CBLN1_HUMAN
ID CBLN1_HUMAN Reviewed; 193 AA.
AC P23435; B2RAN9; P02682; Q52M09;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cerebellin-1;
DE AltName: Full=Precerebellin;
DE Contains:
DE RecName: Full=Cerebellin;
DE Short=CER;
DE Contains:
DE RecName: Full=[des-Ser1]-cerebellin;
DE Flags: Precursor;
GN Name=CBLN1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1704129; DOI=10.1073/pnas.88.3.1069;
RA Urade Y., Oberdick J., Molinar-Rode R., Morgan J.I.;
RT "Precerebellin is a cerebellum-specific protein with similarity to the
RT globular domain of complement C1q B chain.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1069-1073(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 57-72 (CEREBELLIN AND [DES-SER1]-CEREBELLIN).
RC TISSUE=Cerebellum;
RX PubMed=2760624; DOI=10.1111/j.1471-4159.1989.tb11787.x;
RA Yiangou Y., Burnet P., Nikou G., Chrysanthou B.J., Bloom S.R.;
RT "Purification and characterisation of cerebellins from human and porcine
RT cerebellum.";
RL J. Neurochem. 53:886-889(1989).
RN [6] {ECO:0007744|PDB:5KC5, ECO:0007744|PDB:5KC6, ECO:0007744|PDB:5KC7, ECO:0007744|PDB:5KCA}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 58-193, GLYCOSYLATION AT ASN-79,
RP MUTAGENESIS OF CYS-34; CYS-38; TYR-122; ARG-124 AND ASP-147, SUBUNIT,
RP INTERACTION WITH NRXN1 AND GRID2, FUNCTION, AND REGION.
RX PubMed=27418511; DOI=10.1126/science.aae0104;
RA Elegheert J., Kakegawa W., Clay J.E., Shanks N.F., Behiels E., Matsuda K.,
RA Kohda K., Miura E., Rossmann M., Mitakidis N., Motohashi J., Chang V.T.,
RA Siebold C., Greger I.H., Nakagawa T., Yuzaki M., Aricescu A.R.;
RT "Structural basis for integration of GluD receptors within synaptic
RT organizer complexes.";
RL Science 353:295-299(2016).
CC -!- FUNCTION: Required for synapse integrity and synaptic plasticity.
CC During cerebellar synapse formation, essential for the matching and
CC maintenance of pre- and post-synaptic elements at parallel fiber-
CC Purkinje cell synapses, the establishment of the proper pattern of
CC climbing fiber-Purkinje cell innervation, and induction of long-term
CC depression at parallel fiber-Purkinje cell synapses. Plays a role as a
CC synaptic organizer that acts bidirectionally on both pre- and post-
CC synaptic components. On the one hand induces accumulation of synaptic
CC vesicles in the pre-synaptic part by binding with NRXN1 and in other
CC hand induces clustering of GRID2 and its associated proteins at the
CC post-synaptic site through association of GRID2. NRXN1-CBLN1-GRID2
CC complex directly induces parallel fiber protrusions that encapsulate
CC spines of Purkinje cells leading to accumulation of GRID2 and synaptic
CC vesicles. Required for CBLN3 export from the endoplasmic reticulum and
CC secretion (By similarity). NRXN1-CBLN1-GRID2 complex mediates the D-
CC Serine-dependent long term depression signals and AMPA receptor
CC endocytosis (PubMed:27418511). Essential for long-term maintenance but
CC not establishment of excitatory synapses (By similarity). Inhibits the
CC formation and function of inhibitory GABAergic synapses in cerebellar
CC Purkinje cells (By similarity). {ECO:0000250|UniProtKB:Q9R171,
CC ECO:0000269|PubMed:27418511}.
CC -!- FUNCTION: The cerebellin peptide exerts neuromodulatory functions.
CC Directly stimulates norepinephrine release via the adenylate
CC cyclase/PKA-dependent signaling pathway; and indirectly enhances
CC adrenocortical secretion in vivo, through a paracrine mechanism
CC involving medullary catecholamine release (By similarity).
CC {ECO:0000250|UniProtKB:P63182}.
