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Protein

Ephexin-1

Gene

Ngef

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension.3 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular process Source: MGI
  • ephrin receptor signaling pathway Source: UniProtKB
  • negative regulation of dendritic spine morphogenesis Source: UniProtKB
  • regulation of GTPase activity Source: UniProtKB
  • regulation of Rho protein signal transduction Source: InterPro

Keywordsi

Molecular functionDevelopmental protein, Guanine-nucleotide releasing factor
Biological processDifferentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-3928663. EPHA-mediated growth cone collapse.
R-MMU-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephexin-1
Alternative name(s):
Eph-interacting exchange protein
Neuronal guanine nucleotide exchange factor
Gene namesi
Name:Ngef
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1858414. Ngef.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi177Y → F: Loss of ephrin-mediated growth cone collapse. No effect on interaction with EPHA4. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002483891 – 710Ephexin-1Add BLAST710

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei177PhosphotyrosineBy similarity1

Post-translational modificationi

Src-dependent phosphorylation at Tyr-177 upon EPHA4 activation increases the guanine exchange factor activity toward RHOA. Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may regulate dendritic spine morphogenesis.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8CHT1.
PRIDEiQ8CHT1.

PTM databases

iPTMnetiQ8CHT1.
PhosphoSitePlusiQ8CHT1.

Expressioni

Tissue specificityi

Highly expressed in brain and to a lower extent in eye.1 Publication

Developmental stagei

Highly expressed in E7 and to a lower extent in E11, E15 and E17 embryos. Expressed at E16.5 in the lateral regions of the cortex.2 Publications

Gene expression databases

BgeeiENSMUSG00000026259.
CleanExiMM_NGEF.
ExpressionAtlasiQ8CHT1. baseline and differential.
GenevisibleiQ8CHT1. MM.

Interactioni

Subunit structurei

Interacts with CDK5R1 and EPHA4; activated by EPHA4 through the CDK5 kinase.2 Publications

GO - Molecular functioni

  • ephrin receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi207543. 1 interactor.
IntActiQ8CHT1. 2 interactors.
STRINGi10090.ENSMUSP00000066894.

Structurei

3D structure databases

ProteinModelPortaliQ8CHT1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini273 – 457DHPROSITE-ProRule annotationAdd BLAST185
Domaini489 – 601PHPROSITE-ProRule annotationAdd BLAST113
Domaini612 – 673SH3PROSITE-ProRule annotationAdd BLAST62

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 272Regulatory region; modulates activity toward RHOA, RAC1 and CDC42Add BLAST272

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi214 – 226Poly-GluAdd BLAST13

Domaini

The DH domain and the PH domain are both required to mediate interaction with EPHA4.

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3523. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00550000074493.
HOGENOMiHOG000007536.
HOVERGENiHBG058673.
InParanoidiQ8CHT1.
KOiK07525.
PhylomeDBiQ8CHT1.

Family and domain databases

CDDicd11939. SH3_ephexin1. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiView protein in InterPro
IPR000219. DH-domain.
IPR035635. Ephexin-1_SH3.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
PfamiView protein in Pfam
PF00621. RhoGEF. 1 hit.
PF14604. SH3_9. 1 hit.
SMARTiView protein in SMART
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiView protein in PROSITE
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CHT1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
METKNSEDWG KPQRKSESSS RKSNHGPAEM RPALPPENRE APETGEETQN
60 70 80 90 100
EEPRRLIPIQ RHSLFNRAVR HRHKARSTSE RRASDQADLP KMGKSVNERS
110 120 130 140 150
AFNLPQGRLS PWRTPAQRDT GAQEASESSS TPGNGTTPEE CPALTDSPTT
160 170 180 190 200
LTEALQMIHP IPADSWRNLI EQIGLLYQEY RDKSTLQEIE TRRQQDAEIQ
210 220 230 240 250
GNSDGSQVGE DAGEEEEEEE EGEEEELASP PERRALPQIC LLSNPHSRFN
260 270 280 290 300
LWQDLPEIQS SGVLDILQPE EIRLQEAMFE LVTSEASYYK SLNLLVSHFM
310 320 330 340 350
ENERLKKILH PSEAHILFSN VLDVMAVSER FLLELEHRME ENIVISDVCD
360 370 380 390 400
IVYRYAADHF SVYITYVSNQ TYQERTYKQL LQEKAAFREL IAQLELDPKC
410 420 430 440 450
KGLPFSSFLI LPFQRITRLK LLVQNILKRV EERSEREGTA LDAHKELEMV
460 470 480 490 500
VKACNEGVRK MSRTEQMISI QKKMEFKIKS VPIISHSRWL LKQGELQQMS
510 520 530 540 550
GPKTSRTLRT KKLFREIYLF LFNDLLVICR QIPGDKYQVF DSAPRGLLRV
560 570 580 590 600
EELEDQGQTL ANVFILRLLE NADDREATYM LKASSQSEMK RWMTSLAPNR
610 620 630 640 650
RTKFVSFTSR LLDCPQVQCV HPYVAQQPDE LTLELADILN ILEKTEDGWI
660 670 680 690 700
FGERLHDQER GWFPSSMTEE ILNPKIRSQN LKECFRVHKM EDPQRSQNKD
710
RRKLGSRNRQ
Length:710
Mass (Da):82,199
Last modified:March 1, 2003 - v1
Checksum:iF255DE351E02A586
GO
Isoform 2 (identifier: Q8CHT1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-90: Missing.
     91-125: KMGKSVNERSAFNLPQGRLSPWRTPAQRDTGAQEA → MELLAAAFSAACAVDHDSSTSESDTRDSAAGHLPG

Show »
Length:620
Mass (Da):71,416
Checksum:iC0B6A9C4E52A3107
GO

Sequence cautioni

The sequence AAH22680 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC00698 differs from that shown. Reason: Frameshift at position 154.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti530R → W in AAK71494 (PubMed:11336673).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0202621 – 90Missing in isoform 2. 2 PublicationsAdd BLAST90
Alternative sequenceiVSP_02026391 – 125KMGKS…GAQEA → MELLAAAFSAACAVDHDSST SESDTRDSAAGHLPG in isoform 2. 2 PublicationsAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ238898 mRNA. Translation: CAC00698.1. Frameshift.
AY038025 mRNA. Translation: AAK71494.1.
BC022680 mRNA. Translation: AAH22680.1. Different initiation.
BC039279 mRNA. Translation: AAH39279.1.
CCDSiCCDS48306.1. [Q8CHT1-2]
CCDS48307.1. [Q8CHT1-1]
RefSeqiNP_001104784.1. NM_001111314.1.
NP_063920.2. NM_019867.2. [Q8CHT1-2]
UniGeneiMm.435439.

Genome annotation databases

EnsembliENSMUST00000027477; ENSMUSP00000027477; ENSMUSG00000026259. [Q8CHT1-2]
GeneIDi53972.
KEGGimmu:53972.
UCSCiuc007bwx.2. mouse. [Q8CHT1-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNGEF_MOUSE
AccessioniPrimary (citable) accession number: Q8CHT1
Secondary accession number(s): Q8R204, Q923H2, Q9JHT9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: March 1, 2003
Last modified: August 30, 2017
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot