Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5VV41 (ARHGG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rho guanine nucleotide exchange factor 16
Alternative name(s):
Ephexin-4
Gene names
Name:ARHGEF16
Synonyms:EPHEXIN4, NBR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length709 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Subunit structure

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. Ref.8 Ref.10

Subcellular location

Cytoplasm Probable.

Induction

Up-regulated by HPV16 E6 (at protein level). Ref.10

Domain

The PDZ-binding motif mediates interaction with TAX1BP3.

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 PH domain.

Contains 1 SH3 domain.

Sequence caution

The sequence AAH02681.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3 domain
   Molecular functionGuanine-nucleotide releasing factor
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Cdc42 GTPase activity

Inferred from direct assay Ref.10. Source: BHF-UCL

activation of Rac GTPase activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cell chemotaxis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

positive regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype Ref.8. Source: UniProtKB

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.10. Source: BHF-UCL

Rho GTPase binding

Inferred from physical interaction Ref.8. Source: UniProtKB

Rho guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.8. Source: UniProtKB

receptor tyrosine kinase binding

Inferred from physical interaction Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5VV41-1)

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.
Isoform 2 (identifier: Q5VV41-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.11
Chain2 – 709708Rho guanine nucleotide exchange factor 16
PRO_0000233690

Regions

Domain284 – 468185DH
Domain501 – 620120PH
Domain629 – 68961SH3
Region275 – 481207Required for RHOG activation and mediates interaction with EPHA2
Motif707 – 7093PDZ-binding motif

Amino acid modifications

Modified residue21N-acetylalanine Ref.11
Modified residue61Phosphoserine Ref.11
Modified residue411Phosphoserine Ref.6 Ref.9
Modified residue1071Phosphoserine Ref.5 Ref.6 Ref.9 Ref.11
Modified residue1741Phosphoserine Ref.9
Modified residue1911Phosphoserine Ref.9
Modified residue2081Phosphoserine Ref.6 Ref.11
Modified residue2271Phosphoserine Ref.6
Modified residue2301Phosphoserine Ref.6 Ref.11
Modified residue2401Phosphoserine Ref.6

Natural variations

Alternative sequence1 – 288288Missing in isoform 2.
VSP_018149
Natural variant1371V → M.
Corresponds to variant rs3806164 [ dbSNP | Ensembl ].
VAR_059796
Natural variant3701H → Y. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2185639 [ dbSNP | Ensembl ].
VAR_059797
Natural variant6811E → K.
Corresponds to variant rs56309807 [ dbSNP | Ensembl ].
VAR_061796

Experimental info

Sequence conflict157 – 1582AM → RG in AAH02681. Ref.4

Secondary structure

................ 709
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 1.
Checksum: 9672AB3C92311BEB

FASTA70980,105
        10         20         30         40         50         60 
MAQRHSDSSL EEKLLGHRFH SELRLDAGGN PASGLPMVRG SPRVRDDAAF QPQVPAPPQP 

        70         80         90        100        110        120 
RPPGHEEPWP IVLSTESPAA LKLGTQQLIP KSLAVASKAK TPARHQSFGA AVLSREAARR 

       130        140        150        160        170        180 
DPKLLPAPSF SLDDMDVDKD PGGMLRRNLR NQSYRAAMKG LGKPGGQGDA IQLSPKLQAL 

       190        200        210        220        230        240 
AEEPSQPHTR SPAKNKKTLG RKRGHKGSFK DDPQLYQEIQ ERGLNTSQES DDDILDESSS 

       250        260        270        280        290        300 
PEGTQKVDAT IVVKSYRPAQ VTWSQLPEVV ELGILDQLST EERKRQEAMF EILTSEFSYQ 

       310        320        330        340        350        360 
HSLSILVEEF LQSKELRATV TQMEHHHLFS NILDVLGASQ RFFEDLEQRH KAQVLVEDIS 

       370        380        390        400        410        420 
DILEEHAEKH FHPYIAYCSN EVYQQRTLQK LISSNAAFRE ALREIERRPA CGGLPMLSFL 

