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LIN44_CAEEL
ID   LIN44_CAEEL             Reviewed;         348 AA.
AC   Q27886; Q6F3D0;
DT   02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 164.
DE   RecName: Full=Abnormal cell lineage protein 44;
DE   AltName: Full=Wnt protein {ECO:0000312|EMBL:AAA64847.1};
DE   Flags: Precursor;
GN   Name=lin-44 {ECO:0000312|WormBase:E01A2.3};
GN   ORFNames=E01A2.3 {ECO:0000312|WormBase:E01A2.3};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAA64846.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP   STAGE, AND DISRUPTION PHENOTYPE.
RC   STRAIN=Bristol N2 {ECO:0000312|EMBL:AAA64846.1};
RX   PubMed=8026318; DOI=10.1242/dev.120.5.1035;
RA   Herman M.A., Horvitz H.R.;
RT   "The Caenorhabditis elegans gene lin-44 controls the polarity of asymmetric
RT   cell divisions.";
RL   Development 120:1035-1047(1994).
RN   [2] {ECO:0000312|EMBL:AAA64847.1, ECO:0000312|PIR:A57234}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, AND
RP   DEVELOPMENTAL STAGE.
RC   STRAIN=Bristol N2 {ECO:0000312|EMBL:AAA64847.1, ECO:0000312|PIR:A57234};
RX   PubMed=7553861; DOI=10.1016/0092-8674(95)90238-4;
RA   Herman M.A., Vassilieva L.L., Horvitz H.R., Shaw J.E., Herman R.K.;
RT   "The C. elegans gene lin-44, which controls the polarity of certain
RT   asymmetric cell divisions, encodes a Wnt protein and acts cell
RT   nonautonomously.";
RL   Cell 83:101-110(1995).
RN   [3] {ECO:0000305}
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   [4] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=8647436; DOI=10.1101/gad.10.11.1395;
RA   Baumeister R., Liu Y., Ruvkun G.;
RT   "Lineage-specific regulators couple cell lineage asymmetry to the
RT   transcription of the Caenorhabditis elegans POU gene unc-86 during
RT   neurogenesis.";
RL   Genes Dev. 10:1395-1410(1996).
RN   [5] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=11171341; DOI=10.1242/dev.128.4.581;
RA   Herman M.;
RT   "C. elegans POP-1/TCF functions in a canonical Wnt pathway that controls
RT   cell migration and in a noncanonical Wnt pathway that controls cell
RT   polarity.";
RL   Development 128:581-590(2001).
RN   [6] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15369677; DOI=10.1016/j.cell.2004.09.001;
RA   Inoue T., Oz H.S., Wiland D., Gharib S., Deshpande R., Hill R.J.,
RA   Katz W.S., Sternberg P.W.;
RT   "C. elegans LIN-18 is a Ryk ortholog and functions in parallel to LIN-
RT   17/Frizzled in Wnt signaling.";
RL   Cell 118:795-806(2004).
RN   [7] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16226243; DOI=10.1016/j.ydbio.2005.08.034;
RA   Kagoshima H., Sawa H., Mitani S., Burglin T.R., Shigesada K., Kohara Y.;
RT   "The C. elegans RUNX transcription factor RNT-1/MAB-2 is required for
RT   asymmetrical cell division of the T blast cell.";
RL   Dev. Biol. 287:262-273(2005).
RN   [8] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16077003; DOI=10.1101/gad.1322805;
RA   Takeshita H., Sawa H.;
RT   "Asymmetric cortical and nuclear localizations of WRM-1/beta-catenin during
RT   asymmetric cell division in C. elegans.";
RL   Genes Dev. 19:1743-1748(2005).
RN   [9] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16631156; DOI=10.1016/j.ydbio.2005.12.024;
RA   Wu M., Herman M.A.;
RT   "A novel noncanonical Wnt pathway is involved in the regulation of the
RT   asymmetric B cell division in C. elegans.";
RL   Dev. Biol. 293:316-329(2006).
RN   [10] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16930586; DOI=10.1016/j.ydbio.2006.06.050;
RA   Gleason J.E., Szyleyko E.A., Eisenmann D.M.;
RT   "Multiple redundant Wnt signaling components function in two processes
RT   during C. elegans vulval development.";
RL   Dev. Biol. 298:442-457(2006).
RN   [11] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16516840; DOI=10.1016/j.devcel.2006.01.013;
RA   Hilliard M.A., Bargmann C.I.;
RT   "Wnt signals and frizzled activity orient anterior-posterior axon outgrowth
RT   in C. elegans.";
RL   Dev. Cell 10:379-390(2006).
