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Protein

Cerebellin-1

Gene

CBLN1

Organism
Homo sapiens (Human)
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. Plays a role as a synaptic organizer that acts bidirectionally on both pre- and post-synaptic components. 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. NRXN1-CBLN1-GRID2 complex directly induces parallel fiber protrusions that encapsulate spines of Purkinje cells leading to accumulation of GRID2 and synaptic vesicles. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity). NRXN1-CBLN1-GRID2 complex mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:27418511).By similarity1 Publication
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

GO - Biological processi

  • cerebellar granule cell differentiation Source: BHF-UCL
  • chemical synaptic transmission Source: ProtInc
  • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules Source: BHF-UCL
  • negative regulation of excitatory postsynaptic potential Source: UniProtKB
  • nervous system development Source: ProtInc
  • positive regulation of long term synaptic depression Source: UniProtKB
  • positive regulation of synapse assembly Source: Ensembl
  • protein secretion Source: Ensembl

Names & Taxonomyi

Protein namesi
Recommended name:
Cerebellin-1
Alternative name(s):
Precerebellin
Cleaved into the following 2 chains:
Gene namesi
Name:CBLN1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102924.11.
HGNCiHGNC:1543. 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi34C → S: Abolishes hexamer formation; when associated with S-38. Abolishes interaction with NRXN1; when associated with S-38. Abolishes GRID2 interaction; when associated with S-38. 1 Publication1
Mutagenesisi38C → S: Abolishes hexamer formation; when associated with S-34. Abolishes interaction with NRXN1 isoform 3B; when associated with S-34. Abolishes GRID2 interaction.; when associated with S-34. 1 Publication1
Mutagenesisi122Y → A: Abolishes GRID2 interaction.; when associated with A-124 and A-147. 1 Publication1
Mutagenesisi124R → A: Abolishes GRID2 interaction.; when associated with A-122 and A-147. 1 Publication1
Mutagenesisi147D → A: Abolishes GRID2 interaction.; when associated with A-122 and A-124. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000102924.
PharmGKBiPA26118.

Polymorphism and mutation databases

BioMutaiCBLN1.
DMDMi116114.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000027420922 – 193Cerebellin-1Add BLAST172
PeptideiPRO_000000354657 – 72CerebellinAdd BLAST16
PeptideiPRO_000027421058 – 72[des-Ser1]-cerebellinAdd BLAST15

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi34InterchainBy similarity
Disulfide bondi38InterchainBy similarity
Glycosylationi41N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi79N-linked (GlcNAc...) asparagineCombined sources1 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.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP23435.
PaxDbiP23435.
PeptideAtlasiP23435.
PRIDEiP23435.

PTM databases

iPTMnetiP23435.
PhosphoSitePlusiP23435.

Expressioni

Tissue specificityi

In the Purkinje cells postsynaptic structures. In the cerebellum, cerebellin is much less abundant than [des-Ser1]-cerebellin.

Developmental stagei

Low at birth, the cerebellin concentration increases between day 5 and 15, and reaches peak values between day 21 and 56.

Gene expression databases

BgeeiENSG00000102924.
CleanExiHS_CBLN1.
ExpressionAtlasiP23435. baseline and differential.
GenevisibleiP23435. HS.

Organism-specific databases

HPAiHPA056335.

Interactioni

Subunit structurei

Homohexamer; disulfide-linked homotrimers. The trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (PubMed:27418511). May form oligomers with CBLN2, CBLN3 AND CBLN4 prior to secretion. Once secreted, does not interact with other CBLN family members. Interacts with GRID1 (By similarity). 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 (By similarity) (PubMed:27418511). 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:27418511).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9606.ENSP00000219197.

Structurei

Secondary structure

1193
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi63 – 67Combined sources5
Helixi78 – 81Combined sources4
Beta strandi87 – 93Combined sources7
Turni99 – 102Combined sources4
Beta strandi103 – 105Combined sources3
Beta strandi107 – 120Combined sources14
Beta strandi127 – 133Combined sources7
Beta strandi136 – 143Combined sources8
Beta strandi147 – 149Combined sources3
Beta strandi151 – 161Combined sources11
Beta strandi166 – 174Combined sources9
Beta strandi184 – 192Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KC5X-ray2.35A58-193[»]
5KC6X-ray2.80A/B/C24-193[»]
5KC7X-ray7.04A/B/C/D24-193[»]
5KCAX-ray3.10A57-193[»]
ProteinModelPortaliP23435.
SMRiP23435.
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 hexamers1 Publication5
Regioni62 – 193Necessary for interaction with CBLN3, and homotrimerizationBy similarityAdd BLAST132
Regioni122 – 147Essentiel for interaction with GRID21 PublicationAdd BLAST26

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFXA. Eukaryota.
ENOG410Y16R. LUCA.
GeneTreeiENSGT00760000119052.
HOGENOMiHOG000085657.
HOVERGENiHBG108329.
InParanoidiP23435.
OMAiMVIYFDR.
OrthoDBiEOG091G0XK2.
PhylomeDBiP23435.
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.

P23435-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGVLELLLL GAAWLAGPAR 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):21,097
Last modified:November 1, 1991 - v1
Checksum:iD542FC7987E401A5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M58583 mRNA. Translation: AAA35676.1.
AK314276 mRNA. Translation: BAG36936.1.
CH471092 Genomic DNA. Translation: EAW82731.1.
BC093692 mRNA. Translation: AAH93692.1.
BC093718 mRNA. Translation: AAH93718.1.
CCDSiCCDS10736.1.
PIRiA37873.
PL0124.
RefSeqiNP_004343.1. NM_004352.3.
UniGeneiHs.458423.

Genome annotation databases

EnsembliENST00000219197; ENSP00000219197; ENSG00000102924.
ENST00000536749; ENSP00000444651; ENSG00000102924.
GeneIDi869.
KEGGihsa:869.
UCSCiuc002efq.4. human.

Similar proteinsi

Entry informationi

Entry nameiCBLN1_HUMAN
AccessioniPrimary (citable) accession number: P23435
Secondary accession number(s): B2RAN9, P02682, Q52M09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: September 27, 2017
This is version 141 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

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

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references