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Protein

Calsyntenin-3

Gene

CLSTN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May modulate calcium-mediated postsynaptic signals. 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.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Calsyntenin-3
Alternative name(s):
Alcadein-beta
Short name:
Alc-beta
Gene namesi
Name:CLSTN3
Synonyms:CS3, KIAA0726
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:18371. CLSTN3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 847828ExtracellularSequence analysisAdd
BLAST
Transmembranei848 – 86821HelicalSequence analysisAdd
BLAST
Topological domaini869 – 95688CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38320.

Polymorphism and mutation databases

BioMutaiCLSTN3.
DMDMi23396507.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 956937Calsyntenin-3PRO_0000004026Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence analysis
Glycosylationi327 – 3271N-linked (GlcNAc...)Sequence analysis
Glycosylationi347 – 3471N-linked (GlcNAc...)Sequence analysis
Glycosylationi507 – 5071N-linked (GlcNAc...)Sequence analysis
Glycosylationi740 – 7401N-linked (GlcNAc...)Sequence analysis

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 gamma-secretase within the transmembrane domain releases the beta-Alc-beta 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 gamma-secretase (By similarity).By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9BQT9.
MaxQBiQ9BQT9.
PaxDbiQ9BQT9.
PRIDEiQ9BQT9.

PTM databases

iPTMnetiQ9BQT9.
PhosphoSiteiQ9BQT9.

Expressioni

Tissue specificityi

According to PubMed:12498782, expressed predominantly in the brain and in kidney. Low levels in heart, skeletal muscle, liver, placenta, pancreas and lung. According to PubMed:12972431, predominant expression in brain, and only marginal in kidney. In brain, present throughout all cortical layers, highest levels in GABAergic neurons (based on morphology and distribution pattern).2 Publications

Gene expression databases

BgeeiQ9BQT9.
CleanExiHS_CLSTN3.
ExpressionAtlasiQ9BQT9. baseline and differential.
GenevisibleiQ9BQT9. HS.

Organism-specific databases

HPAiHPA046913.

Interactioni

Subunit structurei

Directly interacts with APBA2. Forms a tripartite complex with APBA2 and APP. Interacts with low affinity with KLC1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi115094. 4 interactions.
IntActiQ9BQT9. 1 interaction.
STRINGi9606.ENSP00000266546.

Structurei

3D structure databases

ProteinModelPortaliQ9BQT9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 145117Cadherin 1PROSITE-ProRule annotationAdd
BLAST
Domaini146 – 246101Cadherin 2PROSITE-ProRule annotationAdd
BLAST

Domaini

Binds synaptic Ca2+ with its cytoplasmic domain.By similarity

Sequence similaritiesi

Contains 2 cadherin domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1834. Eukaryota.
ENOG410XT2J. LUCA.
GeneTreeiENSGT00390000010858.
HOGENOMiHOG000037537.
HOVERGENiHBG051146.
InParanoidiQ9BQT9.
OMAiETFNHAL.
OrthoDBiEOG7SFHVX.
PhylomeDBiQ9BQT9.
TreeFamiTF315946.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
2.60.40.60. 2 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR026914. Calsyntenin.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR14139. PTHR14139. 2 hits.
PfamiPF00028. Cadherin. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 2 hits.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 2 hits.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50268. CADHERIN_2. 2 hits.
[Graphical view]