RN   [12] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=16516841; DOI=10.1016/j.devcel.2005.12.016;
RA   Goldstein B., Takeshita H., Mizumoto K., Sawa H.;
RT   "Wnt signals can function as positional cues in establishing cell
RT   polarity.";
RL   Dev. Cell 10:391-396(2006).
RN   [13] {ECO:0000305}
RP   DISRUPTION PHENOTYPE.
RX   PubMed=16600994; DOI=10.1093/hmg/ddl067;
RA   Kraemer B.C., Burgess J.K., Chen J.H., Thomas J.H., Schellenberg G.D.;
RT   "Molecular pathways that influence human tau-induced pathology in
RT   Caenorhabditis elegans.";
RL   Hum. Mol. Genet. 15:1483-1496(2006).
RN   [14] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16645052; DOI=10.1126/science.1124856;
RA   Coudreuse D.Y., Roel G., Betist M.C., Destree O., Korswagen H.C.;
RT   "Wnt gradient formation requires retromer function in Wnt-producing
RT   cells.";
RL   Science 312:921-924(2006).
RN   [15] {ECO:0000305}
RP   FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=17719547; DOI=10.1016/j.cell.2007.06.046;
RA   Klassen M.P., Shen K.;
RT   "Wnt signaling positions neuromuscular connectivity by inhibiting synapse
RT   formation in C. elegans.";
RL   Cell 130:704-716(2007).
RN   [16] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17276345; DOI=10.1016/j.devcel.2007.01.004;
RA   Mizumoto K., Sawa H.;
RT   "Cortical beta-catenin and APC regulate asymmetric nuclear beta-catenin
RT   localization during asymmetric cell division in C. elegans.";
RL   Dev. Cell 12:287-299(2007).
RN   [17] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18077322; DOI=10.1073/pnas.0709989104;
RA   Myers T.R., Greenwald I.;
RT   "Wnt signal from multiple tissues and lin-3/EGF signal from the gonad
RT   maintain vulval precursor cell competence in Caenorhabditis elegans.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:20368-20373(2007).
RN   [18] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18724937; DOI=10.1016/j.cell.2008.06.026;
RA   Green J.L., Inoue T., Sternberg P.W.;
RT   "Opposing Wnt pathways orient cell polarity during organogenesis.";
RL   Cell 134:646-656(2008).
RN   [19] {ECO:0000305}
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20042118; DOI=10.1186/1471-213x-9-74;
RA   Seah A., Sternberg P.W.;
RT   "The roles of EGF and Wnt signaling during patterning of the C. elegans
RT   Bgamma/delta Equivalence Group.";
RL   BMC Dev. Biol. 9:74-74(2009).
RN   [20]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=20711352; DOI=10.1371/journal.pgen.1001056;
RA   Song S., Zhang B., Sun H., Li X., Xiang Y., Liu Z., Huang X., Ding M.;
RT   "A Wnt-Frz/Ror-Dsh pathway regulates neurite outgrowth in Caenorhabditis
RT   elegans.";
RL   PLoS Genet. 6:E1001056-E1001056(2010).
RN   [21]
RP   FUNCTION, AND MUTAGENESIS OF 100-TRP--PHE-348.
RX   PubMed=23376536; DOI=10.1016/j.ydbio.2013.01.014;
RA   Huarcaya Najarro E., Ackley B.D.;
RT   "C. elegans fmi-1/flamingo and Wnt pathway components interact genetically
RT   to control the anteroposterior neurite growth of the VD GABAergic
RT   neurons.";
RL   Dev. Biol. 377:224-235(2013).
