ZAG1_CAEEL
ID ZAG1_CAEEL Reviewed; 596 AA.
AC G5EBU4;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Zinc finger E-box-binding homeobox protein zag-1;
DE AltName: Full=Zinc finger involved in axon guidance 1 {ECO:0000303|PubMed:12835395};
DE Short=ZAG-1 {ECO:0000312|EMBL:AAP37457.1};
GN Name=zag-1 {ECO:0000312|EMBL:CCD70186.1, ECO:0000312|WormBase:F28F9.1};
GN ORFNames=F28F9.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAP43944.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=12835394; DOI=10.1242/dev.00571;
RA Clark S.G., Chiu C.;
RT "C. elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal
RT development and neuronal differentiation.";
RL Development 130:3781-3794(2003).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAP37457.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=12835395; DOI=10.1242/dev.00570;
RA Wacker I., Schwarz V., Hedgecock E.M., Hutter H.;
RT "zag-1, a Zn-finger homeodomain transcription factor controlling neuronal
RT differentiation and axon outgrowth in C. elegans.";
RL Development 130:3795-3805(2003).
RN [3] {ECO:0000312|EMBL:CCD70186.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CCD70186.1};
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 [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25474681; DOI=10.1371/journal.pone.0113893;
RA Ramakrishnan K., Okkema P.G.;
RT "Regulation of C. elegans neuronal differentiation by the ZEB-family factor
RT ZAG-1 and the NK-2 homeodomain factor CEH-28.";
RL PLoS ONE 9:e113893-e113893(2014).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30291162; DOI=10.1242/dev.168096;
RA Zheng C., Jin F.Q., Trippe B.L., Wu J., Chalfie M.;
RT "Inhibition of cell fate repressors secures the differentiation of the
RT touch receptor neurons of Caenorhabditis elegans.";
RL Development 145:0-0(2018).
CC -!- FUNCTION: Transcription factor (PubMed:12835394, PubMed:12835395,
CC PubMed:25474681, PubMed:30291162). Down-regulates expression of genes
CC involved in either the synthesis or reuptake of serotonin, dopamine and
CC GABA (PubMed:12835394). Acts as a transcriptional repressor to regulate
CC multiple, discrete, neuron-specific aspects of terminal
CC differentiation, including cell migration, axonal development and gene
CC expression (PubMed:12835394, PubMed:12835395, PubMed:25474681,
CC PubMed:30291162). Promotes touch receptor neuron differentiation by
CC repressing the expression of egl-44 and egl-46 (PubMed:30291162). As
CC egl-44 and egl-46, probably acting as a heterodimer, repress expression
CC of zag-1 in FLP neurons, together these proteins form a bistable,
CC negative-feedback loop that regulates the choice between neuronal fates
CC (PubMed:30291162). Required for axon guidance (PubMed:12835395).
CC Involved in the proper development of the pharynx (PubMed:12835395).
CC Required for pharynx isthmus peristalsis, probably via a role in the
CC differentiation of the M4 cholinergic motor neuron (PubMed:25474681).
CC Directly represses its own transcription by interacting with conserved
CC E-box sequence motifs 5'-CACCTG-3' in its own promoter
CC (PubMed:12835394, PubMed:12835395). May also act as a transcriptional
CC activator of the homeodomain ceh-28 (PubMed:25474681).
CC {ECO:0000269|PubMed:12835394, ECO:0000269|PubMed:12835395,
CC ECO:0000269|PubMed:25474681, ECO:0000269|PubMed:30291162}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:12835394}.
CC -!- TISSUE SPECIFICITY: Expressed in the six touch receptor neurons (TRNs)
CC but not in the FLP and PVD neurons (PubMed:30291162). Expressed in the
CC M4 cholinergic motor neuron (PubMed:25474681).
CC {ECO:0000269|PubMed:25474681, ECO:0000269|PubMed:30291162}.
