Synaptosomal-associated protein 25 (SNAP-25) is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the SNAP25 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. The SNAP-25 protein is a component of the SNARE complex

SNARE (protein)

SNARE proteins are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells....

, which is proposed to account for the specificity of membrane fusion and to directly execute fusion by forming a tight complex that brings the synaptic vesicle

Synaptic vesicle

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

 and plasma membranes together.

Structure and function

SNAP-25 is a membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 bound protein anchored to the cytosol

Cytosol

The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....

ic face of membranes via palmitoyl side chains in the middle of the molecule

Molecule

A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...

. SNAP-25 is a Q-SNARE protein contributing two α-helices in the formation of the exocytotic

Exocytosis

Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...

 fusion complex in neurons where it assembles with syntaxin-1

Syntaxin

Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.- Domains :Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain , and an N-terminal regulatory domain ....

 and synaptobrevin

Synaptobrevin

Synaptobrevins are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton that are part of the vesicle-associated membrane protein family....

. SNAP-25 inhibits P/Q- and L-type voltage-gated calcium channels

VGCC

VGCC may refer to:* Voltage-gated calcium channel, also known as a voltage-dependent calcium channel* Vance-Granville Community College, a community college in North Carolina...

 located presynaptically and interacts with the synaptotagmin

Synaptotagmin

Synaptotagmins constitute a family of membrane-trafficking proteins that are characterized by an N-terminal transmembrane region , a variable linker, and two C-terminal C2 domains - C2A and C2B. There are 15 members in the mammalian synaptotagmin family...

 C2B domain in Ca²⁺

Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

-independent fashion. In glutamatergic synapse

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s SNAP-25 decreases the Ca²⁺ responsiveness, while it is naturally absent in GABA

Gabâ

Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...

ergic synapses.

Clinical significance

Consistent with the regulation of synaptic Ca²⁺ responsiveness, heterozygous deletion of the SNAP-25 gene in mice results in a hyperactive phenotype similar to attention deficit hyperactivity disorder (ADHD)

Attention-deficit hyperactivity disorder

Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

. In heterozygous mice, a decrease in hyperactivity is observed with dextroamphetamine

Dextroamphetamine

Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....

 (or Dexedrine), an active ingredient in the ADHD drug Adderall

Adderall

Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...

. Homozygous deletions of the SNAP-25 gene are lethal. Subsequent studies have suggested that at least some of the SNAP-25 gene mutations in humans might predispose to ADHD.

A genome wide association study pointed to the rs362584 polymorphism in the gene as possibly associated with the personality trait neuroticism

Neuroticism

Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...

. Botulinum toxins A, C and E cleave SNAP-25 leading to paralysis

Paralysis

Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

 in clinically developed botulism

Botulism

Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...

.

Interactions

SNAP-25 has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with STX4

STX4

Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.-Interactions:STX4 has been shown to interact with SNAP-25, NAPA, STXBP5, SNAP23, Vesicle-associated membrane protein 8, RAB4A, TXLNB, VAMP2, VAMP3, STXBP1 and Syntaxin binding protein 3.-Further reading:...

, STX2

STX2

Syntaxin-2 is a protein that in humans is encoded by the STX2 gene.-Interactions:STX2 has been shown to interact with SNAP-25, SNAP23, STXBP1 and Syntaxin binding protein 3.-Further reading:...

, Syntaxin 3

Syntaxin 3

Syntaxin 3, also known as STX3, is a protein which in humans is encoded by the STX3 gene.- Function :The protein encoded by this gene is a member of the syntaxin family of cellular receptors for transport vesicles which participate in exocytosis in neutrophils...

, STX1A

STX1A

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.- Function :Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization of both synaptic vesicles and calcium channels to...

, KIF5B

KIF5B

Kinesin-1 heavy chain is a protein that in humans is encoded by the KIF5B gene.-Interactions:KIF5B has been shown to interact with SNAP-25, SNAP23, KLC2, YWHAH and KLC1.-Further reading:...

, TRIM9

TRIM9

Tripartite motif-containing protein 9 is a protein that in humans is encoded by the TRIM9 gene.-Further reading:...

, STX11

STX11

Syntaxin 11, also known as STX11, is a human gene that is a member of the t-SNARE family.-Interactions:STX11 has been shown to interact with SNAP-25 and SNAP23.-See also:* Hemophagocytic lymphohistiocytosis-Further reading:...

, CPLX1

CPLX1

Complexin-1 is a protein that in humans is encoded by the CPLX1 gene.-Interactions:CPLX1 has been shown to interact with SNAP-25 and STX1A.-Further reading:...

, SYT1

SYT1

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.SYT1 is the master switch responsible for allowing the human brain to release neurotransmitters...

, VAMP2

VAMP2

Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene.-Interactions:VAMP2 has been shown to interact with STX4, SNAP-25, SNAP23, STX1A and RABAC1.-Further reading:...

, SNAPAP

SNAPAP

SNARE-associated protein Snapin is a protein that in humans is encoded by the SNAPIN gene.-Interactions:SNAPAP has been shown to interact with SNAP-25, BLOC1S1, SNAP23, Dysbindin, TRPV1, PLDN, BLOC1S2 and RGS7.-Further reading:...

 and ITSN1

ITSN1

Intersectin-1 is a protein that, in humans, is encoded by the ITSN1 gene.-Interactions:ITSN1 has been shown to interact with SNAP-25, SOS1, SCAMP1 and CDC42.-Further reading:...

.

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