UniProtKB - O94827 (PKHG5_HUMAN)
Pleckstrin homology domain-containing family G member 5
PLEKHG5
Functioni
Functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons (By similarity).
Involved in the control of neuronal cell differentiation (PubMed:11704860).
Plays a role in angiogenesis through regulation of endothelial cells chemotaxis. Affects also the migration, adhesion, and matrix/bone degradation in macrophages and osteoclasts (PubMed:23777631).
By similarity2 PublicationsGO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: Reactome
GO - Biological processi
- endothelial cell chemotaxis Source: UniProtKB
- endothelial cell migration Source: GO_Central
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- regulation of small GTPase mediated signal transduction Source: Reactome
- Rho protein signal transduction Source: GO_Central
Enzyme and pathway databases
PathwayCommonsi | O94827 |
Reactomei | R-HSA-193648, NRAGE signals death through JNK R-HSA-416482, G alpha (12/13) signalling events R-HSA-8980692, RHOA GTPase cycle R-HSA-9696264, RND3 GTPase cycle R-HSA-9696273, RND1 GTPase cycle |
SignaLinki | O94827 |
SIGNORi | O94827 |
Names & Taxonomyi
Protein namesi | Recommended name: Pleckstrin homology domain-containing family G member 5Short name: PH domain-containing family G member 5 Alternative name(s): Guanine nucleotide exchange factor 720 Short name: GEF720 |
Gene namesi | Name:PLEKHG5 Synonyms:KIAA0720 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:29105, PLEKHG5 |
MIMi | 611101, gene |
neXtProti | NX_O94827 |
VEuPathDBi | HostDB:ENSG00000171680 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Other locations
- perinuclear region By similarity
- Cell junction By similarity
- lamellipodium By similarity
Note: Predominantly cytoplasmic, however when endothelial cells are stimulated with lysophosphatidic acid, PLEKHG5 is found in perinuclear regions and at the cell membrane. Localizes at cell-cell junctions in quiescent endothelial cells, and relocalizes to cytoplasmic vesicle and the leading edge of lamellipodia in migrating endothelial cells.By similarity
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- axon Source: GO_Central
- cell-cell junction Source: UniProtKB
- cytoplasm Source: UniProtKB
- endocytic vesicle Source: UniProtKB
- lamellipodium Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasm, MembranePathology & Biotechi
Involvement in diseasei
Distal spinal muscular atrophy, autosomal recessive, 4 (DSMA4)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035357 | 647 | F → S in DSMA4; stability and intracellular location affected severely impairing the NF-kappa-B transduction pathway. 1 PublicationCorresponds to variant dbSNP:rs63750315EnsemblClinVar. | 1 |
Charcot-Marie-Tooth disease, recessive, intermediate type, C (CMTRIC)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070217 | 663 | T → M in CMTRIC; in vitro assay suggests a defect in activating the NF-kappa-B signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs397515456EnsemblClinVar. | 1 | |
Natural variantiVAR_070218 | 820 | G → R in CMTRIC; in vitro assay suggests a defect in activating the NF-kappa-B signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs202191898EnsemblClinVar. | 1 |
Keywords - Diseasei
Charcot-Marie-Tooth disease, Disease variant, Neurodegeneration, NeuropathyOrganism-specific databases
DisGeNETi | 57449 |
GeneReviewsi | PLEKHG5 |
MalaCardsi | PLEKHG5 |
MIMi | 611067, phenotype 615376, phenotype |
OpenTargetsi | ENSG00000171680 |
Orphaneti | 369867, Autosomal recessive intermediate Charcot-Marie-Tooth disease type C 206580, Autosomal recessive lower motor neuron disease with childhood onset |
PharmGKBi | PA142671164 |
Miscellaneous databases
Pharosi | O94827, Tbio |
Genetic variation databases
BioMutai | PLEKHG5 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000307134 | 1 – 1006 | Pleckstrin homology domain-containing family G member 5Add BLAST | 1006 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 729 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 734 | PhosphoserineBy similarity | 1 | |
Modified residuei | 851 | PhosphoserineBy similarity | 1 | |
Modified residuei | 876 | PhosphoserineBy similarity | 1 | |
Modified residuei | 881 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O94827 |
jPOSTi | O94827 |
MassIVEi | O94827 |
PaxDbi | O94827 |
PeptideAtlasi | O94827 |
PRIDEi | O94827 |
ProteomicsDBi | 24913 25662 50471 [O94827-3] 50472 [O94827-4] 50473 [O94827-5] |
PTM databases
iPTMneti | O94827 |
PhosphoSitePlusi | O94827 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000171680, Expressed in right hemisphere of cerebellum and 142 other tissues |
ExpressionAtlasi | O94827, baseline and differential |
Genevisiblei | O94827, HS |
Organism-specific databases
HPAi | ENSG00000171680, Tissue enhanced (skin) |
Interactioni
Subunit structurei
Interacts with GIPC1/synectin and RHOA.
