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Protein

Ephexin-1

Gene

NGEF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-3928663 EPHA-mediated growth cone collapse
R-HSA-416482 G alpha (12/13) signalling events
SignaLinkiQ8N5V2

Names & Taxonomyi

Protein namesi
Recommended name:
Ephexin-1
Alternative name(s):
Eph-interacting exchange protein
Neuronal guanine nucleotide exchange factor
Gene namesi
Name:NGEF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000066248.14
HGNCiHGNC:7807 NGEF
MIMi605991 gene
neXtProtiNX_Q8N5V2

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

Organism-specific databases

DisGeNETi25791
OpenTargetsiENSG00000066248
PharmGKBiPA31613

Polymorphism and mutation databases

BioMutaiNGEF
DMDMi114152090

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002483881 – 710Ephexin-1Add BLAST710

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei179PhosphotyrosineBy similarity1

Post-translational modificationi

Src-dependent phosphorylation at Tyr-179 upon EPHA4 activation increases the guanine exchange factor activity toward RHOA. Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may regulate dendritic spine morphogenesis (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8N5V2
MaxQBiQ8N5V2
PaxDbiQ8N5V2
PeptideAtlasiQ8N5V2
PRIDEiQ8N5V2
ProteomicsDBi72101
72102 [Q8N5V2-2]

PTM databases

iPTMnetiQ8N5V2
PhosphoSitePlusiQ8N5V2

Expressioni

Tissue specificityi

Highly expressed in brain specifically in caudate nucleus and to a lower extent in amygdala and hippocampus. Also detected in lung.1 Publication

Gene expression databases

BgeeiENSG00000066248 Expressed in 163 organ(s), highest expression level in putamen
CleanExiHS_NGEF
ExpressionAtlasiQ8N5V2 baseline and differential
GenevisibleiQ8N5V2 HS

Organism-specific databases

HPAiHPA008160

Interactioni

Subunit structurei

Interacts with CDK5R1 and EPHA4; activated by EPHA4 through the CDK5 kinase.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117324, 20 interactors
IntActiQ8N5V2, 13 interactors
MINTiQ8N5V2
STRINGi9606.ENSP00000264051

Structurei

3D structure databases

ProteinModelPortaliQ8N5V2
SMRiQ8N5V2
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 – 273Regulatory region; modulates activity toward RHOA, RAC1 and CDC42By similarityAdd BLAST273

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi216 – 226Poly-GluAdd BLAST11

Domaini

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

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG3523 Eukaryota
COG5422 LUCA
GeneTreeiENSGT00550000074493
HOGENOMiHOG000007536
HOVERGENiHBG058673
InParanoidiQ8N5V2
KOiK07525
OMAiGWIFGER
OrthoDBiEOG091G04NI
PhylomeDBiQ8N5V2
TreeFamiTF316357

Family and domain databases

CDDicd00160 RhoGEF, 1 hit
cd11939 SH3_ephexin1, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR035635 Ephexin-1_SH3
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF00621 RhoGEF, 1 hit
PF00018 SH3_1, 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
PROSITEiView protein in PROSITE
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50002 SH3, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q8N5V2-1) [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
METRESEDLE KTRRKSASDQ WNTDNEPAKV KPELLPEKEE TSQADQDIQD
60 70 80 90 100
KEPHCHIPIK RNSIFNRSIR RKSKAKARDN PERNASCLAD SQDNGKSVNE
110 120 130 140 150
PLTLNIPWSR MPPCRTAMQT DPGAQEMSES SSTPGNGATP EEWPALADSP
160 170 180 190 200
TTLTEALRMI HPIPADSWRN LIEQIGLLYQ EYRDKSTLQE IETRRQQDAE
210 220 230 240 250
IEDNTNGSPA SEDTPEEEEE EEEEEEPASP PERKTLPQIC LLSNPHSRFN
260 270 280 290 300
LWQDLPEIRS SGVLEILQPE EIKLQEAMFE LVTSEASYYK SLNLLVSHFM
310 320 330 340 350
ENERIRKILH PSEAHILFSN VLDVLAVSER FLLELEHRME ENIVISDVCD
360 370 380 390 400
IVYRYAADHF SVYITYVSNQ TYQERTYKQL LQEKAAFREL IAQLELDPKC
410 420 430 440 450
RGLPFSSFLI LPFQRITRLK LLVQNILKRV EERSERECTA LDAHKELEMV
460 470 480 490 500
VKACNEGVRK MSRTEQMISI QKKMEFKIKS VPIISHSRWL LKQGELQQMS
510 520 530 540 550
GPKTSRTLRT KKLFHEIYLF LFNDLLVICR QIPGDKYQVF DSAPRGLLRV
560 570 580 590 600
EELEDQGQTL ANVFILRLLE NADDREATYM LKASSQSEMK RWMTSLAPNR
610 620 630 640 650
RTKFVSFTSR LLDCPQVQCV HPYVAQQPDE LTLELADILN ILDKTDDGWI
660 670 680 690 700
FGERLHDQER GWFPSSMTEE ILNPKIRSQN LKECFRVHKM DDPQRSQNKD
710
RRKLGSRNRQ
Length:710
Mass (Da):82,496
Last modified:September 5, 2006 - v2
Checksum:i82A4CA71D4E7AE6E
GO
Isoform 2 (identifier: Q8N5V2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: Missing.
     93-127: DNGKSVNEPLTLNIPWSRMPPCRTAMQTDPGAQEM → MELLAAAFSAACAVDHDSSTSESDARDSAAGHLPG
     331-710: Missing.

