CBLN2_MOUSE
ID CBLN2_MOUSE Reviewed; 224 AA.
AC Q8BGU2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cerebellin-2;
DE Flags: Precursor;
GN Name=Cbln2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16930405; DOI=10.1111/j.1460-9568.2006.04950.x;
RA Miura E., Iijima T., Yuzaki M., Watanabe M.;
RT "Distinct expression of Cbln family mRNAs in developing and adult mouse
RT brains.";
RL Eur. J. Neurosci. 24:750-760(2006).
RN [4]
RP SELF-ASSOCIATION, SUBCELLULAR LOCATION, AND INTERACTION WITH CBLN1; CBLN3
RP AND CBLN4.
RX PubMed=17030622; DOI=10.1128/mcb.01161-06;
RA Bao D., Pang Z., Morgan M.A., Parris J., Rong Y., Li L., Morgan J.I.;
RT "Cbln1 is essential for interaction-dependent secretion of cbln3.";
RL Mol. Cell. Biol. 26:9327-9337(2006).
RN [5]
RP OLIGOMERIZATION WITH CBLN1; CBLN2; CBLN3 AND CBLN4, SUBCELLULAR LOCATION,
RP GLYCOSYLATION AT ASN-53 AND ASN-110, AND MUTAGENESIS OF ASN-53 AND ASN-110.
RX PubMed=17331201; DOI=10.1111/j.1460-9568.2007.05361.x;
RA Iijima T., Miura E., Matsuda K., Kamekawa Y., Watanabe M., Yuzaki M.;
RT "Characterization of a transneuronal cytokine family Cbln - regulation of
RT secretion by heteromeric assembly.";
RL Eur. J. Neurosci. 25:1049-1057(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH NRXN1.
RX PubMed=21410790; DOI=10.1111/j.1460-9568.2011.07638.x;
RA Matsuda K., Yuzaki M.;
RT "Cbln family proteins promote synapse formation by regulating distinct
RT neurexin signaling pathways in various brain regions.";
RL Eur. J. Neurosci. 33:1447-1461(2011).
RN [7]
RP INTERACTION WITH GRID1; GRID2; NRXN1; NRXN2 AND NRXN3.
RX PubMed=22220752; DOI=10.1111/j.1471-4159.2012.07648.x;
RA Wei P., Pattarini R., Rong Y., Guo H., Bansal P.K., Kusnoor S.V.,
RA Deutch A.Y., Parris J., Morgan J.I.;
RT "The Cbln family of proteins interact with multiple signaling pathways.";
RL J. Neurochem. 121:717-729(2012).
RN [8]
RP GLYCOSYLATION AT ASN-53 AND ASN-110, INTERACTION WITH NRXN1 AND NRXN3,
RP SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASN-53 AND ASN-110.
RX PubMed=29782851; DOI=10.1016/j.brainres.2018.05.022;
RA Rong Y., Bansal P.K., Wei P., Guo H., Correia K., Parris J., Morgan J.I.;
RT "Glycosylation of Cblns attenuates their receptor binding.";
RL Brain Res. 1694:129-139(2018).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=29691328; DOI=10.1523/jneurosci.0360-18.2018;
RA Seigneur E., Suedhof T.C.;
RT "Genetic Ablation of All Cerebellins Reveals Synapse Organizer Functions in
RT Multiple Regions Throughout the Brain.";
RL J. Neurosci. 38:4774-4790(2018).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=30287486; DOI=10.1073/pnas.1811086115;
RA Seigneur E., Polepalli J.S., Suedhof T.C.;
RT "Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular
RT projections and contribute to different behavioral outputs.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E10235-E10244(2018).
CC -!- FUNCTION: Acts as a synaptic organizer in specific subsets of neurons
CC in the brain (PubMed:29691328, PubMed:21410790). Essential for long-
CC term maintenance but not establishment of excitatory synapses
CC (PubMed:29691328 PubMed:30287486). {ECO:0000269|PubMed:21410790,
CC ECO:0000269|PubMed:29691328, ECO:0000269|PubMed:30287486}.
