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Protein

FYVE, RhoGEF and PH domain-containing protein 2

Gene

FGD2

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Metal-binding, Zinc

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:
FYVE, RhoGEF and PH domain-containing protein 2
Alternative name(s):
Zinc finger FYVE domain-containing protein 4
Gene namesi
Name:FGD2
Synonyms:ZFYVE4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3664. FGD2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi221472.
MalaCardsiFGD2.
OpenTargetsiENSG00000146192.
PharmGKBiPA28103.

Polymorphism and mutation databases

BioMutaiFGD2.
DMDMi61213572.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809421 – 655FYVE, RhoGEF and PH domain-containing protein 2Add BLAST655

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11PhosphoserineBy similarity1
Modified residuei48PhosphoserineBy similarity1
Modified residuei654PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ7Z6J4.
PaxDbiQ7Z6J4.
PeptideAtlasiQ7Z6J4.
PRIDEiQ7Z6J4.

PTM databases

iPTMnetiQ7Z6J4.
PhosphoSitePlusiQ7Z6J4.

Expressioni

Gene expression databases

BgeeiENSG00000146192.
CleanExiHS_FGD2.
ExpressionAtlasiQ7Z6J4. baseline and differential.
GenevisibleiQ7Z6J4. HS.

Organism-specific databases

HPAiHPA029145.
HPA049692.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
KLHL12Q53G593EBI-1057190,EBI-740929
TMEM239Q8WW343EBI-1057190,EBI-9675724

GO - Molecular functioni

Protein-protein interaction databases

BioGridi128730. 3 interactors.
IntActiQ7Z6J4. 3 interactors.
STRINGi9606.ENSP00000274963.

Structurei

3D structure databases

ProteinModelPortaliQ7Z6J4.
SMRiQ7Z6J4.
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 (By similarity).By similarity
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 (By similarity).By similarity
The DH domain is necessary for its ability to activate JNK1 via CDC42.By similarity

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.
HOVERGENiHBG007506.
InParanoidiQ7Z6J4.
KOiK05721.
OMAiYVVCAKC.
OrthoDBiEOG091G03FU.
PhylomeDBiQ7Z6J4.
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 (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q7Z6J4-1) [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
MKGASEEKLA SVSNLVTVFE NSRTPEAAPR GQRLEDVHHR PECRPPESPG
60 70 80 90 100
PREKTNVGEA VGSEPRTVSR RYLNSLKNKL SSEAWRKSCQ PVTLSGSGTQ
110 120 130 140 150
EPEKKIVQEL LETEQAYVAR LHLLDQVFFQ ELLKTARSSK AFPEDVVRVI
160 170 180 190 200
FSNISSIYQF HSQFFLPELQ RRLDDWTANP RIGDVIQKLA PFLKMYSEYV
210 220 230 240 250
KNFERAAELL ATWTDKSPLF QEVLTRIQSS EASGSLTLQH HMLEPVQRIP
260 270 280 290 300
RYELLLKEYI QKLPAQAPDQ ADAQKALDMI FSAAQHSNAA ITEMERLQDL
310 320 330 340 350
WEVYQRLGLE DDIVDPSNTL LREGPVLKIS FRRNDPMERY LFLFNNMLLY
360 370 380 390 400
CVPRVIQVGA QFQVRTRIDV AGMKVRELMD AEFPHSFLVS GKQRTLELQA
410 420 430 440 450
RSQEEMISWM QAFQAAIDQI EKRNETFKAA AQGPEGDIQE QELQSEELGL
460 470 480 490 500
RAPQWVRDKM VTMCMRCQEP FNALTRRRHH CRACGYVVCA RCSDYRAELK
510 520 530 540 550
YDDNRPNRVC LHCYAFLTGN VLPEAKEDKR RGILEKGSSA TPDQSLMCSF
560 570 580 590 600
LQLIGDKWGK SGPRGWCVIP RDDPLVLYVY AAPQDMRAHT SIPLLGYQVT
610 620 630 640 650
VGPQGDPRVF QLQQSGQLYT FKAETEELKG RWVKAMERAA SGWSPSWPND

GDLSD
Length:655
Mass (Da):74,892
Last modified:October 1, 2003 - v1
Checksum:iDB60098249C2B340
GO
Isoform 2 (identifier: Q7Z6J4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-423: Missing.
     424-442: NETFKAAAQGPEGDIQEQE → MGGRRSPRAHSCPTPLNPQ
     585-655: DMRAHTSIPL...SWPNDGDLSD → VRPPPARPPSGPGLPTACV

Note: No experimental confirmation available.
Show »
Length:180
Mass (Da):20,193
Checksum:i96FB2A2E1FE129C5
GO
Isoform 3 (identifier: Q7Z6J4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-372: Missing.
     488-655: VCARCSDYRA...SWPNDGDLSD → STPASTPASTCVTQASTCITQASTFPT

Note: No experimental confirmation available.
Show »
Length:142
Mass (Da):16,086
Checksum:i3BC622A79372D3FA
GO
Isoform 4 (identifier: Q7Z6J4-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MKGASEEKLASVSNLVTVFENS → MFPKKARHPGAPALGICTRQPKSTPGTCCCFPCSPGRKPSGLSLLL
     101-104: EPEK → VPEG
     105-655: Missing.