CC -!- DEVELOPMENTAL STAGE: Detected in a few nuclei in the embryonic head as
CC the embryo reaches morphogenesis stage. Expressed in an increasing
CC number of nuclei as embryonic development progresses such that by the
CC 1.5-fold stage it is detected in a large number of neuronal cells in
CC the head and a few cells in the pharynx. At the 1.5-fold stage,
CC expression is also prominent in motorneurons in the ventral cord and in
CC neurons in tail ganglia. This expression is maintained during the 3-
CC fold stage, but is reduced to undetectable levels in most cells before
CC hatching. By the L1/L2 stage, expression is detected transiently in
CC postembryonic motorneurons. {ECO:0000269|PubMed:12835394,
CC ECO:0000269|PubMed:12835395}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit a starved appearance, are unable to
CC swallow food and die at the L1 larval stage (PubMed:12835395). RNAi-
CC mediated knockdown causes significant reduction in expression of mec-17
CC (PubMed:30291162). {ECO:0000269|PubMed:12835395,
CC ECO:0000269|PubMed:30291162}.
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DR EMBL; AY289599; AAP43944.1; -; mRNA.
DR EMBL; AY224511; AAP37457.1; -; mRNA.
DR EMBL; FO081249; CCD70186.1; -; Genomic_DNA.
DR PIR; T29204; T29204.
DR RefSeq; NP_500424.3; NM_068023.5.
DR AlphaFoldDB; G5EBU4; -.
DR SMR; G5EBU4; -.
DR BioGRID; 42283; 1.
DR IntAct; G5EBU4; 1.
DR STRING; 6239.F28F9.1; -.
DR EPD; G5EBU4; -.
DR PaxDb; G5EBU4; -.
DR EnsemblMetazoa; F28F9.1.1; F28F9.1.1; WBGene00006970.
DR GeneID; 177144; -.
DR KEGG; cel:CELE_F28F9.1; -.
DR CTD; 177144; -.
DR WormBase; F28F9.1; CE34546; WBGene00006970; zag-1.
DR eggNOG; KOG3623; Eukaryota.
DR GeneTree; ENSGT00870000136508; -.
DR HOGENOM; CLU_464864_0_0_1; -.
DR InParanoid; G5EBU4; -.
DR OMA; CKPYREQ; -.
DR OrthoDB; 890458at2759; -.
DR PhylomeDB; G5EBU4; -.
DR PRO; PR:G5EBU4; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006970; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0016358; P:dendrite development; IMP:UniProtKB.
DR GO; GO:0002164; P:larval development; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0048665; P:neuron fate specification; IMP:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP:WormBase.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 2: Evidence at transcript level;
KW Developmental protein; DNA-binding; Homeobox; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..596
FT /note="Zinc finger E-box-binding homeobox protein zag-1"
FT /id="PRO_0000419767"
FT ZN_FING 24..46
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 52..72
FT /note="C2H2-type 2; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT DNA_BIND 223..282
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT ZN_FING 481..503
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 509..531
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 537..560
FT /note="C2H2-type 5; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 133..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 569..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..359
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 596 AA; 66018 MW; 1491C2D4C9DF0A8E CRC64;
MVDIAEAMPT TASSLPSDEA LRKFKCPECT KAFKFKHHLK EHIRIHSGEK PFECQQCHKR
FSHSGSYSSH MSSKKCVQQA SPSMVTPFNP YQLMMYRNIM LQLQTPQVSF LPSTAANNMD
YMSLLQANLF QSLENGTSPT PTQEPSAPAS PEPKIEVVDE PEVSSEVKTE VKTEVKTEDS
VPEESITPAV SMSLSPAPEQ NGNESMNNGG SGSDGKSSPD WRPLRSRSFL NDSQVAVLQN
HFKRNPFPSK YELSAVAEQI GVNKRVVQVW FQNTRAKERR SNRLPSMPRG SVASAAAAAA
TSPTVWQTPV QLMAAWASQF SNGNNSLTAS QDERNNENTD EVMDHDGLKD GKETPLDLTL
STDDTEPEWS PEKLIGFLDQ TGGVIQELLR QAGNGFVTNQ EDEEEKPIKA EESPVSSGSS
SIWPSFIGQY PSILDSASLS VLEKALDQQK SSEDDASSLC SNESKLLKFP TTPLKEEEGL
FSCDQCDKVF GKQSSLARHK YEHSGQRPYK CDICEKAFKH KHHLTEHKRL HSGEKPFQCD
KCLKRFSHSG SYSQHMNHRY SYCKPYREQP ASPSDVLNGG SVTVSPSSSN TPPPST
