UNC33_CAEEL
ID UNC33_CAEEL Reviewed; 854 AA.
AC Q01630; U4PE21;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Protein unc-33;
DE AltName: Full=Inactive dihydropyrimidinase unc-33 {ECO:0000305};
DE AltName: Full=Uncoordinated protein 33;
GN Name=unc-33 {ECO:0000312|WormBase:Y37E11C.1a};
GN ORFNames=Y37E11C.1 {ECO:0000312|WormBase:Y37E11C.1a};
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 [GENOMIC DNA / MRNA], FUNCTION, AND ALTERNATIVE
RP SPLICING.
RC STRAIN=Bristol N2; TISSUE=Embryo;
RX PubMed=1468626; DOI=10.1093/genetics/132.3.675;
RA Li W., Herman R.K., Shaw J.E.;
RT "Analysis of the Caenorhabditis elegans axonal guidance and outgrowth gene
RT unc-33.";
RL Genetics 132:675-689(1992).
RN [2]
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]
RP FUNCTION.
RX PubMed=10993679; DOI=10.1006/dbio.2000.9853;
RA Branda C.S., Stern M.J.;
RT "Mechanisms controlling sex myoblast migration in Caenorhabditis elegans
RT hermaphrodites.";
RL Dev. Biol. 226:137-151(2000).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-389.
RX PubMed=11493519; DOI=10.1242/dev.128.11.1951;
RA Altun-Gultekin Z., Andachi Y., Tsalik E.L., Pilgrim D., Kohara Y.,
RA Hobert O.;
RT "A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23,
RT controls cell fate specification of a defined interneuron class in C.
RT elegans.";
RL Development 128:1951-1969(2001).
RN [5]
RP FUNCTION, SUBUNIT, INTERACTION WITH UNC-14 AND KLC-2, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY (ISOFORM A), DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP ASP-389.
RX PubMed=16236031; DOI=10.1111/j.1471-4159.2005.03490.x;
RA Tsuboi D., Hikita T., Qadota H., Amano M., Kaibuchi K.;
RT "Regulatory machinery of UNC-33 Ce-CRMP localization in neurites during
RT neuronal development in Caenorhabditis elegans.";
RL J. Neurochem. 95:1629-1641(2005).
RN [6]
RP FUNCTION (ISOFORM A), SUBCELLULAR LOCATION (ISOFORM A), TISSUE SPECIFICITY
RP (ISOFORM A), AND MUTAGENESIS OF 255-GLU--TRP-854; ASP-389 AND GLU-663.
RX PubMed=22101643; DOI=10.1038/nn.2970;
RA Maniar T.A., Kaplan M., Wang G.J., Shen K., Wei L., Shaw J.E.,
RA Koushika S.P., Bargmann C.I.;
RT "UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to
RT polarize axon-dendrite sorting.";
RL Nat. Neurosci. 15:48-56(2011).
RN [7]
RP FUNCTION, INTERACTION WITH FLN-1, AND MUTAGENESIS OF ASP-389.
RX PubMed=25358863; DOI=10.1038/ncomms6325;
RA Nakamura F., Kumeta K., Hida T., Isono T., Nakayama Y.,
RA Kuramata-Matsuoka E., Yamashita N., Uchida Y., Ogura K., Gengyo-Ando K.,
RA Mitani S., Ogino T., Goshima Y.;
RT "Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to
RT mediate Sema3A signalling.";
RL Nat. Commun. 5:5325-5325(2014).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF ASP-389.
RX PubMed=25371370; DOI=10.1242/dev.110437;
RA Norris A.D., Sundararajan L., Morgan D.E., Roberts Z.J., Lundquist E.A.;
RT "The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone
RT filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP.";
RL Development 141:4395-4405(2014).
RN [9]
RP FUNCTION (ISOFORMS A; B AND C), INTERACTION WITH VAB-8, AND MUTAGENESIS OF
RP GLU-168; GLY-328 AND ASP-389.
RX PubMed=27015090; DOI=10.1371/journal.pgen.1005948;
RA Meng L., Chen C.H., Yan D.;
RT "Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP
RT through VAB-8 in C. elegans Neurons.";
RL PLoS Genet. 12:E1005948-E1005948(2016).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ASP-389.
RX PubMed=30045855; DOI=10.1534/genetics.118.301234;
RA Gujar M.R., Sundararajan L., Stricker A., Lundquist E.A.;
RT "Control of Growth Cone Polarity, Microtubule Accumulation, and Protrusion
RT by UNC-6/Netrin and Its Receptors in Caenorhabditis elegans.";
RL Genetics 210:235-255(2018).
RN [11]
RP FUNCTION.