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 (By
CC similarity). May form homooligomers or heterooligomers with CBLN1 and
CC CBLN3 prior to secretion (PubMed:29782851). Once secreted, does not
CC interact with other CBLN family members. Interacts with GRID2, and more
CC weakly with GRID1. Interacts with NRXN1 and NRXN2 long and short
CC isoforms produced by alternative promoter usage (PubMed:21410790,
CC PubMed:22220752, PubMed:29782851). Weakly interacts with NRXN3 short
CC isoform and not at all with NRXN3 long isoform (PubMed:22220752,
CC PubMed:29782851). {ECO:0000250|UniProtKB:Q9R171,
CC ECO:0000269|PubMed:17030622, ECO:0000269|PubMed:21410790,
CC ECO:0000269|PubMed:22220752, ECO:0000269|PubMed:29782851}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17030622,
CC ECO:0000269|PubMed:17331201, ECO:0000269|PubMed:29782851}.
CC -!- TISSUE SPECIFICITY: Expressed in various brain regions with higher
CC levels in the olfactory bulb, cerebral cortex, certain thalamic and
CC hypothalamic nuclei, superior and inferior colliculi and some brainstem
CC nuclei. Highly expressed in the dorsal medial habenula.
CC {ECO:0000269|PubMed:16930405, ECO:0000269|PubMed:29691328,
CC ECO:0000269|PubMed:30287486}.
CC -!- DEVELOPMENTAL STAGE: In the developing brain, expressed as early as 10-
CC 13 dpc. Expression level peaks at 18 dpc and gradually decreases
CC afterwards. {ECO:0000269|PubMed:16930405}.
CC -!- DISRUPTION PHENOTYPE: Mice show impaired synaptic transmission within 3
CC weeks in interpeduncular target neurons whereas significant decrease in
CC both the synapse density and size seen only after 3 months
CC (PubMed:30287486). Display impaired passive avoidance learning, spatial
CC learning and short-term memory (PubMed:30287486). Double CBLN1 and
CC CBLN2 knockout mice exhibit gait abnormalities, impairments in balance
CC and coordination and develop seizures (PubMed:29691328). Synapse
CC density in the hippocampus is normal in 1-2 months old mice, but
CC severely decreased in 6 month old mice (PubMed:29691328). Triple CBLN1,
CC CBLN2 and CBLN4 knockout mice exhibit impairments in sensory processing
CC and sensorimotor gating, in addition to severe motor deficits, seizures
CC and reduced synapse density in the hippocampus of aging mice
CC (PubMed:29691328). {ECO:0000269|PubMed:29691328,
CC ECO:0000269|PubMed:30287486}.
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DR EMBL; AK032112; BAC27710.1; -; mRNA.
DR EMBL; AK042555; BAC31290.1; -; mRNA.
DR EMBL; BC055682; AAH55682.1; -; mRNA.
DR CCDS; CCDS29388.1; -.
DR RefSeq; NP_001289285.1; NM_001302356.1.
DR RefSeq; NP_766221.1; NM_172633.4.
DR RefSeq; XP_006526510.1; XM_006526447.3.
DR RefSeq; XP_006526512.1; XM_006526449.3.
DR RefSeq; XP_006526513.1; XM_006526450.3.
DR RefSeq; XP_017173295.1; XM_017317806.1.
DR AlphaFoldDB; Q8BGU2; -.
DR SMR; Q8BGU2; -.
DR STRING; 10090.ENSMUSP00000113695; -.
DR GlyConnect; 2205; 8 N-Linked glycans (1 site).
DR GlyGen; Q8BGU2; 2 sites, 8 N-linked glycans (1 site).
DR iPTMnet; Q8BGU2; -.
DR PhosphoSitePlus; Q8BGU2; -.
