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TRA2_CAEEL
ID   TRA2_CAEEL              Reviewed;        1475 AA.
AC   P34709; Q8STA8; Q8STE2; Q8T5X5; Q8T5X6; Q8T5X7; Q8T5X8; Q8T5X9; Q8T5Y0;
AC   Q8T5Y1; Q8T5Y2; Q8T5Y3; Q8T5Y4; Q8T5Y5; Q9N5Y5;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   03-AUG-2022, entry version 138.
DE   RecName: Full=Sex-determining transformer protein 2;
DE   AltName: Full=Ce-Tra-2;
DE   Flags: Precursor;
GN   Name=tra-2; ORFNames=C15F1.3;
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 [MRNA] (ISOFORM TRA-2A), FUNCTION, AND SUBCELLULAR
RP   LOCATION.
RC   STRAIN=Bristol N2;
RX   PubMed=1498366; DOI=10.1091/mbc.3.4.461;
RA   Kuwabara P.E., Okkema P.G., Kimble J.;
RT   "tra-2 encodes a membrane protein and may mediate cell communication in the
RT   Caenorhabditis elegans sex determination pathway.";
RL   Mol. Biol. Cell 3:461-473(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TRA-2A), ALTERNATIVE INITIATION
RP   (ISOFORM TRA-2B), FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=Bristol N2;
RX   PubMed=9851857; DOI=10.1006/dbio.1998.9062;
RA   Kuwabara P.E., Okkema P.G., Kimble J.;
RT   "Germ-line regulation of the Caenorhabditis elegans sex-determining gene
RT   tra-2.";
RL   Dev. Biol. 204:251-262(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 11-142.
RC   STRAIN=AB1, AB2, CB4507, CB4851, CB4852, CB4853, CB4854, CB4855, CB4856,
RC   CB4857, CB4858, CB4932, DH424, DR1344, PB303, PB305, PB306, PB307, and
RC   TR388;
RX   PubMed=12019226; DOI=10.1093/genetics/161.1.99;
RA   Graustein A., Gaspar J.M., Walters J.R., Palopoli M.F.;
RT   "Levels of DNA polymorphism vary with mating system in the nematode genus
RT   Caenorhabditis.";
RL   Genetics 161:99-107(2002).
RN   [5]
RP   FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=Bristol N2;
RX   PubMed=1703488; DOI=10.1002/j.1460-2075.1991.tb07933.x;
RA   Okkema P.G., Kimble J.;
RT   "Molecular analysis of tra-2, a sex determining gene in C.elegans.";
RL   EMBO J. 10:171-176(1991).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH FEM-3.
RC   STRAIN=Bristol N2;
RX   PubMed=10364161; DOI=10.1101/gad.13.11.1453;
RA   Mehra A., Gaudet J., Heck L., Kuwabara P.E., Spence A.M.;
RT   "Negative regulation of male development in Caenorhabditis elegans by a
RT   protein-protein interaction between TRA-2A and FEM-3.";
RL   Genes Dev. 13:1453-1463(1999).
RN   [7]
RP   FUNCTION, AND CLEAVAGE BY TRA-3.
RX   PubMed=10783162;
RA   Sokol S.B., Kuwabara P.E.;
RT   "Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-
RT   2A by TRA-3.";
RL   Genes Dev. 14:901-906(2000).
RN   [8]
RP   FUNCTION, INTERACTION WITH TRA-1, AND MUTAGENESIS OF CYS-1392; GLU-1393 AND
RP   ARG-1400.
RX   PubMed=11124807;
RA   Lum D.H., Kuwabara P.E., Zarkower D., Spence A.M.;
RT   "Direct protein-protein interaction between the intracellular domain of
RT   TRA-2 and the transcription factor TRA-1A modulates feminizing activity in
RT   C. elegans.";
RL   Genes Dev. 14:3153-3165(2000).
RN   [9]
RP   FUNCTION, INTERACTION WITH TRA-1, AND MUTAGENESIS OF GLU-1393; ARG-1400 AND
RP   PRO-1411.
RC   STRAIN=Bristol N2;
RX   PubMed=11250902; DOI=10.1093/emboj/20.6.1363;
RA   Wang S., Kimble J.;
RT   "The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in
RT   Caenorhabditis elegans.";
RL   EMBO J. 20:1363-1372(2001).
RN   [10]
RP   FUNCTION, AND INTERACTION WITH FEM-3.
RX   PubMed=12477393; DOI=10.1016/s0960-9822(02)01333-7;
RA   Haag E.S., Wang S., Kimble J.;
RT   "Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2.";
RL   Curr. Biol. 12:2035-2041(2002).
