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Protein

Rho guanine nucleotide exchange factor 3

Gene

ARHGEF3

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

Functioni

Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.1 Publication

GO - Molecular functioni

  • Rho guanyl-nucleotide exchange factor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiREACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 3
Alternative name(s):
Exchange factor found in platelets and leukemic and neuronal tissues
Short name:
XPLN
Gene namesi
Name:ARHGEF3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:683. ARHGEF3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24973.

Polymorphism and mutation databases

BioMutaiARHGEF3.
DMDMi52782760.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 526526Rho guanine nucleotide exchange factor 3PRO_0000080911Add
BLAST

Proteomic databases

MaxQBiQ9NR81.
PaxDbiQ9NR81.
PRIDEiQ9NR81.

PTM databases

PhosphoSiteiQ9NR81.

Expressioni

Tissue specificityi

Widely expressed. Highest levels are found in adult brain and skeletal muscle. Lower levels are found in heart and kidney.2 Publications

Gene expression databases

BgeeiQ9NR81.
CleanExiHS_ARHGEF3.
ExpressionAtlasiQ9NR81. baseline and differential.
GenevestigatoriQ9NR81.

Organism-specific databases

HPAiHPA034715.

Interactioni

Subunit structurei

Interacts with RHOA and RHOB.

Binary interactionsi

WithEntry#Exp.IntActNotes
CEP70Q8NHQ13EBI-10312733,EBI-739624
TRIM23P364063EBI-10312733,EBI-740098
TRIM27P143733EBI-10312733,EBI-719493

Protein-protein interaction databases

BioGridi119115. 12 interactions.
IntActiQ9NR81. 3 interactions.
MINTiMINT-3034386.

Structurei

3D structure databases

ProteinModelPortaliQ9NR81.
SMRiQ9NR81. Positions 114-449.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini122 – 304183DHPROSITE-ProRule annotationAdd
BLAST
Domaini291 – 449159PHPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5422.
GeneTreeiENSGT00760000119193.
HOVERGENiHBG050567.
InParanoidiQ9NR81.
OMAiTKLEQMD.
OrthoDBiEOG7J446D.
PhylomeDBiQ9NR81.
TreeFamiTF328974.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015721. RhoGEF-like.
[Graphical view]
PANTHERiPTHR22825. PTHR22825. 1 hit.
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NR81-1) [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
MVAKDYPFYL TVKRANCSLE LPPASGPAKD AEEPSNKRVK PLSRVTSLAN
60 70 80 90 100
LIPPVKATPL KRFSQTLQRS ISFRSESRPD ILAPRPWSRN AAPSSTKRRD
110 120 130 140 150
SKLWSETFDV CVNQMLTSKE IKRQEAIFEL SQGEEDLIED LKLAKKAYHD
160 170 180 190 200
PMLKLSIMTE QELNQIFGTL DSLIPLHEEL LSQLRDVRKP DGSTEHVGPI
210 220 230 240 250
LVGWLPCLSS YDSYCSNQVA AKALLDHKKQ DHRVQDFLQR CLESPFSRKL
260 270 280 290 300
DLWNFLDIPR SRLVKYPLLL REILRHTPND NPDQQHLEEA INIIQGIVAE
310 320 330 340 350
INTKTGESEC RYYKERLLYL EEGQKDSLID SSRVLCCHGE LKNNRGVKLH
360 370 380 390 400
VFLFQEVLVI TRAVTHNEQL CYQLYRQPIP VKDLLLEDLQ DGEVRLGGSL
410 420 430 440 450
RGAFSNNERI KNFFRVSFKN GSQSQTHSLQ ANDTFNKQQW LNCIRQAKET
460 470 480 490 500
VLCAAGQAGV LDSEGSFLNP TTGSRELQGE TKLEQMDQSD SESDCSMDTS
510 520
EVSLDCERME QTDSSCGNSR HGESNV
Length:526
Mass (Da):59,783
Last modified:October 1, 2000 - v1
Checksum:i0FE8248AB52D1CBC
GO
Isoform 2 (identifier: Q9NR81-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MVAKDYPFYLTVKRANCSLELPPASGPAKDAE → MDSSTAMNQC...AVSLCSLDIS

Note: No experimental confirmation available.

