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HM35_CAEEL
ID   HM35_CAEEL              Reviewed;         335 AA.
AC   O17894;
DT   16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2005, sequence version 2.
DT   03-AUG-2022, entry version 156.
DE   RecName: Full=Homeobox protein unc-39 {ECO:0000305};
DE   AltName: Full=Homeobox protein ceh-35 {ECO:0000312|WormBase:F56A12.1};
DE   AltName: Full=Uncoordinated protein 39 {ECO:0000312|WormBase:F56A12.1};
GN   Name=unc-39 {ECO:0000312|WormBase:F56A12.1};
GN   Synonyms=ceh-35 {ECO:0000312|WormBase:F56A12.1},
GN   mig-3 {ECO:0000312|WormBase:F56A12.1};
GN   ORFNames=F56A12.1 {ECO:0000312|WormBase:F56A12.1};
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|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   [2] {ECO:0000305}
RP   FUNCTION, AND MUTAGENESIS OF ILE-220.
RX   PubMed=2361334; DOI=10.1002/dvg.1020110107;
RA   Manser J., Wood W.B.;
RT   "Mutations affecting embryonic cell migrations in Caenorhabditis elegans.";
RL   Dev. Genet. 11:49-64(1990).
RN   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP   AND MUTAGENESIS OF ARG-203; ILE-220 AND PRO-283.
RX   PubMed=15282156; DOI=10.1016/j.ydbio.2004.05.010;
RA   Yanowitz J.L., Shakir M.A., Hedgecock E., Hutter H., Fire A.Z.,
RA   Lundquist E.A.;
RT   "UNC-39, the C. elegans homolog of the human myotonic dystrophy-associated
RT   homeodomain protein Six5, regulates cell motility and differentiation.";
RL   Dev. Biol. 272:389-402(2004).
RN   [4] {ECO:0000305}
RP   FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF ARG-203 AND PRO-298.
RX   PubMed=27855782; DOI=10.7554/elife.19887;
RA   Lim M.A., Chitturi J., Laskova V., Meng J., Findeis D., Wiekenberg A.,
RA   Mulcahy B., Luo L., Li Y., Lu Y., Hung W., Qu Y., Ho C.Y., Holmyard D.,
RA   Ji N., McWhirter R., Samuel A.D., Miller D.M., Schnabel R., Calarco J.A.,
RA   Zhen M.;
RT   "Neuroendocrine modulation sustains the C. elegans forward motor state.";
RL   Elife 5:0-0(2016).
RN   [5]
RP   ERRATUM OF PUBMED:27855782.
RX   PubMed=28271995; DOI=10.7554/elife.26528;
RA   Lim M., Chitturi J., Laskova V., Meng J., Findeis D., Wiekenberg A.,
RA   Mulcahy B., Luo L., Li Y., Lu Y., Hung W., Qu Y., Ho C., Holmyard D.,
RA   Ji N., McWhirter R.D., Samuel A.D., Miller D.M., Schnabel R., Calarco J.A.,
RA   Zhen M.;
RT   "Correction: Neuroendocrine modulation sustains the C. elegans forward
RT   motor state.";
RL   Elife 6:0-0(2017).
CC   -!- FUNCTION: Probable transcription factor required for differentiation
CC       and migration of neuronal cells, such as RID and CAN neurons
CC       (PubMed:2361334, PubMed:15282156). Specifically, plays a role in the
CC       terminal differentiation of RID peptidergic neurons (PubMed:27855782).
CC       Also required for CAN neuron axon guidance (PubMed:15282156).
CC       {ECO:0000269|PubMed:15282156, ECO:0000269|PubMed:2361334,
CC       ECO:0000269|PubMed:27855782}.
CC   -!- INTERACTION:
CC       O17894; O17670: eya-1; NbExp=5; IntAct=EBI-317698, EBI-311862;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC       ECO:0000269|PubMed:15282156}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in muscles and neurons from
CC       embryogenesis to adulthood (PubMed:15282156, PubMed:27855782). First
CC       expressed post-fertilization, then accumulates in anterior cells of the
CC       embryo that give rise to neuronal and mesodermal tissues and body wall
CC       muscle cells, where expression persists and increases
CC       (PubMed:15282156). Also expressed in posterior nuclei post-
CC       fertilization (PubMed:15282156). At the 2-fold stage of embryogenesis,
CC       expression is restricted to fewer cells (PubMed:15282156).
CC       {ECO:0000269|PubMed:15282156, ECO:0000269|PubMed:27855782}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in 60% larval
CC       lethality (PubMed:15282156). Surviving animals display uncoordinated
CC       locomotion, withered tail morphology, and defects in both CAN neuronal
CC       cell migration and axon guidance (PubMed:15282156).
CC       {ECO:0000269|PubMed:15282156}.
CC   -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family.
CC       {ECO:0000305}.
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DR   EMBL; BX284605; CAB04483.2; -; Genomic_DNA.
DR   PIR; T22761; T22761.
DR   RefSeq; NP_506563.2; NM_074162.2.
DR   AlphaFoldDB; O17894; -.
DR   SMR; O17894; -.
DR   DIP; DIP-24571N; -.
DR   IntAct; O17894; 8.
DR   STRING; 6239.F56A12.1; -.
DR   PaxDb; O17894; -.
DR   EnsemblMetazoa; F56A12.1.1; F56A12.1.1; WBGene00006775.
DR   GeneID; 191623; -.
DR   KEGG; cel:CELE_F56A12.1; -.
DR   UCSC; F56A12.1; c. elegans.
DR   CTD; 191623; -.
DR   WormBase; F56A12.1; CE37921; WBGene00006775; unc-39.
DR   eggNOG; KOG0775; Eukaryota.
DR   GeneTree; ENSGT00940000167410; -.
DR   HOGENOM; CLU_872206_0_0_1; -.
DR   InParanoid; O17894; -.
DR   OMA; RYKESQL; -.
DR   OrthoDB; 1360664at2759; -.
DR   PhylomeDB; O17894; -.
DR   PRO; PR:O17894; -.
DR   Proteomes; UP000001940; Chromosome V.
DR   Bgee; WBGene00006775; Expressed in embryo and 3 other tissues.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR   GO; GO:0040011; P:locomotion; IMP:WormBase.
DR   GO; GO:0008078; P:mesodermal cell migration; IMP:WormBase.
DR   GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR   GO; GO:0018991; P:oviposition; IMP:WormBase.
DR   GO; GO:0040017; P:positive regulation of locomotion; IMP:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR   GO; GO:0110037; P:regulation of nematode male tail tip morphogenesis; 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; IPR031701; SIX1_SD.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF16878; SIX1_SD; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
PE   1: Evidence at protein level;
KW   Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..335
FT                   /note="Homeobox protein unc-39"
FT                   /id="PRO_0000446110"
FT   DNA_BIND        225..277
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          27..56
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          269..294
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        277..294
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         203
FT                   /note="R->Q: In e257; uncoordinated locomotion, withered
FT                   tail morphology, egg-laying defects, protruding vulvae and
FT                   multiple vulvae. Defective pharyngeal development, which
FT                   results in animals appearing starved. Mesodermal lineage
FT                   and neuronal cell migration and specification defects.
FT                   Abolishes differentiation of RID peptidergic neurons."
FT                   /evidence="ECO:0000269|PubMed:15282156,
FT                   ECO:0000269|PubMed:27855782"
FT   MUTAGEN         220
FT                   /note="I->IQF: In ct73; uncoordinated locomotion, withered
FT                   tail morphology, egg-laying defects, protruding vulvae and
FT                   multiple vulvae. Defective pharyngeal development, which
FT                   results in animals appearing starved. Mesodermal lineage
FT                   and neuronal cell migration and specification defects."
FT                   /evidence="ECO:0000269|PubMed:15282156,
FT                   ECO:0000269|PubMed:2361334"
FT   MUTAGEN         283
FT                   /note="P->L: In rh72; uncoordinated locomotion, withered
FT                   tail morphology, egg-laying defects, protruding vulvae and
FT                   multiple vulvae. Defective pharyngeal development, which
FT                   results in animals appearing starved. Mesodermal lineage
FT                   and neuronal cell migration and specification defects."
FT                   /evidence="ECO:0000269|PubMed:15282156"
FT   MUTAGEN         298
FT                   /note="P->L: In hp701; abolishes differentiation of RID
FT                   peptidergic neurons."
FT                   /evidence="ECO:0000269|PubMed:27855782"
SQ   SEQUENCE   335 AA;  38130 MW;  C98DC467D75A77DC CRC64;
     MTDHPPIDTS SYFDCYQQHQ LPLQYTFTSS SNSNTSNSST SPSHISDQFS SSGGPPYELS
     SHILTPSSVI PTPSPSVASA SISSPTIPAF GCTMSEYSME QMEAISTSLF QARDGDRLVA
     FFKQLESLYG PNAVDHLRSE AIIVAYTYAL YHSNEFETLF HLLSNRHFQQ RHYNDLQDIW
     HHARYKESQL KRGKELNPVE KYRLRRKFPA PKTIWDGEEI VYSFKDSSRK FLKQFFRNVS
     EYPTQEQKRE ISRATGLKIV QISNWFKNRR QRDKSNNSAK CSPPSSSSST NGGSDFLPII
     TPQSFNLAAA PFNMNMIYGT LRDSQSDNDQ FTFNP
 
 
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