UniProtKB - Q9EPL2 (CSTN1_MOUSE)
Protein
Calsyntenin-1
Gene
Clstn1
Organism
Mus musculus (Mouse)
Status
Functioni
Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. As intracellular fragment AlcICD, suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding. May modulate calcium-mediated postsynaptic signals.2 Publications
GO - Molecular functioni
- amyloid-beta binding Source: MGI
- calcium ion binding Source: UniProtKB
- kinesin binding Source: MGI
- X11-like protein binding Source: MGI
GO - Biological processi
- cellular calcium ion homeostasis Source: MGI
- chemical synaptic transmission Source: UniProtKB
- homophilic cell adhesion via plasma membrane adhesion molecules Source: InterPro
- neurotransmitter receptor transport to postsynaptic membrane Source: SynGO
- positive regulation of synapse assembly Source: MGI
- positive regulation of synaptic transmission Source: MGI
- regulation of cell growth Source: MGI
- regulation of synapse maturation Source: SynGO
- vesicle-mediated transport in synapse Source: SynGO
Keywordsi
Biological process | Cell adhesion |
Ligand | Calcium |
Names & Taxonomyi
Protein namesi | Recommended name: Calsyntenin-1CuratedAlternative name(s): Alcadein-alpha1 Publication Short name: Alc-alpha1 Publication Cleaved into the following 2 chains: |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1929895, Clstn1 |
Subcellular locationi
Endoplasmic reticulum
Golgi apparatus
Plasma membrane
Nucleus
- Nucleus By similarity
Other locations
- neuron projection 2 Publications
- Vesicle 1 Publication
Note: Neurite tips. Localized in the postsynaptic membrane of both excitatory and inhibitory synapses. The AlcICD fragment is translocated to the nucleus upon interaction with APBB1 (By similarity).By similarity
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: UniProtKB
Golgi apparatus
- Golgi membrane Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB-SubCell
Plasma Membrane
- integral component of postsynaptic density membrane Source: MGI
- postsynaptic membrane Source: UniProtKB
Other locations
- cell surface Source: MGI
- GABA-ergic synapse Source: MGI
- glutamatergic synapse Source: SynGO
- integral component of membrane Source: MGI
- integral component of spine apparatus membrane Source: MGI
- postsynaptic density Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 29 – 859 | ExtracellularSequence analysisAdd BLAST | 831 | |
Transmembranei | 860 – 880 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 881 – 979 | CytoplasmicSequence analysisAdd BLAST | 99 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus, Postsynaptic cell membrane, SynapsePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 900 | E → A: Marked reduction in KLC1-binding. 1 Publication | 1 | |
Mutagenesisi | 901 | M → A: Almost completely abolishes KLC1-binding. 1 Publication | 1 | |
Mutagenesisi | 902 | D → A: Marked reduction in KLC1-binding. 1 Publication | 1 | |
Mutagenesisi | 903 | W → A: Marked reduction in KLC1-binding; when associated with A-972. Marked alteration in anterograde axonal transport. 1 Publication | 1 | |
Mutagenesisi | 904 | D → A: Almost completely abolishes KLC1-binding. 1 Publication | 1 | |
Mutagenesisi | 905 | D → A: Almost completely abolishes KLC1-binding. 1 Publication | 1 | |
Mutagenesisi | 972 | W → A: Marked reduction in KLC1-binding; when associated with A-903. Marked alteration in anterograde axonal transport. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | By similarityAdd BLAST | 28 | |
ChainiPRO_0000004022 | 29 – 979 | Calsyntenin-1Add BLAST | 951 | |
ChainiPRO_0000323599 | 29 – 825 | Soluble Alc-alphaBy similarityAdd BLAST | 797 | |
ChainiPRO_0000323600 | 826 – 979 | CTF1-alphaBy similarityAdd BLAST | 154 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 346 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 366 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 515 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta-Alc-alpha chain in the extracellular milieu and produces an intracellular fragment (AlcICD). Beta-Alc-alpha secretion is largely dependent upon PSEN1 and PSEN2. This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 824 – 825 | CleavageBy similarity | 2 | |
Sitei | 853 – 854 | CleavageBy similarity | 2 |
Keywords - PTMi
GlycoproteinProteomic databases
PaxDbi | Q9EPL2 |
PeptideAtlasi | Q9EPL2 |
PRIDEi | Q9EPL2 |
PTM databases
GlyGeni | Q9EPL2, 3 sites |
iPTMneti | Q9EPL2 |
PhosphoSitePlusi | Q9EPL2 |
Expressioni
Tissue specificityi
Highly expressed in the brain (at protein level), with over 90% of the neurons expressing detectable amounts. In the brain, relatively high levels in the cerebral cortex, striatum, hippocampus and thalamus. Moderate levels in the cerebellum. Low levels in the olfactory bulb, midbrain and pons (at protein level). Not detected in Purkinje cells. Expressed at low levels in the lung (at protein level). At the mRNA level, weakly detected in the kidney, lung, skeletal muscle, heart and testis. Not expressed in the sciatic nerve fiber.3 Publications
Developmental stagei
Expression in the brain gradually increases during the first postnatal week, reaching a peak at P7. In the gray matter, highly expressed in both developing and adult brain. In the white matter, at P6 highly expressed in all major fiber tracts, including the anterior commissure and the corpus callosum, as well as the external and internal capsules, while in the adult, axonal expression in fiber tracts is only faint (at protein level).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000039953, Expressed in brain and 297 other tissues |
Genevisiblei | Q9EPL2, MM |
Interactioni
Subunit structurei
Directly interacts with APBA2.
