UniProt functional annotation for Q7LDG7



	UniProt functional annotation for Q7LDG7

UniProt code: Q7LDG7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. {ECO:0000269|PubMed:10918068, ECO:0000269|PubMed:14702343, ECO:0000269|PubMed:17576779, ECO:0000269|PubMed:17702895, ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135}.

Activity regulation: Isoform 1 and isoform 2 are differently regulated by calcium and DAG. {ECO:0000269|PubMed:10918068}.

Subunit: Forms a signaling complex with RAP1 and BRAF (By similarity). Interacts with RAP1. Interacts with F-actin. {ECO:0000250, ECO:0000269|PubMed:14702343, ECO:0000269|PubMed:14988412}.

Subcellular location: Cytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Cell junction, synapse, synaptosome {ECO:0000305}. Cell projection, ruffle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Found both in the cytosol and associated with membranes. Isoform 2 mainly localizes to the cell membrane. Enriched at juxtamembrane areas and membrane ruffles through association with F-actin. Localizes to the cell bodies and axons of striatal neurons (By similarity). {ECO:0000250}.

Tissue specificity: Detected in platelets, neutrophils and T lymphocytes (at protein level). Expressed in brain where it is enriched in the striatum. Also expressed in the hematopoietic system. Detected in heart, brain, lung, placenta, liver, skeletal muscle and kidney. {ECO:0000269|PubMed:10918068, ECO:0000269|PubMed:17576779, ECO:0000269|PubMed:17702895, ECO:0000269|PubMed:9341881, ECO:0000269|PubMed:9789079}.

Developmental stage: Expressed in fetal brain, lung, liver and kidney. {ECO:0000269|PubMed:9789079}.

Domain: The N-terminal Ras-GEF domain mediates association with F- actin.

Ptm: Isoform 2 is palmitoylated and myristoylated. {ECO:0000269|PubMed:10918068}.

Disease: Bleeding disorder, platelet-type 18 (BDPLT18) [MIM:615888]: A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. {ECO:0000269|PubMed:24958846, ECO:0000269|PubMed:27235135, ECO:0000269|PubMed:28726538, ECO:0000269|PubMed:28762304}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: The corresponding protein is not undetectable. {ECO:0000305}.

Similarity: Belongs to the RASGRP family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway. {ECO:0000269\|PubMed:10918068, ECO:0000269\|PubMed:14702343, ECO:0000269\|PubMed:17576779, ECO:0000269\|PubMed:17702895, ECO:0000269\|PubMed:24958846, ECO:0000269\|PubMed:27235135}.


Activity regulation:		Isoform 1 and isoform 2 are differently regulated by calcium and DAG. {ECO:0000269\|PubMed:10918068}.
Subunit:		Forms a signaling complex with RAP1 and BRAF (By similarity). Interacts with RAP1. Interacts with F-actin. {ECO:0000250, ECO:0000269\|PubMed:14702343, ECO:0000269\|PubMed:14988412}.
Subcellular location:		Cytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Cell junction, synapse, synaptosome {ECO:0000305}. Cell projection, ruffle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Note=Found both in the cytosol and associated with membranes. Isoform 2 mainly localizes to the cell membrane. Enriched at juxtamembrane areas and membrane ruffles through association with F-actin. Localizes to the cell bodies and axons of striatal neurons (By similarity). {ECO:0000250}.
Tissue specificity:		Detected in platelets, neutrophils and T lymphocytes (at protein level). Expressed in brain where it is enriched in the striatum. Also expressed in the hematopoietic system. Detected in heart, brain, lung, placenta, liver, skeletal muscle and kidney. {ECO:0000269\|PubMed:10918068, ECO:0000269\|PubMed:17576779, ECO:0000269\|PubMed:17702895, ECO:0000269\|PubMed:9341881, ECO:0000269\|PubMed:9789079}.
Developmental stage:		Expressed in fetal brain, lung, liver and kidney. {ECO:0000269\|PubMed:9789079}.
Domain:		The N-terminal Ras-GEF domain mediates association with F- actin.
Ptm:		Isoform 2 is palmitoylated and myristoylated. {ECO:0000269\|PubMed:10918068}.
Disease:		Bleeding disorder, platelet-type 18 (BDPLT18) [MIM:615888]: A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. {ECO:0000269\|PubMed:24958846, ECO:0000269\|PubMed:27235135, ECO:0000269\|PubMed:28726538, ECO:0000269\|PubMed:28762304}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: The corresponding protein is not undetectable. {ECO:0000305}.
Similarity:		Belongs to the RASGRP family. {ECO:0000305}.