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Protein

FYVE, RhoGEF and PH domain-containing protein 2

Gene

Fgd2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri458 – 518FYVE-typePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • phosphatidylinositol phosphate binding Source: MGI
  • Rho guanyl-nucleotide exchange factor activity Source: MGI

GO - Biological processi

  • positive regulation of JUN kinase activity Source: MGI
  • regulation of Rho protein signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
FYVE, RhoGEF and PH domain-containing protein 2
Gene namesi
Name:Fgd2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1347084. Fgd2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Early endosome 1 Publication
  • Early endosome membrane 1 Publication
  • Cell projectionruffle membrane 1 Publication
  • Cytoplasmcytoskeleton 1 Publication

  • Note: Recruitment to the endosome and ruffle membrane requires the presence of phosphoinositides.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoskeleton Source: UniProtKB-SubCell
  • early endosome Source: MGI
  • early endosome membrane Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • ruffle Source: MGI
  • ruffle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi287S → A: No effect on early endosome localization and reduced JNK1 activation; when associated with A-288. 1 Publication1
Mutagenesisi288N → A: No effect on early endosome localization and reduced JNK1 activation; when associated with A-287. 1 Publication1
Mutagenesisi454Q → K: Loss of early endosome localization; when associated with T-455. 1 Publication1
Mutagenesisi455W → T: Loss of early endosome localization; when associated with K-454. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809431 – 655FYVE, RhoGEF and PH domain-containing protein 2Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineCombined sources1
Modified residuei39PhosphoserineCombined sources1
Modified residuei47PhosphoserineCombined sources1
Modified residuei644PhosphothreonineCombined sources1
Modified residuei654PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8BY35.
PaxDbiQ8BY35.
PeptideAtlasiQ8BY35.
PRIDEiQ8BY35.

PTM databases

iPTMnetiQ8BY35.
PhosphoSitePlusiQ8BY35.

Expressioni

Tissue specificityi

Lymph node, spleen, B-lymphocytes and macrophages (at protein level). Expressed at high levels in lymph node, spleen, B-lymphocytes and bone marrow macrophages. Expressed at lower levels in mature bone marrow dendritic cells. In both immature and mature B-cells, expression is down-regulated by prior B-cell receptor signaling. Expression remains high in resting B and memory cells but declines upon differentiation into plasma cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000024013.
CleanExiMM_FGD2.
ExpressionAtlasiQ8BY35. baseline and differential.
GenevisibleiQ8BY35. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024810.

Structurei

3D structure databases

ProteinModelPortaliQ8BY35.
SMRiQ8BY35.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini102 – 290DHPROSITE-ProRule annotationAdd BLAST189
Domaini319 – 418PH 1PROSITE-ProRule annotationAdd BLAST100
Domaini544 – 641PH 2PROSITE-ProRule annotationAdd BLAST98

Domaini

The FYVE-type zinc-finger is necessary for early endosome localization. Recruitment to endosomal membranes via this domain requires the presence of phosphatidylinositol 3-phosphate or other phosphatidylinositides.1 Publication
The PH domain is necessary for localization to the ruffle membrane. Recruitment to ruffle membrane occurs through binding of phosphoinositides by the PH domain. This domain also contributes to the lipid-binding properties of the protein.1 Publication
The DH domain is necessary for its ability to activate JNK1 via CDC42.1 Publication

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotation
Contains 2 PH domains.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri458 – 518FYVE-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4424. Eukaryota.
ENOG410XRXV. LUCA.
GeneTreeiENSGT00750000117280.
HOGENOMiHOG000220866.
HOVERGENiHBG007506.
InParanoidiQ8BY35.
KOiK05721.
OMAiYVVCAKC.
OrthoDBiEOG091G03FU.
PhylomeDBiQ8BY35.
TreeFamiTF316247.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 2 hits.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8BY35-1) [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
MERACEKQDS VCNLVAVFEN NRTPGEAPGS HSLEDQPHSP EHQLSLSPEP
60 70 80 90 100
WEAPPVKEAL KSEFRPVSRT YLSSLKNKLS SGAWRRSCQP GVSPGPETQE
110 120 130 140 150
PEEKRVVREL LETEQAYVAR LHLLDQVFFQ ELLREAGRSK AFPEDVVKLI
160 170 180 190 200
FSNISSIYRF HAQFFLPELQ RRVDDWAATP RIGDVIQKLA PFLKMYSEYV
210 220 230 240 250
KNFERAAELL ATWMDKSQPF QEVVTRIQCS EASSSLTLQH HMLEPVQRIP
260 270 280 290 300
RYELLLKEYV QKLPAQAPDL EDAQRALDMI FSAAQHSNAA IAEMERLQGL
310 320 330 340 350
WDVYQRLGLE DDIVDPSNTL LREGPVLKIS FRRSDPMERY LVLFNNMLLY
360 370 380 390 400
CVPRVLQVGA QFQVRTRIDV AGMKVRELTD AEFPHSFLVS GKQRTLELQA
410 420 430 440 450
RSRDEMVSWM QACQAAIDQV EKRSETFKAA VQGPQGDTQE PKPQVEELGL
460 470 480 490 500
RAPQWVRDKM VTMCMRCQEP FNALTRRRHH CRACGYVVCA KCSDYRAELK
510 520 530 540 550
YDSNRPNRVC LTCYTFLTGN VLPQGKEDKR RGILEKEASA APEQSLVCSF
560 570 580 590 600
LQLIGDKCSR SLPRSWCVIP RDDPLVLYVY AAPQDTKAHT SIPLLGYQVI
610 620 630 640 650
SGPQGDPRVF QLQQSGQQYT FKAESVELQG RWVTAIKRAA SGRTPEGPDE

