /note="S->A: Prevents cleavage and generation of Myelin
FT regulatory factor homolog 1, N-terminal part. Lethality at
FT the larval developmental stage; when associated with A-488.
FT Only localizes to the cell membrane during viable stages;
FT when associated with A-488. Defective synaptic rewiring of
FT DD GABAergic motor neurons; when associated with A-488."
FT /evidence="ECO:0000269|PubMed:28441531,
FT ECO:0000269|PubMed:33950834"
FT MUTAGEN 488
FT /note="K->A: Lethality at the larval developmental stage;
FT when associated with A-483. Only localizes to the cell
FT membrane during viable stages; when associated with A-483.
FT Defective synaptic rewiring of DD GABAergic motor neurons;
FT when associated with A-483."
FT /evidence="ECO:0000269|PubMed:33950834"
FT MUTAGEN 657..931
FT /note="Missing: Lethality at the L2 larval stage. Localizes
FT to the nucleus. Defective synaptic rewiring of DD GABAergic
FT motor neurons."
FT /evidence="ECO:0000269|PubMed:33950834"
FT MUTAGEN 701..931
FT /note="Missing: Lethality at the L2 larval stage. Localizes
FT to the cytoplasm during the viable stages. Localizes to
FT nuclei of seam cells, epidermal cells, and intestinal
FT cells. Precocious synaptic rewiring of DD GABAergic motor
FT neurons whereby dorsal synapses are not uniformly
FT distributed along the dorsal cord, meaning some synaptic
FT rewiring of DD GABAergic motor neurons occurs, but not
FT always. Advances M-cell lineage division. Delays M-cell
FT lineage division in a myrf-2 ybq42 mutant background."
FT /evidence="ECO:0000269|PubMed:33950834"
FT MUTAGEN 791..931
FT /note="Missing: Lethality at the L2 larval stage. Only
FT localizes to the cytoplasm during the viable stages.
FT Abolishes synaptic rewiring of DD GABAergic motor neurons
FT in a myrf-2 ybq42 mutant background."
FT /evidence="ECO:0000269|PubMed:33950834"
SQ SEQUENCE 931 AA; 104463 MW; C1B7F38712BBF6CD CRC64;
MSSSDLLKGE FDGLNSEHFN MMQYLTQDTD EDDGSMVSPT SSADSMHQNL GVQQQQQQML
QAQQRQNQNG IFQPRRFPES PAMTDPCGNV SSSSSSSHHS DPMFSPNEFN GYAGANDNGN
QTMNNIQSQQ LSQQQHQQTR GGNLMMPQQS SIHAQMQNMN APQFWSQPGT AAVNQPTNTL
AQLNLFNIIR GGADSGMPSP VLEMPRKRSR LDTPCETPRI APSFAGIDGF PDENYSQQQA
IRFSKFQEEQ WSPLYDINAQ PLQQLQVHVV ADKGFNYNSN DNCFVNQKKN HFQISVNVEA
SDTMPPKYVN FNNRLVPIRD FKLSFCGVKA EMPSSEITIR QSRADRKPHT HTPVLFEIQE
RRMTKVCVPR LHFSETTLNN QRKQKNRPNP EQKFFLLVVR LFASIDESEH GVLIQSYASE
KVIVRATNPG SFEPQDTDIG WQRNGGALYT QGAVSVGTEH QVESAKLTVA GDIYMSGRII
NPSDIRLKEA ITERETAEAI ENLLKLRVVD YRYKPEVADI WGLDEQQRHR TGLIAQELQA
VLPDAVRDIG DYLTIDEGRV FYETVMATQQ LCRMTGDLDS KIDEKVAEIS RRLNEYAVRK
KLASSMASNL NGDNKSLSYS RCSLTSTATN ATSQPKRSRK HRAIKQAQSC GSRLSQGTVV
TLVSIMAACL LAMSALYVLD WHNRNYGYHQ HFETNTPSTK GELANLVISP ANFMPSFQPD
APILLEKCFN PSCKTYCCTD TPPVVEDSRA IATHGLDNGD EVYPESPSNR TNGIARAPNL
EHMAFETGVE IRIPALNVTL DQRYCVERSC NKRKGIFNVF VPVSRYMPDV ALEIEIKAPI
SKVVSNCGAF PSTEFNHKVC PLSRTQQSES PVPTSTRLFD NIFELSMGSF IQSAYRFRVG
YSTETCFSED SNGSYEEYNL IFYRMCTLSS S
