UniProt functional annotation for Q6P3S1



	UniProt functional annotation for Q6P3S1

UniProt code: Q6P3S1.

Organism: Homo sapiens (Human).

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

Function: Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP- bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:24520163, ECO:0000269|PubMed:26774822}.

Subunit: Interacts with RAB35 (PubMed:24520163, PubMed:22065758). Interacts with clathrin heavy chain/CLTC (PubMed:20154091). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (PubMed:20154091). Interacts with CD3E (By similarity). {ECO:0000250|UniProtKB:Q3U1T9, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:22065758, ECO:0000269|PubMed:24520163}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:20154091}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:20154091}.

Tissue specificity: Highly expressed in dendritic and natural killer cells and at lower levels in other myeloid lineage cells and in pituitary. Significantly up-regulated in effector memory T-cells as compared with naive T-cells. {ECO:0000269|PubMed:20032318}.

Domain: The FXDXF motif mediates interaction the AP-2 complex. {ECO:0000250|UniProtKB:Q3U1T9}.

Domain: The clathrin box motif mediates interaction with clathrin. {ECO:0000250|UniProtKB:Q3U1T9}.

Ptm: Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity. {ECO:0000269|PubMed:26055712}.

Disease: Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi. {ECO:0000269|PubMed:20032318, ECO:0000269|PubMed:26774822}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes (PubMed:26774822). {ECO:0000269|PubMed:26774822}.

Sequence caution: Sequence=AAH74735.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA90918.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15024.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=EAW91280.1; Type=Erroneous gene model prediction; Evidence={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:		Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP- bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822). {ECO:0000269\|PubMed:20154091, ECO:0000269\|PubMed:20937701, ECO:0000269\|PubMed:24520163, ECO:0000269\|PubMed:26774822}.


Subunit:		Interacts with RAB35 (PubMed:24520163, PubMed:22065758). Interacts with clathrin heavy chain/CLTC (PubMed:20154091). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (PubMed:20154091). Interacts with CD3E (By similarity). {ECO:0000250\|UniProtKB:Q3U1T9, ECO:0000269\|PubMed:20154091, ECO:0000269\|PubMed:22065758, ECO:0000269\|PubMed:24520163}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:20154091}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269\|PubMed:20154091}.
Tissue specificity:		Highly expressed in dendritic and natural killer cells and at lower levels in other myeloid lineage cells and in pituitary. Significantly up-regulated in effector memory T-cells as compared with naive T-cells. {ECO:0000269\|PubMed:20032318}.
Domain:		The FXDXF motif mediates interaction the AP-2 complex. {ECO:0000250\|UniProtKB:Q3U1T9}.
Domain:		The clathrin box motif mediates interaction with clathrin. {ECO:0000250\|UniProtKB:Q3U1T9}.
Ptm:		Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity. {ECO:0000269\|PubMed:26055712}.
Disease:		Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi. {ECO:0000269\|PubMed:20032318, ECO:0000269\|PubMed:26774822}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes (PubMed:26774822). {ECO:0000269\|PubMed:26774822}.
Sequence caution:		Sequence=AAH74735.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA90918.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15024.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=EAW91280.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};