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Protein

Cerebellin-1

Gene

Cbln1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the matching and maintenance of pre- and post-synaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses (PubMed:16234806). Plays a role as a synaptic organizer that acts bidirectionally on both pre- and post-synaptic components (PubMed:20395510). On the one hand induces accumulation of synaptic vesicles in the pre-synaptic part by binding with NRXN1 and in other hand induces clustering of GRID2 and its associated proteins at the post-synaptic site through association of GRID2 (PubMed:21410790). NRXN1-CBLN1-GRID2 complex directly induces parallel fiber protrusions that encapsulate spines of Purkinje cells leading to accumulation of GRID2 and synaptic vesicles (PubMed:23141067). Required for CBLN3 export from the endoplasmic reticulum and secretion (PubMed:17030622, PubMed:17331201). NRXN1-CBLN1-GRID2 complex mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (By similarity).By similarity6 Publications
The cerebellin peptide exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release (By similarity).By similarity

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

GO - Biological processi

  • cerebellar granule cell differentiation Source: BHF-UCL
  • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: BHF-UCL
  • negative regulation of excitatory postsynaptic potential Source: MGI
  • positive regulation of long term synaptic depression Source: MGI
  • positive regulation of synapse assembly Source: MGI
  • protein secretion Source: MGI

Names & Taxonomyi

Protein namesi
Recommended name:
Cerebellin-1
Alternative name(s):
Brain protein D3
Precerebellin
Cleaved into the following 2 chains:
Cerebellin
Short name:
CER
[des-Ser1]-cerebellin
Short name:
des-Ser1-cerebellin
Gene namesi
Name:Cbln1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:88281. Cbln1.

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

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Secreted, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice (reeler, weaver and staggerer) show defects in granule cell migration and parallel fiber formation, synaptogenesis, Purkinje cell dendritic maturation and establishment of adult cytoarchitecture show a correlation between the formation and number of parallel fiber-Purkinje cell synapses and cerebellin levels.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23N → Q: Loss of N-glycosylation; when associated with Q-79. 1 Publication1
Mutagenesisi34C → A: Abolishes homohexamer formation from homotrimers; when associated with A-38. 1 Publication1
Mutagenesisi38C → A: Abolishes homohexamer formation from homotrimers; when associated with A-34. 1 Publication1
Mutagenesisi79N → Q: Loss of N-glycosylation; when associated with Q-23. 1 Publication1
Mutagenesisi110G → E: Retention in the endoplasmic reticulum/cis-Golgi; when associated with H-112. 1 Publication1
Mutagenesisi112Y → H: Retention in the endoplasmic reticulum/cis-Golgi; when associated with E-110. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000027421122 – 193Cerebellin-1Add BLAST172
PeptideiPRO_000000354957 – 72CerebellinAdd BLAST16
PeptideiPRO_000027421258 – 72[des-Ser1]-cerebellinAdd BLAST15

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi34Interchain
Disulfide bondi38Interchain
Glycosylationi79N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

The proteolytic processing to yield cerebellin seems to occur either prior to the secretion by presynaptic neurons and subsequent oligomerization or in some other location after release of the mature protein. In the cerebellum, cerebellin is much more abundant than [des-Ser1]-cerebellin.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9R171.
PaxDbiQ9R171.
PRIDEiQ9R171.

PTM databases

iPTMnetiQ9R171.
PhosphoSitePlusiQ9R171.

Expressioni

Tissue specificityi

Expressed and secreted by presynaptic neurons, such as cerebellar granule cells. Following secretion, the protein binds to GRID2 on the postsynaptic Purkinje cell membranes. Expressed at the highest level in the cerebellar cortex. High levels are also seen in the olfactory bulb, posterior part of the cerebral cortex, certain thalamic nuclei, and deep cerebellar nuclei. Low to moderate levels are detected in some hypothalamic and brainstem nuclei. In the thalamus, expressed in parafascicular nucleus neurons and other regions (at protein level).6 Publications

Developmental stagei

In the developing brain, expressed as early as embryonic day 10-13, and transiently up-regulated during the late embryonic and neonatal periods. Cerebellin and [des-Ser1]-cerebellin are expressed as easly as postnatal day 3-4. The levels of both peptides rise rapidly to a maximum at approximately day 25-30 after birth, whereafter they fall to stable adult values.2 Publications

Gene expression databases

BgeeiENSMUSG00000031654.
CleanExiMM_CBLN1.
ExpressionAtlasiQ9R171. baseline and differential.
GenevisibleiQ9R171. MM.