       430        440        450        460        470        480 
ILPMQRVTRL PLLMDTLCLK TQGHSERYKA ASRALKAISK LVRQCNEGAH RMERMEQMYT 

       490        500        510        520        530        540 
LHTQLDFSKV KSLPLISASR WLLKRGELFL VEETGLFRKI ASRPTCYLFL FNDVLVVTKK 

       550        560        570        580        590        600 
KSEESYMVQD YAQMNHIQVE KIEPSELPLP GGGNRSSSVP HPFQVTLLRN SEGRQEQLLL 

       610        620        630        640        650        660 
SSDSASDRAR WIVALTHSER QWQGLSSKGD LPQVEITKAF FAKQADEVTL QQADVVLVLQ 

       670        680        690        700 
QEDGWLYGER LRDGETGWFP EDFARFITSR VAVEGNVRRM ERLRVETDV 

« Hide

Isoform 2 [UniParc].

Checksum: 7A75C46922C40EA4
Show »

FASTA42148,629

References

« Hide 'large scale' references
[1]"Isolation and characterization of a candidate gene for human neuroblastoma mapped to 1p36.3, NBR: a new member of the Rho/Rac GEF family."
Sasaki S., Takei Y., Ito M., Nakagawara A., Fujiwara T., Takahashi E., Muto T., Tokino T., Nakamura Y.
Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT TYR-370.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT TYR-370.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-709, VARIANT TYR-370.
Tissue: PNS.
[5]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-107; SER-208; SER-227; SER-230 AND SER-240, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism."
Hiramoto-Yamaki N., Takeuchi S., Ueda S., Harada K., Fujimoto S., Negishi M., Katoh H.
J. Cell Biol. 190:461-477(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ELMO2; EPHA2; RAC1 AND RHOG.
[9]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-107; SER-174 AND SER-191, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42."
Oliver A.W., He X., Borthwick K., Donne A.J., Hampson L., Hampson I.N.
Br. J. Cancer 104:324-331(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDC42 AND TAX1BP3, INDUCTION BY HPV16 E6.
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6; SER-107; SER-208 AND SER-230, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"Solution structures of the SH3 domain of human rho guanine exchange factor (GEF) 16."
RIKEN structural genomics initiative (RSGI)
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
Cited for: STRUCTURE BY NMR OF 622-687.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_055263.2. NM_014448.3.
UniGeneHs.87435.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1X6BNMR-A622-687[»]
ProteinModelPortalQ5VV41.
SMRQ5VV41. Positions 276-618, 628-688.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118085. 3 interactions.
IntActQ5VV41. 2 interactions.
MINTMINT-3295714.
STRING9606.ENSP00000367629.

PTM databases

PhosphoSiteQ5VV41.

Polymorphism databases

DMDM74747198.

Proteomic databases

PaxDbQ5VV41.
PRIDEQ5VV41.

Protocols and materials databases

DNASU27237.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378371; ENSP00000367622; ENSG00000130762. [Q5VV41-2]
ENST00000378373; ENSP00000367624; ENSG00000130762. [Q5VV41-2]
ENST00000378378; ENSP00000367629; ENSG00000130762. [Q5VV41-1]
GeneID27237.
KEGGhsa:27237.
UCSCuc001akg.4. human. [Q5VV41-1]

Organism-specific databases

CTD27237.
GeneCardsGC01P003394.
HGNCHGNC:15515. ARHGEF16.
HPAHPA010609.
neXtProtNX_Q5VV41.
PharmGKBPA24971.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5422.
HOGENOMHOG000007536.
HOVERGENHBG059167.
InParanoidQ5VV41.
OMAASQRFFE.
OrthoDBEOG73NG2P.
PhylomeDBQ5VV41.
TreeFamTF316357.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ5VV41.
BgeeQ5VV41.
CleanExHS_ARHGEF16.
GenevestigatorQ5VV41.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProIPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSARHGEF16. human.
EvolutionaryTraceQ5VV41.
GenomeRNAi27237.
NextBio50111.
PROQ5VV41.

Entry information

Entry nameARHGG_HUMAN
AccessionPrimary (citable) accession number: Q5VV41
Secondary accession number(s): Q86TF0, Q99434
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2006
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM