ID  O94827;
PN  Pleckstrin homology domain-containing family G member 5;
GN  PLEKHG5;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: Cytoplasm {ECO:0000250|UniProtKB:Q66T02}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q66T02}. Cell membrane {ECO:0000250|UniProtKB:Q66T02}. Cell junction {ECO:0000250|UniProtKB:Q66T02}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q66T02}. 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. {ECO:0000250|UniProtKB:Q66T02}.
DR  UNIPROT: O94827;
DR  UNIPROT: B3KU07;
DR  UNIPROT: B7Z2M3;
DR  UNIPROT: B7Z5X2;
DR  UNIPROT: F5GZ21;
DR  UNIPROT: F5H1I0;
DR  UNIPROT: Q5SY17;
DR  UNIPROT: Q5T8W5;
DR  UNIPROT: Q5T8W9;
DR  UNIPROT: Q6ZNM0;
DR  UNIPROT: Q7Z436;
DR  UNIPROT: Q86YD8;
DR  UNIPROT: Q96BS1;
DR  Pfam: PF00621;
DR  PROSITE: PS50010;
DR  PROSITE: PS50003;
DR  OMIM: 611067;
DR  OMIM: 611101;
DR  OMIM: 615376;
DR  DisGeNET: 57449;
DE  Function: 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). {ECO:0000250|UniProtKB:Q66T02, ECO:0000269|PubMed:11704860, ECO:0000269|PubMed:23777631}.
DE  Disease: Distal spinal muscular atrophy, autosomal recessive, 4 (DSMA4) [MIM:611067]: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. DSMA4 is characterized by childhood onset, generalized muscle weakness and atrophy with denervation and normal sensation. Bulbar symptoms and pyramidal signs are absent. {ECO:0000269|PubMed:17564964}. Note=The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, recessive, intermediate type, C (CMTRIC) [MIM:615376]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269|PubMed:23777631, ECO:0000269|PubMed:23844677}. Note=The disease is caused by variants affecting the gene represented in this entry.
DE  Reference Proteome: Yes;
DE  Interaction: A0A6L7HHZ0; IntAct: EBI-2827572; Score: 0.00
DE  Interaction: A0A5P8YKG0; IntAct: EBI-2846040; Score: 0.00
DE  Interaction: O43865; IntAct: EBI-25250609; Score: 0.56
DE  Interaction: P61587; IntAct: EBI-22760144; Score: 0.56
DE  Interaction: Q15669; IntAct: EBI-22760016; Score: 0.56
DE  Interaction: Q9Y297; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: Q9UKB1; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: Q9P0J1; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: Q9HAV0; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: Q93009; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: Q04917; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: P63104; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: P62258; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: P61981; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: P27348; IntAct: EBI-21860334; Score: 0.35
DE  Interaction: P31946; IntAct: EBI-21903886; Score: 0.35
DE  Interaction: Q8N3R9; IntAct: EBI-21911733; Score: 0.35
DE  Interaction: Q8NI35; IntAct: EBI-21910914; Score: 0.35
GO  GO:0030424;
GO  GO:0005911;
GO  GO:0005737;
GO  GO:0005829;
GO  GO:0030139;
GO  GO:0030027;
GO  GO:0048471;
GO  GO:0005886;
GO  GO:0005085;
GO  GO:0035767;
GO  GO:0043542;
GO  GO:0043123;
GO  GO:0051056;
GO  GO:0007266;
TP  Membrane Topology: Unknown; Source: UniProt - Sequence Analysis;
SQ  MHYDGHVRFDLPPQGSVLARNVSTRSCPPRTSPAVDLEEEEEESSVDGKGDRKSTGLKLSKKKARRRHTDDPSKECFTLK
SQ  FDLNVDIETEIVPAMKKKSLGEVLLPVFERKGIALGKVDIYLDQSNTPLSLTFEAYRFGGHYLRVKAPAKPGDEGKVEQG
SQ  MKDSKSLSLPILRPAGTGPPALERVDAQSRRESLDILAPGRRRKNMSEFLGEASIPGQEPPTPSSCSLPSGSSGSTNTGD
SQ  SWKNRAASRFSGFFSSGPSTSAFGREVDKMEQLEGKLHTYSLFGLPRLPRGLRFDHDSWEEEYDEDEDEDNACLRLEDSW
SQ  RELIDGHEKLTRRQCHQQEAVWELLHTEASYIRKLRVIINLFLCCLLNLQESGLLCEVEAERLFSNIPEIAQLHRRLWAS
SQ  VMAPVLEKARRTRALLQPGDFLKGFKMFGSLFKPYIRYCMEEEGCMEYMRGLLRDNDLFRAYITWAEKHPQCQRLKLSDM
SQ  LAKPHQRLTKYPLLLKSVLRKTEEPRAKEAVVAMIGSVERFIHHVNACMRQRQERQRLAAVVSRIDAYEVVESSSDEVDK
SQ  LLKEFLHLDLTAPIPGASPEETRQLLLEGSLRMKEGKDSKMDVYCFLFTDLLLVTKAVKKAERTRVIRPPLLVDKIVCRE
SQ  LRDPGSFLLIYLNEFHSAVGAYTFQASGQALCRGWVDTIYNAQNQLQQLRAQEPPGSQQPLQSLEEEEDEQEEEEEEEEE
SQ  EEEGEDSGTSAASSPTIMRKSSGSPDSQHCASDGSTETLAMVVVEPGDTLSSPEFDSGPFSSQSDETSLSTTASSATPTS
SQ  ELLPLGPVDGRSCSMDSAYGTLSPTSLQDFVAPGPMAELVPRAPESPRVPSPPPSPRLRRRTPVQLLSCPPHLLKSKSEA
SQ  SLLQLLAGAGTHGTPSAPSRSLSELCLAVPAPGIRTQGSPQEAGPSWDCRGAPSPGSGPGLVGCLAGEPAGSHRKRCGDL
SQ  PSGASPRVQPEPPPGVSAQHRKLTLAQLYRIRTTLLLNSTLTASEV
//