UniProt functional annotation for Q07699



	UniProt functional annotation for Q07699

UniProt code: Q07699.

Organism: Homo sapiens (Human).

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

Function: Regulatory subunit of multiple voltage-gated sodium channel complexes that play important roles in excitable membranes in brain, heart and skeletal muscle. Enhances the presence of the pore-forming alpha subunit at the cell surface and modulates channel gating characteristics and the rate of channel inactivation. Modulates the activity of multiple pore-forming alpha subunits, such as SCN1A, SCN2A, SCN3A, SCN4A, SCN5A and SCN10A. {ECO:0000269|PubMed:14622265, ECO:0000269|PubMed:15525788, ECO:0000269|PubMed:18464934, ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:21994374, ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:8125980, ECO:0000269|PubMed:8394762}.

Function: [Isoform 2]: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth (PubMed:21994374). Has no regulatory function on the SCN2A sodium channel complex (PubMed:14622265). {ECO:0000269|PubMed:14622265, ECO:0000269|PubMed:21994374}.

Subunit: Component of a voltage-sensitive sodium channel complex that consists of a pore-forming alpha subunit and one or more regulatory beta subunits (PubMed:15525788, PubMed:21994374, PubMed:30190309). Interacts with SCN4A (PubMed:8125980). Interacts with NFASC. Interacts with SCN10A (By similarity). Interacts with SCN1A (PubMed:15525788, PubMed:21994374, PubMed:17928445). Interacts with SCN3A (PubMed:21994374). Interacts with SCN5A (PubMed:21994374). Interacts with SCN8A (PubMed:26900580). {ECO:0000250|UniProtKB:Q00954, ECO:0000269|PubMed:15525788, ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:21994374, ECO:0000269|PubMed:26900580, ECO:0000269|PubMed:30190309, ECO:0000269|PubMed:8125980}.

Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:21994374, ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:30190309, ECO:0000305|PubMed:8125980}; Single-pass type I membrane protein {ECO:0000269|PubMed:30190309, ECO:0000305|PubMed:8125980}. Perikaryon {ECO:0000250|UniProtKB:P97952}. Cell projection {ECO:0000250|UniProtKB:P97952}. Cell projection, axon {ECO:0000250|UniProtKB:Q00954}. Note=Detected at nodes of Ranvier on the sciatic nerve. {ECO:0000250|UniProtKB:Q00954}.

Subcellular location: [Isoform 2]: Perikaryon {ECO:0000269|PubMed:14622265}. Cell projection {ECO:0000269|PubMed:14622265}. Secreted {ECO:0000269|PubMed:21994374}. Note=Detected on Purkinje cells and their cell projections and on neuronal cell projections. {ECO:0000269|PubMed:14622265}.

Tissue specificity: The overall expression of isoform 1 and isoform 2 is very similar. Isoform 1 is abundantly expressed in skeletal muscle, heart and brain. Isoform 2 is highly expressed in brain and skeletal muscle and present at a very low level in heart, placenta, lung, liver, kidney and pancreas. In brain, isoform 2 is most abundant in the cerebellum, followed by the cerebral cortex and occipital lobe, while isoform 1 levels are higher in the cortex compared to the cerebellum. Isoform 2 is expressed in many regions of the brain, including cerebellar Purkinje cells, cortex pyramidal neurons and many of the neuronal fibers throughout the brain (at protein level). Also detected in dorsal root ganglion, in fibers of the spinal nerve and in cortical neurons and their processes (at protein level). {ECO:0000269|PubMed:14622265, ECO:0000269|PubMed:8125980, ECO:0000269|PubMed:8394762}.

Disease: Generalized epilepsy with febrile seizures plus 1 (GEFS+1) [MIM:604233]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. {ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:21040232, ECO:0000269|PubMed:9697698}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Brugada syndrome 5 (BRGDA5) [MIM:612838]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:18464934}. Note=The gene represented in this entry may be involved in disease pathogenesis.

Disease: Atrial fibrillation, familial, 13 (ATFB13) [MIM:615377]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:19808477}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Developmental and epileptic encephalopathy 52 (DEE52) [MIM:617350]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE52 inheritance is autosomal recessive. {ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:23148524}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 2]: Due to intron 3 retention. {ECO:0000305}.

Similarity: Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) 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:		Regulatory subunit of multiple voltage-gated sodium channel complexes that play important roles in excitable membranes in brain, heart and skeletal muscle. Enhances the presence of the pore-forming alpha subunit at the cell surface and modulates channel gating characteristics and the rate of channel inactivation. Modulates the activity of multiple pore-forming alpha subunits, such as SCN1A, SCN2A, SCN3A, SCN4A, SCN5A and SCN10A. {ECO:0000269\|PubMed:14622265, ECO:0000269\|PubMed:15525788, ECO:0000269\|PubMed:18464934, ECO:0000269\|PubMed:19710327, ECO:0000269\|PubMed:21994374, ECO:0000269\|PubMed:29992740, ECO:0000269\|PubMed:8125980, ECO:0000269\|PubMed:8394762}.



Function:		[Isoform 2]: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth (PubMed:21994374). Has no regulatory function on the SCN2A sodium channel complex (PubMed:14622265). {ECO:0000269\|PubMed:14622265, ECO:0000269\|PubMed:21994374}.


Subunit:		Component of a voltage-sensitive sodium channel complex that consists of a pore-forming alpha subunit and one or more regulatory beta subunits (PubMed:15525788, PubMed:21994374, PubMed:30190309). Interacts with SCN4A (PubMed:8125980). Interacts with NFASC. Interacts with SCN10A (By similarity). Interacts with SCN1A (PubMed:15525788, PubMed:21994374, PubMed:17928445). Interacts with SCN3A (PubMed:21994374). Interacts with SCN5A (PubMed:21994374). Interacts with SCN8A (PubMed:26900580). {ECO:0000250\|UniProtKB:Q00954, ECO:0000269\|PubMed:15525788, ECO:0000269\|PubMed:17928445, ECO:0000269\|PubMed:21994374, ECO:0000269\|PubMed:26900580, ECO:0000269\|PubMed:30190309, ECO:0000269\|PubMed:8125980}.
Subcellular location:		[Isoform 1]: Cell membrane {ECO:0000269\|PubMed:17928445, ECO:0000269\|PubMed:19710327, ECO:0000269\|PubMed:21994374, ECO:0000269\|PubMed:29992740, ECO:0000269\|PubMed:30190309, ECO:0000305\|PubMed:8125980}; Single-pass type I membrane protein {ECO:0000269\|PubMed:30190309, ECO:0000305\|PubMed:8125980}. Perikaryon {ECO:0000250\|UniProtKB:P97952}. Cell projection {ECO:0000250\|UniProtKB:P97952}. Cell projection, axon {ECO:0000250\|UniProtKB:Q00954}. Note=Detected at nodes of Ranvier on the sciatic nerve. {ECO:0000250\|UniProtKB:Q00954}.
Subcellular location:		[Isoform 2]: Perikaryon {ECO:0000269\|PubMed:14622265}. Cell projection {ECO:0000269\|PubMed:14622265}. Secreted {ECO:0000269\|PubMed:21994374}. Note=Detected on Purkinje cells and their cell projections and on neuronal cell projections. {ECO:0000269\|PubMed:14622265}.
Tissue specificity:		The overall expression of isoform 1 and isoform 2 is very similar. Isoform 1 is abundantly expressed in skeletal muscle, heart and brain. Isoform 2 is highly expressed in brain and skeletal muscle and present at a very low level in heart, placenta, lung, liver, kidney and pancreas. In brain, isoform 2 is most abundant in the cerebellum, followed by the cerebral cortex and occipital lobe, while isoform 1 levels are higher in the cortex compared to the cerebellum. Isoform 2 is expressed in many regions of the brain, including cerebellar Purkinje cells, cortex pyramidal neurons and many of the neuronal fibers throughout the brain (at protein level). Also detected in dorsal root ganglion, in fibers of the spinal nerve and in cortical neurons and their processes (at protein level). {ECO:0000269\|PubMed:14622265, ECO:0000269\|PubMed:8125980, ECO:0000269\|PubMed:8394762}.
Disease:		Generalized epilepsy with febrile seizures plus 1 (GEFS+1) [MIM:604233]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. {ECO:0000269\|PubMed:17928445, ECO:0000269\|PubMed:21040232, ECO:0000269\|PubMed:9697698}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Brugada syndrome 5 (BRGDA5) [MIM:612838]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269\|PubMed:18464934}. Note=The gene represented in this entry may be involved in disease pathogenesis.
Disease:		Atrial fibrillation, familial, 13 (ATFB13) [MIM:615377]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269\|PubMed:19808477}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Developmental and epileptic encephalopathy 52 (DEE52) [MIM:617350]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE52 inheritance is autosomal recessive. {ECO:0000269\|PubMed:19710327, ECO:0000269\|PubMed:23148524}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 2]: Due to intron 3 retention. {ECO:0000305}.
Similarity:		Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) family. {ECO:0000305}.