EDVSD
Length:655
Mass (Da):74,634
Last modified:March 1, 2003 - v1
Checksum:iF5272F107A29BDBE
GO
Isoform 2 (identifier: Q8BY35-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-194: Missing.

Note: No experimental confirmation available.
Show »
Length:461
Mass (Da):52,531
Checksum:iEFAFDF5AE884928C
GO

Sequence cautioni

The sequence AAC35430 differs from that shown. Reason: Frameshift at position 606.Curated
The sequence AAP45200 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39S → I in ABC70180 (PubMed:10458911).Curated1
Sequence conflicti39S → I in AAC35430 (Ref. 2) Curated1
Sequence conflicti543E → D in ABC70180 (PubMed:10458911).Curated1
Sequence conflicti560 – 561RS → ST in BAE33605 (PubMed:16141072).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0130731 – 194Missing in isoform 2. 1 PublicationAdd BLAST194

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017368 mRNA. Translation: AAC35430.1. Frameshift.
DQ344523 mRNA. Translation: ABC70180.1.
AK042260 mRNA. Translation: BAC31206.1.
AK156151 mRNA. Translation: BAE33605.1.
AY301264 Genomic DNA. Translation: AAP45199.1.
AY301264 Genomic DNA. Translation: AAP45200.1. Sequence problems.
BC021845 mRNA. Translation: AAH21845.1.
CCDSiCCDS37537.1. [Q8BY35-1]
RefSeqiNP_001153010.1. NM_001159538.1.
NP_038738.2. NM_013710.4. [Q8BY35-1]
XP_006524363.1. XM_006524300.3. [Q8BY35-2]
XP_011244775.1. XM_011246473.2. [Q8BY35-2]
UniGeneiMm.279187.

Genome annotation databases

EnsembliENSMUST00000024810; ENSMUSP00000024810; ENSMUSG00000024013. [Q8BY35-1]
GeneIDi26382.
KEGGimmu:26382.
UCSCiuc008bsx.2. mouse. [Q8BY35-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017368 mRNA. Translation: AAC35430.1. Frameshift.
DQ344523 mRNA. Translation: ABC70180.1.
AK042260 mRNA. Translation: BAC31206.1.
AK156151 mRNA. Translation: BAE33605.1.
AY301264 Genomic DNA. Translation: AAP45199.1.
AY301264 Genomic DNA. Translation: AAP45200.1. Sequence problems.
BC021845 mRNA. Translation: AAH21845.1.
CCDSiCCDS37537.1. [Q8BY35-1]
RefSeqiNP_001153010.1. NM_001159538.1.
NP_038738.2. NM_013710.4. [Q8BY35-1]
XP_006524363.1. XM_006524300.3. [Q8BY35-2]
XP_011244775.1. XM_011246473.2. [Q8BY35-2]
UniGeneiMm.279187.

3D structure databases

ProteinModelPortaliQ8BY35.
SMRiQ8BY35.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000024810.

PTM databases

iPTMnetiQ8BY35.
PhosphoSitePlusiQ8BY35.

Proteomic databases

EPDiQ8BY35.
PaxDbiQ8BY35.
PeptideAtlasiQ8BY35.
PRIDEiQ8BY35.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000024810; ENSMUSP00000024810; ENSMUSG00000024013. [Q8BY35-1]
GeneIDi26382.
KEGGimmu:26382.
UCSCiuc008bsx.2. mouse. [Q8BY35-1]

Organism-specific databases

CTDi221472.
MGIiMGI:1347084. Fgd2.

Phylogenomic databases

eggNOGiKOG4424. Eukaryota.
ENOG410XRXV. LUCA.
GeneTreeiENSGT00750000117280.
HOGENOMiHOG000220866.
HOVERGENiHBG007506.
InParanoidiQ8BY35.
KOiK05721.
OMAiYVVCAKC.
OrthoDBiEOG091G03FU.
PhylomeDBiQ8BY35.
TreeFamiTF316247.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ8BY35.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024013.
CleanExiMM_FGD2.
ExpressionAtlasiQ8BY35. baseline and differential.
GenevisibleiQ8BY35. MM.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 2 hits.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFGD2_MOUSE
AccessioniPrimary (citable) accession number: Q8BY35
Secondary accession number(s): O88841
, Q2L9D2, Q3U195, Q7TSE3, Q8VDH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.