RX PubMed=30254025; DOI=10.1242/jcs.223107;
RA Harterink M., Edwards S.L., de Haan B., Yau K.W., van den Heuvel S.,
RA Kapitein L.C., Miller K.G., Hoogenraad C.C.;
RT "Local microtubule organization promotes cargo transport in C. elegans
RT dendrites.";
RL J. Cell Sci. 131:0-0(2018).
CC -!- FUNCTION: During neurogenesis, plays an essential role in axonal
CC guidance and outgrowth by regulating the polarization of both
CC microtubule and actin cytoskeletons (PubMed:1468626, PubMed:11493519,
CC PubMed:16236031, PubMed:22101643, PubMed:25358863, PubMed:30045855).
CC Establishes the asymmetry of axonal and dendrite microtubules and the
CC polarized sorting of neuronal proteins (PubMed:22101643). This is
CC achieved in part by regulating the localization of kinesin-like protein
CC unc-104 (PubMed:22101643). In neurons without a distal microtubule-
CC organizing center (MTOC), also controls the organization of
CC microtubules in dendrites (PubMed:30254025). During the dorso-ventral
CC axonal guidance and outgrowth of VD neurons, required downstream of Rac
CC GTPases ced-10 and mig-2 to inhibit growth cone filopodial protrusion
CC mediated by the unc-6/netrin receptor unc-40-unc-5 (PubMed:25371370).
CC Specifically, regulates growth cone filopodial protrusion polarity, and
CC thus migration, by promoting F-actin polarization and by restricting
CC plus-end microtubule accumulation in the growth cone (PubMed:30045855).
CC Probably downstream of mab-20/Sema2a and mab-20 receptor plx-2,
CC regulates the guidance of DD/VD neuron axons by modulating fln-1
CC interaction with F-actin which results in the remodeling of the actin
CC cytoskeleton (PubMed:25358863). In hermaphrodites, involved in sex
CC myoblast (SM) migration by regulating the gonad-dependent repulsion of
CC SMs (PubMed:10993679). {ECO:0000269|PubMed:10993679,
CC ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:1468626,
CC ECO:0000269|PubMed:16236031, ECO:0000269|PubMed:22101643,
CC ECO:0000269|PubMed:25358863, ECO:0000269|PubMed:25371370,
CC ECO:0000269|PubMed:30045855, ECO:0000269|PubMed:30254025}.
CC -!- FUNCTION: [Isoform a]: In neurons, required for the polarized sorting
CC of axonal proteins (PubMed:22101643). In PLM neuron, regulates innexin
CC unc-9 gap junction turnover by suppressing unc-9 transport out of gap
CC junctions (PubMed:27015090). Plays a role in locomotion and egg-laying
CC (PubMed:22101643). {ECO:0000269|PubMed:22101643,
CC ECO:0000269|PubMed:27015090}.
CC -!- FUNCTION: [Isoform b]: In PLM neuron, regulates innexin unc-9 gap
CC junction turnover by suppressing unc-9 transport out of gap junctions.
CC {ECO:0000269|PubMed:27015090}.
CC -!- FUNCTION: [Isoform c]: In PLM neuron, regulates innexin unc-9 gap
CC junction turnover by suppressing unc-9 transport out of gap junctions.
CC {ECO:0000269|PubMed:27015090}.
CC -!- SUBUNIT: Isoform a: Probable monomer (PubMed:16236031). Isoform b:
CC Probable homodimer (PubMed:16236031). Isoform c: Probable homodimer
CC (PubMed:16236031). Probable heterodimer composed of isoform b and
CC isoform c (PubMed:16236031). Interacts with unc-14 and kinesin-1 motor
CC complex light chain klc-1; both interactions regulate unc-33 neurite
CC localization (PubMed:16236031). Interacts with fln-1 (via calponin-
CC homology (CH) domains and filamin repeat 18-19) (PubMed:25358863).
CC Isoform c: Interacts with vab-8 isoform a (PubMed:27015090).
CC {ECO:0000269|PubMed:16236031, ECO:0000269|PubMed:25358863,
CC ECO:0000269|PubMed:27015090}.
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000269|PubMed:16236031}. Cell projection, dendrite
CC {ECO:0000269|PubMed:16236031}.