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: Q9BQT9-1) [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
MTLLLLPLLL ASLLASCSCN KANKHKPWIE AEYQGIVMEN DNTVLLNPPL
60 70 80 90 100
FALDKDAPLR YAGEICGFRL HGSGVPFEAV ILDKATGEGL IRAKEPVDCE
110 120 130 140 150
AQKEHTFTIQ AYDCGEGPDG ANTKKSHKAT VHVRVNDVNE FAPVFVERLY
160 170 180 190 200
RAAVTEGKLY DRILRVEAID GDCSPQYSQI CYYEILTPNT PFLIDNDGNI
210 220 230 240 250
ENTEKLQYSG ERLYKFTVTA YDCGKKRAAD DAEVEIQVKP TCKPSWQGWN
260 270 280 290 300
KRIEYAPGAG SLALFPGIRL ETCDEPLWNI QATIELQTSH VAKGCDRDNY
310 320 330 340 350
SERALRKLCG AATGEVDLLP MPGPNANWTA GLSVHYSQDS SLIYWFNGTQ
360 370 380 390 400
AVQVPLGGPS GLGSGPQDSL SDHFTLSFWM KHGVTPNKGK KEEETIVCNT
410 420 430 440 450
VQNEDGFSHY SLTVHGCRIA FLYWPLLESA RPVKFLWKLE QVCDDEWHHY
460 470 480 490 500
ALNLEFPTVT LYTDGISFDP ALIHDNGLIH PPRREPALMI GACWTEEKNK
510 520 530 540 550
EKEKGDNSTD TTQGDPLSIH HYFHGYLAGF SVRSGRLESR EVIECLYACR
560 570 580 590 600
EGLDYRDFES LGKGMKVHVN PSQSLLTLEG DDVETFNHAL QHVAYMNTLR
610 620 630 640 650
FATPGVRPLR LTTAVKCFSE ESCVSIPEVE GYVVVLQPDA PQILLSGTAH
660 670 680 690 700
FARPAVDFEG TNGVPLFPDL QITCSISHQV EAKKDESWQG TVTDTRMSDE
710 720 730 740 750
IVHNLDGCEI SLVGDDLDPE RESLLLDTTS LQQRGLELTN TSAYLTIAGV
760 770 780 790 800
ESITVYEEIL RQARYRLRHG AALYTRKFRL SCSEMNGRYS SNEFIVEVNV
810 820 830 840 850
LHSMNRVAHP SHVLSSQQFL HRGHQPPPEM AGHSLASSHR NSMIPSAATL
860 870 880 890 900
IIVVCVGFLV LMVVLGLVRI HSLHRRVSGA GGPPGASSDP KDPDLFWDDS
910 920 930 940 950
ALTIIVNPME SYQNRQSCVT GAVGGQQEDE DSSDSEVADS PSSDERRIIE

TPPHRY
Length:956
Mass (Da):106,098
Last modified:June 1, 2001 - v1
Checksum:i5BE96722C604B173
GO
Isoform 2 (identifier: Q9BQT9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MTLLLLPLLLASLLASCSCNK → MVLGCELSGSTRVVVGVEALLTGASSPLPGVGP

Show »
Length:968
Mass (Da):107,033
Checksum:iECCB3E0214C50B8E
GO

Sequence cautioni

The sequence BAA34446.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti209 – 2091S → G.
Corresponds to variant rs7302230 [ dbSNP | Ensembl ].
VAR_048583
Natural varianti874 – 8741H → Y in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036114

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2121MTLLL…CSCNK → MVLGCELSGSTRVVVGVEAL LTGASSPLPGVGP in isoform 2. 2 PublicationsVSP_043748Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277460 mRNA. Translation: CAC33084.1.
AY753302 mRNA. Translation: AAV30552.1.
AB018269 mRNA. Translation: BAA34446.2. Different initiation.
AC018653 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88677.1.
CH471116 Genomic DNA. Translation: EAW88678.1.
CH471116 Genomic DNA. Translation: EAW88679.1.
BC104767 mRNA. Translation: AAI04768.1.
BC111491 mRNA. Translation: AAI11492.1.
BC112283 mRNA. Translation: AAI12284.1.
CCDSiCCDS8575.1. [Q9BQT9-1]
RefSeqiNP_055533.2. NM_014718.3. [Q9BQT9-1]
XP_006719226.1. XM_006719163.2. [Q9BQT9-2]
UniGeneiHs.535378.