By similarityBinary interactionsi
Isoform 3 [O94827-4]
With | #Exp. | IntAct |
---|---|---|
AHCYL1 [O43865] | 3 | EBI-11980215,EBI-2371423 |
RHOH [Q15669] | 3 | EBI-11980215,EBI-1244971 |
RND3 [P61587] | 3 | EBI-11980215,EBI-1111534 |
Protein-protein interaction databases
BioGRIDi | 121522, 28 interactors |
IntActi | O94827, 18 interactors |
STRINGi | 9606.ENSP00000439625 |
Miscellaneous databases
RNActi | O94827, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 336 – 528 | DHPROSITE-ProRule annotationAdd BLAST | 193 | |
Domaini | 584 – 684 | PHPROSITE-ProRule annotationAdd BLAST | 101 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 71 | DisorderedSequence analysisAdd BLAST | 71 | |
Regioni | 148 – 198 | DisorderedSequence analysisAdd BLAST | 51 | |
Regioni | 212 – 242 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 690 – 754 | DisorderedSequence analysisAdd BLAST | 65 | |
Regioni | 768 – 820 | DisorderedSequence analysisAdd BLAST | 53 | |
Regioni | 837 – 863 | DisorderedSequence analysisAdd BLAST | 27 | |
Regioni | 950 – 979 | DisorderedSequence analysisAdd BLAST | 30 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 218 – 242 | Polar residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 703 – 727 | Acidic residuesSequence analysisAdd BLAST | 25 | |
Compositional biasi | 728 – 754 | Polar residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 774 – 801 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 845 – 859 | Pro residuesSequence analysisAdd BLAST | 15 |
Phylogenomic databases
eggNOGi | KOG3521, Eukaryota |
GeneTreei | ENSGT00510000046843 |
HOGENOMi | CLU_005851_0_0_1 |
InParanoidi | O94827 |
OrthoDBi | 556467at2759 |
PhylomeDBi | O94827 |
TreeFami | TF316755 |
Family and domain databases
CDDi | cd00160, RhoGEF, 1 hit |
Gene3Di | 1.20.900.10, 1 hit 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR035899, DBL_dom_sf IPR000219, DH-domain IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR040181, PKHG5/7 IPR029071, Ubiquitin-like_domsf |
PANTHERi | PTHR13217, PTHR13217, 1 hit |
Pfami | View protein in Pfam PF00621, RhoGEF, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00325, RhoGEF, 1 hit |
SUPFAMi | SSF48065, SSF48065, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50010, DH_2, 1 hit PS50003, PH_DOMAIN, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MHYDGHVRFD LPPQGSVLAR NVSTRSCPPR TSPAVDLEEE EEESSVDGKG
60 70 80 90 100
DRKSTGLKLS KKKARRRHTD DPSKECFTLK FDLNVDIETE IVPAMKKKSL
110 120 130 140 150
GEVLLPVFER KGIALGKVDI YLDQSNTPLS LTFEAYRFGG HYLRVKAPAK
160 170 180 190 200
PGDEGKVEQG MKDSKSLSLP ILRPAGTGPP ALERVDAQSR RESLDILAPG
210 220 230 240 250
RRRKNMSEFL GEASIPGQEP PTPSSCSLPS GSSGSTNTGD SWKNRAASRF
260 270 280 290 300
SGFFSSGPST SAFGREVDKM EQLEGKLHTY SLFGLPRLPR GLRFDHDSWE
310 320 330 340 350
EEYDEDEDED NACLRLEDSW RELIDGHEKL TRRQCHQQEA VWELLHTEAS
360 370 380 390 400
YIRKLRVIIN LFLCCLLNLQ ESGLLCEVEA ERLFSNIPEI AQLHRRLWAS
410 420 430 440 450
VMAPVLEKAR RTRALLQPGD FLKGFKMFGS LFKPYIRYCM EEEGCMEYMR
460 470 480 490 500
GLLRDNDLFR AYITWAEKHP QCQRLKLSDM LAKPHQRLTK YPLLLKSVLR
510 520 530 540 550
KTEEPRAKEA VVAMIGSVER FIHHVNACMR QRQERQRLAA VVSRIDAYEV
560 570 580 590 600
VESSSDEVDK LLKEFLHLDL TAPIPGASPE ETRQLLLEGS LRMKEGKDSK