Show »
Length:558
Mass (Da):63,755
Checksum:iC01C434F0858A58C
GO
Isoform 3 (identifier: Q9NR81-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MVAKDYPFYLTVKRANCSLELPPASGPAKDAE → MIEVCHHNWLLWLCPSKFGIFMCCLASTTGQMELRRTR

Note: No experimental confirmation available.

Show »
Length:532
Mass (Da):60,813
Checksum:i64940517719915C0
GO
Isoform 4 (identifier: Q9NR81-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-202: Missing.
     203-204: GW → MK

Note: No experimental confirmation available.

Show »
Length:324
Mass (Da):36,981
Checksum:iDF90022C9392296E
GO

Sequence cautioni

The sequence AAH68513.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB14891.1 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAD92898.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti410 – 4101I → T in AAP97313 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131K → R.
Corresponds to variant rs3732507 [ dbSNP | Ensembl ].
VAR_021935
Natural varianti335 – 3351L → V.4 Publications
Corresponds to variant rs3772219 [ dbSNP | Ensembl ].
VAR_021936

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 202202Missing in isoform 4. 1 PublicationVSP_027204Add
BLAST
Alternative sequencei1 – 3232MVAKD…AKDAE → MDSSTAMNQCSCRGMEENKE RPKRQRQNNFPMFPSPKAWN FRGRKRKQSTQDEDAVSLCS LDIS in isoform 2. 1 PublicationVSP_011612Add
BLAST
Alternative sequencei1 – 3232MVAKD…AKDAE → MIEVCHHNWLLWLCPSKFGI FMCCLASTTGQMELRRTR in isoform 3. 1 PublicationVSP_027205Add
BLAST
Alternative sequencei203 – 2042GW → MK in isoform 4. 1 PublicationVSP_027206

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF249744 mRNA. Translation: AAF79954.1.
AL136832 mRNA. Translation: CAB66766.1.
AF433662 mRNA. Translation: AAP97313.1.
AK024340 mRNA. Translation: BAB14891.1. Different initiation.
AK291412 mRNA. Translation: BAF84101.1.
AB209661 mRNA. Translation: BAD92898.1. Different initiation.
CH471055 Genomic DNA. Translation: EAW65326.1.
BC054345 mRNA. Translation: AAH54345.2.
BC068513 mRNA. Translation: AAH68513.1. Different initiation.
BC098122 mRNA. Translation: AAH98122.2.
BC098272 mRNA. Translation: AAH98272.2.
BC099715 mRNA. Translation: AAH99715.1.
BC104723 mRNA. Translation: AAI04724.2.
CCDSiCCDS2878.1. [Q9NR81-1]
CCDS46854.1. [Q9NR81-2]
CCDS46855.1. [Q9NR81-3]
RefSeqiNP_001122087.1. NM_001128615.1. [Q9NR81-2]
NP_001122088.1. NM_001128616.1. [Q9NR81-3]
NP_001276627.1. NM_001289698.1.
NP_062455.1. NM_019555.2. [Q9NR81-1]
XP_005265243.1. XM_005265186.3. [Q9NR81-2]
XP_005265244.1. XM_005265187.2. [Q9NR81-2]
UniGeneiHs.476402.

Genome annotation databases

EnsembliENST00000296315; ENSP00000296315; ENSG00000163947. [Q9NR81-1]
ENST00000338458; ENSP00000341071; ENSG00000163947. [Q9NR81-2]
ENST00000413728; ENSP00000410922; ENSG00000163947. [Q9NR81-3]
GeneIDi50650.
KEGGihsa:50650.
UCSCiuc003dif.2. human. [Q9NR81-3]
uc003dig.2. human. [Q9NR81-1]
uc003dih.2. human. [Q9NR81-2]
uc010hmy.1. human. [Q9NR81-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF249744 mRNA. Translation: AAF79954.1.
AL136832 mRNA. Translation: CAB66766.1.
AF433662 mRNA. Translation: AAP97313.1.
AK024340 mRNA. Translation: BAB14891.1. Different initiation.
AK291412 mRNA. Translation: BAF84101.1.
AB209661 mRNA. Translation: BAD92898.1. Different initiation.
CH471055 Genomic DNA. Translation: EAW65326.1.
BC054345 mRNA. Translation: AAH54345.2.
BC068513 mRNA. Translation: AAH68513.1. Different initiation.
BC098122 mRNA. Translation: AAH98122.2.
BC098272 mRNA. Translation: AAH98272.2.
BC099715 mRNA. Translation: AAH99715.1.
BC104723 mRNA. Translation: AAI04724.2.
CCDSiCCDS2878.1. [Q9NR81-1]
CCDS46854.1. [Q9NR81-2]
CCDS46855.1. [Q9NR81-3]
RefSeqiNP_001122087.1. NM_001128615.1. [Q9NR81-2]
NP_001122088.1. NM_001128616.1. [Q9NR81-3]
NP_001276627.1. NM_001289698.1.
NP_062455.1. NM_019555.2. [Q9NR81-1]
XP_005265243.1. XM_005265186.3. [Q9NR81-2]
XP_005265244.1. XM_005265187.2. [Q9NR81-2]
UniGeneiHs.476402.