Forms a tripartite complex with APBA2 and APP. The CTF1 chain interacts with PSEN1. The intracellular fragment AlcICD interacts with APBB1; this interaction stabilizes AlcICD metabolism.
Interacts with KLC1 and APBB1.
3 PublicationsBinary interactionsi
Q9EPL2
With | #Exp. | IntAct |
---|---|---|
Klc1 [Q8CD76] | 3 | EBI-2013142,EBI-6271950 |
GO - Molecular functioni
- kinesin binding Source: MGI
- X11-like protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 211147, 8 interactors |
ELMi | Q9EPL2 |
IntActi | Q9EPL2, 54 interactors |
MINTi | Q9EPL2 |
STRINGi | 10090.ENSMUSP00000036962 |
Miscellaneous databases
RNActi | Q9EPL2, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 38 – 164 | Cadherin 1PROSITE-ProRule annotationAdd BLAST | 127 | |
Domaini | 165 – 265 | Cadherin 2PROSITE-ProRule annotationAdd BLAST | 101 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 916 – 957 | Glu-rich (highly acidic)Add BLAST | 42 |
Domaini
The cytoplasmic domain is involved in interaction with APBA2, as well as the binding of synaptic Ca2+.By similarity
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1834, Eukaryota |
GeneTreei | ENSGT00950000183086 |
HOGENOMi | CLU_008904_0_0_1 |
InParanoidi | Q9EPL2 |
OMAi | GACWHGR |
OrthoDBi | 302557at2759 |
PhylomeDBi | Q9EPL2 |
TreeFami | TF315946 |
Family and domain databases
InterProi | View protein in InterPro IPR002126, Cadherin-like_dom IPR015919, Cadherin-like_sf IPR026914, Calsyntenin IPR013320, ConA-like_dom_sf |
PANTHERi | PTHR14139, PTHR14139, 1 hit |
Pfami | View protein in Pfam PF00028, Cadherin, 1 hit |
PRINTSi | PR00205, CADHERIN |
SMARTi | View protein in SMART SM00112, CA, 2 hits |
SUPFAMi | SSF49313, SSF49313, 2 hits SSF49899, SSF49899, 1 hit |
PROSITEi | View protein in PROSITE PS50268, CADHERIN_2, 2 hits |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9EPL2-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLRRPAPALA PAVRLLLAGL LCGGGVWAAR VNKHKPWLEP TYHGIVTEND
60 70 80 90 100
NTVLLDPPLI ALDKDSPLRF AESFEVTVTK EGEICGFKIH GQNVPFDAVV
110 120 130 140 150
VDKSTGEGII RSKEKLDCEL QKDYTFTIQA YDCGKGPDGT GVKKSHKATV
160 170 180 190 200
HIQVNDVNEY APVFKEKSYK AAVVEGKQHS SILRVEAVDA DCSPQFSQIC
210 220 230 240 250
SYEILTPDVP FTVDKDGYIK NTEKLNYGKE HQYKLTVTAY DCGKKRATED
260 270 280 290 300
VLVKISVKPT CSPGWQGWSS RIEYEPGTGA LAVFPSIHLE TCDEPVASVQ
310 320 330 340 350
ATVELETSHI GKGCDRDTYS EKSLHRLCGA AAGTSELLPS PSSSFNWTVG
360 370 380 390 400
LPTDNGHDSD QVFEFNGTQA VRIPDGVVTL DPKEPFTISV WMRHGPFGRK
410 420 430 440 450
KETILCSSDK TDMNRHHYSL YVHGCRLVFL LRQDPSEEKK YRPAEFHWKL
460 470 480 490 500
NQVCDEDWHH FVLNVEVPSV TLYVDGIPHE PFSVTEDYPL HPTKIETQLV
510 520 530 540 550
VGACWQEYSG VESGNETEPA TMASAGGDLH MTQFFRGNLA GLTVRSGKLA
560 570 580 590 600
DKKVIDCLYT CKEGLDLQVP EDANRGVQIQ ASSSQAVLTL EGDNVGELDK
610 620 630 640 650
AMQHISYLNS RQFPTPGIRR LKITSTVKCF NEAACIEVPP VEGYVMVLQP
660 670 680 690 700
EEPKISLSGV HHFARAASEF ESAEGISLFP ELRIISTITR EVEPEADGSE
710 720 730 740 750
DPTVQESLVS EEIVHDLDTC EVTVEGDELN AEQESLEVDV TRLQQKGIEA
760 770 780 790 800
SHSDLGVVFT GVETMASYEE VLHLLRYRNW HTRSLLDRKF KLICSELNGR
810 820 830 840 850
YLSNEFKVEV NVIHTANPVE HANHMAAQPQ FVHPEHRSFV DLSGHNLANP
860 870 880 890 900
HPFAVVPSTA TVVIVVCVSF LVFMIILGVF RIRAAHQRTM RDQDTGKENE
910 920 930 940 950
MDWDDSALTI TVNPMETYED QHSSEEEEEE EEEEESEDGE EEEDITSAES
960 970
ESSEEEEGGP GDGQNATRQL EWDDSTLSY
Sequence cautioni