CC   -!- FUNCTION: Plays a major role in controlling sexual cell fates. Promotes
CC       female development in XX animals where it sequesters one or more of the
CC       FEM proteins to the membrane thereby freeing the tra-1 protein (a
CC       putative transcription factor) to enter the nucleus and promote female
CC       development. In XO animals it acts as a receptor for her-1 which
CC       prevents it from binding to FEM proteins thereby repressing the
CC       activity of tra-1. Negatively regulates male development when bound to
CC       fem-3 and is required together with tra-1 for promoting
CC       spermatogenesis. Also required for feminizing tra-3 activity.
CC       {ECO:0000269|PubMed:10364161, ECO:0000269|PubMed:10783162,
CC       ECO:0000269|PubMed:11124807, ECO:0000269|PubMed:11250902,
CC       ECO:0000269|PubMed:12477393, ECO:0000269|PubMed:1498366,
CC       ECO:0000269|PubMed:1703488, ECO:0000269|PubMed:9851857}.
CC   -!- SUBUNIT: Interacts with tra-1 and fem-3. {ECO:0000269|PubMed:10364161,
CC       ECO:0000269|PubMed:11124807, ECO:0000269|PubMed:11250902,
CC       ECO:0000269|PubMed:12477393}.
CC   -!- INTERACTION:
CC       P34709; P34691: fem-3; NbExp=4; IntAct=EBI-367223, EBI-445465;
CC       P34709; P34708: tra-1; NbExp=5; IntAct=EBI-367223, EBI-367204;
CC       P34709; P34708-1: tra-1; NbExp=5; IntAct=EBI-367223, EBI-367214;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:1498366}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:1498366}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC       Name=Tra-2A; Synonyms=a;
CC         IsoId=P34709-1; Sequence=Displayed;
CC       Name=b;
CC         IsoId=P34709-2; Sequence=VSP_011746, VSP_011747;
CC       Name=Tra-2B;
CC         IsoId=P34709-3; Sequence=VSP_018823;
CC   -!- TISSUE SPECIFICITY: Somatic and germline tissues. Isoform Tra-2B is
CC       specific to oocytes. {ECO:0000269|PubMed:1703488,
CC       ECO:0000269|PubMed:9851857}.
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC       {ECO:0000269|PubMed:1703488, ECO:0000269|PubMed:9851857}.
CC   -!- PTM: Undergoes cleavage by tra-3 to produce a feminizing carboxy-
CC       terminal isoform Tra-2B. {ECO:0000269|PubMed:10783162}.
CC   -!- MISCELLANEOUS: Isoform Tra-2B is likely to be cytoplasmic because it
CC       lacks an N-terminal sequence and potential membrane spanning domains.
CC   -!- MISCELLANEOUS: The MX region mediates a post-translational regulation,
CC       essential for the onset of hermaphrodite spermatogenesis.
CC   -!- MISCELLANEOUS: [Isoform Tra-2B]: Produced by alternative initiation at
CC       Met-1089 of isoform Tra-2A. {ECO:0000305}.
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DR   EMBL; M91371; AAA28150.1; -; mRNA.
DR   EMBL; S42187; AAB22845.1; -; mRNA.
DR   EMBL; FO080553; CCD64611.1; -; Genomic_DNA.
DR   EMBL; FO080553; CCD64612.1; -; Genomic_DNA.
DR   EMBL; AF491489; AAM09771.1; -; Genomic_DNA.
DR   EMBL; AF491490; AAM09772.1; -; Genomic_DNA.
DR   EMBL; AF491491; AAM09773.1; -; Genomic_DNA.
DR   EMBL; AF491492; AAM09774.1; -; Genomic_DNA.
DR   EMBL; AF491493; AAM09775.1; -; Genomic_DNA.
DR   EMBL; AF491494; AAM09776.1; -; Genomic_DNA.
DR   EMBL; AF491495; AAM09777.1; -; Genomic_DNA.
DR   EMBL; AF491496; AAM09778.1; -; Genomic_DNA.
DR   EMBL; AF491497; AAM09779.1; -; Genomic_DNA.
DR   EMBL; AF491498; AAM09780.1; -; Genomic_DNA.
DR   EMBL; AF491499; AAM09781.1; -; Genomic_DNA.
DR   EMBL; AF491500; AAM09782.1; -; Genomic_DNA.
DR   EMBL; AF491501; AAM09783.1; -; Genomic_DNA.
DR   EMBL; AF491502; AAM09784.1; -; Genomic_DNA.
