ID   CPLX2_HUMAN             Reviewed;         134 AA.
AC   Q6PUV4; B2RAG2; O09056; Q13329; Q28184; Q52M15; Q64386;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 2.
DT   24-JAN-2024, entry version 142.
DE   RecName: Full=Complexin-2;
DE   AltName: Full=Complexin II;
DE            Short=CPX II;
DE   AltName: Full=Synaphin-1;
GN   Name=CPLX2;
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].
RC   TISSUE=Brain;
RX   PubMed=7553862; DOI=10.1016/0092-8674(95)90239-2;
RA   McMahon H.T., Missler M., Li C., Suedhof T.C.;
RT   "Complexins: cytosolic proteins that regulate SNAP receptor function.";
RL   Cell 83:111-119(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cerebellum;
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 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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-114, AND TISSUE SPECIFICITY.
RC   TISSUE=Cerebellum;
RX   PubMed=16162394; DOI=10.1016/j.gene.2005.07.005;
RA   Raevskaya N.M., Dergunova L.V., Vladychenskaya I.P., Stavchansky V.V.,
RA   Oborina M.V., Poltaraus A.B., Limborska S.A.;
RT   "Structural organization of the human complexin 2 gene (CPLX2) and aspects
RT   of its functional activity.";
RL   Gene 359:127-137(2005).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=9853440; DOI=10.1016/s0140-6736(98)03341-8;
RA   Harrison P.J., Eastwood S.L.;
RT   "Preferential involvement of excitatory neurons in medial temporal lobe in
RT   schizophrenia.";
RL   Lancet 352:1669-1673(1998).
RN   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=11576753; DOI=10.1016/s0361-9230(01)00530-5;
RA   Eastwood S.L., Harrison P.J.;
RT   "Synaptic pathology in the anterior cingulate cortex in schizophrenia and
RT   mood disorders. A review and a Western blot study of synaptophysin, GAP-43
RT   and the complexins.";
RL   Brain Res. Bull. 55:569-578(2001).
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=11483314; DOI=10.1016/s0306-4522(01)00141-5;
RA   Eastwood S.L., Cotter D., Harrison P.J.;
RT   "Cerebellar synaptic protein expression in schizophrenia.";
RL   Neuroscience 105:219-229(2001).
RN   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=15906159; DOI=10.1007/s11068-004-0514-8;
RA   DiProspero N.A., Chen E.-Y., Charles V., Plomann M., Kordower J.H.,
RA   Tagle D.A.;
RT   "Early changes in Huntington's disease patient brains involve alterations
RT   in cytoskeletal and synaptic elements.";
RL   J. Neurocytol. 33:517-533(2004).
CC   -!- FUNCTION: Negatively regulates the formation of synaptic vesicle
CC       clustering at active zone to the presynaptic membrane in postmitotic
CC       neurons. Positively regulates a late step in exocytosis of various
CC       cytoplasmic vesicles, such as synaptic vesicles and other secretory
CC       vesicles. Also involved in mast cell exocytosis (By similarity).
CC       {ECO:0000250|UniProtKB:P84086, ECO:0000250|UniProtKB:P84088}.
CC   -!- SUBUNIT: Binds to the SNARE core complex containing SNAP25, VAMP2 and
CC       STX1A. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q6PUV4; Q9HB07: MYG1; NbExp=3; IntAct=EBI-2689453, EBI-709754;
CC       Q6PUV4; Q9ULP0-2: NDRG4; NbExp=3; IntAct=EBI-2689453, EBI-11978907;
CC       Q6PUV4; Q96AL5: PBX3; NbExp=3; IntAct=EBI-2689453, EBI-741171;
CC       Q6PUV4; P43897: TSFM; NbExp=3; IntAct=EBI-2689453, EBI-1049298;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P84087}. Presynapse
CC       {ECO:0000250|UniProtKB:P84087}. Nucleus {ECO:0000250|UniProtKB:P84087}.