Note: No experimental confirmation available.
Show »
Length:238
Mass (Da):26,595
Checksum:i7BE95285400E6900
GO
Isoform 3 (identifier: Q8N5V2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: Missing.
     93-127: DNGKSVNEPLTLNIPWSRMPPCRTAMQTDPGAQEM → MELLAAAFSAACAVDHDSSTSESDARDSAAGHLPG

Note: No experimental confirmation available.
Show »
Length:618
Mass (Da):71,387
Checksum:i715379B007A5E8BF
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JTV7C9JTV7_HUMAN
Ephexin-1
NGEF
187Annotation score:
H7BZ39H7BZ39_HUMAN
Ephexin-1
NGEF
150Annotation score:
H7C2C2H7C2C2_HUMAN
Ephexin-1
NGEF
97Annotation score:

Sequence cautioni

The sequence AAH73962 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAX93288 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC00686 differs from that shown. Reason: Frameshift at position 156.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti147A → T in CAC00686 (PubMed:10777665).Curated1
Sequence conflicti543A → R in CAC00686 (PubMed:10777665).Curated1
Sequence conflicti578T → I in CAC00686 (PubMed:10777665).Curated1
Sequence conflicti604F → S in BAG59830 (PubMed:14702039).Curated1
Sequence conflicti702R → M in BAG59830 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02728978R → G. Corresponds to variant dbSNP:rs2271703Ensembl.1
Natural variantiVAR_027290111M → T1 PublicationCorresponds to variant dbSNP:rs4973588Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0202591 – 92Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST92
Alternative sequenceiVSP_02026093 – 127DNGKS…GAQEM → MELLAAAFSAACAVDHDSST SESDARDSAAGHLPG in isoform 2 and isoform 3. 2 PublicationsAdd BLAST35
Alternative sequenceiVSP_020261331 – 710Missing in isoform 2. 1 PublicationAdd BLAST380

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK297390 mRNA Translation: BAG59830.1
AC016692 Genomic DNA Translation: AAX93288.1 Different initiation.
AC106876 Genomic DNA Translation: AAY24359.1
BC031573 mRNA Translation: AAH31573.1
BC073962 mRNA Translation: AAH73962.1 Different initiation.
AJ238899 mRNA Translation: CAC00686.1 Frameshift.
CCDSiCCDS2500.1 [Q8N5V2-1]
CCDS46544.1 [Q8N5V2-3]
RefSeqiNP_001107562.1, NM_001114090.1 [Q8N5V2-3]
NP_062824.2, NM_019850.2 [Q8N5V2-1]
XP_011509225.1, XM_011510923.2 [Q8N5V2-1]
UniGeneiHs.97316

Genome annotation databases

EnsembliENST00000264051; ENSP00000264051; ENSG00000066248 [Q8N5V2-1]
ENST00000373552; ENSP00000362653; ENSG00000066248 [Q8N5V2-3]
ENST00000409079; ENSP00000387033; ENSG00000066248 [Q8N5V2-2]
GeneIDi25791
KEGGihsa:25791
UCSCiuc002vts.3 human [Q8N5V2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNGEF_HUMAN
AccessioniPrimary (citable) accession number: Q8N5V2
Secondary accession number(s): B4DMB8
, B9A045, E9PC42, Q53QQ4, Q53ST7, Q6GMQ5, Q9NQD6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: September 12, 2018
This is version 139 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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