610 620 630 640 650
MDVYCFLFTD LLLVTKAVKK AERTRVIRPP LLVDKIVCRE LRDPGSFLLI
660 670 680 690 700
YLNEFHSAVG AYTFQASGQA LCRGWVDTIY NAQNQLQQLR AQEPPGSQQP
710 720 730 740 750
LQSLEEEEDE QEEEEEEEEE EEEGEDSGTS AASSPTIMRK SSGSPDSQHC
760 770 780 790 800
ASDGSTETLA MVVVEPGDTL SSPEFDSGPF SSQSDETSLS TTASSATPTS
810 820 830 840 850
ELLPLGPVDG RSCSMDSAYG TLSPTSLQDF VAPGPMAELV PRAPESPRVP
860 870 880 890 900
SPPPSPRLRR RTPVQLLSCP PHLLKSKSEA SLLQLLAGAG THGTPSAPSR
910 920 930 940 950
SLSELCLAVP APGIRTQGSP QEAGPSWDCR GAPSPGSGPG LVGCLAGEPA
960 970 980 990 1000
GSHRKRCGDL PSGASPRVQP EPPPGVSAQH RKLTLAQLYR IRTTLLLNST
LTASEV
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5SY18 | Q5SY18_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 852 | Annotation score: | ||
A0A5F9ZHW8 | A0A5F9ZHW8_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 1,105 | Annotation score: | ||
A0A804EMX3 | A0A804EMX3_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 1,075 | Annotation score: | ||
A0A6Q8PG76 | A0A6Q8PG76_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 775 | Annotation score: | ||
A0A7I2PMD6 | A0A7I2PMD6_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 1,064 | Annotation score: | ||
A0A6Q8PF22 | A0A6Q8PF22_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 295 | Annotation score: | ||
A0A6Q8PHJ1 | A0A6Q8PHJ1_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 105 | Annotation score: | ||
A0A6Q8PHR5 | A0A6Q8PHR5_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 104 | Annotation score: | ||
A0A6Q8PHD3 | A0A6Q8PHD3_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 118 | Annotation score: | ||
A0A6Q8PHS0 | A0A6Q8PHS0_HUMAN | Pleckstrin homology domain-containi... | PLEKHG5 | 61 | Annotation score: | ||
There is more potential isoformShow all |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 106 | P → L in BAH11909 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 238 | T → S in BAA34440 (PubMed:9872452).Curated | 1 | |
Sequence conflicti | 514 | M → T in BAG53269 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 904 | E → G in BAG53269 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_035357 | 647 | F → S in DSMA4; stability and intracellular location affected severely impairing the NF-kappa-B transduction pathway. 1 PublicationCorresponds to variant dbSNP:rs63750315EnsemblClinVar. | 1 | |
Natural variantiVAR_070217 | 663 | T → M in CMTRIC; in vitro assay suggests a defect in activating the NF-kappa-B signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs397515456EnsemblClinVar. | 1 | |
Natural variantiVAR_070218 | 820 | G → R in CMTRIC; in vitro assay suggests a defect in activating the NF-kappa-B signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs202191898EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_060959 | 1 | M → MDKGRAAKVCHHADCQQLHR RGPLNLCEACDSKFHSTM in isoform 2. | 1 | |
Alternative sequenceiVSP_060960 | 1 | M → MGTGPGVSGRLAASRPGPGL PLRDSEPSWAGGRARDGESQ VCHHADCQQLHRRGPLNLCE ACDSKFHSTM in isoform 4. | 1 | |
Alternative sequenceiVSP_060961 | 913 – 930 | GIRTQ…SWDCR → AQEADPGPALPNQDHPAA in isoform 3. Add BLAST | 18 | |