CC -!- SUBUNIT: Homohexamer; disulfide-linked homotrimers. The trimers
CC associate via N-terminal cysteine residues to form disulfide-linked
CC hexamers (PubMed:27418511). May form oligomers with CBLN2, CBLN3 AND
CC CBLN4 prior to secretion. Once secreted, does not interact with other
CC CBLN family members. Interacts with GRID1 (By similarity). Interacts
CC with NRXN1 and NRXN2 long (alpha) and short (beta) isoforms produced by
CC alternative promoter usage. Competes with NLGN1 for NRXN1-binding.
CC Weakly interacts with NRXN3 short isoform and not at all with NRXN3
CC long isoform (PubMed:27418511). Interacts (via C1q domain) with GRID2;
CC GRID2-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-
CC terminal domain dimers to monomeric NRXN1 isoform beta; promotes
CC synaptogenesis and mediates the D-Serine-dependent long term depression
CC signals and AMPA receptor endocytosis (PubMed:27418511). Interacts with
CC OTOL1 (By similarity). {ECO:0000250|UniProtKB:Q9R171,
CC ECO:0000269|PubMed:27418511}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9R171}.
CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q9R171}.
CC -!- TISSUE SPECIFICITY: In the Purkinje cells postsynaptic structures. In
CC the cerebellum, cerebellin is much less abundant than [des-Ser1]-
CC cerebellin.
CC -!- DEVELOPMENTAL STAGE: Low at birth, the cerebellin concentration
CC increases between day 5 and 15, and reaches peak values between day 21
CC and 56.
CC -!- PTM: The proteolytic processing to yield cerebellin seems to occur
CC either prior to the secretion by presynaptic neurons and subsequent
CC oligomerization or in some other location after release of the mature
CC protein. {ECO:0000250|UniProtKB:Q9R171}.
CC -!- PTM: Sialoglycoprotein. {ECO:0000250|UniProtKB:Q9R171}.
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DR EMBL; M58583; AAA35676.1; -; mRNA.
DR EMBL; AK314276; BAG36936.1; -; mRNA.
DR EMBL; CH471092; EAW82731.1; -; Genomic_DNA.
DR EMBL; BC093692; AAH93692.1; -; mRNA.
DR EMBL; BC093718; AAH93718.1; -; mRNA.
DR CCDS; CCDS10736.1; -.
DR PIR; A37873; A37873.
DR PIR; PL0124; PL0124.
DR RefSeq; NP_004343.1; NM_004352.3.
DR PDB; 5KC5; X-ray; 2.35 A; A=58-193.
DR PDB; 5KC6; X-ray; 2.80 A; A/B/C=24-193.
DR PDB; 5KC7; X-ray; 7.04 A; A/B/C/D=24-193.
DR PDB; 5KCA; X-ray; 3.10 A; A=57-193.
DR PDBsum; 5KC5; -.
DR PDBsum; 5KC6; -.
DR PDBsum; 5KC7; -.
DR PDBsum; 5KCA; -.
DR AlphaFoldDB; P23435; -.
DR SMR; P23435; -.
DR STRING; 9606.ENSP00000219197; -.
DR GlyConnect; 2026; 1 N-Linked glycan (1 site).
DR GlyGen; P23435; 4 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P23435; -.
DR PhosphoSitePlus; P23435; -.
DR BioMuta; CBLN1; -.
DR DMDM; 116114; -.
DR MassIVE; P23435; -.
DR PaxDb; P23435; -.
DR PeptideAtlas; P23435; -.
DR PRIDE; P23435; -.
DR ProteomicsDB; 54094; -.
DR Antibodypedia; 14491; 220 antibodies from 32 providers.
DR DNASU; 869; -.
DR Ensembl; ENST00000219197.11; ENSP00000219197.5; ENSG00000102924.12.
DR Ensembl; ENST00000536749.1; ENSP00000444651.1; ENSG00000102924.12.
DR GeneID; 869; -.
DR KEGG; hsa:869; -.
DR MANE-Select; ENST00000219197.11; ENSP00000219197.5; NM_004352.4; NP_004343.1.
DR UCSC; uc002efq.4; human.
DR CTD; 869; -.
DR DisGeNET; 869; -.
DR GeneCards; CBLN1; -.
DR HGNC; HGNC:1543; CBLN1.
DR HPA; ENSG00000102924; Group enriched (brain, testis).
DR MIM; 600432; gene.
DR neXtProt; NX_P23435; -.
DR OpenTargets; ENSG00000102924; -.
DR PharmGKB; PA26118; -.
DR VEuPathDB; HostDB:ENSG00000102924; -.
