APR1_CAEEL
ID APR1_CAEEL Reviewed; 1188 AA.
AC Q21227; O62302;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Adenomatous polyposis coli protein-related protein 1;
DE Short=APC-related protein 1;
GN Name=apr-1 {ECO:0000312|EMBL:AAC47747.1, ECO:0000312|WormBase:K04G2.8a};
GN ORFNames=K04G2.8;
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:AAC47747.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC47747.1};
RX PubMed=9288750; DOI=10.1016/s0092-8674(00)80531-0;
RA Rocheleau C.E., Downs W.D., Lin R., Wittmann C., Bei Y., Cha Y.-H., Ali M.,
RA Priess J.R., Mello C.C.;
RT "Wnt signaling and an APC-related gene specify endoderm in early C. elegans
RT embryos.";
RL Cell 90:707-716(1997).
RN [2] {ECO:0000312|EMBL:CAB00045.1}
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 [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10766743;
RA Hoier E.F., Mohler W.A., Kim S.K., Hajnal A.;
RT "The Caenorhabditis elegans APC-related gene apr-1 is required for
RT epithelial cell migration and Hox gene expression.";
RL Genes Dev. 14:874-886(2000).
RN [4] {ECO:0000305}
RP INTERACTION WITH BAR-1 AND HMP-2.
RX PubMed=11560894; DOI=10.1093/genetics/159.1.159;
RA Natarajan L., Witwer N.E., Eisenmann D.M.;
RT "The divergent Caenorhabditis elegans beta-catenin proteins BAR-1, WRM-1
RT and HMP-2 make distinct protein interactions but retain functional
RT redundancy in vivo.";
RL Genetics 159:159-172(2001).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=12023306; DOI=10.1101/gad.981602;
RA Gleason J.E., Korswagen H.C., Eisenmann D.M.;
RT "Activation of Wnt signaling bypasses the requirement for RTK/Ras signaling
RT during C. elegans vulval induction.";
RL Genes Dev. 16:1281-1290(2002).
RN [6] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH PRY-1.
RX PubMed=12023307; DOI=10.1101/gad.981802;
RA Korswagen H.C., Coudreuse D.Y.M., Betist M.C., van de Water S.,
RA Zivkovic D., Clevers H.C.;
RT "The axin-like protein PRY-1 is a negative regulator of a canonical Wnt
RT pathway in C. elegans.";
RL Genes Dev. 16:1291-1302(2002).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [8]
RP FUNCTION, AND MUTAGENESIS OF GLY-338.
RX PubMed=19607822; DOI=10.1016/j.ydbio.2009.07.005;
RA Huang X., Tian E., Xu Y., Zhang H.;
RT "The C. elegans engrailed homolog ceh-16 regulates the self-renewal
RT expansion division of stem cell-like seam cells.";
RL Dev. Biol. 333:337-347(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20805471; DOI=10.1073/pnas.1006600107;
RA Putzke A.P., Rothman J.H.;
RT "Repression of Wnt signaling by a Fer-type nonreceptor tyrosine kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:16154-16159(2010).
CC -!- FUNCTION: Has a role in endoderm cell specification and pharyngeal
CC development (PubMed:9288750). Required for the migration of epithelial
CC cells, organization of the anterior seam cells and ceh-13 expression
CC during embryo morphogenesis. Prevents hyperactivation of the Wnt
CC signaling pathway during endoderm development, probably by preventing
CC hmp-2 nuclear translocation (PubMed:20805471). During larval
CC development, apr-1 is required for expression of lin-39 in P3-8.p
CC (PubMed:10766743). Shown to negatively regulate Wnt signaling in vulval
CC precursor cells (PubMed:12023306). Has a role in cell division by
CC establishing the polarity of the mother cell which forms the
CC asymmetries of the daughter nuclei (PubMed:17276345). During the L4
CC larval stage, it is required for the asymmetric division and self-
CC renewal of seam cells (PubMed:19607822). Thought to regulate export of
CC wrm-1 from the nucleus possibly as part of a complex involving pry-1
CC (PubMed:12023307). {ECO:0000269|PubMed:10766743,
CC ECO:0000269|PubMed:12023306, ECO:0000269|PubMed:12023307,
CC ECO:0000269|PubMed:17276345, ECO:0000269|PubMed:19607822,
CC ECO:0000269|PubMed:20805471, ECO:0000269|PubMed:9288750}.
CC -!- SUBUNIT: Interacts (via N-terminus) with bar-1 and hmp-2; the
CC interaction with hmp-2 is relatively weak. Interacts (via C-terminus)
CC with pry-1 (via N-terminus). Probably associates with bar-1, gsk-3,
CC pry-1 in a complex. {ECO:0000269|PubMed:11560894,
CC ECO:0000269|PubMed:12023307}.