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Cell projection, axon
CC {ECO:0000269|PubMed:22101643}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:Y37E11C.1a}; Synonyms=I
CC {ECO:0000303|PubMed:1468626}, L {ECO:0000303|PubMed:16236031};
CC IsoId=Q01630-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y37E11C.1b}; Synonyms=II
CC {ECO:0000303|PubMed:1468626}, M {ECO:0000303|PubMed:16236031};
CC IsoId=Q01630-2; Sequence=VSP_001310;
CC Name=c {ECO:0000305}; Synonyms=III {ECO:0000303|PubMed:1468626}, S
CC {ECO:0000303|PubMed:16236031};
CC IsoId=Q01630-3; Sequence=VSP_001311;
CC -!- TISSUE SPECIFICITY: Expressed in ventral cord and nerve ring (at
CC protein level) (PubMed:16236031). Isoform a: Expressed in nerve ring
CC (at protein level) (PubMed:16236031, PubMed:22101643). Expressed in the
CC nervous system, two amphid socket cells and weakly in non-neuronal
CC pharyngeal cells (PubMed:11493519). {ECO:0000269|PubMed:11493519,
CC ECO:0000269|PubMed:16236031, ECO:0000269|PubMed:22101643}.
CC -!- DEVELOPMENTAL STAGE: Expressed in L1 larval stage and in adults (at
CC protein level) (PubMed:16236031). Isoform a: Expressed in L1 larval
CC stage and in adults (at protein level) (PubMed:16236031).
CC {ECO:0000269|PubMed:16236031}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Hydantoinase/dihydropyrimidinase family. {ECO:0000305}.
CC -!- CAUTION: Lacks most of the conserved residues that are essential for
CC binding the metal cofactor and hence for dihydropyrimidinase activity.
CC Its enzyme activity is therefore unsure. {ECO:0000305}.
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DR EMBL; Z14148; CAA78520.1; -; Genomic_DNA.
DR EMBL; Z14148; CAA78521.1; -; Genomic_DNA.
DR EMBL; Z14148; CAA78522.1; -; Genomic_DNA.
DR EMBL; Z14146; CAA78516.1; -; mRNA.
DR EMBL; Z14146; CAA78517.1; -; mRNA.
DR EMBL; Z14146; CAA78518.1; -; mRNA.
DR EMBL; BX284604; CCD64037.1; -; Genomic_DNA.
DR EMBL; BX284604; CDH93000.1; -; Genomic_DNA.
DR PIR; S33558; S33558.
DR RefSeq; NP_001033438.1; NM_001038349.2. [Q01630-1]
DR RefSeq; NP_001294298.1; NM_001307369.1.
DR AlphaFoldDB; Q01630; -.
DR SMR; Q01630; -.
DR BioGRID; 42252; 5.
DR STRING; 6239.Y37E11C.1a; -.
DR iPTMnet; Q01630; -.
DR EPD; Q01630; -.
DR PaxDb; Q01630; -.
DR PeptideAtlas; Q01630; -.
DR PRIDE; Q01630; -.
DR EnsemblMetazoa; Y37E11C.1a.1; Y37E11C.1a.1; WBGene00006769. [Q01630-1]
DR EnsemblMetazoa; Y37E11C.1b.1; Y37E11C.1b.1; WBGene00006769. [Q01630-2]
DR GeneID; 177112; -.
DR KEGG; cel:CELE_Y37E11C.1; -.
DR UCSC; Y37E11C.1; c. elegans. [Q01630-1]
DR CTD; 177112; -.
DR WormBase; Y37E11C.1a; CE21557; WBGene00006769; unc-33. [Q01630-1]
DR WormBase; Y37E11C.1b; CE31638; WBGene00006769; unc-33. [Q01630-2]
DR eggNOG; KOG2584; Eukaryota.
DR HOGENOM; CLU_015572_7_0_1; -.
DR InParanoid; Q01630; -.
DR OMA; QQGTKYY; -.
DR OrthoDB; 719800at2759; -.
DR PhylomeDB; Q01630; -.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR Reactome; R-CEL-437239; Recycling pathway of L1.
DR PRO; PR:Q01630; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006769; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q01630; baseline and differential.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IDA:WormBase.
DR GO; GO:0004157; F:dihydropyrimidinase activity; IBA:GO_Central.
DR GO; GO:0031005; F:filamin binding; IPI:WormBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IMP:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR GO; GO:0061643; P:chemorepulsion of axon; IMP:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:UniProtKB.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IMP:UniProtKB.
DR GO; GO:0038007; P:netrin-activated signaling pathway; IMP:UniProtKB.
DR GO; GO:0006208; P:pyrimidine nucleobase catabolic process; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR GO; GO:1905815; P:regulation of dorsal/ventral axon guidance; IMP:UniProtKB.
DR GO; GO:0097374; P:sensory neuron axon guidance; IMP:UniProtKB.
DR Gene3D; 2.30.40.10; -; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR Pfam; PF01979; Amidohydro_1; 1.
DR SUPFAM; SSF51338; SSF51338; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Neurogenesis; Reference proteome.
