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Protein

Calsyntenin-1

Gene

CLSTN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. The 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • amyloid-beta binding Source: UniProtKB
  • calcium ion binding Source: InterPro
  • kinesin binding Source: UniProtKB
  • X11-like protein binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCell adhesion
LigandCalcium

Names & Taxonomyi

Protein namesi
Recommended name:
Calsyntenin-1
Alternative name(s):
Alcadein-alpha
Short name:
Alc-alpha
Alzheimer-related cadherin-like protein
Non-classical cadherin XB31alpha
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, KIAA0911
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000171603.16.
HGNCiHGNC:17447. 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 – 981CytoplasmicSequence analysisAdd BLAST101

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
Mutagenesisi913 – 914NP → AA: Abolishes interaction with APBA2. 1 Publication2
Mutagenesisi918Y → A: No effect on APBA2-binding. 1 Publication1

Organism-specific databases

DisGeNETi22883.
OpenTargetsiENSG00000171603.
PharmGKBiPA38238.

Polymorphism and mutation databases

BioMutaiCLSTN1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 281 PublicationAdd BLAST28
ChainiPRO_000000402129 – 981Calsyntenin-1Add BLAST953
ChainiPRO_000032359729 – 825Soluble Alc-alphaAdd BLAST797
ChainiPRO_0000323598826 – 981CTF1-alphaAdd BLAST156

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). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1.1 Publication

Sites

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

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO94985.
PaxDbiO94985.
PeptideAtlasiO94985.
PRIDEiO94985.

PTM databases

iPTMnetiO94985.
PhosphoSitePlusiO94985.

Miscellaneous databases

PMAP-CutDBiO94985.

Expressioni

Tissue specificityi

Expressed in the brain and, a lower level, in the heart, skeletal muscle, kidney and placenta. Accumulates in dystrophic neurites around the amyloid core of Alzheimer disease senile plaques (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000171603.
CleanExiHS_CLSTN1.
ExpressionAtlasiO94985. baseline and differential.
GenevisibleiO94985. HS.

Organism-specific databases

HPAiHPA012412.

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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Klc1Q8CD767EBI-522075,EBI-6271950From Mus musculus.

GO - Molecular functioni

  • kinesin binding Source: UniProtKB
  • X11-like protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116550. 29 interactors.
DIPiDIP-31694N.
ELMiO94985.
IntActiO94985. 13 interactors.
MINTiMINT-4544144.
STRINGi9606.ENSP00000366513.

Structurei

3D structure databases

ProteinModelPortaliO94985.
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 – 959Glu-rich (highly acidic)Add BLAST44

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.
HOGENOMiHOG000037537.
HOVERGENiHBG051146.
InParanoidiO94985.
OMAiITSTVKC.
OrthoDBiEOG091G05I8.
PhylomeDBiO94985.
TreeFamiTF315946.

Family and domain databases

InterProiView protein in InterPro
IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR026914. Calsyntenin.
IPR013320. ConA-like_dom.
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: O94985-1) [UniParc]FASTAAdd to basket
Also known as: Alcalpha2