3D structure databases

ProteinModelPortaliQ9NR81.
SMRiQ9NR81. Positions 114-449.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119115. 12 interactions.
IntActiQ9NR81. 3 interactions.
MINTiMINT-3034386.

PTM databases

PhosphoSiteiQ9NR81.

Polymorphism and mutation databases

BioMutaiARHGEF3.
DMDMi52782760.

Proteomic databases

MaxQBiQ9NR81.
PaxDbiQ9NR81.
PRIDEiQ9NR81.

Protocols and materials databases

DNASUi50650.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296315; ENSP00000296315; ENSG00000163947. [Q9NR81-1]
ENST00000338458; ENSP00000341071; ENSG00000163947. [Q9NR81-2]
ENST00000413728; ENSP00000410922; ENSG00000163947. [Q9NR81-3]
GeneIDi50650.
KEGGihsa:50650.
UCSCiuc003dif.2. human. [Q9NR81-3]
uc003dig.2. human. [Q9NR81-1]
uc003dih.2. human. [Q9NR81-2]
uc010hmy.1. human. [Q9NR81-4]

Organism-specific databases

CTDi50650.
GeneCardsiGC03M056736.
HGNCiHGNC:683. ARHGEF3.
HPAiHPA034715.
MIMi612115. gene.
neXtProtiNX_Q9NR81.
PharmGKBiPA24973.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5422.
GeneTreeiENSGT00760000119193.
HOVERGENiHBG050567.
InParanoidiQ9NR81.
OMAiTKLEQMD.
OrthoDBiEOG7J446D.
PhylomeDBiQ9NR81.
TreeFamiTF328974.

Enzyme and pathway databases

ReactomeiREACT_11051. Rho GTPase cycle.
REACT_13638. NRAGE signals death through JNK.
REACT_18407. G alpha (12/13) signalling events.

Miscellaneous databases

ChiTaRSiARHGEF3. human.
GeneWikiiARHGEF3.
GenomeRNAii50650.
NextBioi53200.
PROiQ9NR81.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NR81.
CleanExiHS_ARHGEF3.
ExpressionAtlasiQ9NR81. baseline and differential.
GenevestigatoriQ9NR81.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR001849. PH_domain.
IPR011993. PH_like_dom.
IPR015721. RhoGEF-like.
[Graphical view]
PANTHERiPTHR22825. PTHR22825. 1 hit.
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
PROSITEiPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of two novel human RhoGEFs, ARHGEF3 and ARHGEF4, in 3p13-21 and 2q22."
    Thiesen S., Kuebart S., Ropers H.-H., Nothwang H.G.
    Biochem. Biophys. Res. Commun. 273:364-369(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  3. Guo J.H., Yu L.
    Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT VAL-335.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 71-526 (ISOFORMS 1/2/3), VARIANT VAL-335.
    Tissue: Brain and Placenta.
  5. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Brain.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT VAL-335.
  7. "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] (ISOFORMS 1 AND 4), VARIANT VAL-335.
    Tissue: Hippocampus and Uterus.
  8. "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC."
    Arthur W.T., Ellerbroek S.M., Der C.J., Burridge K., Wennerberg K.
    J. Biol. Chem. 277:42964-42972(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiARHG3_HUMAN
AccessioniPrimary (citable) accession number: Q9NR81
Secondary accession number(s): A8K5U7
, Q4FZB6, Q4QQI5, Q4QQQ0, Q59F00, Q6NUN3, Q7Z4U2, Q7Z5T2, Q9H7T4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: October 1, 2000
Last modified: May 27, 2015
This is version 122 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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

External Data

Dasty 3

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 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.