DR eggNOG; ENOG502QVN9; Eukaryota.
DR GeneTree; ENSGT00940000159811; -.
DR HOGENOM; CLU_001074_8_2_1; -.
DR InParanoid; P23435; -.
DR OMA; NRTMLIY; -.
DR OrthoDB; 1398761at2759; -.
DR PhylomeDB; P23435; -.
DR TreeFam; TF329591; -.
DR PathwayCommons; P23435; -.
DR BioGRID-ORCS; 869; 71 hits in 1060 CRISPR screens.
DR GenomeRNAi; 869; -.
DR Pharos; P23435; Tbio.
DR PRO; PR:P23435; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P23435; protein.
DR Bgee; ENSG00000102924; Expressed in cerebellar cortex and 102 other tissues.
DR ExpressionAtlas; P23435; baseline and differential.
DR Genevisible; P23435; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IBA:GO_Central.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0043083; C:synaptic cleft; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; ISS:BHF-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; ISS:BHF-UCL.
DR GO; GO:0099558; P:maintenance of synapse structure; ISS:UniProtKB.
DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; IMP:UniProtKB.
DR GO; GO:1905703; P:negative regulation of inhibitory synapse assembly; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0009306; P:protein secretion; IEA:Ensembl.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; IEA:Ensembl.
DR GO; GO:1905606; P:regulation of presynapse assembly; IEA:Ensembl.
DR GO; GO:0007416; P:synapse assembly; IEA:Ensembl.
DR GO; GO:0050808; P:synapse organization; ISS:UniProtKB.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 1.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Membrane; Postsynaptic cell membrane; Reference proteome;
KW Secreted; Sialic acid; Signal; Synapse.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..193
FT /note="Cerebellin-1"
FT /id="PRO_0000274209"
FT PEPTIDE 57..72
FT /note="Cerebellin"
FT /id="PRO_0000003546"
FT PEPTIDE 58..72
FT /note="[des-Ser1]-cerebellin"
FT /id="PRO_0000274210"
FT DOMAIN 57..193
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 34..38
FT /note="Essential for interaction with NRXN1 and linker of
FT two C1q trimers into disulfide-linked hexamers"
FT /evidence="ECO:0000269|PubMed:27418511"
FT REGION 62..193
FT /note="Necessary for interaction with CBLN3, and
FT homotrimerization"
FT /evidence="ECO:0000250|UniProtKB:Q9R171"
FT REGION 122..147
FT /note="Essential for interaction with GRID2"
FT /evidence="ECO:0000269|PubMed:27418511"
FT CARBOHYD 23
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27418511,
FT ECO:0007744|PDB:5KC5, ECO:0007744|PDB:5KC6"
FT DISULFID 34
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9R171"
FT DISULFID 38
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9R171"
FT MUTAGEN 34
FT /note="C->S: Abolishes hexamer formation; when associated
FT with S-38. Abolishes interaction with NRXN1; when
FT associated with S-38. Abolishes GRID2 interaction; when
FT associated with S-38."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 38
FT /note="C->S: Abolishes hexamer formation; when associated
FT with S-34. Abolishes interaction with NRXN1 isoform 3B;
FT when associated with S-34. Abolishes GRID2 interaction.;
FT when associated with S-34."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 122
FT /note="Y->A: Abolishes GRID2 interaction.; when associated
FT with A-124 and A-147."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 124
FT /note="R->A: Abolishes GRID2 interaction.; when associated
FT with A-122 and A-147."
FT /evidence="ECO:0000269|PubMed:27418511"
FT MUTAGEN 147
FT /note="D->A: Abolishes GRID2 interaction.; when associated
FT with A-122 and A-124."
FT /evidence="ECO:0000269|PubMed:27418511"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:5KC5"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:5KC5"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 107..120
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 151..161
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:5KC5"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:5KC5"
SQ SEQUENCE 193 AA; 21097 MW; D542FC7987E401A5 CRC64;
MLGVLELLLL GAAWLAGPAR GQNETEPIVL EGKCLVVCDS NPTSDPTGTA LGISVRSGSA
KVAFSAIRST NHEPSEMSNR TMIIYFDQVL VNIGNNFDSE RSTFIAPRKG IYSFNFHVVK
VYNRQTIQVS LMLNGWPVIS AFAGDQDVTR EAASNGVLIQ MEKGDRAYLK LERGNLMGGW
KYSTFSGFLV FPL