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction
CC {ECO:0000269|PubMed:10766743, ECO:0000269|PubMed:17276345}. Cytoplasm
CC {ECO:0000269|PubMed:10766743, ECO:0000269|PubMed:17276345}. Nucleus
CC {ECO:0000269|PubMed:10766743, ECO:0000269|PubMed:17276345}. Note=Found
CC in clusters near the ends of microtubules that extend into regions of
CC actively migrating plasma membranes. Shuttles between the cytoplasm and
CC nucleus. {ECO:0000269|PubMed:10766743, ECO:0000269|PubMed:17276345}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:K04G2.8b};
CC IsoId=Q21227-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:K04G2.8a};
CC IsoId=Q21227-2; Sequence=VSP_052859;
CC -!- TISSUE SPECIFICITY: During the L1 stage, expressed in vulval precursor
CC cells (P3-8.p), seam cells and excretory cells.
CC {ECO:0000269|PubMed:10766743, ECO:0000269|PubMed:17276345}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit lack of endoderm, excessive
CC pharyngeal tissue and premature division of the E daughter blastomeres
CC during embryogenesis. Two-thirds arrest during embryogenesis and the
CC remaining third during the L1 stage (PubMed:9288750). RNAi-mediated
CC knockdown causes partial nuclear re-localization of hmp-2 in the
CC embryonic epidermis and the production of supernumerary gut nuclei
CC probably resulting from epithelial cell hyperproliferation
CC (PubMed:20805471). {ECO:0000269|PubMed:20805471,
CC ECO:0000269|PubMed:9288750}.
CC -!- SIMILARITY: Belongs to the adenomatous polyposis coli (APC) family.
CC {ECO:0000255}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF013950; AAC47747.1; -; mRNA.
DR EMBL; BX284601; CAB00045.1; -; Genomic_DNA.
DR EMBL; BX284601; CAB00048.1; -; Genomic_DNA.
DR PIR; T23327; T23327.
DR PIR; T23330; T23330.
DR RefSeq; NP_001021547.1; NM_001026376.4. [Q21227-1]
DR RefSeq; NP_492217.2; NM_059816.4. [Q21227-2]
DR AlphaFoldDB; Q21227; -.
DR SMR; Q21227; -.
DR BioGRID; 38025; 24.
DR DIP; DIP-41257N; -.
DR IntAct; Q21227; 19.
DR STRING; 6239.K04G2.8b; -.
DR EPD; Q21227; -.
DR PaxDb; Q21227; -.
DR PeptideAtlas; Q21227; -.
DR EnsemblMetazoa; K04G2.8a.1; K04G2.8a.1; WBGene00000156. [Q21227-2]
DR EnsemblMetazoa; K04G2.8b.1; K04G2.8b.1; WBGene00000156. [Q21227-1]
DR GeneID; 172591; -.
DR KEGG; cel:CELE_K04G2.8; -.
DR UCSC; K04G2.8b; c. elegans. [Q21227-1]
DR CTD; 172591; -.
DR WormBase; K04G2.8a; CE06102; WBGene00000156; apr-1. [Q21227-2]
DR WormBase; K04G2.8b; CE18016; WBGene00000156; apr-1. [Q21227-1]
DR eggNOG; KOG2122; Eukaryota.
DR GeneTree; ENSGT00530000063749; -.
DR InParanoid; Q21227; -.
DR OMA; CVDDEDY; -.
DR OrthoDB; 268832at2759; -.
DR Reactome; R-CEL-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-CEL-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-CEL-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-CEL-3769402; Deactivation of the beta-catenin transactivating complex.
DR SignaLink; Q21227; -.
DR PRO; PR:Q21227; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000156; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q21227; baseline and differential.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0030877; C:beta-catenin destruction complex; IBA:GO_Central.
DR GO; GO:0016342; C:catenin complex; IBA:GO_Central.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0008013; F:beta-catenin binding; IPI:WormBase.
DR GO; GO:0045295; F:gamma-catenin binding; IBA:GO_Central.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0008356; P:asymmetric cell division; IMP:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0001708; P:cell fate specification; IMP:WormBase.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IGI:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:UniProtKB.
DR GO; GO:0007492; P:endoderm development; IMP:UniProtKB.
DR GO; GO:0001714; P:endodermal cell fate specification; IMP:WormBase.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IMP:WormBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0051782; P:negative regulation of cell division; IMP:UniProtKB.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IBA:GO_Central.
DR GO; GO:0040027; P:negative regulation of vulval development; IGI:WormBase.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0007389; P:pattern specification process; IBA:GO_Central.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:WormBase.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; IMP:WormBase.