CC       Perikaryon {ECO:0000250|UniProtKB:P84087}. Note=Translocated from the
CC       perikaryon to the presynaptic terminals during maturation of neuronal
CC       cells. In mast cells, cytosol and nucleus. Becomes enriched near plasma
CC       membrane following stimulation. {ECO:0000250|UniProtKB:P84087}.
CC   -!- TISSUE SPECIFICITY: Nervous system. In hippocampus and cerebellum,
CC       expressed mainly by excitatory neurons. Down-regulated in brain cortex
CC       from patients suffering from Huntington disease, bipolar disorder or
CC       major depression. Down-regulated in cerebellum from patients with
CC       schizophrenia. {ECO:0000269|PubMed:11483314,
CC       ECO:0000269|PubMed:11576753, ECO:0000269|PubMed:15906159,
CC       ECO:0000269|PubMed:16162394, ECO:0000269|PubMed:9853440}.
CC   -!- SIMILARITY: Belongs to the complexin/synaphin family. {ECO:0000305}.
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DR   EMBL; U35100; AAC50229.1; -; mRNA.
DR   EMBL; AK314177; BAG36859.1; -; mRNA.
DR   EMBL; BC093706; AAH93706.1; -; mRNA.
DR   EMBL; BC112287; AAI12288.1; -; mRNA.
DR   EMBL; AY576870; AAS93622.1; -; mRNA.
DR   EMBL; BN000499; CAG26663.1; -; mRNA.
DR   EMBL; BN000500; CAG26664.1; -; mRNA.
DR   CCDS; CCDS4396.1; -.
DR   PIR; E57233; E57233.
DR   RefSeq; NP_001008221.1; NM_001008220.1.
DR   RefSeq; NP_006641.1; NM_006650.3.
DR   RefSeq; XP_005265855.1; XM_005265798.1.
DR   RefSeq; XP_005265856.1; XM_005265799.1.
DR   RefSeq; XP_011532721.1; XM_011534419.1.
DR   RefSeq; XP_016864453.1; XM_017008964.1.
DR   AlphaFoldDB; Q6PUV4; -.
DR   SMR; Q6PUV4; -.
DR   BioGRID; 116027; 24.
DR   CORUM; Q6PUV4; -.
DR   IntAct; Q6PUV4; 14.
DR   MINT; Q6PUV4; -.
DR   STRING; 9606.ENSP00000352544; -.
DR   iPTMnet; Q6PUV4; -.
DR   PhosphoSitePlus; Q6PUV4; -.
DR   BioMuta; CPLX2; -.
DR   DMDM; 51316998; -.
DR   jPOST; Q6PUV4; -.
DR   MassIVE; Q6PUV4; -.
DR   MaxQB; Q6PUV4; -.
DR   PaxDb; 9606-ENSP00000352544; -.
DR   PeptideAtlas; Q6PUV4; -.
DR   ProteomicsDB; 67260; -.
DR   TopDownProteomics; Q6PUV4; -.
DR   Antibodypedia; 45968; 201 antibodies from 26 providers.
DR   DNASU; 10814; -.
DR   Ensembl; ENST00000359546.8; ENSP00000352544.4; ENSG00000145920.15.
DR   Ensembl; ENST00000393745.8; ENSP00000377346.3; ENSG00000145920.15.
DR   Ensembl; ENST00000515094.1; ENSP00000421825.1; ENSG00000145920.15.
DR   GeneID; 10814; -.
DR   KEGG; hsa:10814; -.
DR   MANE-Select; ENST00000393745.8; ENSP00000377346.3; NM_001008220.2; NP_001008221.1.
DR   UCSC; uc003mde.2; human.
DR   AGR; HGNC:2310; -.
DR   CTD; 10814; -.
DR   DisGeNET; 10814; -.
DR   GeneCards; CPLX2; -.
DR   HGNC; HGNC:2310; CPLX2.
DR   HPA; ENSG00000145920; Group enriched (brain, epididymis).
DR   MIM; 605033; gene.
DR   neXtProt; NX_Q6PUV4; -.
DR   OpenTargets; ENSG00000145920; -.
DR   PharmGKB; PA26827; -.