Interactioni

Subunit structurei

Homohexamer; disulfide-linked homotrimers. The trimers are assembled via the globular C1q domains. The trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (PubMed:16135095). May form oligomers with CBLN2, CBLN3 AND CBLN4 prior to secretion. Once secreted, does not interact with other CBLN family members (PubMed:17030622, PubMed:17331201, PubMed:10964938). Interacts with GRID1 (PubMed:20395510, PubMed:22220752). Interacts with NRXN1 and NRXN2 long (alpha) and short (beta) isoforms produced by alternative promoter usage. Competes with NLGN1 for NRXN1-binding. Weakly interacts with NRXN3 short isoform and not at all with NRXN3 long isoform (PubMed:21410790, PubMed:22220752). Interacts (via C1q domain) with GRID2; GRID2-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:20395510, PubMed:22220752).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

IntActiQ9R171. 3 interactors.
STRINGi10090.ENSMUSP00000034076.

Structurei

3D structure databases

ProteinModelPortaliQ9R171.
SMRiQ9R171.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 193C1qPROSITE-ProRule annotationAdd BLAST137

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni34 – 38Essential for interaction with NRXN1 and linker of two C1q trimers into disulfide-linked hexamersBy similarity5
Regioni62 – 193Necessary for interaction with CBLN3, and homotrimerizationAdd BLAST132
Regioni122 – 147Essentiel for interaction with GRID2By similarityAdd BLAST26

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFXA. Eukaryota.
ENOG410Y16R. LUCA.
GeneTreeiENSGT00760000119052.
HOGENOMiHOG000085657.
HOVERGENiHBG108329.
InParanoidiQ9R171.
OMAiMVIYFDR.
OrthoDBiEOG091G0XK2.
PhylomeDBiQ9R171.
TreeFamiTF329591.

Family and domain databases

Gene3Di2.60.120.40. 1 hit.
InterProiView protein in InterPro
IPR001073. C1q_dom.
IPR008983. Tumour_necrosis_fac-like_dom.
PfamiView protein in Pfam
PF00386. C1q. 1 hit.
PRINTSiPR00007. COMPLEMNTC1Q.
SMARTiView protein in SMART
SM00110. C1Q. 1 hit.
SUPFAMiSSF49842. SSF49842. 1 hit.
PROSITEiView protein in PROSITE
PS50871. C1Q. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q9R171-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGVVELLLL GTAWLAGPAR GQNETEPIVL EGKCLVVCDS NPTSDPTGTA
60 70 80 90 100
LGISVRSGSA KVAFSAIRST NHEPSEMSNR TMIIYFDQVL VNIGNNFDSE
110 120 130 140 150
RSTFIAPRKG IYSFNFHVVK VYNRQTIQVS LMLNGWPVIS AFAGDQDVTR
160 170 180 190
EAASNGVLIQ MEKGDRAYLK LERGNLMGGW KYSTFSGFLV FPL
Length:193
Mass (Da):21,113
Last modified:May 1, 2000 - v1
Checksum:iA23C796C7D11BE5F
GO

Sequence cautioni

The sequence CAA43688 differs from that shown. Reason: Erroneous translation. Wrong choice of frame.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti5V → L no nucleotide entry (PubMed:7877445).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF164680 Genomic DNA. Translation: AAD47280.1.
X61448 mRNA. Translation: CAA43688.1. Sequence problems.
CCDSiCCDS22506.1.
PIRiS16862.
RefSeqiNP_062600.2. NM_019626.3.
UniGeneiMm.4880.

Genome annotation databases

EnsembliENSMUST00000034076; ENSMUSP00000034076; ENSMUSG00000031654.
ENSMUST00000169693; ENSMUSP00000126575; ENSMUSG00000031654.
GeneIDi12404.
KEGGimmu:12404.
UCSCiuc009mqr.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiCBLN1_MOUSE
AccessioniPrimary (citable) accession number: Q9R171
Secondary accession number(s): P28655, Q9QVT5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: October 25, 2017
This is version 136 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot