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UniProtKB - Q9EPL2 (CSTN1_MOUSE)

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
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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
CTF1-alpha
Alternative name(s):
C-terminal fragment 1-alpha
Gene namesi
Name:Clstn1
Synonyms:Cs1, Cstn1, Kiaa0911
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
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 Expressed in 282 organ(s), highest expression level in brain
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

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ9EPL2
SMRiQ9EPL2
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
KOiK22659
OMAiCDEPITS
OrthoDBiEOG091G05I8
PhylomeDBiQ9EPL2
TreeFamiTF315946

Family and domain databases

InterProiView protein in InterPro
IPR002126 Cadherin-like_dom
IPR015919 Cadherin-like_sf
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

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 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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6F9IX-ray3.99C/X965-979[»]
ProteinModelPortaliQ9EPL2
SMRiQ9EPL2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiQ9EPL2
PhosphoSitePlusiQ9EPL2

Proteomic databases

PaxDbiQ9EPL2
PeptideAtlasiQ9EPL2
PRIDEiQ9EPL2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi22883
MGIiMGI:1929895 Clstn1
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1834 Eukaryota
ENOG410XT2J LUCA
GeneTreeiENSGT00390000010858
HOVERGENiHBG051146
InParanoidiQ9EPL2
KOiK22659
OMAiCDEPITS
OrthoDBiEOG091G05I8
PhylomeDBiQ9EPL2
TreeFamiTF315946

Miscellaneous databases

ChiTaRSiClstn1 mouse
PROiPR:Q9EPL2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039953 Expressed in 282 organ(s), highest expression level in brain
CleanExiMM_CLSTN1
GenevisibleiQ9EPL2 MM

Family and domain databases

InterProiView protein in InterPro
IPR002126 Cadherin-like_dom
IPR015919 Cadherin-like_sf
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
ProtoNetiSearch...

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: November 7, 2018
This is version 142 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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