DR   VEuPathDB; HostDB:ENSG00000145920; -.
DR   eggNOG; ENOG502RXXI; Eukaryota.
DR   GeneTree; ENSGT00950000182938; -.
DR   HOGENOM; CLU_132159_1_0_1; -.
DR   InParanoid; Q6PUV4; -.
DR   OMA; KHTRMEA; -.
DR   PhylomeDB; Q6PUV4; -.
DR   TreeFam; TF315172; -.
DR   PathwayCommons; Q6PUV4; -.
DR   SignaLink; Q6PUV4; -.
DR   BioGRID-ORCS; 10814; 21 hits in 1143 CRISPR screens.
DR   ChiTaRS; CPLX2; human.
DR   GeneWiki; CPLX2; -.
DR   GenomeRNAi; 10814; -.
DR   Pharos; Q6PUV4; Tbio.
DR   PRO; PR:Q6PUV4; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q6PUV4; Protein.
DR   Bgee; ENSG00000145920; Expressed in right hemisphere of cerebellum and 135 other cell types or tissues.
DR   ExpressionAtlas; Q6PUV4; baseline and differential.
DR   GO; GO:0044305; C:calyx of Held; IEA:Ensembl.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR   GO; GO:0031201; C:SNARE complex; IBA:GO_Central.
DR   GO; GO:0070033; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex; IEA:Ensembl.
DR   GO; GO:0070554; C:synaptobrevin 2-SNAP-25-syntaxin-3-complexin complex; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR   GO; GO:0048306; F:calcium-dependent protein binding; IEA:Ensembl.
DR   GO; GO:0000149; F:SNARE binding; IBA:GO_Central.
DR   GO; GO:0017075; F:syntaxin-1 binding; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0043303; P:mast cell degranulation; IEA:UniProtKB-KW.
DR   GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR   GO; GO:0031915; P:positive regulation of synaptic plasticity; ISS:UniProtKB.
DR   GO; GO:0017157; P:regulation of exocytosis; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0046928; P:regulation of neurotransmitter secretion; IBA:GO_Central.
DR   GO; GO:0031630; P:regulation of synaptic vesicle fusion to presynaptic active zone membrane; IEA:Ensembl.
DR   GO; GO:0016079; P:synaptic vesicle exocytosis; IBA:GO_Central.
DR   GO; GO:0006904; P:vesicle docking involved in exocytosis; TAS:ProtInc.
DR   CDD; cd22808; Complexin_NTD_CPLX_I_II; 1.
DR   Gene3D; 1.20.5.580; Single Helix bin; 1.
DR   InterPro; IPR008849; Synaphin.
DR   PANTHER; PTHR16705; COMPLEXIN; 1.
DR   PANTHER; PTHR16705:SF9; COMPLEXIN-2; 1.
DR   Pfam; PF05835; Synaphin; 1.
DR   SUPFAM; SSF58038; SNARE fusion complex; 1.
DR   Genevisible; Q6PUV4; HS.
PE   1: Evidence at protein level;
KW   Cell projection; Coiled coil; Cytoplasm; Differentiation; Exocytosis;
KW   Mast cell degranulation; Neurogenesis; Neurotransmitter transport; Nucleus;
KW   Phosphoprotein; Reference proteome; Synapse; Transport.
FT   CHAIN           1..134
FT                   /note="Complexin-2"
FT                   /id="PRO_0000144875"
FT   REGION          1..114
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          41..97
FT                   /note="Interaction with the SNARE complex"
FT                   /evidence="ECO:0000250"
FT   COILED          28..84
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        18..86
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         93
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P84087"
SQ   SEQUENCE   134 AA;  15394 MW;  7791812FD4194AC5 CRC64;
     MDFVMKQALG GATKDMGKML GGEEEKDPDA QKKEEERQEA LRQQEEERKA KHARMEAERE
     KVRQQIRDKY GLKKKEEKEA EEKAALEQPC EGSLTRPKKA IPAGCGDEEE EEEESILDTV
     LKYLPGPLQD MFKK
//