DR GO; GO:0016476; P:regulation of embryonic cell shape; IMP:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0040025; P:vulval development; IMP:WormBase.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR026818; Apc_fam.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR PANTHER; PTHR12607; PTHR12607; 2.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Cell junction; Cytoplasm;
KW Developmental protein; Nucleus; Protein transport; Reference proteome;
KW Transport; Wnt signaling pathway.
FT CHAIN 1..1188
FT /note="Adenomatous polyposis coli protein-related protein
FT 1"
FT /id="PRO_0000347250"
FT REPEAT 314..358
FT /note="ARM"
FT /evidence="ECO:0000255"
FT REGION 1..486
FT /note="Required for interaction with bar-1 and hmp-2"
FT /evidence="ECO:0000269|PubMed:11560894"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 600..1188
FT /note="Required for interaction with pry-1"
FT /evidence="ECO:0000269|PubMed:12023307"
FT REGION 670..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 726..751
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 778..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1003..1092
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1157..1181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 604..624
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..827
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 870..901
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 906..948
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1003..1059
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1159..1181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 552..553
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9288750"
FT /id="VSP_052859"
FT MUTAGEN 338
FT /note="G->E: In bp298; at the L4 larval stage, seam cells
FT divide asymmetrically as opposed to symmetrically leading
FT to an increased number of seam cells at the young adult
FT stage. Defective asymmetric division of the V5.p seam cell
FT and 45.5% of animals develop two postdeirids due to
FT symmetric division of the V5.p seam cell."
FT /evidence="ECO:0000269|PubMed:19607822"
SQ SEQUENCE 1188 AA; 131990 MW; F3CDA53B5D3527A0 CRC64;
MSSSSSDENE TTIHRTGSNT GGSGIYSQPR AGSSKRTSNV RHDVSDVDDE EEHYARFRED
TAIEVDDAIT VLLSSLHFEH KRDIVPTDED DNKLRELHEK IFALITSESD VNRKRRLKKA
LPASNCVREQ VYYLRRKPST PPASYYHRLN AALHTIVKES FGEEYRKVAT VLGLVEALAE
VLILEVHTFG INETNPGEHR NIRKLIANAL TNLTYGQIHS KRRLCSYDGF IRCVVRIVIE
SPNITQVYAG LIRNLSWNAD SGMSEALQPT VHALSIAAVH AHTHRFDVTA TLSALWNLAG
HSVENKRTIC DTPNCLKVLA SLLSPDARFT SLVDSATGIL KYVSQYLANT STHLELRSLL
ITRMLTLLKS ASFTCVTNTL GAIANLIVKD PHMQQMIRQD MAAVQQLNVL RNSNRDDIRT
AVKSVLNTLN QPCSHRYGDM SHSVGGGATG MQMLSEPQLQ MQTSHHAYHG TASPRLLSLR
ATRASPGKYI QPQAQQQLIQ TPQVDQRSSS LPRHFAVQRN GFVMAQSYNQ QMDQHQQQQM
IYQLQQQQQI MFQTEDQAQM EHHQQIMYLQ QQQQQFHQIQ QQQQMQKAQE ADPVPPTDDD
LDIPTSTVMG TRSNSERSLG SMNPGSVMTN WNSSLDTAAN SSRALSPVSY NDIPASPTMC
AQVFNLPKST ESEHHQLTSQ QQNTTHYSSG SANTMTRSDG ATTVPMDNII TPTYAILNPI
LVHEQTPNGT VPRKTSEELD SPDDVLPGPS LEEEEGDYAI IGGAAQKTDD ELLTRSIQSE
MPTSSSTPKM KVSPRLNGFF SPTQKTTSSP AWSHPDTSPI PKSSSHRTQP NRRQDASDAD
RLLMESIMSE MPKSRIISPR LAGTQQYLEP EPERRSHSKN EEADRRDAFT ASHEPSDHNG
IDVARGSDWS PQQQLHRMES LESQASSEDS FGLTAEEPNS STSGAAANTM RFDDEIDASL
PMDCVDDDDY DYTYDHFEDY EDEEDPDATQ FDDGVDAQLT IDCSMISSGS GSSQRNETTT
TSRDSKALAT STPKGSASSL PGVRQATRVS TNGKSRLPVP KTNGSLVDKN PKPIIASRRP
RLPPKPTLLK DKHYPEEDSI ENQTRDDTIY VNAPVVEAEQ ERIYMNALKQ QKNIEQSPSI
GNGSPIAKSA IVTPYNYQKP PFTGRNNGEM SNEKSVTPNP KQMLVTIV