Alternative sequenceiVSP_060962 | 931 – 1006 | Missing in isoform 3. Add BLAST | 76 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
AlphaFoldDBi | O94827 |
SMRi | O94827 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 121522, 28 interactors |
IntActi | O94827, 18 interactors |
STRINGi | 9606.ENSP00000439625 |
PTM databases
iPTMneti | O94827 |
PhosphoSitePlusi | O94827 |
Genetic variation databases
BioMutai | PLEKHG5 |
Proteomic databases
EPDi | O94827 |
jPOSTi | O94827 |
MassIVEi | O94827 |
PaxDbi | O94827 |
PeptideAtlasi | O94827 |
PRIDEi | O94827 |
ProteomicsDBi | 24913 25662 50471 [O94827-3] 50472 [O94827-4] 50473 [O94827-5] |
Protocols and materials databases
Antibodypediai | 27380, 151 antibodies from 25 providers |
DNASUi | 57449 |
Genome annotation databases
Organism-specific databases
CTDi | 57449 |
DisGeNETi | 57449 |
GeneCardsi | PLEKHG5 |
GeneReviewsi | PLEKHG5 |
HGNCi | HGNC:29105, PLEKHG5 |
HPAi | ENSG00000171680, Tissue enhanced (skin) |
MalaCardsi | PLEKHG5 |
MIMi | 611067, phenotype 611101, gene 615376, phenotype |
neXtProti | NX_O94827 |
OpenTargetsi | ENSG00000171680 |
Orphaneti | 369867, Autosomal recessive intermediate Charcot-Marie-Tooth disease type C 206580, Autosomal recessive lower motor neuron disease with childhood onset |
PharmGKBi | PA142671164 |
VEuPathDBi | HostDB:ENSG00000171680 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3521, Eukaryota |
GeneTreei | ENSGT00510000046843 |
HOGENOMi | CLU_005851_0_0_1 |
InParanoidi | O94827 |
OrthoDBi | 556467at2759 |
PhylomeDBi | O94827 |
TreeFami | TF316755 |
Enzyme and pathway databases
PathwayCommonsi | O94827 |
Reactomei | R-HSA-193648, NRAGE signals death through JNK R-HSA-416482, G alpha (12/13) signalling events R-HSA-8980692, RHOA GTPase cycle R-HSA-9696264, RND3 GTPase cycle R-HSA-9696273, RND1 GTPase cycle |
SignaLinki | O94827 |
SIGNORi | O94827 |
Miscellaneous databases
BioGRID-ORCSi | 57449, 22 hits in 1070 CRISPR screens |
ChiTaRSi | PLEKHG5, human |
GeneWikii | PLEKHG5 |
GenomeRNAii | 57449 |
Pharosi | O94827, Tbio |
PROi | PR:O94827 |
RNActi | O94827, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000171680, Expressed in right hemisphere of cerebellum and 142 other tissues |
ExpressionAtlasi | O94827, baseline and differential |
Genevisiblei | O94827, HS |
Family and domain databases
CDDi | cd00160, RhoGEF, 1 hit |
Gene3Di | 1.20.900.10, 1 hit 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR035899, DBL_dom_sf IPR000219, DH-domain IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR040181, PKHG5/7 IPR029071, Ubiquitin-like_domsf |
PANTHERi | PTHR13217, PTHR13217, 1 hit |
Pfami | View protein in Pfam PF00621, RhoGEF, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00325, RhoGEF, 1 hit |
SUPFAMi | SSF48065, SSF48065, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50010, DH_2, 1 hit PS50003, PH_DOMAIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PKHG5_HUMAN | |
Accessioni | O94827Primary (citable) accession number: O94827 Secondary accession number(s): B3KU07 Q96BS1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 23, 2007 |
Last sequence update: | April 7, 2021 | |
Last modified: | May 25, 2022 | |
This is version 172 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot