UniProt functional annotation for Q9CS84



	UniProt functional annotation for Q9CS84

UniProt code: Q9CS84.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N- terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may effect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom. {ECO:0000269|PubMed:12827191, ECO:0000269|PubMed:14983056, ECO:0000269|PubMed:16406382, ECO:0000269|PubMed:17035546, ECO:0000269|PubMed:21410790, ECO:0000269|PubMed:9430716}.

Subunit: Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1 forming a heterotetramer, where one NLGN1 dimer interacts with one NRXN1 dimer (By similarity). Interacts (via cytoplasmic C-terminal region) with CASK (via the PDZ, SH3 and guanylate kinase-like domains) (PubMed:25385611). Interacts (via cytoplasmic C-terminus) with CASKIN1 and APBA1 (By similarity). Interacts (via laminin G-like domain 2) with NXPH1 and NXPH3 (By similarity). Alpha-type isoforms (neurexin-1-alpha) interact (via laminin G-like domain 2 and/or laminin G-like domain 6) with DAG1 (via alpha-dystroglycan chain). Alpha-type isoforms interact with alpha- latrotoxin from spider venom. Interacts with LRRTM1, LRRTM2, LRRTM3 and LRRTM4 (By similarity). Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1, NLGN2, NLGN3 and NLGN4L; these interactions are calcium-dependent. Interacts with SYT13 and SYTL1. Interacts with CBLN1, CBLN2 and, less avidly, with CBLN4. {ECO:0000250, ECO:0000250|UniProtKB:Q28146, ECO:0000250|UniProtKB:Q63372, ECO:0000269|PubMed:11171101, ECO:0000269|PubMed:11243866, ECO:0000269|PubMed:18334216, ECO:0000269|PubMed:18434543, ECO:0000269|PubMed:20624592, ECO:0000269|PubMed:21410790, ECO:0000269|PubMed:25385611}.

Subcellular location: Cell junction, synapse, presynaptic cell membrane {ECO:0000269|PubMed:21410790}; Single-pass type I membrane protein {ECO:0000269|PubMed:21410790}.

Ptm: N-glycosylated. {ECO:0000250}.

Ptm: O-glycosylated. {ECO:0000250}.

Disruption phenotype: No visible phenotype, but mice display subtle behavorial deficits. Females show deficits in nest building and taking care of pups. Mice lacking the alpha-type isoforms of NRXN1, NRXN2 and NRXN3 are born at the expected Mendelian rate, but die during the first day after birth, probably due to neurological defects in the brainstem that impair normal breathing. These mice express normal levels of the beta-type isoforms of NRXN1, NRXN2 and NRXN3. Mice show reduced density of synapses in the brainstem, especially a reduction in the numbers of GABA-releasing synapses. Their brains display a reduced frequency of spontaneous neurotransmitter release, and decreased neurotransmitter release in response to an action potential. Likewise, the activity of voltage-gated calcium channels is strongly decreased. A small proportion (5-10%) of mice lacking the alpha-type isoforms of both NRXN1 and NRXN2 survive to adulthood; these mice do not show any gross anatomical defects in their brains or changes in the distribution of synaptic proteins, but they have fewer synapses in the neocortex and show defects in neurotransmitter release at neuromuscular junctions. {ECO:0000269|PubMed:12827191, ECO:0000269|PubMed:14983056, ECO:0000269|PubMed:16406382, ECO:0000269|PubMed:17035546, ECO:0000269|PubMed:17347997, ECO:0000269|PubMed:19822762, ECO:0000269|PubMed:9430716}.

Miscellaneous: [Isoform 6]: Produced by alternative promoter usage and alternative splicing. {ECO:0000303|PubMed:25737549}.

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

Sequence caution: Sequence=AAH47146.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAC41433.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N- terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may effect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom. {ECO:0000269\|PubMed:12827191, ECO:0000269\|PubMed:14983056, ECO:0000269\|PubMed:16406382, ECO:0000269\|PubMed:17035546, ECO:0000269\|PubMed:21410790, ECO:0000269\|PubMed:9430716}.


Subunit:		Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1 forming a heterotetramer, where one NLGN1 dimer interacts with one NRXN1 dimer (By similarity). Interacts (via cytoplasmic C-terminal region) with CASK (via the PDZ, SH3 and guanylate kinase-like domains) (PubMed:25385611). Interacts (via cytoplasmic C-terminus) with CASKIN1 and APBA1 (By similarity). Interacts (via laminin G-like domain 2) with NXPH1 and NXPH3 (By similarity). Alpha-type isoforms (neurexin-1-alpha) interact (via laminin G-like domain 2 and/or laminin G-like domain 6) with DAG1 (via alpha-dystroglycan chain). Alpha-type isoforms interact with alpha- latrotoxin from spider venom. Interacts with LRRTM1, LRRTM2, LRRTM3 and LRRTM4 (By similarity). Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1, NLGN2, NLGN3 and NLGN4L; these interactions are calcium-dependent. Interacts with SYT13 and SYTL1. Interacts with CBLN1, CBLN2 and, less avidly, with CBLN4. {ECO:0000250, ECO:0000250\|UniProtKB:Q28146, ECO:0000250\|UniProtKB:Q63372, ECO:0000269\|PubMed:11171101, ECO:0000269\|PubMed:11243866, ECO:0000269\|PubMed:18334216, ECO:0000269\|PubMed:18434543, ECO:0000269\|PubMed:20624592, ECO:0000269\|PubMed:21410790, ECO:0000269\|PubMed:25385611}.
Subcellular location:		Cell junction, synapse, presynaptic cell membrane {ECO:0000269\|PubMed:21410790}; Single-pass type I membrane protein {ECO:0000269\|PubMed:21410790}.
Ptm:		N-glycosylated. {ECO:0000250}.
Ptm:		O-glycosylated. {ECO:0000250}.
Disruption phenotype:		No visible phenotype, but mice display subtle behavorial deficits. Females show deficits in nest building and taking care of pups. Mice lacking the alpha-type isoforms of NRXN1, NRXN2 and NRXN3 are born at the expected Mendelian rate, but die during the first day after birth, probably due to neurological defects in the brainstem that impair normal breathing. These mice express normal levels of the beta-type isoforms of NRXN1, NRXN2 and NRXN3. Mice show reduced density of synapses in the brainstem, especially a reduction in the numbers of GABA-releasing synapses. Their brains display a reduced frequency of spontaneous neurotransmitter release, and decreased neurotransmitter release in response to an action potential. Likewise, the activity of voltage-gated calcium channels is strongly decreased. A small proportion (5-10%) of mice lacking the alpha-type isoforms of both NRXN1 and NRXN2 survive to adulthood; these mice do not show any gross anatomical defects in their brains or changes in the distribution of synaptic proteins, but they have fewer synapses in the neocortex and show defects in neurotransmitter release at neuromuscular junctions. {ECO:0000269\|PubMed:12827191, ECO:0000269\|PubMed:14983056, ECO:0000269\|PubMed:16406382, ECO:0000269\|PubMed:17035546, ECO:0000269\|PubMed:17347997, ECO:0000269\|PubMed:19822762, ECO:0000269\|PubMed:9430716}.
Miscellaneous:		[Isoform 6]: Produced by alternative promoter usage and alternative splicing. {ECO:0000303\|PubMed:25737549}.
Similarity:		Belongs to the neurexin family. {ECO:0000305}.
Sequence caution:		Sequence=AAH47146.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; Sequence=BAC41433.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};