UniProt functional annotation for Q8WXF7



	UniProt functional annotation for Q8WXF7

UniProt code: Q8WXF7.

Organism: Homo sapiens (Human).

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

Function: GTPase tethering membranes through formation of trans- homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:27619977). May also regulate Golgi biogenesis. May regulate axonal development. {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:18270207, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:21220294, ECO:0000269|PubMed:23334294, ECO:0000269|PubMed:25751282, ECO:0000269|PubMed:27619977}.

Subunit: Monomer as apoprotein and in the GDP-bound form. Homodimer in the GTP-bound form. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). Interacts with REEP5, RTN3 and RTN4 (via the transmembrane region). Interacts with SPAST; interaction is direct. May interact with TMED2. Interacts with REEP1. Interacts with CPT1C. Interacts with ARL6IP1 (By similarity). Interacts with ZFYVE27 (PubMed:23969831). {ECO:0000250|UniProtKB:Q6PST4, ECO:0000250|UniProtKB:Q8BH66, ECO:0000269|PubMed:12387898, ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:16815977, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:20200447, ECO:0000269|PubMed:21220294, ECO:0000269|PubMed:21368113, ECO:0000269|PubMed:23334294, ECO:0000269|PubMed:23969831}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:19665976, ECO:0000269|PubMed:27619977}; Multi-pass membrane protein {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:16339213, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:19665976}. Golgi apparatus membrane {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:17321752}; Multi-pass membrane protein {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:17321752}. Cell projection, axon {ECO:0000250|UniProtKB:Q6PST4}. Note=Localizes to endoplasmic reticulum tubular network (PubMed:27619977). {ECO:0000269|PubMed:27619977}.

Tissue specificity: Expressed predominantly in the adult and fetal central nervous system. Measurable expression in all tissues examined, although expression in adult brain is at least 50-fold higher than in other tissues. Detected predominantly in pyramidal neurons in the cerebral cortex and the hippocampus of the brain. Expressed in upper and lower motor neurons (at protein level). {ECO:0000269|PubMed:14506257, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:18270207}.

Disease: Spastic paraplegia 3, autosomal dominant (SPG3) [MIM:182600]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:11685207, ECO:0000269|PubMed:12112092, ECO:0000269|PubMed:12939451, ECO:0000269|PubMed:14695538, ECO:0000269|PubMed:15184642, ECO:0000269|PubMed:16533974, ECO:0000269|PubMed:17321752, ECO:0000269|PubMed:17427918, ECO:0000269|PubMed:20718791, ECO:0000269|PubMed:20932283, ECO:0000269|PubMed:21336785, ECO:0000269|PubMed:23483706, ECO:0000269|PubMed:24473461, ECO:0000269|PubMed:24604904}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Neuropathy, hereditary sensory, 1D (HSN1D) [MIM:613708]: A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. {ECO:0000269|PubMed:21194679}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU01052}.

Sequence caution: Sequence=AAD20047.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAK51160.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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:		GTPase tethering membranes through formation of trans- homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:27619977). May also regulate Golgi biogenesis. May regulate axonal development. {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:18270207, ECO:0000269\|PubMed:19665976, ECO:0000269\|PubMed:21220294, ECO:0000269\|PubMed:23334294, ECO:0000269\|PubMed:25751282, ECO:0000269\|PubMed:27619977}.


Subunit:		Monomer as apoprotein and in the GDP-bound form. Homodimer in the GTP-bound form. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). Interacts with REEP5, RTN3 and RTN4 (via the transmembrane region). Interacts with SPAST; interaction is direct. May interact with TMED2. Interacts with REEP1. Interacts with CPT1C. Interacts with ARL6IP1 (By similarity). Interacts with ZFYVE27 (PubMed:23969831). {ECO:0000250\|UniProtKB:Q6PST4, ECO:0000250\|UniProtKB:Q8BH66, ECO:0000269\|PubMed:12387898, ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:16339213, ECO:0000269\|PubMed:16815977, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:19665976, ECO:0000269\|PubMed:20200447, ECO:0000269\|PubMed:21220294, ECO:0000269\|PubMed:21368113, ECO:0000269\|PubMed:23334294, ECO:0000269\|PubMed:23969831}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:16339213, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:19665976, ECO:0000269\|PubMed:27619977}; Multi-pass membrane protein {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:16339213, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:19665976}. Golgi apparatus membrane {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:17321752}; Multi-pass membrane protein {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:17321752}. Cell projection, axon {ECO:0000250\|UniProtKB:Q6PST4}. Note=Localizes to endoplasmic reticulum tubular network (PubMed:27619977). {ECO:0000269\|PubMed:27619977}.
Tissue specificity:		Expressed predominantly in the adult and fetal central nervous system. Measurable expression in all tissues examined, although expression in adult brain is at least 50-fold higher than in other tissues. Detected predominantly in pyramidal neurons in the cerebral cortex and the hippocampus of the brain. Expressed in upper and lower motor neurons (at protein level). {ECO:0000269\|PubMed:14506257, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:18270207}.
Disease:		Spastic paraplegia 3, autosomal dominant (SPG3) [MIM:182600]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269\|PubMed:11685207, ECO:0000269\|PubMed:12112092, ECO:0000269\|PubMed:12939451, ECO:0000269\|PubMed:14695538, ECO:0000269\|PubMed:15184642, ECO:0000269\|PubMed:16533974, ECO:0000269\|PubMed:17321752, ECO:0000269\|PubMed:17427918, ECO:0000269\|PubMed:20718791, ECO:0000269\|PubMed:20932283, ECO:0000269\|PubMed:21336785, ECO:0000269\|PubMed:23483706, ECO:0000269\|PubMed:24473461, ECO:0000269\|PubMed:24604904}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Neuropathy, hereditary sensory, 1D (HSN1D) [MIM:613708]: A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement. {ECO:0000269\|PubMed:21194679}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily. {ECO:0000255\|PROSITE-ProRule:PRU01052}.
Sequence caution:		Sequence=AAD20047.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAK51160.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};