EFA6_CAEEL
ID EFA6_CAEEL Reviewed; 818 AA.
AC G5EET6; D4YWC5; G5EBY7; Q9XWG7;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Exchange factor for Arf-6 {ECO:0000303|PubMed:26339988};
DE AltName: Full=Arf guanine nucleotide exchange factor efa-6 {ECO:0000303|PubMed:21943602};
DE AltName: Full=Pleckstrin homology domain-containing protein efa-6 {ECO:0000303|PubMed:17676955};
GN Name=efa-6 {ECO:0000303|PubMed:17676955, ECO:0000312|WormBase:Y55D9A.1a};
GN ORFNames=Y55D9A.1 {ECO:0000312|WormBase:Y55D9A.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] {ECO:0000312|EMBL:ABQ42569.1, ECO:0000312|EMBL:ABQ42570.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:ABQ42569.1};
RX PubMed=17676955; DOI=10.1371/journal.pgen.0030128;
RA O'Rourke S.M., Dorfman M.D., Carter J.C., Bowerman B.;
RT "Dynein modifiers in C. elegans: light chains suppress conditional heavy
RT chain mutants.";
RL PLoS Genet. 3:E128-E128(2007).
RN [2] {ECO:0000312|EMBL:CAA21701.1, ECO:0000312|EMBL:CAC70120.1, ECO:0000312|EMBL:CAM82814.1, ECO:0000312|EMBL:CBL43465.1, ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAC70120.1,
RC 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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLU-449.
RX PubMed=21076413; DOI=10.1038/ncb2128;
RA O'Rourke S.M., Christensen S.N., Bowerman B.;
RT "Caenorhabditis elegans EFA-6 limits microtubule growth at the cell
RT cortex.";
RL Nat. Cell Biol. 12:1235-1241(2010).
RN [4]
RP FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-449.
RX PubMed=21943602; DOI=10.1016/j.neuron.2011.07.009;
RA Chen L., Wang Z., Ghosh-Roy A., Hubert T., Yan D., O'Rourke S.,
RA Bowerman B., Wu Z., Jin Y., Chisholm A.D.;
RT "Axon regeneration pathways identified by systematic genetic screening in
RT C. elegans.";
RL Neuron 71:1043-1057(2011).
RN [5]
RP FUNCTION, INTERACTION WITH TAC-1 AND ZYG-8, SUBCELLULAR LOCATION, DOMAIN,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=26339988; DOI=10.7554/elife.08695;
RA Chen L., Chuang M., Koorman T., Boxem M., Jin Y., Chisholm A.D.;
RT "Axon injury triggers EFA-6 mediated destabilization of axonal microtubules
RT via TACC and doublecortin like kinase.";
RL Elife 4:0-0(2015).
CC -!- FUNCTION: Guanine nucleotide exchange factor for arf-6 (By similarity).
CC Involved in response to injury in mechanosensory neurons. Inhibits axon
CC regrowth via microtubule dynamics, possibly by inducing axonal
CC microtubule catastrophes (PubMed:21943602, PubMed:26339988). Limits
CC microtubule growth near the cellular cortex of early embryonic cells
CC (PubMed:21076413). {ECO:0000250|UniProtKB:Q9NYI0,
CC ECO:0000269|PubMed:21076413, ECO:0000269|PubMed:21943602,
CC ECO:0000269|PubMed:26339988}.
CC -!- SUBUNIT: Interacts (via short N-terminal region) with microtubule-
CC associated proteins tac-1 and zyg-8. {ECO:0000269|PubMed:26339988}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:17676955, ECO:0000269|PubMed:21076413,
CC ECO:0000269|PubMed:26339988}. Cell membrane
CC {ECO:0000269|PubMed:26339988}. Note=Present throughout the embryonic
CC cortex during the first embryonic mitosis, but at reduced levels in the
CC posterior cortex (PubMed:21076413). Localizes to the plasma membrane of
CC the soma and processes of neurons. Localizes to the cellular cortex in
CC the steady (uninjured) state. Following injury, transiently relocalizes
CC to the sites marked by the microtubule minus end binding protein ptrn-1
CC together with tac-1 (PubMed:26339988). {ECO:0000269|PubMed:21076413,
CC ECO:0000269|PubMed:26339988}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=b {ECO:0000303|PubMed:17676955, ECO:0000303|PubMed:9851916};
CC IsoId=G5EET6-1; Sequence=Displayed;
CC Name=a {ECO:0000303|PubMed:9851916};
CC IsoId=G5EET6-2; Sequence=VSP_058547;
CC Name=c {ECO:0000303|PubMed:17676955, ECO:0000303|PubMed:9851916};
CC IsoId=G5EET6-3; Sequence=VSP_058547, VSP_058548;
CC Name=d {ECO:0000303|PubMed:9851916};
CC IsoId=G5EET6-4; Sequence=VSP_058546;
CC -!- DEVELOPMENTAL STAGE: Isoform b: Enriched cortically both in the
CC anterior portion of the one-cell zygote and at the blastomere boundary
CC in two-cell embryos. Isoform c: Localizes to nonpolarized cellular
CC cortex in oocytes and early one-cell zygotes and anterior cellular
CC cortex in one-cell embryos subsequent to pseudocleavage. Present at the
CC interface of the AB and P1 cells. Undetectable by the four-cell stage.