The sequence BAD32337 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_032036 | 72 – 81 | Missing in isoform 2. 2 Publications | 10 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ289016 mRNA Translation: CAC17788.1 AK173059 mRNA Translation: BAD32337.1 Different initiation. AL607078 Genomic DNA No translation available. CU207384 Genomic DNA No translation available. CU210912 Genomic DNA No translation available. BC029027 mRNA Translation: AAH29027.1 BC053843 mRNA Translation: AAH53843.1 |
CCDSi | CCDS18963.1 [Q9EPL2-1] CCDS71522.1 [Q9EPL2-2] |
RefSeqi | NP_001277918.1, NM_001290989.1 [Q9EPL2-2] NP_075538.1, NM_023051.5 [Q9EPL2-1] |
Genome annotation databases
Ensembli | ENSMUST00000039144; ENSMUSP00000036962; ENSMUSG00000039953 [Q9EPL2-1] ENSMUST00000105691; ENSMUSP00000101316; ENSMUSG00000039953 [Q9EPL2-2] |
GeneIDi | 65945 |
KEGGi | mmu:65945 |
UCSCi | uc008vwo.2, mouse [Q9EPL2-1] uc008vwp.2, mouse [Q9EPL2-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ289016 mRNA Translation: CAC17788.1 AK173059 mRNA Translation: BAD32337.1 Different initiation. AL607078 Genomic DNA No translation available. CU207384 Genomic DNA No translation available. CU210912 Genomic DNA No translation available. BC029027 mRNA Translation: AAH29027.1 BC053843 mRNA Translation: AAH53843.1 |
CCDSi | CCDS18963.1 [Q9EPL2-1] CCDS71522.1 [Q9EPL2-2] |
RefSeqi | NP_001277918.1, NM_001290989.1 [Q9EPL2-2] NP_075538.1, NM_023051.5 [Q9EPL2-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6F9I | X-ray | 3.99 | C/X | 965-979 | [»] | |
SMRi | Q9EPL2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 211147, 8 interactors |
ELMi | Q9EPL2 |
IntActi | Q9EPL2, 54 interactors |
MINTi | Q9EPL2 |
STRINGi | 10090.ENSMUSP00000036962 |
PTM databases
GlyGeni | Q9EPL2, 3 sites |
iPTMneti | Q9EPL2 |
PhosphoSitePlusi | Q9EPL2 |
Proteomic databases
PaxDbi | Q9EPL2 |
PeptideAtlasi | Q9EPL2 |
PRIDEi | Q9EPL2 |
Protocols and materials databases
Antibodypediai | 2632, 169 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000039144; ENSMUSP00000036962; ENSMUSG00000039953 [Q9EPL2-1] ENSMUST00000105691; ENSMUSP00000101316; ENSMUSG00000039953 [Q9EPL2-2] |
GeneIDi | 65945 |
KEGGi | mmu:65945 |
UCSCi | uc008vwo.2, mouse [Q9EPL2-1] uc008vwp.2, mouse [Q9EPL2-2] |
Organism-specific databases
CTDi | 22883 |
MGIi | MGI:1929895, Clstn1 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG1834, Eukaryota |
GeneTreei | ENSGT00950000183086 |
HOGENOMi | CLU_008904_0_0_1 |
InParanoidi | Q9EPL2 |
OMAi | GACWHGR |
OrthoDBi | 302557at2759 |
PhylomeDBi | Q9EPL2 |
TreeFami | TF315946 |
Miscellaneous databases
BioGRID-ORCSi | 65945, 0 hits in 17 CRISPR screens |
ChiTaRSi | Clstn1, mouse |
PROi | PR:Q9EPL2 |
RNActi | Q9EPL2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000039953, Expressed in brain and 297 other tissues |
Genevisiblei | Q9EPL2, MM |
Family and domain databases
InterProi | View protein in InterPro IPR002126, Cadherin-like_dom IPR015919, Cadherin-like_sf IPR026914, Calsyntenin IPR013320, ConA-like_dom_sf |
PANTHERi | PTHR14139, PTHR14139, 1 hit |
Pfami | View protein in Pfam PF00028, Cadherin, 1 hit |
PRINTSi | PR00205, CADHERIN |
SMARTi | View protein in SMART SM00112, CA, 2 hits |
SUPFAMi | SSF49313, SSF49313, 2 hits SSF49899, SSF49899, 1 hit |
PROSITEi | View protein in PROSITE PS50268, CADHERIN_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CSTN1_MOUSE | |
Accessioni | Q9EPL2Primary (citable) accession number: Q9EPL2 Secondary accession number(s): A2A800 Q8K103 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 19, 2002 |
Last sequence update: | March 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 157 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references