DR PaxDb; Q8BGU2; -.
DR PeptideAtlas; Q8BGU2; -.
DR PRIDE; Q8BGU2; -.
DR ProteomicsDB; 265343; -.
DR Antibodypedia; 42209; 168 antibodies from 26 providers.
DR DNASU; 12405; -.
DR Ensembl; ENSMUST00000068423; ENSMUSP00000068863; ENSMUSG00000024647.
DR Ensembl; ENSMUST00000122079; ENSMUSP00000113695; ENSMUSG00000024647.
DR Ensembl; ENSMUST00000122464; ENSMUSP00000113996; ENSMUSG00000024647.
DR Ensembl; ENSMUST00000169470; ENSMUSP00000126810; ENSMUSG00000024647.
DR GeneID; 12405; -.
DR KEGG; mmu:12405; -.
DR UCSC; uc008fva.1; mouse.
DR CTD; 147381; -.
DR MGI; MGI:88282; Cbln2.
DR VEuPathDB; HostDB:ENSMUSG00000024647; -.
DR eggNOG; ENOG502QT93; Eukaryota.
DR GeneTree; ENSGT00940000159988; -.
DR HOGENOM; CLU_001074_8_2_1; -.
DR InParanoid; Q8BGU2; -.
DR OMA; ACYPVRA; -.
DR OrthoDB; 1398761at2759; -.
DR PhylomeDB; Q8BGU2; -.
DR TreeFam; TF329591; -.
DR BioGRID-ORCS; 12405; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Cbln2; mouse.
DR PRO; PR:Q8BGU2; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q8BGU2; protein.
DR Bgee; ENSMUSG00000024647; Expressed in habenula and 99 other tissues.
DR Genevisible; Q8BGU2; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0099558; P:maintenance of synapse structure; IMP:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IDA:MGI.
DR GO; GO:1905606; P:regulation of presynapse assembly; IDA:SynGO.
DR GO; GO:0098814; P:spontaneous synaptic transmission; IMP:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IDA:MGI.
DR GO; GO:0050808; P:synapse organization; IMP: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 Disulfide bond; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..51
FT /evidence="ECO:0000255"
FT CHAIN 52..224
FT /note="Cerebellin-2"
FT /id="PRO_0000003552"
FT DOMAIN 88..224
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17331201,
FT ECO:0000269|PubMed:29782851"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17331201,
FT ECO:0000269|PubMed:29782851"
FT DISULFID 64
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9R171"
FT DISULFID 68
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9R171"
FT MUTAGEN 53
FT /note="N->Q: No effect on its ability to form homohexameric
FT or heteromeric complexes with other CBLN family members.
FT Increased interaction with NRXN1 and NRXN3. Total loss of
FT N-glycosylation; when associated with Q-110."
FT /evidence="ECO:0000269|PubMed:17331201,
FT ECO:0000269|PubMed:29782851"
FT MUTAGEN 110
FT /note="N->Q: No effect on its ability to form homohexameric
FT or heteromeric complexes with other CBLN family members.
FT Increased interaction with NRXN1. Total loss of N-
FT glycosylation; when associated with Q-53."
FT /evidence="ECO:0000269|PubMed:17331201,
FT ECO:0000269|PubMed:29782851"
SQ SEQUENCE 224 AA; 24051 MW; 6FCB1A1D0D430F04 CRC64;
MPAPGQGPRG PLLSMPGRRG ALREPADFGS SLGAVLALLL LLLPACCPVR AQNDTEPIVL
EGKCLVVCDS SPSGDGAVTS SLGISVRSGS AKVAFSATRS TNHEPSEMSN RTMTIYFDQV
LVNIGNHFDL ASSIFVAPRK GIYSFSFHVV KVYNRQTIQV SLMQNGYPVI SAFAGDQDVT
REAASNGVLL LMEREDKVHL KLERGNLMGG WKYSTFSGFL VFPL
