NGEF_PONAB
ID NGEF_PONAB Reviewed; 709 AA.
AC Q5RDX5;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Ephexin-1;
DE AltName: Full=Eph-interacting exchange protein;
DE AltName: Full=Neuronal guanine nucleotide exchange factor;
GN Name=NGEF;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CDK5R1 and EPHA4; activated by EPHA4 through
CC the CDK5 kinase. {ECO:0000250}.
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 -!- DOMAIN: The DH domain and the PH domain are both required to mediate
CC interaction with EPHA4. {ECO:0000250}.
CC -!- PTM: Src-dependent phosphorylation at Tyr-179 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 (By similarity). {ECO:0000250}.
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DR EMBL; CR857767; CAH90032.1; -; mRNA.
DR RefSeq; NP_001124968.1; NM_001131496.1.
DR AlphaFoldDB; Q5RDX5; -.
DR SMR; Q5RDX5; -.
DR STRING; 9601.ENSPPYP00000014853; -.
DR Ensembl; ENSPPYT00000015450; ENSPPYP00000014853; ENSPPYG00000013287.
DR GeneID; 100171841; -.
DR KEGG; pon:100171841; -.
DR CTD; 25791; -.
DR eggNOG; KOG3523; Eukaryota.
DR GeneTree; ENSGT01030000234571; -.
DR InParanoid; Q5RDX5; -.
DR OrthoDB; 1176939at2759; -.
DR Proteomes; UP000001595; Chromosome 2B.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0061002; P:negative regulation of dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cell projection; Cytoplasm; Developmental protein; Differentiation;
KW Guanine-nucleotide releasing factor; Membrane; Neurogenesis;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..709
FT /note="Ephexin-1"
FT /id="PRO_0000248390"
FT DOMAIN 272..456
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 488..600
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 611..672
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 /evidence="ECO:0000250"
FT REGION 1..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..38
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..138
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..226
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 686..702
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 179
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q5BKC9"
SQ SEQUENCE 709 AA; 82212 MW; F513134DF28FC008 CRC64;
METRESEDLE KTWRKSASDQ RNTDNEPAKV KPELLPEEEE TSQADQDIQD KEPHCHIPIK
RNSIFNRSIR RKSKAKARDT PERNASCLAD SQDNGKSVND SLTLNIPRSR MPPCRTAMQT
GPGAQKMSES SSTPGNGATP EEWPALADSP TTLTEALRMI HPIPADSWRN LIEQIGLLYQ
EYRDKSTLQE IETRRQQDAE IEDNTNGSPA SEDTPEEEEE EEEEEPASPP ERKALPQICL
LSNPHSRFNL WQDLPEIRSS GVLEILQPEE IKLQEAMFEL VTSEASYYKS LNLLVSHFME
NERIRKILHP SEAHILFSNV LDVLAVSERF LLELEHRMEE NIVISDVCDI VYRYAADHFS
VYITYVSNQT YQERTYKQLL QEKAAFRELI AQLELDPKCR GLPFSSFLIL PFQRITRLKL
LVQNILKRVE ERSERECTAL DAHKELEMVV KACNEGVRKM SRTEQMISIQ KKMEFKIKSV
PIISHSRWLL KQGELQQMSG PKTSRTLRTK KLFHEIYLFL FNDLLVICRQ IPGDKYQVFD
SAPRGLLRVE ELEDQGQTLA NVFILRLLEN ADDREATYML KASSQSEMKR WMTSLAPNRR
TKFVSFTSRL LDCPQVQCVH PYVAQQPDEL TLELADILNI LDKTDDGWIF GERLHDQERG
WFPSSMTEEI LNPKIRSQNL KECFRVHKMD DPQRSQNKDR RKLGSRNRQ
