NGEF_RAT
ID NGEF_RAT Reviewed; 701 AA.
AC Q5BKC9;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Ephexin-1;
DE AltName: Full=Eph-interacting exchange protein;
DE AltName: Full=Neuronal guanine nucleotide exchange factor;
GN Name=Ngef;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 341-701.
RC TISSUE=Brain;
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE,
RP AND INTERACTION WITH EPHA4.
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 [4]
RP PHOSPHORYLATION AT TYR-172 BY SRC FAMILY KINASES.
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).
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 -!- SUBUNIT: Interacts with CDK5R1 and EPHA4; activated by EPHA4 through
CC the CDK5 kinase. {ECO:0000269|PubMed:11336673}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11336673}. Membrane
CC {ECO:0000269|PubMed:11336673}. Cell projection, growth cone
CC {ECO:0000269|PubMed:11336673}. Note=Associated with membranes.
CC Localizes to axonal growth cones.
CC -!- TISSUE SPECIFICITY: Expressed in telencephalic neurons (at protein
CC level). Expressed in brain, spinal cord and testis.
CC {ECO:0000269|PubMed:11336673}.
CC -!- DEVELOPMENTAL STAGE: First detected at E15. Expression increases
CC gradually throughout embryonic development and peaks at postnatal day
CC 10. Expressed at E17 in the eye and the deep layers of the cortex. At
CC postnatal day 6, expression is restricted to retinal glanglion cell
CC layer in the eye. {ECO:0000269|PubMed:11336673}.
CC -!- DOMAIN: The DH domain and the PH domain are both required to mediate
CC interaction with EPHA4. {ECO:0000250}.
CC -!- PTM: Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may
CC regulate dendritic spine morphogenesis. Src-dependent phosphorylation
CC at Tyr-172 upon EPHA4 activation increases the guanine exchange factor
CC activity toward RHOA. {ECO:0000269|PubMed:15848799}.
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DR EMBL; AABR03069437; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03069439; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03069922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC091122; AAH91122.1; -; mRNA.
DR AlphaFoldDB; Q5BKC9; -.
DR SMR; Q5BKC9; -.
DR STRING; 10116.ENSRNOP00000022485; -.
DR iPTMnet; Q5BKC9; -.
DR PhosphoSitePlus; Q5BKC9; -.
DR PaxDb; Q5BKC9; -.
DR PRIDE; Q5BKC9; -.
DR UCSC; RGD:1309055; rat.
DR RGD; 1309055; Ngef.
DR eggNOG; KOG3523; Eukaryota.
DR InParanoid; Q5BKC9; -.
DR PhylomeDB; Q5BKC9; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR PRO; PR:Q5BKC9; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
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; 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 GO; GO:0098883; P:synapse pruning; ISO:RGD.
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 Cell projection; Cytoplasm; Developmental protein; Differentiation;
KW Guanine-nucleotide releasing factor; Membrane; Neurogenesis;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..701
FT /note="Ephexin-1"
FT /id="PRO_0000248391"
FT DOMAIN 264..448
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 480..592
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 603..664
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 1..264
FT /note="Regulatory region; modulates activity toward RHOA,
FT RAC1 and CDC42"
FT /evidence="ECO:0000250"
FT REGION 1..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 679..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 116..141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..218
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..694
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 172
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15848799"
SQ SEQUENCE 701 AA; 81008 MW; 9697A2C747C120A8 CRC64;
METKNSEDQG KPQRKSVSSL WKSKHGPAEM RPELPPETAK ETQNEEPRCL IPIQRNSLFN
RAMRHKHKAR SMSERRANDQ AGDLPETRKS VNEPLAFNLP QGRLPPWRTP AQRGPGAQEA
SESSSTPGNG TTPEECPALT DSPTTLTEAL QMIHPIPADS WRNLIEQIGL LYQEYRDKST
LQEIETRRQQ DAEIQGNSDG SQAGEDNAEE EEEEEEEPAS PPERRALPQI CLLSNPHSRF
NLWQDLPEIQ SSGVLDILQP EETKLQEAMF ELVTSEASYY KSLNLLVSHF MENERLKKIL
HPSEAHILFS NVLDVMAVSE RFLLELEHRM EENIVISDVC DIVYRYAADH FSVYITYVSN
QTYQERTYKQ LLQEKTAFRE LIAQLELDPK CKGLPLSSFL ILPFQRITRL KLLVQNILKR
VEEGSEREGT ALDAHKELEM VVKACNEGVR KMSRTEQMIS IQKKMEFKIK SVPIISHSRW
LLKQGELQQM SGPKTSRTLR TKKLFREIYL FLFNDLLVIC RQIPGDKYQV FDSAPRGLLR
VEELEDQGQT LANVFILRLL ENADDREATY MLKASSQSEM KRWMTSLAPN RRTKFVSFTS
RLLDCPQVQC VHPYVAQQPD ELTLELADIL NILEKTEDGW IFGERLHDQE RGWFPSSMTE
EILNPKIRSQ NLKECFRVHK MEDPQRSQNK DRRKLGSRNR Q
