CBLN1_RAT
ID CBLN1_RAT Reviewed; 193 AA.
AC P63182; P02682; P23436;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 114.
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 AltName: Full=des-Ser(1)-cerebellin;
DE Short=[des-Ser1]CER;
DE Short=des-CER;
DE Short=des-Ser1CER;
DE Flags: Precursor;
GN Name=Cbln1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP PROTEIN SEQUENCE OF 57-72 (CEREBELLIN AND [DES-SER1]-CEREBELLIN).
RX PubMed=16593526; DOI=10.1073/pnas.81.21.6866;
RA Slemmon J.R., Blacher R., Danho W., Hempstead J.L., Morgan J.I.;
RT "Isolation and sequencing of two cerebellum-specific peptides.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:6866-6870(1984).
RN [3]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION (CEREBELLIN).
RX PubMed=3399060; DOI=10.1016/0306-4522(88)90262-x;
RA Burnet P.W., Bretherton-Watt D., Ghatei M.A., Bloom S.R.;
RT "Cerebellin-like peptide: tissue distribution in rat and guinea-pig and its
RT release from rat cerebellum, hypothalamus and cerebellar synaptosomes in
RT vitro.";
RL Neuroscience 25:605-612(1988).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=3420533; DOI=10.1002/syn.890020203;
RA Morgan J.I., Slemmon J.R., Danho W., Hempstead J., Berrebi A.S.,
RA Mugnaini E.;
RT "Cerebellin and related postsynaptic peptides in the brain of normal and
RT neurodevelopmentally mutant vertebrates.";
RL Synapse 2:117-124(1988).
RN [5]
RP FUNCTION (CEREBELLIN).
RX PubMed=10688962; DOI=10.1054/npep.1999.0779;
RA Albertin G., Malendowicz L.K., Macchi C., Markowska A., Nussdorfer G.G.;
RT "Cerebellin stimulates the secretory activity of the rat adrenal gland: in
RT vitro and in vivo studies.";
RL Neuropeptides 34:7-11(2000).
RN [6]
RP FUNCTION ([DES-SER1]-CEREBELLIN), AND TISSUE SPECIFICITY.
RX PubMed=15702230;
RA Rucinski M., Albertin G., Spinazzi R., Ziolkowska A., Nussdorfer G.G.,
RA Malendowicz L.K.;
RT "Cerebellin in the rat adrenal gland: gene expression and effects of CER
RT and [des-Ser1]CER on the secretion and growth of cultured adrenocortical
RT cells.";
RL Int. J. Mol. Med. 15:411-415(2005).
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 (By similarity). 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:P23435,
CC ECO:0000250|UniProtKB:Q9R171}.
CC -!- FUNCTION: The cerebellin exerts neuromodulatory functions. Directly
CC stimulates norepinephrine release via the adenylate cyclase/PKA-
CC dependent signaling pathway; and indirectly enhances adrenocortical
CC secretion in vivo, through a paracrine mechanism involving medullary
CC catecholamine release. A conversion to [des-Ser1]-cerebellin by
CC endopeptidases seems to be required for its autocrine-paracrine
CC regulatory functions. {ECO:0000269|PubMed:10688962,
CC ECO:0000269|PubMed:15702230}.
CC -!- SUBUNIT: Homohexamer; disulfide-linked homotrimers. The trimers are
CC assembled via the globular C1q domains. The trimers associate via N-
CC terminal cysteine residues to form disulfide-linked hexamers. May form
CC oligomers with CBLN2, CBLN3 AND CBLN4 prior to secretion. Once
CC secreted, does not interact with other CBLN family members. Interacts
CC with GRID1. Interacts with NRXN1 and NRXN2 long (alpha) and short
CC (beta) isoforms produced by alternative promoter usage. Competes with
CC NLGN1 for NRXN1-binding. Weakly interacts with NRXN3 short isoform and
CC not at all with NRXN3 long isoform (By similarity). Interacts (via C1q
CC domain) with GRID2; GRID2-binding is calcium-independent; CBLN1
CC hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1
CC isoform beta; promotes synaptogenesis and mediates the D-Serine-
CC dependent long term depression signals and AMPA receptor endocytosis
CC (By similarity). Interacts with OTOL1 (By similarity).