Note: May be due to an intron retention. No experimental confirmation available.
Show »
Length:128
Mass (Da):13,825
Checksum:iB6EB12FF70E7A602
GO

Sequence cautioni

The sequence BAB15746 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC85129 differs from that shown. Reason: Frameshift at position 460.Curated
The sequence BAC85129 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAI20471 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02149132Q → H.1 PublicationCorresponds to variant rs831510dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0130651 – 423Missing in isoform 2. 1 PublicationAdd BLAST423
Alternative sequenceiVSP_0130661 – 372Missing in isoform 3. 1 PublicationAdd BLAST372
Alternative sequenceiVSP_0130671 – 22MKGAS…VFENS → MFPKKARHPGAPALGICTRQ PKSTPGTCCCFPCSPGRKPS GLSLLL in isoform 4. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_013068101 – 104EPEK → VPEG in isoform 4. 1 Publication4
Alternative sequenceiVSP_038219105 – 655Missing in isoform 4. 1 PublicationAdd BLAST551
Alternative sequenceiVSP_013070424 – 442NETFK…IQEQE → MGGRRSPRAHSCPTPLNPQ in isoform 2. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_013071488 – 655VCARC…GDLSD → STPASTPASTCVTQASTCIT QASTFPT in isoform 3. 1 PublicationAdd BLAST168
Alternative sequenceiVSP_013072585 – 655DMRAH…GDLSD → VRPPPARPPSGPGLPTACV in isoform 2. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024456 mRNA. Translation: BAB15746.1. Different initiation.
AK097230 mRNA. Translation: BAC04982.1.
AK131079 mRNA. Translation: BAC85129.1. Sequence problems.
AL160264 Genomic DNA. Translation: CAI20471.1. Sequence problems.
BC023645 mRNA. Translation: AAH23645.1.
BC053655 mRNA. Translation: AAH53655.1.
CCDSiCCDS4829.1. [Q7Z6J4-1]
RefSeqiNP_775829.2. NM_173558.3. [Q7Z6J4-1]
UniGeneiHs.509664.

Genome annotation databases

EnsembliENST00000274963; ENSP00000274963; ENSG00000146192. [Q7Z6J4-1]
GeneIDi221472.
KEGGihsa:221472.
UCSCiuc010jwp.2. human. [Q7Z6J4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024456 mRNA. Translation: BAB15746.1. Different initiation.
AK097230 mRNA. Translation: BAC04982.1.
AK131079 mRNA. Translation: BAC85129.1. Sequence problems.
AL160264 Genomic DNA. Translation: CAI20471.1. Sequence problems.
BC023645 mRNA. Translation: AAH23645.1.
BC053655 mRNA. Translation: AAH53655.1.
CCDSiCCDS4829.1. [Q7Z6J4-1]
RefSeqiNP_775829.2. NM_173558.3. [Q7Z6J4-1]
UniGeneiHs.509664.

3D structure databases

ProteinModelPortaliQ7Z6J4.
SMRiQ7Z6J4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128730. 3 interactors.
IntActiQ7Z6J4. 3 interactors.
STRINGi9606.ENSP00000274963.

PTM databases

iPTMnetiQ7Z6J4.
PhosphoSitePlusiQ7Z6J4.

Polymorphism and mutation databases

BioMutaiFGD2.
DMDMi61213572.

Proteomic databases

MaxQBiQ7Z6J4.
PaxDbiQ7Z6J4.
PeptideAtlasiQ7Z6J4.
PRIDEiQ7Z6J4.

Protocols and materials databases

DNASUi221472.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274963; ENSP00000274963; ENSG00000146192. [Q7Z6J4-1]
GeneIDi221472.
KEGGihsa:221472.
UCSCiuc010jwp.2. human. [Q7Z6J4-1]

Organism-specific databases

CTDi221472.
DisGeNETi221472.
GeneCardsiFGD2.
HGNCiHGNC:3664. FGD2.
HPAiHPA029145.
HPA049692.
MalaCardsiFGD2.
MIMi605091. gene.
neXtProtiNX_Q7Z6J4.
OpenTargetsiENSG00000146192.
PharmGKBiPA28103.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4424. Eukaryota.
ENOG410XRXV. LUCA.
GeneTreeiENSGT00750000117280.
HOVERGENiHBG007506.
InParanoidiQ7Z6J4.
KOiK05721.
OMAiYVVCAKC.
OrthoDBiEOG091G03FU.
PhylomeDBiQ7Z6J4.
TreeFamiTF316247.

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

ChiTaRSiFGD2. human.
GeneWikiiFGD2.
GenomeRNAii221472.
PROiQ7Z6J4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000146192.
CleanExiHS_FGD2.
ExpressionAtlasiQ7Z6J4. baseline and differential.
GenevisibleiQ7Z6J4. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q7Z6J4
Secondary accession number(s): Q5T8I1
, Q6P6A8, Q6ZNL5, Q8IZ32, Q8N868, Q9H7M2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2003
Last modified: November 30, 2016
This is version 129 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 6
    Human chromosome 6: 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

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.