CC {ECO:0000269|PubMed:17676955}.
CC -!- DOMAIN: A short conserved N-terminal region is necessary for the
CC function of this protein (PubMed:21943602, PubMed:26339988). Transient
CC relocalization to microtubule minus ends after neuronal injury also
CC requires this region (PubMed:26339988). {ECO:0000269|PubMed:21943602,
CC ECO:0000269|PubMed:26339988}.
CC -!- DISRUPTION PHENOTYPE: Abnormally long and dense microtubules at the
CC cellular cortex of early embryonic cells and growing microtubule plus
CC ends reside at the cortex for up to five times longer. Causes excess
CC centrosome separation and displacement towards the cellular cortex
CC early in mitosis and subsequently a loss of anaphase spindle-pole
CC oscillations and increased rates of spindle elongation. The centrosome
CC separation phenotype is dependent on the motor protein dynein. Weakly
CC delayed nuclear envelope breakdown (PubMed:21076413). Displays mild
CC posterior lateral microtubule (PLM) axon overshooting in development
CC and enhanced PLM regrowth following neuronal injury acting early in
CC regrowth (PubMed:21943602). Axons display elevated numbers of growing
CC microtubules in the steady (uninjured) state and display impenetrant
CC developmental overgrowth in the absence of injury (PubMed:26339988).
CC {ECO:0000269|PubMed:21076413, ECO:0000269|PubMed:21943602,
CC ECO:0000269|PubMed:26339988}.
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DR EMBL; EF473217; ABQ42569.1; -; mRNA.
DR EMBL; EF473218; ABQ42570.1; -; mRNA.
DR EMBL; BX284604; CAA21701.1; -; Genomic_DNA.
DR EMBL; BX284604; CAC70120.1; -; Genomic_DNA.
DR EMBL; BX284604; CAM82814.1; -; Genomic_DNA.
DR EMBL; BX284604; CBL43465.1; -; Genomic_DNA.
DR PIR; T27189; T27189.
DR RefSeq; NP_001122818.1; NM_001129346.1. [G5EET6-3]
DR RefSeq; NP_001255652.1; NM_001268723.1. [G5EET6-4]
DR RefSeq; NP_502416.1; NM_070015.4. [G5EET6-1]
DR RefSeq; NP_502417.1; NM_070016.3. [G5EET6-2]
DR AlphaFoldDB; G5EET6; -.
DR SMR; G5EET6; -.
DR STRING; 6239.Y55D9A.1b; -.
DR PaxDb; G5EET6; -.
DR EnsemblMetazoa; Y55D9A.1a.1; Y55D9A.1a.1; WBGene00013223. [G5EET6-2]
DR EnsemblMetazoa; Y55D9A.1b.1; Y55D9A.1b.1; WBGene00013223. [G5EET6-1]
DR EnsemblMetazoa; Y55D9A.1c.1; Y55D9A.1c.1; WBGene00013223. [G5EET6-3]
DR EnsemblMetazoa; Y55D9A.1d.1; Y55D9A.1d.1; WBGene00013223. [G5EET6-4]
DR GeneID; 178217; -.
DR KEGG; cel:CELE_Y55D9A.1; -.
DR UCSC; Y55D9A.1b; c. elegans.
DR CTD; 178217; -.
DR WormBase; Y55D9A.1a; CE19234; WBGene00013223; efa-6. [G5EET6-2]
DR WormBase; Y55D9A.1b; CE29066; WBGene00013223; efa-6. [G5EET6-1]
DR WormBase; Y55D9A.1c; CE40826; WBGene00013223; efa-6. [G5EET6-3]
DR WormBase; Y55D9A.1d; CE44770; WBGene00013223; efa-6. [G5EET6-4]
DR eggNOG; KOG0932; Eukaryota.
