Q5VV41 (ARHGG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Rho guanine nucleotide exchange factor 16

Alternative name(s):
Ephexin-4

Gene names

Name:	ARHGEF16
Synonyms:	EPHEXIN4, NBR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	709 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
Molecular function	Guanine-nucleotide releasing factor
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation 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 process Traceable author statement. Source: Reactome cell chemotaxis Inferred from mutant phenotype Ref.8. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of establishment of protein localization to plasma membrane Inferred from mutant phenotype Ref.8. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.8. Source: UniProtKB phospholipid binding Inferred from electronic annotation. Source: InterPro
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.11

Chain

2 – 709

708

Rho guanine nucleotide exchange factor 16

PRO_0000233690

Regions

Domain

284 – 468

185

DH

Domain

501 – 620

120

PH

Domain

629 – 689

61

SH3

Region

275 – 481

207

Required for RHOG activation and mediates interaction with EPHA2

Motif

707 – 709

3

PDZ-binding motif

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.11

Modified residue

6

1

Phosphoserine Ref.11

Modified residue

41

1

Phosphoserine Ref.6 Ref.9

Modified residue

107

1

Phosphoserine Ref.5 Ref.6 Ref.9 Ref.11

Modified residue

174

1

Phosphoserine Ref.9

Modified residue

191

1

Phosphoserine Ref.9

Modified residue

208

1

Phosphoserine Ref.6 Ref.11

Modified residue

227

1

Phosphoserine Ref.6

Modified residue

230

1

Phosphoserine Ref.6 Ref.11

Modified residue

240

1

Phosphoserine Ref.6

Natural variations

Alternative sequence

1 – 288

288

Missing in isoform 2.

VSP_018149

Natural variant

137

1

V → M.
Corresponds to variant rs3806164 [ dbSNP | Ensembl ].

VAR_059796

Natural variant

370

1

H → Y. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2185639 [ dbSNP | Ensembl ].

VAR_059797

Natural variant

681

1

E → K.
Corresponds to variant rs56309807 [ dbSNP | Ensembl ].

VAR_061796

Experimental info

Sequence conflict

157 – 158

2

AM → RG in AAH02681. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

709

Helix Strand Turn

Details...

Beta strand

633 – 638

6

Beta strand

644 – 647

4

Beta strand

654 – 662

9

Beta strand

665 – 670

6

Turn

671 – 673

3

Beta strand

676 – 679

4

Helix

681 – 683

3

Beta strand

685 – 687

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 7, 2004. Version 1. Checksum: 9672AB3C92311BEB	FASTA	709	80,105
	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
	Isoform 2 [UniParc]. Checksum: 7A75C46922C40EA4	FASTA	421	48,629
	10 20 30 40 50 60 MFEILTSEFS YQHSLSILVE EFLQSKELRA TVTQMEHHHL FSNILDVLGA SQRFFEDLEQ 70 80 90 100 110 120 RHKAQVLVED ISDILEEHAE KHFHPYIAYC SNEVYQQRTL QKLISSNAAF REALREIERR 130 140 150 160 170 180 PACGGLPMLS FLILPMQRVT RLPLLMDTLC LKTQGHSERY KAASRALKAI SKLVRQCNEG 190 200 210 220 230 240 AHRMERMEQM YTLHTQLDFS KVKSLPLISA SRWLLKRGEL FLVEETGLFR KIASRPTCYL 250 260 270 280 290 300 FLFNDVLVVT KKKSEESYMV QDYAQMNHIQ VEKIEPSELP LPGGGNRSSS VPHPFQVTLL 310 320 330 340 350 360 RNSEGRQEQL LLSSDSASDR ARWIVALTHS ERQWQGLSSK GDLPQVEITK AFFAKQADEV 370 380 390 400 410 420 TLQQADVVLV LQQEDGWLYG ERLRDGETGW FPEDFARFIT SRVAVEGNVR RMERLRVETD V

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[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.

IPI

IPI00328544.
IPI00550506.

RefSeq

NP_055263.2. NM_014448.3.

UniGene

Hs.87435.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X6B	NMR	-	A	622-687	[»]

ProteinModelPortal

Q5VV41.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-3295714.

STRING

9606.ENSP00000367629.

PTM databases

PhosphoSite

Q5VV41.

Polymorphism databases

DMDM

74747198.

Proteomic databases

PaxDb

Q5VV41.

PRIDE

Q5VV41.

Protocols and materials databases

DNASU

27237.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378371; ENSP00000367622; ENSG00000130762.
ENST00000378373; ENSP00000367624; ENSG00000130762.
ENST00000378378; ENSP00000367629; ENSG00000130762.

GeneID

27237.

KEGG

hsa:27237.

UCSC

uc001akg.4. human.

Organism-specific databases

CTD

27237.

GeneCards

GC01P003394.

HGNC

HGNC:15515. ARHGEF16.

HPA

HPA010609.

neXtProt

NX_Q5VV41.

PharmGKB

PA24971.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5422.

HOGENOM

HOG000007536.

HOVERGEN

HBG059167.

InParanoid

Q5VV41.

OMA

ASQRFFE.

OrthoDB

EOG4FXR77.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q5VV41.

Bgee

Q5VV41.

CleanEx

HS_ARHGEF16.

Genevestigator

Q5VV41.

GermOnline

ENSG00000130762. Homo sapiens.

Family and domain databases

Gene3D

1.20.900.10. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF48065. DH-domain. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS00741. DH_1. False negative.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ARHGEF16. human.

EvolutionaryTrace

Q5VV41.

GenomeRNAi

27237.

NextBio

50111.

Entry information

Entry name

ARHGG_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.