CC   -!- FUNCTION: Ligand for members of the frizzled family of seven
CC       transmembrane receptors (By similarity). Affects male tail development,
CC       vulval precursor cell specification and egg laying. Involved in
CC       morphogenesis by influencing polarity of asymmetric cell divisions of
CC       the B, U, and F cells in the male, and the T cell in males and
CC       hermaphrodites. Controls spindle orientation in B-gamma cell division
CC       during male copulatory spicule development. Involved in specification
CC       of the P7.p lineage during vulval development. Has a role in providing
CC       polarity and default lin-17 localization in axon development and
CC       positioning of neuromuscular synapses in DA9 regions by negatively
CC       regulating synaptogenesis. Plays a role in motorneuron development by
CC       promoting the extension of the anterior neurite of ventral D-type
CC       GABAergic motorneurons along the anterior-posterior axis of the ventral
CC       nerve cord (PubMed:23376536). {ECO:0000250,
CC       ECO:0000269|PubMed:11171341, ECO:0000269|PubMed:15369677,
CC       ECO:0000269|PubMed:16077003, ECO:0000269|PubMed:16226243,
CC       ECO:0000269|PubMed:16516840, ECO:0000269|PubMed:16516841,
CC       ECO:0000269|PubMed:16631156, ECO:0000269|PubMed:16645052,
CC       ECO:0000269|PubMed:16930586, ECO:0000269|PubMed:17276345,
CC       ECO:0000269|PubMed:17719547, ECO:0000269|PubMed:18077322,
CC       ECO:0000269|PubMed:18724937, ECO:0000269|PubMed:20042118,
CC       ECO:0000269|PubMed:23376536, ECO:0000269|PubMed:7553861,
CC       ECO:0000269|PubMed:8026318, ECO:0000269|PubMed:8647436}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250|UniProtKB:P24383}.
CC   -!- TISSUE SPECIFICITY: Expressed in the tail hypodermis.
CC       {ECO:0000269|PubMed:17719547, ECO:0000269|PubMed:20711352,
CC       ECO:0000269|PubMed:7553861, ECO:0000269|PubMed:8026318}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis and larval
CC       development (PubMed:17719547, PubMed:7553861, PubMed:8026318). Mainly
CC       expressed in the tail during larval stages (PubMed:20711352).
CC       {ECO:0000269|PubMed:17719547, ECO:0000269|PubMed:20711352,
CC       ECO:0000269|PubMed:7553861, ECO:0000269|PubMed:8026318}.
CC   -!- PTM: Palmitoleoylation is required for efficient binding to frizzled
CC       receptors. Depalmitoleoylation leads to Wnt signaling pathway
CC       inhibition. {ECO:0000250|UniProtKB:P27467,
CC       ECO:0000250|UniProtKB:P56704}.
CC   -!- DISRUPTION PHENOTYPE: Cell fate decisions disrupted, protein
CC       localization altered and neuron translocation disrupted. Defective tail
CC       development in males. Defective in egg laying in hermaphrodites.
CC       Nuclear localization of wrm-1 and lit-1 appears disrupted. Similar to
CC       tau-induced unc phenotype. Deviations in vulval precursor cell fate are
CC       observed when knocked down in conjunction with cwn-1 and egl-20.
CC       Bivulval phenotype when accompanied by mom-2 and/or cwn-2 knockdowns.
CC       Increase in ectopic synaptic vesicle puncta.
CC       {ECO:0000269|PubMed:15369677, ECO:0000269|PubMed:16077003,
CC       ECO:0000269|PubMed:16226243, ECO:0000269|PubMed:16516840,
CC       ECO:0000269|PubMed:16600994, ECO:0000269|PubMed:16631156,
CC       ECO:0000269|PubMed:16645052, ECO:0000269|PubMed:16930586,
CC       ECO:0000269|PubMed:17276345, ECO:0000269|PubMed:18077322,
CC       ECO:0000269|PubMed:18724937, ECO:0000269|PubMed:20042118,
CC       ECO:0000269|PubMed:8026318}.
CC   -!- SIMILARITY: Belongs to the Wnt family. {ECO:0000255}.
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DR   EMBL; U22179; AAA64846.1; -; mRNA.
DR   EMBL; U22184; AAA64847.1; -; Genomic_DNA.
DR   EMBL; BX284601; CCD68574.1; -; Genomic_DNA.
DR   PIR; A57234; A57234.
DR   RefSeq; NP_001021081.1; NM_001025910.4.
DR   AlphaFoldDB; Q27886; -.
DR   SMR; Q27886; -.
DR   BioGRID; 37465; 2.
DR   STRING; 6239.E01A2.3a; -.
DR   EPD; Q27886; -.
DR   PaxDb; Q27886; -.
DR   EnsemblMetazoa; E01A2.3.1; E01A2.3.1; WBGene00003029.
DR   GeneID; 171994; -.
DR   KEGG; cel:CELE_E01A2.3; -.
DR   UCSC; E01A2.3b; c. elegans.
DR   CTD; 171994; -.
DR   WormBase; E01A2.3; CE24870; WBGene00003029; lin-44.
DR   eggNOG; KOG3913; Eukaryota.
DR   GeneTree; ENSGT00940000167538; -.
