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Protein

Ephexin-1

Gene

NGEF

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Guanine-nucleotide releasing factor

Keywords - Biological processi

Differentiation, 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

HGNCiHGNC:7807. NGEF.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31613.

Polymorphism and mutation databases

BioMutaiNGEF.
DMDMi114152090.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 710710Ephexin-1PRO_0000248388Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei179 – 1791PhosphotyrosineBy similarity

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.

PTM databases

iPTMnetiQ8N5V2.
PhosphoSiteiQ8N5V2.

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.
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

Protein-protein interaction databases

BioGridi117324. 17 interactions.
IntActiQ8N5V2. 13 interactions.
MINTiMINT-1425703.
STRINGi9606.ENSP00000264051.

Structurei

3D structure databases

ProteinModelPortaliQ8N5V2.
SMRiQ8N5V2. Positions 265-593, 613-674.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini273 – 457185DHPROSITE-ProRule annotationAdd
BLAST
Domaini489 – 601113PHPROSITE-ProRule annotationAdd
BLAST
Domaini612 – 67362SH3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 273273Regulatory region; modulates activity toward RHOA, RAC1 and CDC42By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi216 – 22611Poly-GluAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

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

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti147 – 1471A → T in CAC00686 (PubMed:10777665).Curated
Sequence conflicti543 – 5431A → R in CAC00686 (PubMed:10777665).Curated
Sequence conflicti578 – 5781T → I in CAC00686 (PubMed:10777665).Curated
Sequence conflicti604 – 6041F → S in BAG59830 (PubMed:14702039).Curated
Sequence conflicti702 – 7021R → M in BAG59830 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti78 – 781R → G.
Corresponds to variant rs2271703 [ dbSNP | Ensembl ].
VAR_027289
Natural varianti111 – 1111M → T.1 Publication
Corresponds to variant rs4973588 [ dbSNP | Ensembl ].
VAR_027290

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9292Missing in isoform 2 and isoform 3. 2 PublicationsVSP_020259Add
BLAST
Alternative sequencei93 – 12735DNGKS…GAQEM → MELLAAAFSAACAVDHDSST SESDARDSAAGHLPG in isoform 2 and isoform 3. 2 PublicationsVSP_020260Add
BLAST
Alternative sequencei331 – 710380Missing in isoform 2. 1 PublicationVSP_020261Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8N5V2.
SMRiQ8N5V2. Positions 265-593, 613-674.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117324. 17 interactions.
IntActiQ8N5V2. 13 interactions.
MINTiMINT-1425703.
STRINGi9606.ENSP00000264051.

PTM databases

iPTMnetiQ8N5V2.
PhosphoSiteiQ8N5V2.

Polymorphism and mutation databases

BioMutaiNGEF.
DMDMi114152090.

Proteomic databases

EPDiQ8N5V2.
MaxQBiQ8N5V2.
PaxDbiQ8N5V2.
PeptideAtlasiQ8N5V2.
PRIDEiQ8N5V2.

Protocols and materials databases

DNASUi25791.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi25791.
GeneCardsiNGEF.
H-InvDBHIX0002931.
HGNCiHGNC:7807. NGEF.
HPAiHPA008160.
MIMi605991. gene.
neXtProtiNX_Q8N5V2.
PharmGKBiPA31613.
GenAtlasiSearch...

Phylogenomic databases

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

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.

Miscellaneous databases

ChiTaRSiNGEF. human.
GenomeRNAii25791.
PROiQ8N5V2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000066248.
CleanExiHS_NGEF.
ExpressionAtlasiQ8N5V2. baseline and differential.
GenevisibleiQ8N5V2. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNGEF_HUMAN
AccessioniPrimary (citable) accession number: Q8N5V2
Secondary accession number(s): B4DMB8
, B9A045, E9PC42, Q53QQ4, Q53ST7, Q6GMQ5, Q9NQD6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: September 7, 2016
This is version 122 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.