DR GeneTree; ENSGT00940000155061; -.
DR InParanoid; G5EET6; -.
DR OMA; EWCEKIN; -.
DR OrthoDB; 532213at2759; -.
DR PhylomeDB; G5EET6; -.
DR PRO; PR:G5EET6; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00013223; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0036449; C:microtubule minus-end; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0007019; P:microtubule depolymerization; IMP:UniProtKB.
DR GO; GO:0007077; P:mitotic nuclear membrane disassembly; IMP:UniProtKB.
DR GO; GO:0048692; P:negative regulation of axon extension involved in regeneration; IMP:UniProtKB.
DR GO; GO:0048681; P:negative regulation of axon regeneration; IMP:WormBase.
DR GO; GO:1902845; P:negative regulation of mitotic spindle elongation; IMP:UniProtKB.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; IMP:UniProtKB.
DR GO; GO:0048678; P:response to axon injury; IDA:UniProtKB.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041681; PH_9.
DR InterPro; IPR001605; PH_dom-spectrin-type.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR Pfam; PF15410; PH_9; 1.
DR Pfam; PF01369; Sec7; 1.
DR PRINTS; PR00683; SPECTRINPH.
DR SMART; SM00233; PH; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Reference proteome.
FT CHAIN 1..818
FT /note="Exchange factor for Arf-6"
FT /id="PRO_0000437502"
FT DOMAIN 356..532
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 569..681
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 92..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 782..818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 251..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 782..803
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..184
FT /note="Missing (in isoform d)"
FT /id="VSP_058546"
FT VAR_SEQ 99..100
FT /note="Missing (in isoform a and isoform c)"
FT /id="VSP_058547"
FT VAR_SEQ 180..230
FT /note="Missing (in isoform c)"
FT /id="VSP_058548"
FT MUTAGEN 449
FT /note="E->K: Localizes to the cellular cortex of embryo and
FT promotes robust spindle rocking as in wild-type during the
FT first embryonic mitosis. Inhibits axon regrowth following
FT neuronal injury."
FT /evidence="ECO:0000269|PubMed:21076413,
FT ECO:0000269|PubMed:21943602"
SQ SEQUENCE 818 AA; 90646 MW; 9E0B4E87563262C0 CRC64;
MAKVASSGAE EALATIDGAP RRNVKKSEAF VMSGDVLISL NRNVSSTYAK LLGDQLPPGT
TVASSIHPHQ LSRATASAGV SFPSMNRNGA AAQKLSRLPV PVSTSQIERR GSLARKTSEE
SSPTAIRMLK TAPIERMEST DVEESEEETV MMTTDEKENQ KKPNENDDEV MVVDEEQFIV
VSNDMKSPNE EIVAKSLRSA MFTMPTDNHH HSYNSSPQIS TLSPHLRSNG DGPSRSPVYD
DVDDDLNGSL DAKDMSNNSH QQSFRSPENY SEKDTPSKHS VVTIDGSGVS NHYDQDGMFS
HVYYSTQDTT PKHGSPSLRK QIFESRTTPN TAASNSSASA SPSLHATSES RGATGGVSLR
SAESSNLNQT AVPSTSTNSV GGEREAAQIA RNLYELKNCT STQVADRLNE QNEFSFLILV
KYLELFQFST TRIDAALREF LSRVELRGES SARERLLRVF SARYLECNPA IFDSLDEVHT
LTCALLLLNS DLHGPNMGKK MTARDFITNI AHTGCTFKRE MLKTLFQSIK DNAISLQNSA
KNSTANGSVA STSRRQPQQI YEVDPDSVVE YYSGFLMRKY VRETDGGKTP FGRRSWRMVY
ARLRGLVLYF DTDEHPKATS RYASLENAVS LHHALAEPAP DYKKKSFVFR VRIAHGGEIL
FQTSNQKELQ EWCEKINFVA AAFSSPTLPL PVTSKPETAP MPRLPRIPCL APITKQLSTH
EARVAELNEM IEIVSQSVSP NQPQQLITDR WVLLSFEKRR YSTYINVLRR SLEARKASSA
TTMNIMMTPT RRQQQNQKPV VSEDRLSYTD AVNGAAAH