DR   EMBL; AF491503; AAM09785.1; -; Genomic_DNA.
DR   EMBL; AF491504; AAM09786.1; -; Genomic_DNA.
DR   EMBL; AF491505; AAM09787.1; -; Genomic_DNA.
DR   EMBL; AF491506; AAM09788.1; -; Genomic_DNA.
DR   EMBL; AF491507; AAM09789.1; -; Genomic_DNA.
DR   PIR; A60026; A60026.
DR   RefSeq; NP_001021954.1; NM_001026783.3. [P34709-2]
DR   RefSeq; NP_495426.1; NM_063025.7. [P34709-1]
DR   AlphaFoldDB; P34709; -.
DR   BioGRID; 39475; 9.
DR   IntAct; P34709; 2.
DR   MINT; P34709; -.
DR   STRING; 6239.C15F1.3a; -.
DR   iPTMnet; P34709; -.
DR   EPD; P34709; -.
DR   PaxDb; P34709; -.
DR   PRIDE; P34709; -.
DR   EnsemblMetazoa; C15F1.3a.1; C15F1.3a.1; WBGene00006605. [P34709-1]
DR   EnsemblMetazoa; C15F1.3b.1; C15F1.3b.1; WBGene00006605. [P34709-2]
DR   GeneID; 174137; -.
DR   KEGG; cel:CELE_C15F1.3; -.
DR   UCSC; C15F1.3a.1; c. elegans. [P34709-1]
DR   CTD; 174137; -.
DR   WormBase; C15F1.3a; CE23546; WBGene00006605; tra-2. [P34709-1]
DR   WormBase; C15F1.3b; CE23547; WBGene00006605; tra-2. [P34709-2]
DR   eggNOG; ENOG502R9RT; Eukaryota.
DR   InParanoid; P34709; -.
DR   OMA; SIWTIER; -.
DR   OrthoDB; 1388750at2759; -.
DR   SignaLink; P34709; -.
DR   PRO; PR:P34709; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00006605; Expressed in embryo and 4 other tissues.
DR   ExpressionAtlas; P34709; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR   GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR   GO; GO:0044214; C:spanning component of plasma membrane; IDA:WormBase.
DR   GO; GO:0038023; F:signaling receptor activity; TAS:UniProtKB.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:WormBase.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0018992; P:germ-line sex determination; IBA:GO_Central.
DR   GO; GO:0040021; P:hermaphrodite germ-line sex determination; IMP:WormBase.
DR   GO; GO:0042001; P:hermaphrodite somatic sex determination; IMP:WormBase.
DR   GO; GO:0007530; P:sex determination; IMP:UniProtKB.
DR   GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR   InterPro; IPR032848; Ce-Tra-2.
DR   PANTHER; PTHR39365; PTHR39365; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Alternative splicing; Developmental protein;
KW   Differentiation; Membrane; Receptor; Reference proteome;
KW   Sexual differentiation; Signal; Spermatogenesis; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255"
FT   CHAIN           32..1475
FT                   /note="Sex-determining transformer protein 2"
FT                   /id="PRO_0000022574"
FT   TRANSMEM        446..466
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        474..494
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        496..516
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        589..609
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        737..757
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        902..922
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        928..948
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        952..972
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        979..999
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1034..1054
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        1060..1080
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1133..1273
FT                   /note="Interaction with fem-3"
FT   REGION          1142..1194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1267..1330
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1392..1413
FT                   /note="MX regulatory domain; required for tra-1 binding"
FT   REGION          1424..1475
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1267..1311
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1428..1442
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1449..1475
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            1088..1089
FT                   /note="Cleavage; by tra-3"
FT   VAR_SEQ         1..1088
FT                   /note="Missing (in isoform Tra-2B)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018823"
FT   VAR_SEQ         1044..1147
FT                   /note="AFSILAIICSIVPELNIFFVPTVILIVIQIVAVFNSIIVSIATKQMFESEVR
FT                   HYLHRDLRGSTTAVRVYNLVQKQRLASSLDEPQVELDEFSIKRSSPPCRYYA -> EFP
FT                   KREVTCQNWWPFSSSRSSICSFFFHSHPSSIILATLSIFRQYIYLFSLFSFSHSSSDVS
FT                   NKKSRGYCRCMSCFSIFFQRVWPQEHWNTANNEKGTQKESGC (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_011746"
FT   VAR_SEQ         1148..1475
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_011747"
FT   MUTAGEN         1392
FT                   /note="C->Y: Prevents binding with tra-1."
