NGEF_MOUSE
ID NGEF_MOUSE Reviewed; 710 AA.
AC Q8CHT1; Q8R204; Q923H2; Q9JHT9;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Ephexin-1;
DE AltName: Full=Eph-interacting exchange protein;
DE AltName: Full=Neuronal guanine nucleotide exchange factor;
GN Name=Ngef;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=10777665; DOI=10.1006/geno.2000.6138;
RA Rodrigues N.R., Theodosiou A.M., Nesbit M.A., Campbell L., Tandle A.T.,
RA Saranath D., Davies K.E.;
RT "Characterization of Ngef, a novel member of the Dbl family of genes
RT expressed predominantly in the caudate nucleus.";
RL Genomics 65:53-61(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND INTERACTION WITH
RP EPHA4.
RC STRAIN=C57BL/6J;
RX PubMed=11336673; DOI=10.1016/s0092-8674(01)00314-2;
RA Shamah S.M., Lin M.Z., Goldberg J.L., Estrach S., Sahin M., Hu L.,
RA Bazalakova M., Neve R.L., Corfas G., Debant A., Greenberg M.E.;
RT "EphA receptors regulate growth cone dynamics through the novel guanine
RT nucleotide exchange factor ephexin.";
RL Cell 105:233-244(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=15142957; DOI=10.1093/cercor/bhh063;
RA Funatsu N., Inoue T., Nakamura S.;
RT "Gene expression analysis of the late embryonic mouse cerebral cortex using
RT DNA microarray: identification of several region- and layer-specific
RT genes.";
RL Cereb. Cortex 14:1031-1044(2004).
RN [5]
RP PHOSPHORYLATION BY SRC FAMILY KINASES.
RX PubMed=15254079; DOI=10.1523/jneurosci.0985-04.2004;
RA Knoell B., Drescher U.;
RT "Src family kinases are involved in EphA receptor-mediated retinal axon
RT guidance.";
RL J. Neurosci. 24:6248-6257(2004).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF TYR-177.
RX PubMed=15848799; DOI=10.1016/j.neuron.2005.01.030;
RA Sahin M., Greer P.L., Lin M.Z., Poucher H., Eberhart J., Schmidt S.,
RA Wright T.M., Shamah S.M., O'connell S., Cowan C.W., Hu L., Goldberg J.L.,
RA Debant A., Corfas G., Krull C.E., Greenberg M.E.;
RT "Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone
RT collapse.";
RL Neuron 46:191-204(2005).
RN [7]
RP FUNCTION IN DENDRITIC SPINE MORPHOGENESIS, INTERACTION WITH EPHA4 AND
RP CDK5R1, AND PHOSPHORYLATION BY CDK5.
RX PubMed=17143272; DOI=10.1038/nn1811;
RA Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O.,
RA Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.;
RT "Cdk5 regulates EphA4-mediated dendritic spine retraction through an
RT ephexin1-dependent mechanism.";
RL Nat. Neurosci. 10:67-76(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Acts as a guanine nucleotide exchange factor (GEF) which
CC differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role
CC in axon guidance regulating ephrin-induced growth cone collapse and
CC dendritic spine morphogenesis. Upon activation by ephrin through EPHA4,
CC the GEF activity switches toward RHOA resulting in its activation.
CC Activated RHOA promotes cone retraction at the expense of RAC1- and
CC CDC42-stimulated growth cone extension. {ECO:0000269|PubMed:11336673,
CC ECO:0000269|PubMed:15848799, ECO:0000269|PubMed:17143272}.
CC -!- SUBUNIT: Interacts with CDK5R1 and EPHA4; activated by EPHA4 through
CC the CDK5 kinase. {ECO:0000269|PubMed:11336673,
CC ECO:0000269|PubMed:17143272}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250}.
CC Cell projection, growth cone {ECO:0000250}. Note=Associated with
CC membranes. Localizes to axonal growth cones (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8CHT1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CHT1-2; Sequence=VSP_020262, VSP_020263;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and to a lower extent in
CC eye. {ECO:0000269|PubMed:10777665}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in 7 dpc and to a lower extent in
CC 11 dpc, 15 dpc and 17 dpc embryos. Expressed at 16.5 dpc in the lateral
CC regions of the cortex. {ECO:0000269|PubMed:10777665,
CC ECO:0000269|PubMed:15142957}.
CC -!- DOMAIN: The DH domain and the PH domain are both required to mediate
CC interaction with EPHA4.
CC -!- PTM: Src-dependent phosphorylation at Tyr-177 upon EPHA4 activation
CC increases the guanine exchange factor activity toward RHOA.
CC Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may regulate
CC dendritic spine morphogenesis. {ECO:0000269|PubMed:15254079,
CC ECO:0000269|PubMed:17143272}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22680.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAC00698.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AJ238898; CAC00698.1; ALT_FRAME; mRNA.
DR EMBL; AY038025; AAK71494.1; -; mRNA.
DR EMBL; BC022680; AAH22680.1; ALT_INIT; mRNA.
DR EMBL; BC039279; AAH39279.1; -; mRNA.
DR CCDS; CCDS48306.1; -. [Q8CHT1-2]
DR CCDS; CCDS48307.1; -. [Q8CHT1-1]
DR RefSeq; NP_001104784.1; NM_001111314.1.
