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Protein

Rho guanine nucleotide exchange factor 16

Gene

ARHGEF16

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanyl-nucleotide exchange factor of the RHOG GTPase stimulating the exchange of RHOG-associated GDP for GTP. May play a role in chemotactic cell migration by mediating the activation of RAC1 by EPHA2. May also activate CDC42 and mediate activation of CDC42 by the viral protein HPV16 E6.1 Publication

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • guanyl-nucleotide exchange factor activity Source: Reactome
  • PDZ domain binding Source: BHF-UCL
  • receptor tyrosine kinase binding Source: UniProtKB
  • Rho GTPase binding Source: UniProtKB
  • Rho guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

  • activation of GTPase activity Source: UniProtKB
  • cell chemotaxis Source: UniProtKB
  • positive regulation of apoptotic process Source: Reactome
  • positive regulation of establishment of protein localization to plasma membrane Source: UniProtKB
  • regulation of Rho protein signal transduction Source: InterPro
  • regulation of small GTPase mediated signal transduction Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 16
Alternative name(s):
Ephexin-4
Gene namesi
Name:ARHGEF16
Synonyms:EPHEXIN4, NBR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:15515. ARHGEF16.

Subcellular locationi

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • cytosol Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi27237.
OpenTargetsiENSG00000130762.
PharmGKBiPA24971.

Polymorphism and mutation databases

BioMutaiARHGEF16.
DMDMi74747198.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002336902 – 709Rho guanine nucleotide exchange factor 16Add BLAST708

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei6PhosphoserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei107PhosphoserineCombined sources1
Modified residuei174PhosphoserineCombined sources1
Modified residuei191PhosphoserineCombined sources1
Modified residuei208PhosphoserineCombined sources1
Modified residuei226PhosphothreonineBy similarity1
Modified residuei227PhosphoserineCombined sources1
Modified residuei230PhosphoserineCombined sources1
Modified residuei240PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ5VV41.
MaxQBiQ5VV41.
PaxDbiQ5VV41.
PeptideAtlasiQ5VV41.
PRIDEiQ5VV41.

PTM databases

iPTMnetiQ5VV41.
PhosphoSitePlusiQ5VV41.

Expressioni

Inductioni

Up-regulated by HPV16 E6 (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000130762.
CleanExiHS_ARHGEF16.
ExpressionAtlasiQ5VV41. baseline and differential.
GenevisibleiQ5VV41. HS.

Organism-specific databases

HPAiHPA010609.

Interactioni

Subunit structurei

Interacts with ELMO2, EPHA2, RAC1 and RHOG; mediates activation of RAC1 by EPHA2. Interacts with TAX1BP3 (via PDZ domain). May interact with CDC42; stimulated by HPV16 E6.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPK1IP1LQ8NDC03EBI-1057448,EBI-741424
TFGQ05BK63EBI-1057448,EBI-10246902
TFGQ927343EBI-1057448,EBI-357061

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • PDZ domain binding Source: BHF-UCL
  • receptor tyrosine kinase binding Source: UniProtKB
  • Rho GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi118085. 12 interactors.
IntActiQ5VV41. 6 interactors.
MINTiMINT-3295714.
STRINGi9606.ENSP00000367629.

Structurei

Secondary structure

1709
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi633 – 638Combined sources6
Beta strandi644 – 647Combined sources4
Beta strandi654 – 662Combined sources9
Beta strandi665 – 670Combined sources6
Turni671 – 673Combined sources3
Beta strandi676 – 679Combined sources4
Helixi681 – 683Combined sources3
Beta strandi685 – 687Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X6BNMR-A622-687[»]
ProteinModelPortaliQ5VV41.
SMRiQ5VV41.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5VV41.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini284 – 468DHPROSITE-ProRule annotationAdd BLAST185
Domaini501 – 620PHPROSITE-ProRule annotationAdd BLAST120
Domaini629 – 689SH3PROSITE-ProRule annotationAdd BLAST61

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni275 – 481Required for RHOG activation and mediates interaction with EPHA21 PublicationAdd BLAST207

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi707 – 709PDZ-binding motif3

Domaini

The PDZ-binding motif mediates interaction with TAX1BP3.

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.
HOVERGENiHBG059167.
InParanoidiQ5VV41.
KOiK20688.
OMAiQTEHHHL.
OrthoDBiEOG091G01WI.
PhylomeDBiQ5VV41.
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.
PF14604. SH3_9. 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 (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q5VV41-1) [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
MAQRHSDSSL EEKLLGHRFH SELRLDAGGN PASGLPMVRG SPRVRDDAAF
60 70 80 90 100
QPQVPAPPQP RPPGHEEPWP IVLSTESPAA LKLGTQQLIP KSLAVASKAK
110 120 130 140 150
TPARHQSFGA AVLSREAARR DPKLLPAPSF SLDDMDVDKD PGGMLRRNLR
160 170 180 190 200
NQSYRAAMKG LGKPGGQGDA IQLSPKLQAL AEEPSQPHTR SPAKNKKTLG
210 220 230 240 250
RKRGHKGSFK DDPQLYQEIQ ERGLNTSQES DDDILDESSS PEGTQKVDAT
260 270 280 290 300
IVVKSYRPAQ VTWSQLPEVV ELGILDQLST EERKRQEAMF EILTSEFSYQ
310 320 330 340 350
HSLSILVEEF LQSKELRATV TQMEHHHLFS NILDVLGASQ RFFEDLEQRH
360 370 380 390 400
KAQVLVEDIS DILEEHAEKH FHPYIAYCSN EVYQQRTLQK LISSNAAFRE
410 420 430 440 450
ALREIERRPA CGGLPMLSFL ILPMQRVTRL PLLMDTLCLK TQGHSERYKA
460 470 480 490 500
ASRALKAISK LVRQCNEGAH RMERMEQMYT LHTQLDFSKV KSLPLISASR
510 520 530 540 550
WLLKRGELFL VEETGLFRKI ASRPTCYLFL FNDVLVVTKK KSEESYMVQD
560 570 580 590 600
YAQMNHIQVE KIEPSELPLP GGGNRSSSVP HPFQVTLLRN SEGRQEQLLL
610 620 630 640 650
SSDSASDRAR WIVALTHSER QWQGLSSKGD LPQVEITKAF FAKQADEVTL
660 670 680 690 700
QQADVVLVLQ QEDGWLYGER LRDGETGWFP EDFARFITSR VAVEGNVRRM

