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SEM4_CAEEL
ID   SEM4_CAEEL              Reviewed;         744 AA.
AC   G5EFF4; Q7JNU7;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 1.
DT   03-AUG-2022, entry version 92.
DE   RecName: Full=Spalt-like protein sem-4 {ECO:0000305};
DE   AltName: Full=Sex muscle abnormal protein sem-4 {ECO:0000312|WormBase:F15C11.1};
DE   AltName: Full=Transcription factor sem-4 {ECO:0000305};
GN   Name=sem-4 {ECO:0000312|WormBase:F15C11.1};
GN   ORFNames=F15C11.1 {ECO:0000312|WormBase:F15C11.1};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN   [1] {ECO:0000312|EMBL:AAB03333.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF HIS-323 AND
RP   569-GLN--SER-744.
RC   STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB03333.1};
RX   PubMed=8756352; DOI=10.1101/gad.10.15.1953;
RA   Basson M., Horvitz H.R.;
RT   "The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal
RT   cell development and encodes a zinc finger protein.";
RL   Genes Dev. 10:1953-1965(1996).
RN   [2] {ECO:0000312|Proteomes:UP000001940}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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   [3] {ECO:0000305}
RP   FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF HIS-323; 383-ALA--SER-744
RP   AND 569-GLN--SER-744.
RX   PubMed=10926783; DOI=10.1006/dbio.2000.9774;
RA   Grant K., Hanna-Rose W., Han M.;
RT   "sem-4 promotes vulval cell-fate determination in Caenorhabditis elegans
RT   through regulation of lin-39 Hox.";
RL   Dev. Biol. 224:496-506(2000).
RN   [4] {ECO:0000305}
RP   FUNCTION, AND MUTAGENESIS OF HIS-323 AND 569-GLN--SER-744.
RX   PubMed=12835398; DOI=10.1242/dev.00398;
RA   Toker A.S., Teng Y., Ferreira H.B., Emmons S.W., Chalfie M.;
RT   "The Caenorhabditis elegans spalt-like gene sem-4 restricts touch cell fate
RT   by repressing the selector Hox gene egl-5 and the effector gene mec-3.";
RL   Development 130:3831-3840(2003).
RN   [5] {ECO:0000305}
RP   FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 275-TRP--SER-744 AND
RP   569-GLN--SER-744.
RX   PubMed=28614700; DOI=10.1016/j.ydbio.2017.06.011;
RA   Shen Q., Shi H., Tian C., Ghai V., Liu J.;
RT   "The C. elegans Spalt-like protein SEM-4 functions through the SoxC
RT   transcription factor SEM-2 to promote a proliferative blast cell fate in
RT   the postembryonic mesoderm.";
RL   Dev. Biol. 429:335-342(2017).
RN   [6] {ECO:0000305}
RP   FUNCTION, AND MUTAGENESIS OF 569-GLN--SER-744.
RX   PubMed=32718932; DOI=10.1534/g3.120.401316;
RA   Rafikova A., Hu Q., Kubiseski T.J.;
RT   "The SEM-4 Transcription Factor Is Required for Regulation of the Oxidative
RT   Stress Response in Caenorhabditis elegans.";
RL   G3 (Bethesda) 10:3379-3385(2020).
CC   -!- FUNCTION: Transcription factor, involved in positive and negative
CC       modulation of transcription (PubMed:12835398, PubMed:28614700). Binds
CC       to multiple DNA sequence motifs in the regulatory elements of target
CC       genes, including homeobox selector egl-5 and LIM homeobox mec-3
CC       (PubMed:12835398). Involved in cell-fate regulation in multiple
CC       lineages, including neuronal, mesodermal and vulval (PubMed:8756352,
CC       PubMed:28614700, PubMed:12835398, PubMed:10926783). Required to
CC       regulate the fate of PLM touch receptor neurons, acting via negative
CC       modulation of transcription of egl-5 and mec-3 (PubMed:12835398). May
CC       modulate gene expression by interacting with different transcription
CC       factors during neuronal and mesodermal cell development
CC       (PubMed:8756352). Promotes the proliferative sex myoblast (SM) fate, in
CC       a cell autonomous manner, acting via the SoxC transcription factor sem-
CC       2 (PubMed:28614700). Involved in vulval cell-fate determination, acting
CC       by regulating expression of homeobox protein lin-39, and may link lin-
CC       39 to incoming signaling pathways (PubMed:10926783). Plays a role in
CC       detoxification of reactive oxygen species (ROS), by regulating
CC       expression of transcription factor skn-1 and the phase II
CC       detoxification genes (PubMed:32718932). {ECO:0000269|PubMed:10926783,
CC       ECO:0000269|PubMed:12835398, ECO:0000269|PubMed:28614700,
CC       ECO:0000269|PubMed:32718932, ECO:0000269|PubMed:8756352}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- DEVELOPMENTAL STAGE: Expressed throughout the mesodermal (M) lineage
CC       from the 1-M stage to the 18-M stage, and in the sex myoblast (SM) sub-
CC       lineage from the 2-SM stage to the 16-SM stage, before the cells
CC       differentiate (PubMed:28614700). Expression declines significantly in
CC       the differentiated coelomocytes (CC) and vulval muscles, but remains in
CC       the differentiated body-wall muscles (BWM) (PubMed:28614700). Expressed
CC       in the vulval precursor cells (VPC) during larval development
CC       (PubMed:10926783). {ECO:0000269|PubMed:10926783,
CC       ECO:0000269|PubMed:28614700}.