DR   HOGENOM; CLU_033039_1_0_1; -.
DR   InParanoid; Q27886; -.
DR   OMA; ESAYLWA; -.
DR   OrthoDB; 787436at2759; -.
DR   PhylomeDB; Q27886; -.
DR   Reactome; R-CEL-3238698; WNT ligand biogenesis and trafficking.
DR   Reactome; R-CEL-4086398; Ca2+ pathway.
DR   Reactome; R-CEL-4086400; PCP/CE pathway.
DR   PRO; PR:Q27886; -.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00003029; Expressed in tail and 25 other tissues.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0005109; F:frizzled binding; ISS:WormBase.
DR   GO; GO:0048018; F:receptor ligand activity; ISS:WormBase.
DR   GO; GO:0008356; P:asymmetric cell division; IGI:UniProtKB.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR   GO; GO:0060573; P:cell fate specification involved in pattern specification; IMP:WormBase.
DR   GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:WormBase.
DR   GO; GO:1904936; P:interneuron migration; IGI:UniProtKB.
DR   GO; GO:0097475; P:motor neuron migration; IGI:UniProtKB.
DR   GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:WormBase.
DR   GO; GO:0097402; P:neuroblast migration; IGI:UniProtKB.
DR   GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR   GO; GO:0001764; P:neuron migration; IGI:UniProtKB.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
DR   GO; GO:1905485; P:positive regulation of motor neuron migration; IGI:UniProtKB.
DR   GO; GO:0010623; P:programmed cell death involved in cell development; IMP:UniProtKB.
DR   GO; GO:0046662; P:regulation of oviposition; IMP:WormBase.
DR   GO; GO:0040028; P:regulation of vulval development; IGI:WormBase.
DR   GO; GO:0040025; P:vulval development; IMP:WormBase.
DR   GO; GO:0016055; P:Wnt signaling pathway; IGI:WormBase.
DR   Gene3D; 3.30.2460.20; -; 1.
DR   InterPro; IPR005817; Wnt.
DR   InterPro; IPR043158; Wnt_C.
DR   InterPro; IPR018161; Wnt_CS.
DR   PANTHER; PTHR12027; PTHR12027; 1.
DR   Pfam; PF00110; wnt; 1.
DR   PRINTS; PR01349; WNTPROTEIN.
DR   SMART; SM00097; WNT1; 1.
DR   PROSITE; PS00246; WNT1; 1.
PE   1: Evidence at protein level;
KW   Developmental protein; Disulfide bond; Extracellular matrix; Glycoprotein;
KW   Lipoprotein; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..348
FT                   /note="Abnormal cell lineage protein 44"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000400090"
FT   LIPID           219
FT                   /note="O-palmitoleoyl serine; by mom-1"
FT                   /evidence="ECO:0000250|UniProtKB:P56704"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        91..102
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        141..149
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        151..165
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        213..227
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        215..222
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        272..299
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        282..294
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        298..338
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        314..329
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        316..326
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   DISULFID        321..322
FT                   /evidence="ECO:0000250|UniProtKB:P28026"
FT   MUTAGEN         100..348
FT                   /note="Missing: In n1792; mild defects in neurite
FT                   positioning along the anterior posterior axis with ventral
FT                   D-type GABAergic neurons displaying posterior neurites,
FT                   instead of anterior neurites, which results in ventrodorsal
FT                   commissures positioned on the posterior side of their cell
FT                   body."
FT                   /evidence="ECO:0000269|PubMed:23376536"
SQ   SEQUENCE   348 AA;  38381 MW;  3DD9F50DF2C89C6D CRC64;
     MRAAPFDFFF QSTALSTFFI LCSLATNEIP TISGAPAGKI VQPPKPNILK QGCPSDLLHS
     RALRSIQLAC RTHPATVISA FEGVQEGLQN CANRLRFQQW DCSEAGNIMH DPPLLRQGFR
     ESSLIWALSS ASAAWGVATA CAQGWIDDCA CNNQMGQNEY EFGGCTHGVQ HGITASRKLL
     TKVGAVNTLL RKVEKHNLKA GRLAIKKTLI SSCKCHGVSG SCQQKTCWKR TATLEHITDY
     LVEKYARAKL YTDDSVVKTT DLIYLEASPD VCKAKSVAGR VCAWRNETHT QGDCDRLCCG
     NGFSIRHEVV RVKCDCEFVW CCNLVCKDCI QHRWISTCNG TPPKSLIF
 
 
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