DR RefSeq; NP_063920.2; NM_019867.2. [Q8CHT1-2]
DR AlphaFoldDB; Q8CHT1; -.
DR SMR; Q8CHT1; -.
DR BioGRID; 207543; 12.
DR IntAct; Q8CHT1; 6.
DR MINT; Q8CHT1; -.
DR STRING; 10090.ENSMUSP00000066894; -.
DR iPTMnet; Q8CHT1; -.
DR PhosphoSitePlus; Q8CHT1; -.
DR MaxQB; Q8CHT1; -.
DR PaxDb; Q8CHT1; -.
DR PRIDE; Q8CHT1; -.
DR ProteomicsDB; 252961; -. [Q8CHT1-1]
DR ProteomicsDB; 252962; -. [Q8CHT1-2]
DR Antibodypedia; 2119; 143 antibodies from 21 providers.
DR Ensembl; ENSMUST00000027477; ENSMUSP00000027477; ENSMUSG00000026259. [Q8CHT1-2]
DR GeneID; 53972; -.
DR KEGG; mmu:53972; -.
DR UCSC; uc007bwx.2; mouse. [Q8CHT1-2]
DR CTD; 25791; -.
DR MGI; MGI:1858414; Ngef.
DR VEuPathDB; HostDB:ENSMUSG00000026259; -.
DR eggNOG; KOG3523; Eukaryota.
DR GeneTree; ENSGT01030000234571; -.
DR HOGENOM; CLU_012820_5_1_1; -.
DR InParanoid; Q8CHT1; -.
DR OrthoDB; 1176939at2759; -.
DR PhylomeDB; Q8CHT1; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR BioGRID-ORCS; 53972; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Ngef; mouse.
DR PRO; PR:Q8CHT1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8CHT1; protein.
DR Bgee; ENSMUSG00000026259; Expressed in caudate-putamen and 149 other tissues.
DR ExpressionAtlas; Q8CHT1; baseline and differential.
DR Genevisible; Q8CHT1; MM.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0043087; P:regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0098883; P:synapse pruning; IDA:SynGO.
DR CDD; cd00160; RhoGEF; 1.
DR CDD; cd11939; SH3_ephexin1; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR035635; Ephexin-1_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cytoplasm; Developmental protein;
KW Differentiation; Guanine-nucleotide releasing factor; Membrane;
KW Neurogenesis; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..710
FT /note="Ephexin-1"
FT /id="PRO_0000248389"
FT DOMAIN 273..457
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 489..601
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 612..673
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..272
FT /note="Regulatory region; modulates activity toward RHOA,
FT RAC1 and CDC42"
FT REGION 1..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 192..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..710
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..226
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..703
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 177
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q5BKC9"
FT VAR_SEQ 1..90
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10777665,
FT ECO:0000303|PubMed:11336673"
FT /id="VSP_020262"
FT VAR_SEQ 91..125
FT /note="KMGKSVNERSAFNLPQGRLSPWRTPAQRDTGAQEA -> MELLAAAFSAACA
FT VDHDSSTSESDTRDSAAGHLPG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10777665,
FT ECO:0000303|PubMed:11336673"
FT /id="VSP_020263"
FT MUTAGEN 177
FT /note="Y->F: Loss of ephrin-mediated growth cone collapse.
FT No effect on interaction with EPHA4."
FT /evidence="ECO:0000269|PubMed:15848799"
FT CONFLICT 530
FT /note="R -> W (in Ref. 2; AAK71494)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 710 AA; 82199 MW; F255DE351E02A586 CRC64;
METKNSEDWG KPQRKSESSS RKSNHGPAEM RPALPPENRE APETGEETQN EEPRRLIPIQ
RHSLFNRAVR HRHKARSTSE RRASDQADLP KMGKSVNERS AFNLPQGRLS PWRTPAQRDT
GAQEASESSS TPGNGTTPEE CPALTDSPTT LTEALQMIHP IPADSWRNLI EQIGLLYQEY
RDKSTLQEIE TRRQQDAEIQ GNSDGSQVGE DAGEEEEEEE EGEEEELASP PERRALPQIC
LLSNPHSRFN LWQDLPEIQS SGVLDILQPE EIRLQEAMFE LVTSEASYYK SLNLLVSHFM
ENERLKKILH PSEAHILFSN VLDVMAVSER FLLELEHRME ENIVISDVCD IVYRYAADHF
SVYITYVSNQ TYQERTYKQL LQEKAAFREL IAQLELDPKC KGLPFSSFLI LPFQRITRLK
LLVQNILKRV EERSEREGTA LDAHKELEMV VKACNEGVRK MSRTEQMISI QKKMEFKIKS
VPIISHSRWL LKQGELQQMS GPKTSRTLRT KKLFREIYLF LFNDLLVICR QIPGDKYQVF
DSAPRGLLRV EELEDQGQTL ANVFILRLLE NADDREATYM LKASSQSEMK RWMTSLAPNR
RTKFVSFTSR LLDCPQVQCV HPYVAQQPDE LTLELADILN ILEKTEDGWI FGERLHDQER
GWFPSSMTEE ILNPKIRSQN LKECFRVHKM EDPQRSQNKD RRKLGSRNRQ