CC   -!- SIMILARITY: Belongs to the sal C2H2-type zinc-finger protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB03334.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305, ECO:0000312|WormBase:F15C11.1};
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DR   EMBL; U60112; AAB03333.1; -; mRNA.
DR   EMBL; U60113; AAB03334.1; ALT_INIT; mRNA.
DR   EMBL; BX284601; CAA95798.1; -; Genomic_DNA.
DR   PIR; T20969; T20969.
DR   RefSeq; NP_491997.1; NM_059596.4.
DR   AlphaFoldDB; G5EFF4; -.
DR   IntAct; G5EFF4; 21.
DR   STRING; 6239.F15C11.1; -.
DR   EPD; G5EFF4; -.
DR   PaxDb; G5EFF4; -.
DR   PeptideAtlas; G5EFF4; -.
DR   EnsemblMetazoa; F15C11.1.1; F15C11.1.1; WBGene00004773.
DR   GeneID; 172435; -.
DR   KEGG; cel:CELE_F15C11.1; -.
DR   CTD; 172435; -.
DR   WormBase; F15C11.1; CE17673; WBGene00004773; sem-4.
DR   eggNOG; KOG1074; Eukaryota.
DR   GeneTree; ENSGT00940000167374; -.
DR   HOGENOM; CLU_344259_0_0_1; -.
DR   InParanoid; G5EFF4; -.
DR   OMA; DIREHKC; -.
DR   OrthoDB; 1318335at2759; -.
DR   PhylomeDB; G5EFF4; -.
DR   Reactome; R-CEL-8943724; Regulation of PTEN gene transcription.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00004773; 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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR   GO; GO:0048333; P:mesodermal cell differentiation; IMP:UniProtKB.
DR   GO; GO:0042692; P:muscle cell differentiation; IMP:WormBase.
DR   GO; GO:0048626; P:myoblast fate specification; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:WormBase.
DR   GO; GO:0014016; P:neuroblast differentiation; IMP:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0043618; P:regulation of transcription from RNA polymerase II promoter in response to stress; IMP:UniProtKB.
DR   GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR   GO; GO:0060290; P:transdifferentiation; IMP:WormBase.
DR   GO; GO:0072326; P:vulval cell fate determination; IMP:UniProtKB.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   SMART; SM00355; ZnF_C2H2; 8.
DR   SUPFAM; SSF57667; SSF57667; 2.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 7.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE   1: Evidence at protein level;
KW   Metal-binding; Nucleus; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..744
FT                   /note="Spalt-like protein sem-4"
FT                   /id="PRO_0000454590"
FT   ZN_FING         99..124
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         305..327
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         333..355
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         411..433
FT                   /note="C2H2-type 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         589..611
FT                   /note="C2H2-type 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         617..639
FT                   /note="C2H2-type 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         701..723
FT                   /note="C2H2-type 7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          6..32
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          487..530
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          542..562
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          725..744
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        511..530
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         275..744
FT                   /note="Missing: In h769; sex myoblasts (SM) are transformed
FT                   into body-wall muscles (BWM), and coelomocytes transformed
FT                   into their ventral counterparts, the SM progenitors, which
FT                   subsequently give rise to two BWMs. Expression of sem-2 is
FT                   abolished in the M mesoblast-derived lineage."