CC {ECO:0000250|UniProtKB:P23435, ECO:0000250|UniProtKB:Q9R171}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:3399060}.
CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q9R171}.
CC -!- TISSUE SPECIFICITY: Localized in the Purkinje cells. Cerebellin is
CC expressed in adrenal gland /adrenal cortex (at protein level). In the
CC cerebellum, [des-Ser1]-cerebellin is more abundant than cerebellin. At
CC lower levels also found in heart, kidney stomach and gastrointestinal
CC tract. {ECO:0000269|PubMed:15702230, ECO:0000269|PubMed:3399060,
CC ECO:0000269|PubMed:3420533}.
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}.
CC -!- CAUTION: Initially the cerebellin peptide was thought to present the
CC biological active entity. {ECO:0000305}.
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DR EMBL; AABR03113474; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A03135; CQRT.
DR RefSeq; NP_001102597.1; NM_001109127.1.
DR PDB; 5H48; X-ray; 2.20 A; A=22-193.
DR PDB; 5H49; X-ray; 2.80 A; A/B/C=22-193.
DR PDB; 5KWR; X-ray; 1.79 A; A=57-193.
DR PDBsum; 5H48; -.
DR PDBsum; 5H49; -.
DR PDBsum; 5KWR; -.
DR AlphaFoldDB; P63182; -.
DR SMR; P63182; -.
DR BioGRID; 270231; 1.
DR STRING; 10116.ENSRNOP00000000011; -.
DR GlyGen; P63182; 2 sites.
DR PaxDb; P63182; -.
DR PRIDE; P63182; -.
DR Ensembl; ENSRNOT00000000011; ENSRNOP00000000011; ENSRNOG00000000010.
DR GeneID; 498922; -.
DR KEGG; rno:498922; -.
DR CTD; 869; -.
DR RGD; 1562813; Cbln1.
DR eggNOG; ENOG502QVN9; Eukaryota.
DR GeneTree; ENSGT00940000159811; -.
DR HOGENOM; CLU_001074_8_2_1; -.
DR InParanoid; P63182; -.
DR OMA; NRTMLIY; -.
DR OrthoDB; 1398761at2759; -.
DR PhylomeDB; P63182; -.
DR TreeFam; TF329591; -.
DR PRO; PR:P63182; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000000010; Expressed in cerebellum and 7 other tissues.
DR Genevisible; P63182; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; ISO:RGD.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0043083; C:synaptic cleft; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; ISS:BHF-UCL.
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; ISO:RGD.
DR GO; GO:1905703; P:negative regulation of inhibitory synapse assembly; ISS:UniProtKB.
DR GO; GO:1900454; P:positive regulation of long-term synaptic depression; ISO:RGD.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:RGD.
DR GO; GO:0009306; P:protein secretion; ISO:RGD.
DR GO; GO:0099151; P:regulation of postsynaptic density assembly; ISO:RGD.
DR GO; GO:1905606; P:regulation of presynapse assembly; ISO:RGD.
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_0000274215"
FT PEPTIDE 57..72
FT /note="Cerebellin"
FT /id="PRO_0000043588"
FT PEPTIDE 58..72
FT /note="[des-Ser1]-cerebellin"
FT /id="PRO_0000274216"
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:0000250|UniProtKB:P23435"
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:0000250|UniProtKB:P23435"
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:0000255"
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 HELIX 58..60
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:5KWR"
FT HELIX 76..81
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:5KWR"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 107..120
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 151..161
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:5KWR"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:5KWR"
SQ SEQUENCE 193 AA; 21083 MW; 5E451C6C681E0E50 CRC64;
MLGVVELLLL GAAWLAGPAR GQNETEPIVL EGKCLVVCDS NPTSDPTGTA LGISVRSGSA
KVAFSAIRST NHEPSEMSNR TMIIYFDQVL VNIGNNFDSE RSTFIAPRKG IYSFNFHVVK
VYNRQTIQVS LMLNGWPVIS AFAGDQDVTR EAASNGVLIQ MEKGDRAYLK LERGNLMGGW
KYSTFSGFLV FPL