Genome annotation databases

EnsembliENST00000266546; ENSP00000266546; ENSG00000139182. [Q9BQT9-1]
ENST00000537408; ENSP00000440679; ENSG00000139182. [Q9BQT9-2]
GeneIDi9746.
KEGGihsa:9746.
UCSCiuc001qsr.4. human. [Q9BQT9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ277460 mRNA. Translation: CAC33084.1.
AY753302 mRNA. Translation: AAV30552.1.
AB018269 mRNA. Translation: BAA34446.2. Different initiation.
AC018653 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88677.1.
CH471116 Genomic DNA. Translation: EAW88678.1.
CH471116 Genomic DNA. Translation: EAW88679.1.
BC104767 mRNA. Translation: AAI04768.1.
BC111491 mRNA. Translation: AAI11492.1.
BC112283 mRNA. Translation: AAI12284.1.
CCDSiCCDS8575.1. [Q9BQT9-1]
RefSeqiNP_055533.2. NM_014718.3. [Q9BQT9-1]
XP_006719226.1. XM_006719163.2. [Q9BQT9-2]
UniGeneiHs.535378.

3D structure databases

ProteinModelPortaliQ9BQT9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115094. 4 interactions.
IntActiQ9BQT9. 1 interaction.
STRINGi9606.ENSP00000266546.

PTM databases

iPTMnetiQ9BQT9.
PhosphoSiteiQ9BQT9.

Polymorphism and mutation databases

BioMutaiCLSTN3.
DMDMi23396507.

Proteomic databases

EPDiQ9BQT9.
MaxQBiQ9BQT9.
PaxDbiQ9BQT9.
PRIDEiQ9BQT9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266546; ENSP00000266546; ENSG00000139182. [Q9BQT9-1]
ENST00000537408; ENSP00000440679; ENSG00000139182. [Q9BQT9-2]
GeneIDi9746.
KEGGihsa:9746.
UCSCiuc001qsr.4. human. [Q9BQT9-1]

Organism-specific databases

CTDi9746.
GeneCardsiCLSTN3.
HGNCiHGNC:18371. CLSTN3.
HPAiHPA046913.
MIMi611324. gene.
neXtProtiNX_Q9BQT9.
PharmGKBiPA38320.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1834. Eukaryota.
ENOG410XT2J. LUCA.
GeneTreeiENSGT00390000010858.
HOGENOMiHOG000037537.
HOVERGENiHBG051146.
InParanoidiQ9BQT9.
OMAiETFNHAL.
OrthoDBiEOG7SFHVX.
PhylomeDBiQ9BQT9.
TreeFamiTF315946.

Miscellaneous databases

ChiTaRSiCLSTN3. human.
GenomeRNAii9746.
PROiQ9BQT9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BQT9.
CleanExiHS_CLSTN3.
ExpressionAtlasiQ9BQT9. baseline and differential.
GenevisibleiQ9BQT9. HS.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
2.60.40.60. 2 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR026914. Calsyntenin.
IPR013320. ConA-like_dom.
[Graphical view]
PANTHERiPTHR14139. PTHR14139. 2 hits.
PfamiPF00028. Cadherin. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 2 hits.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 2 hits.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50268. CADHERIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The calsyntenins - a family of postsynaptic membrane proteins with distinct neuronal expression patterns."
    Hintsch G., Zurlinden A., Meskenaite V., Steuble M., Fink-Widmer K., Kinter J., Sonderegger P.
    Mol. Cell. Neurosci. 21:393-409(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation."
    Araki Y., Miyagi N., Kato N., Yoshida T., Wada S., Nishimura M., Komano H., Yamamoto T., De Strooper B., Yamamoto K., Suzuki T.
    J. Biol. Chem. 279:24343-24354(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING.
  3. "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  4. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Blood and Brain.
  7. "Novel cadherin-related membrane proteins, Alcadeins, enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism."
    Araki Y., Tomita S., Yamaguchi H., Miyagi N., Sumioka A., Kirino Y., Suzuki T.
    J. Biol. Chem. 278:49448-49458(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INTERACTION WITH APBA2.
  8. Cited for: VARIANT [LARGE SCALE ANALYSIS] TYR-874.

Entry informationi

Entry nameiCSTN3_HUMAN
AccessioniPrimary (citable) accession number: Q9BQT9
Secondary accession number(s): D3DUT6
, O94831, Q2T9J5, Q5UE57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: June 1, 2001
Last modified: June 8, 2016
This is version 133 of the entry and version 1 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.