ERLRVETDV
Length:709
Mass (Da):80,105
Last modified:December 7, 2004 - v1
Checksum:i9672AB3C92311BEB
GO
Isoform 2 (identifier: Q5VV41-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-288: Missing.

Show »
Length:421
Mass (Da):48,629
Checksum:i7A75C46922C40EA4
GO

Sequence cautioni

The sequence AAH02681 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti157 – 158AM → RG in AAH02681 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059796137V → M.Corresponds to variant rs3806164dbSNPEnsembl.1
Natural variantiVAR_059797370H → Y.3 PublicationsCorresponds to variant rs2185639dbSNPEnsembl.1
Natural variantiVAR_061796681E → K.Corresponds to variant rs56309807dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0181491 – 288Missing in isoform 2. 3 PublicationsAdd BLAST288

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89016 mRNA. Translation: BAA13745.1.
BT007270 mRNA. Translation: AAP35934.1.
AL512413 Genomic DNA. Translation: CAH70832.1.
AL512413 Genomic DNA. Translation: CAH70833.1.
BC002681 mRNA. Translation: AAH02681.1. Different initiation.
BC051838 mRNA. Translation: AAH51838.1.
CCDSiCCDS46.2. [Q5VV41-1]
RefSeqiNP_055263.2. NM_014448.3. [Q5VV41-1]
XP_016856539.1. XM_017001050.1. [Q5VV41-1]
XP_016856540.1. XM_017001051.1. [Q5VV41-1]
UniGeneiHs.87435.

Genome annotation databases

EnsembliENST00000378371; ENSP00000367622; ENSG00000130762. [Q5VV41-2]
ENST00000378373; ENSP00000367624; ENSG00000130762. [Q5VV41-2]
ENST00000378378; ENSP00000367629; ENSG00000130762. [Q5VV41-1]
GeneIDi27237.
KEGGihsa:27237.
UCSCiuc001akg.5. human. [Q5VV41-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D89016 mRNA. Translation: BAA13745.1.
BT007270 mRNA. Translation: AAP35934.1.
AL512413 Genomic DNA. Translation: CAH70832.1.
AL512413 Genomic DNA. Translation: CAH70833.1.
BC002681 mRNA. Translation: AAH02681.1. Different initiation.
BC051838 mRNA. Translation: AAH51838.1.
CCDSiCCDS46.2. [Q5VV41-1]
RefSeqiNP_055263.2. NM_014448.3. [Q5VV41-1]
XP_016856539.1. XM_017001050.1. [Q5VV41-1]
XP_016856540.1. XM_017001051.1. [Q5VV41-1]
UniGeneiHs.87435.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X6BNMR-A622-687[»]
ProteinModelPortaliQ5VV41.
SMRiQ5VV41.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118085. 12 interactors.
IntActiQ5VV41. 6 interactors.
MINTiMINT-3295714.
STRINGi9606.ENSP00000367629.

PTM databases

iPTMnetiQ5VV41.
PhosphoSitePlusiQ5VV41.

Polymorphism and mutation databases

BioMutaiARHGEF16.
DMDMi74747198.

Proteomic databases

EPDiQ5VV41.
MaxQBiQ5VV41.
PaxDbiQ5VV41.
PeptideAtlasiQ5VV41.
PRIDEiQ5VV41.

Protocols and materials databases

DNASUi27237.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378371; ENSP00000367622; ENSG00000130762. [Q5VV41-2]
ENST00000378373; ENSP00000367624; ENSG00000130762. [Q5VV41-2]
ENST00000378378; ENSP00000367629; ENSG00000130762. [Q5VV41-1]
GeneIDi27237.
KEGGihsa:27237.
UCSCiuc001akg.5. human. [Q5VV41-1]

Organism-specific databases

CTDi27237.
DisGeNETi27237.
GeneCardsiARHGEF16.
HGNCiHGNC:15515. ARHGEF16.
HPAiHPA010609.
neXtProtiNX_Q5VV41.
OpenTargetsiENSG00000130762.
PharmGKBiPA24971.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3523. Eukaryota.
COG5422. LUCA.
GeneTreeiENSGT00550000074493.
HOGENOMiHOG000007536.
HOVERGENiHBG059167.
InParanoidiQ5VV41.
KOiK20688.
OMAiQTEHHHL.
OrthoDBiEOG091G01WI.
PhylomeDBiQ5VV41.
TreeFamiTF316357.

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSiARHGEF16. human.
EvolutionaryTraceiQ5VV41.
GenomeRNAii27237.
PROiQ5VV41.

Gene expression databases

BgeeiENSG00000130762.
CleanExiHS_ARHGEF16.
ExpressionAtlasiQ5VV41. baseline and differential.
GenevisibleiQ5VV41. 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.
PF14604. SH3_9. 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 nameiARHGG_HUMAN
AccessioniPrimary (citable) accession number: Q5VV41
Secondary accession number(s): Q86TF0, Q99434
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2006
Last sequence update: December 7, 2004
Last modified: November 30, 2016
This is version 124 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.