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 PAARLLLAGL LCGGGVWAAR VNKHKPWLEP TYHGIVTEND
60 70 80 90 100
NTVLLDPPLI ALDKDAPLRF AESFEVTVTK EGEICGFKIH GQNVPFDAVV
110 120 130 140 150
VDKSTGEGVI RSKEKLDCEL QKDYSFTIQA YDCGKGPDGT NVKKSHKATV
160 170 180 190 200
HIQVNDVNEY APVFKEKSYK ATVIEGKQYD SILRVEAVDA DCSPQFSQIC
210 220 230 240 250
SYEIITPDVP FTVDKDGYIK NTEKLNYGKE HQYKLTVTAY DCGKKRATED
260 270 280 290 300
VLVKISIKPT CTPGWQGWNN RIEYEPGTGA LAVFPNIHLE TCDEPVASVQ
310 320 330 340 350
ATVELETSHI GKGCDRDTYS EKSLHRLCGA AAGTAELLPS PSGSLNWTMG
360 370 380 390 400
LPTDNGHDSD QVFEFNGTQA VRIPDGVVSV SPKEPFTISV WMRHGPFGRK
410 420 430 440 450
KETILCSSDK TDMNRHHYSL YVHGCRLIFL FRQDPSEEKK YRPAEFHWKL
460 470 480 490 500
NQVCDEEWHH YVLNVEFPSV TLYVDGTSHE PFSVTEDYPL HPSKIETQLV
510 520 530 540 550
VGACWQEFSG VENDNETEPV TVASAGGDLH MTQFFRGNLA GLTLRSGKLA
560 570 580 590 600
DKKVIDCLYT CKEGLDLQVL EDSGRGVQIQ AHPSQLVLTL EGEDLGELDK
610 620 630 640 650
AMQHISYLNS RQFPTPGIRR LKITSTIKCF NEATCISVPP VDGYVMVLQP
660 670 680 690 700
EEPKISLSGV HHFARAASEF ESSEGVFLFP ELRIISTITR EVEPEGDGAE
710 720 730 740 750
DPTVQESLVS EEIVHDLDTC EVTVEGEELN HEQESLEVDM ARLQQKGIEV
760 770 780 790 800
SSSELGMTFT GVDTMASYEE VLHLLRYRNW HARSLLDRKF KLICSELNGR
810 820 830 840 850
YISNEFKVEV NVIHTANPME HANHMAAQPQ FVHPEHRSFV DLSGHNLANP
860 870 880 890 900
HPFAVVPSTA TVVIVVCVSF LVFMIILGVF RIRAAHRRTM RDQDTGKENE
910 920 930 940 950
MDWDDSALTI TVNPMETYED QHSSEEEEEE EEEEESEDGE EEDDITSAES
960 970 980
ESSEEEEGEQ GDPQNATRQQ QLEWDDSTLS Y
Length:981
Mass (Da):109,793
Last modified:May 1, 1999 - v1
Checksum:i01856284DEC3FC73
GO
Isoform 2 (identifier: O94985-2) [UniParc]FASTAAdd to basket
Also known as: Alcalpha1

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

Show »
Length:971
Mass (Da):108,643
Checksum:iE772045354046E4F
GO

Sequence cautioni

The sequence BAA74934 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti102D → G in BAF82487 (PubMed:14702039).Curated1
Sequence conflicti553K → R in BAF82487 (PubMed:14702039).Curated1
Sequence conflicti886 – 887HR → ST in AAQ04552 (PubMed:12972431).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048582332A → T. Corresponds to variant dbSNP:rs7550295Ensembl.1
Natural variantiVAR_039552474V → A1 PublicationCorresponds to variant dbSNP:rs17853245Ensembl.1
Natural variantiVAR_039553524S → C1 PublicationCorresponds to variant dbSNP:rs17853244Ensembl.1
Natural variantiVAR_039554583P → R1 PublicationCorresponds to variant dbSNP:rs17853243Ensembl.1
Natural variantiVAR_039555857P → H1 PublicationCorresponds to variant dbSNP:rs17855572Ensembl.1
Natural variantiVAR_039556870F → S1 PublicationCorresponds to variant dbSNP:rs17855573Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03203572 – 81Missing in isoform 2. 3 Publications10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF438482 mRNA. Translation: AAQ04552.1.
AY753301 mRNA. Translation: AAV30551.1.
AB020718 mRNA. Translation: BAA74934.2. Different initiation.
AK289798 mRNA. Translation: BAF82487.1.
AL691449, AL357140 Genomic DNA. Translation: CAI15699.1.
AL691449, AL357140 Genomic DNA. Translation: CAI15700.1.
AL357140, AL691449 Genomic DNA. Translation: CAI16884.1.
AL357140, AL691449 Genomic DNA. Translation: CAI16885.1.
BC033902 mRNA. Translation: AAH33902.1.
CCDSiCCDS105.1. [O94985-2]
CCDS30580.1. [O94985-1]
RefSeqiNP_001009566.1. NM_001009566.2. [O94985-1]
NP_001289812.1. NM_001302883.1.
NP_055759.3. NM_014944.4. [O94985-2]
UniGeneiHs.29665.

Genome annotation databases

EnsembliENST00000361311; ENSP00000354997; ENSG00000171603. [O94985-2]
ENST00000377298; ENSP00000366513; ENSG00000171603. [O94985-1]
GeneIDi22883.
KEGGihsa:22883.
UCSCiuc001aqh.4. human. [O94985-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCSTN1_HUMAN
AccessioniPrimary (citable) accession number: O94985
Secondary accession number(s): A8K183
, Q5SR52, Q5UE58, Q71MN0, Q8N4K9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: May 1, 1999
Last modified: September 27, 2017
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot