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Protein

Calsyntenin-1

Gene

Clstn1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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
  • positive regulation of synapse assembly Source: MGI
  • positive regulation of synaptic transmission Source: MGI
  • regulation of cell growth Source: MGI

Keywordsi

Biological processCell adhesion
LigandCalcium

Names & Taxonomyi

Protein namesi
Recommended name:
Calsyntenin-1
Alternative name(s):
Alcadein-alpha
Short name:
Alc-alpha
Cleaved into the following 2 chains:
Soluble Alc-alpha
Short name:
SAlc-alpha
Alternative name(s):
C-terminal fragment 1-alpha
Gene namesi
Name:Clstn1
Synonyms:Cs1, Cstn1, Kiaa0911
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1929895 Clstn1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini29 – 859ExtracellularSequence analysisAdd BLAST831
Transmembranei860 – 880HelicalSequence analysisAdd BLAST21
Topological domaini881 – 979CytoplasmicSequence analysisAdd BLAST99

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi900E → A: Marked reduction in KLC1-binding. 1 Publication1
Mutagenesisi901M → A: Almost completely abolishes KLC1-binding. 1 Publication1
Mutagenesisi902D → A: Marked reduction in KLC1-binding. 1 Publication1
Mutagenesisi903W → A: Marked reduction in KLC1-binding; when associated with A-972. Marked alteration in anterograde axonal transport. 1 Publication1
Mutagenesisi904D → A: Almost completely abolishes KLC1-binding. 1 Publication1
Mutagenesisi905D → A: Almost completely abolishes KLC1-binding. 1 Publication1
Mutagenesisi972W → A: Marked reduction in KLC1-binding; when associated with A-903. Marked alteration in anterograde axonal transport. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28By similarityAdd BLAST28
ChainiPRO_000000402229 – 979Calsyntenin-1Add BLAST951
ChainiPRO_000032359929 – 825Soluble Alc-alphaBy similarityAdd BLAST797
ChainiPRO_0000323600826 – 979CTF1-alphaBy similarityAdd BLAST154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi346N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi366N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi515N-linked (GlcNAc...) asparagineSequence analysis1

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei824 – 825CleavageBy similarity2
Sitei853 – 854CleavageBy similarity2

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9EPL2
PeptideAtlasiQ9EPL2
PRIDEiQ9EPL2

PTM databases

iPTMnetiQ9EPL2
PhosphoSitePlusiQ9EPL2

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

BgeeiENSMUSG00000039953
CleanExiMM_CLSTN1
GenevisibleiQ9EPL2 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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Klc1Q8CD763EBI-2013142,EBI-6271950

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211147, 1 interactor
ELMiQ9EPL2
IntActiQ9EPL2, 54 interactors
MINTiQ9EPL2
STRINGi10090.ENSMUSP00000036962

Structurei

3D structure databases

ProteinModelPortaliQ9EPL2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 164Cadherin 1PROSITE-ProRule annotationAdd BLAST127
Domaini165 – 265Cadherin 2PROSITE-ProRule annotationAdd BLAST101

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi916 – 957Glu-rich (highly acidic)Add BLAST42

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 helix

Phylogenomic databases

eggNOGiKOG1834 Eukaryota
ENOG410XT2J LUCA
GeneTreeiENSGT00390000010858
HOVERGENiHBG051146
InParanoidiQ9EPL2
OMAiITSTVKC
OrthoDBiEOG091G05I8
PhylomeDBiQ9EPL2
TreeFamiTF315946

Family and domain databases

InterProiView protein in InterPro
IPR002126 Cadherin
IPR015919 Cadherin-like
IPR026914 Calsyntenin
IPR013320 ConA-like_dom_sf
PANTHERiPTHR14139 PTHR14139, 1 hit
PfamiView protein in Pfam
PF00028 Cadherin, 1 hit
PRINTSiPR00205 CADHERIN
SMARTiView protein in SMART
SM00112 CA, 2 hits
SUPFAMiSSF49313 SSF49313, 2 hits
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50268 CADHERIN_2, 2 hits

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9EPL2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:979
Mass (Da):108,900
Last modified:March 1, 2001 - v1
Checksum:i898D62AE9C10A99C
GO
Isoform 2 (identifier: Q9EPL2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-81: Missing.

Show »
Length:969
Mass (Da):107,749
Checksum:iA7E02BD853875097
GO

Sequence cautioni

The sequence BAD32337 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03203672 – 81Missing in isoform 2. 2 Publications10

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 Translation: CAM23910.1
AL607078 Genomic DNA Translation: CAM23911.1
CU210912, CU207384 Genomic DNA Translation: CAQ51663.1
CU210912, CU207384 Genomic DNA Translation: CAQ51664.1
CU207384, CU210912 Genomic DNA Translation: CAQ51676.1
CU207384, CU210912 Genomic DNA Translation: CAQ51677.1
BC029027 mRNA Translation: AAH29027.1
BC053843 mRNA Translation: AAH53843.1
CCDSiCCDS18963.1 [Q9EPL2-1]
CCDS71522.1 [Q9EPL2-2]
RefSeqiNP_001277918.1, NM_001290989.1 [Q9EPL2-2]
NP_075538.1, NM_023051.5 [Q9EPL2-1]
UniGeneiMm.38993

Genome annotation databases

EnsembliENSMUST00000039144; ENSMUSP00000036962; ENSMUSG00000039953 [Q9EPL2-1]
ENSMUST00000105691; ENSMUSP00000101316; ENSMUSG00000039953 [Q9EPL2-2]
GeneIDi65945
KEGGimmu:65945
UCSCiuc008vwo.2 mouse [Q9EPL2-1]
uc008vwp.2 mouse [Q9EPL2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCSTN1_MOUSE
AccessioniPrimary (citable) accession number: Q9EPL2
Secondary accession number(s): A2A800
, B2KFP1, B2KFP2, Q69ZV9, Q7TS67, Q8K103
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: March 1, 2001
Last modified: May 23, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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