FT CHAIN 1..854
FT /note="Protein unc-33"
FT /id="PRO_0000165927"
FT REGION 57..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 238..253
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 254..303
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..828
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..331
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_001311"
FT VAR_SEQ 1..175
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_001310"
FT MUTAGEN 168
FT /note="E->K: In yad26; in the PLM neuron axon, increases
FT the number of unc-9 puncta close to the two original gap
FT junctions and the length of the first gap junction, also
FT causes mis-localization of unc-1, loss of unc-1-unc-9 co-
FT localization and a reduction in the number of unc-9 leaving
FT the gap junction; when associated with D-328."
FT /evidence="ECO:0000269|PubMed:27015090"
FT MUTAGEN 255..854
FT /note="Missing: In ky869; axonal proteins are mislocalized
FT to dendrites."
FT /evidence="ECO:0000269|PubMed:22101643"
FT MUTAGEN 328
FT /note="G->D: In yad26; in the PLM neuron axon, increases
FT the number of unc-9 puncta close to the two original gap
FT junctions and the length of the first gap junction, also
FT causes mis-localization of unc-1, loss of unc-1-unc-9 co-
FT localization and a reduction in the number of unc-9 leaving
FT the gap junction; when associated with K-168."
FT /evidence="ECO:0000269|PubMed:27015090"
FT MUTAGEN 389
FT /note="D->N: In e204; uncoordinated. In AIY, ASI, D-type
FT neurons, impairs axonal guidance and outgrowth and in some
FT cases causes ectopic axonal branching. In VD neurons,
FT increases growth cone filopodial protrusion associated with
FT a loss of F-actin polarity and an accumulation of plus-end
FT microtubule in the growth cone. Causes mislocalization of
FT several axonal and dendrite proteins. In the PLM neuron
FT axon, increases the number of unc-9 puncta close to the two
FT original gap junctions and the length of the first gap
FT junction. Causes unc-33 mislocalization to the perikaryon.
FT Reduces its expression, homodimerization and
FT heterodimerization; in isoform b. Prevents homodimerization
FT and heterodimerization; in isoform c."
FT /evidence="ECO:0000269|PubMed:11493519,
FT ECO:0000269|PubMed:16236031, ECO:0000269|PubMed:22101643,
FT ECO:0000269|PubMed:25358863, ECO:0000269|PubMed:25371370,
FT ECO:0000269|PubMed:27015090, ECO:0000269|PubMed:30045855"
FT MUTAGEN 663
FT /note="E->K: In ky880; axonal proteins including unc-104
FT and synaptic proteins are mislocalized to dendrites.
FT Increases tubulin levels in dendrites while decreasing
FT tubulin levels in axons."
FT /evidence="ECO:0000269|PubMed:22101643"
SQ SEQUENCE 854 AA; 90819 MW; A8073DDE251D2D77 CRC64;
MFPFLAPIRS ANHVEQQGTK YYVEITFLAD SPYSRAPSST GTEKSVIPTL RNLDDLETVS
NKSRSSEGVN KLGSRPNSRS SAIVKKTSVS SLPTSARSEG KSSPIPVKDA IPAPARHKNK
GLEMSSAMME LFGGGGSTSP APSKRENPAD APSDRVVSNA KLSQPGPEWF EGFEQMDMTD
IELPPDPNCP AEKVLRGEKS TPDFDSDWQE AKEDVLDPQS YPKSFNPAES LPGPDIGAGV
DDEEEPEAEA QEMEEPQYES KVDEKDDDDN GSSSSKKGHP SEDGDSTRNG ETPTDRRNSG
AIEETADGES SAQSAAEKKN SGDDGNGGGG EMSILLVKNA QIVNDDAIFV ADILIEDGII
QNVAPNLEAP EGAEVLDAAG KLALPAGIDV YTQVTDSSVD DLSTGCKSAI AGGTGTIVEV
VRPRGAESVV SAVKRVKNQL EKSGISCHVA LSVAITDFCE QEMSELVKNE GINSFVLDGV
SLTDDKLLEL FEHVKRLGAL IRVVPENKSI VAMLEKKMLK LGVTGPEGFP QSRPESLEAD
RVSGVCVLGN LASCPISIVQ VSSADSLAAI EKARASGALA HAEIASAAVT ADGSALFSQD
LRFASAHLTD VPLRRGAPDR MIGALSTQPL VVCTSGHRPV NSATRVAAKD FAIAQKGSTG
AEERMAVVWE RAVRSGRIDA MRFVAVTSTN AAKMFNMYPK KGRIAVGADA DLVIWDASGK
RVLESSRAQS SQENSMYDGL TVHSVVTATI VGGKIAYQNG EVREAPVAGG FLRLSPNSPY
LFSMVGQRDK FANVERVERE ASSQQQKPQQ NGHHKNSGDF DRNRTKVMES SIDFGGSAAN
RPRNPPGGRT TGFW