FT                   /evidence="ECO:0000269|PubMed:11124807"
FT   MUTAGEN         1393
FT                   /note="E->K: Causes weak somatic masculinization; prevents
FT                   binding with tra-1."
FT                   /evidence="ECO:0000269|PubMed:11124807,
FT                   ECO:0000269|PubMed:11250902"
FT   MUTAGEN         1400
FT                   /note="R->Q: Causes weak somatic masculinization; prevents
FT                   binding with tra-1."
FT                   /evidence="ECO:0000269|PubMed:11124807,
FT                   ECO:0000269|PubMed:11250902"
FT   MUTAGEN         1411
FT                   /note="P->L: Causes weak somatic masculinization."
FT                   /evidence="ECO:0000269|PubMed:11250902"
FT   CONFLICT        134..139
FT                   /note="LLEMQR -> FLKCNV (in Ref. 4; AAM09789)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1475 AA;  170353 MW;  F8C6456B3D3654BE CRC64;
     MKLKYNKLLV SVVIVTFVTF GLLLAECFGK SIDYQEKSIF PSFVSQGFFE TRTNNEEYII
     EKIAQTQENG VDMRSTLHFT QHGYLLNNIS NLKIKFRQKT YTLNDVCFKP HITIFQQSSS
     SDQNEYPHYI QRLLLEMQRL SPCLIVTPLN CFYDIYRIHG EISNWNKNTD FLNRRLRNSY
     IEAIGENDER PYVKSNYGPS LIKSWADHMF DLPSKSFTNS TKDALFQKIK LWLLSIEPRQ
     KTCAASIHSC DTPLDSEHYF NICTDMQSVD NFAEKKTKFK LEDVDEEFAM NLDCVDDQEQ
     FIEWMQELEI RKMYSHVTEK PDYPNVVNQT CDKIFHDLNS TGIEFFDGSR SFSSTKSQFD
     TMQTEIVLLT PEMLLSAMQH SDFVNGFESI WTIEKAEELI HEFRLALKEE TEKFKENRMS
     KMIRVTSRVL DNTVTTKLQS FSEKQTIHFV VNVHSLIVIL FTIFVWSGAP LRSAFMFFVR
     DALTCLLFCF VCSTDGVIVL DTELIKYIIV LTLANLYFTT RSSFCTERLS RCIQREKRFP
     INSNFASLIT VDTMTDSRQI QYFLSTVTKY QAAQDSYSNE LFERFPKNWG CTSILIFPIV
     FVYWYFIDSN FDKICVSVLP SFCLAAGEEL FAKNMFWKER EAMQAKQRLE NEEQAESITG
     SSLEKLFAGN KPVSNTDKAN IVKKSSIIRN QKPCLQDLSP GTYDVSNFMK YPHQASRIFR
     EKIIGLYLRI LKLRTLGVIL CIPAILLIVI SIGLLFIPVK RETLHTDSKQ DDIFIEFEIF
     NFSTNWKIVN QNLKQFSEDI ESIGTLYTIS NWQKSFERFE QETNKNASAE WNILFKWIND
     EPINSAVTLF SEKSSGNQTI ANPFKFRLRY GFDAKNETTV IEIVQKIDEL LSKCSKNLSP
     KAVGVLYEHY HRIAVVWNLF AFNQLTTAGI FIILLSIITF IFAITPTIKA TFLFSLLVVG
     TQIEVAALVH LFSLDHHQIY TNLALFAGFL AAWDPFCALL RYRRRILYKS ETRRTPELAS
     KRRVLLPIVA TADIAQFFVL LITAFSILAI ICSIVPELNI FFVPTVILIV IQIVAVFNSI
     IVSIATKQMF ESEVRHYLHR DLRGSTTAVR VYNLVQKQRL ASSLDEPQVE LDEFSIKRSS
     PPCRYYAPPP KYSCKKRSRS SDEDEDSDPN QPGPSNRRSP KTGNKRVRGN GDNTELYIPN
     RYELIVSGKS VGGNTSAAWN GPGSTLEQNM NALEECFELG VDEYDFDEHD GDEGCELVQD
     MLDRERNLMN KRSTAQRRES RNIEKMKKSQ ENLDKEKSEE KISESKKNQD DSIESPNLPG
     TPANLPVDEP LPPVGRLYIV EHVLPEEYRR DPLTEPPSME DCIRAHSDPN LPPHPRADQY
     PASFTRPMVE YCEDIYWTHR TGQLPPGLQV PRRPYDYYHI TERTPPPEDL NWVPPAESPP
     IPIPQQAFDL LEERRRNHRE QQDEAREGDL SDPEV
 
 
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