FT                   /evidence="ECO:0000269|PubMed:28614700"
FT   MUTAGEN         323
FT                   /note="H->Y: In n2654; severe pleiotropic abnormalities,
FT                   including defects in the development of the sex myoblasts,
FT                   a mesodermal cell type, and of two classes of neurons, the
FT                   DVB and AVL GABAergic motor neurons. Absence of sex
FT                   myoblasts in 7% of L3 larvae, defects in differentiation of
FT                   hermaphrodite-specific neurons (HSN), and M mesoblast-
FT                   derived coelomocytes (CC) absent in 2% of L3 larvae.
FT                   Distended intestine in 84% of adults. Vulval precursor
FT                   cells (VPC), P5.p and P7.p, appear to adopt normal cell
FT                   fates. Reduced touch-response."
FT                   /evidence="ECO:0000269|PubMed:10926783,
FT                   ECO:0000269|PubMed:12835398, ECO:0000269|PubMed:8756352"
FT   MUTAGEN         383..744
FT                   /note="Missing: In ku200; disrupts function in the vulva
FT                   and mesoderm. Vulval precursor cells (VPC), P5.p and P7.p,
FT                   adopt abnormal cell fates. Expression of lin-39 in vulval
FT                   cells reduced drastically."
FT                   /evidence="ECO:0000269|PubMed:10926783"
FT   MUTAGEN         569..744
FT                   /note="Missing: In n1378; severe pleiotropic abnormalities,
FT                   including defects in the development of the sex myoblasts,
FT                   a mesodermal cell type, and of two classes of neurons, the
FT                   DVB and AVL GABAergic motor neurons. Absence of sex
FT                   myoblasts in 98% of L3 larvae, defects in differentiation
FT                   of hermaphrodite-specific neurons (HSN), and M mesoblast-
FT                   derived coelomocytes (CC) absent in 30% of L3 larvae. Sex
FT                   myoblasts (SM) are transformed into body-wall muscles
FT                   (BWM), and coelomocytes transformed into their ventral
FT                   counterparts, the SM progenitors, which subsequently give
FT                   rise to two BWMs. Distended intestine in only 2% of adults.
FT                   Vulval precursor cells (VPC), P5.p and P7.p, adopt abnormal
FT                   cell fates. Reduced touch-response. Reduced gst-4
FT                   expression."
FT                   /evidence="ECO:0000269|PubMed:10926783,
FT                   ECO:0000269|PubMed:12835398, ECO:0000269|PubMed:28614700,
FT                   ECO:0000269|PubMed:32718932, ECO:0000269|PubMed:8756352"
SQ   SEQUENCE   744 AA;  81694 MW;  BCF468C639A30182 CRC64;
     MNELLAEMAA VSSRRKQSKP RRMSGEGDAM MSPIDLSTKS FDENNCEKGA GGALPLEDRS
     NILPHFSVPF ANPQQFLSLC AQLGNSSSRN VSSTASTTSS CPIQSCSQSF SSPAALTWHV
     LDAHEDEQEI FSCDVCTTTF SNGQDIREHK CQKTLASRST SVPPSTIPSS VCFLSTPTTP
     CLQFSINESI GTSEIREEDE EEDMDVEDGE HVANQLFGHL LQKSDDKSKM ASLFNHAFPP
     FAAFPNMPPP FLMRQPFDPR ADVFAAGRHD NDDDWEALME ISTSDEAEKI RALVGDKAVP
     TTDPNQCILC RRVLSCKSAL QMHYRTHTGE RPFKCKICQR AFTTKGNLKT HMGVHRSKHS
     FRGLPISLPP QLAAMHQHQH QIAPPQRIHI HNPPTSAASA AAAVAQIQAS QQCPICQQRF
     LNAGELAVHI TEHRNSLTQP PRVMPTPTTT RVQTFPFVPF FTTPPSLNAT DMSTQFNLAN
     ILSAQLKNDS SPNTDTSSVE EKITRDDPPK MASLSPSNSS DSSSSVRQDI LESSEFEEKL
     KKLEEPPILE QQVSTTPNPK NENPLLAMQK MWAETEPPPP RQMPVLSKHQ CGVCFKHFSS
     SSALQIHMRT HTGDKPFKCD MCGRAFTTRG NLKVHMGTHS WQQSPSRRGR RIFDVASSVT
     EKPMLQSPIL PTSGAPGASP LAMLGPNGLS GLEMMMMLWR TVCSVCQKVC QSPNELEQHL
     KEHLNNGSSA APTPLASAAT PPPS
 
 
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