CACB2_RAT
ID CACB2_RAT Reviewed; 655 AA.
AC Q8VGC3; Q811Q6; Q811Q7; Q91ZJ8; Q9QUU7;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit beta-2;
DE Short=CAB2;
DE AltName: Full=Calcium channel voltage-dependent subunit beta 2;
GN Name=Cacnb2; Synonyms=Cacnlb2;
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 [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=1370480; DOI=10.1016/s0021-9258(18)46015-2;
RA Perez-Reyes E., Castellano A., Kim H.S., Bertrand P., Baggstrom E.,
RA Lacerda A.E., Wei X.Y., Birnbaumer L.;
RT "Cloning and expression of a cardiac/brain beta subunit of the L-type
RT calcium channel.";
RL J. Biol. Chem. 267:1792-1797(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=Wistar; TISSUE=Heart;
RX PubMed=11604404; DOI=10.1074/jbc.m108049200;
RA Yamada Y., Nagashima M., Tsutsuura M., Kobayashi T., Seki S., Makita N.,
RA Horio Y., Tohse N.;
RT "Cloning of a functional splice variant of L-type calcium channel beta2
RT subunit from rat heart.";
RL J. Biol. Chem. 276:47163-47170(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=12042350; DOI=10.1113/jphysiol.2002.018515;
RA Colecraft H.M., Alseikhan B., Takahashi S.X., Chaudhuri D., Mittman S.,
RA Yegnasubramanian V., Alvania R.S., Johns D.C., Marban E., Yue D.T.;
RT "Novel functional properties of Ca(2+) channel beta subunits revealed by
RT their expression in adult rat heart cells.";
RL J. Physiol. (Lond.) 541:435-452(2002).
RN [4]
RP INTERACTION WITH CAMK2D, AND PHOSPHORYLATION AT THR-549 BY CAMK2D.
RX PubMed=20194790; DOI=10.1073/pnas.0913760107;
RA Koval O.M., Guan X., Wu Y., Joiner M.L., Gao Z., Chen B., Grumbach I.M.,
RA Luczak E.D., Colbran R.J., Song L.S., Hund T.J., Mohler P.J.,
RA Anderson M.E.;
RT "CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and
RT afterdepolarizations.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4996-5000(2010).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200 AND SER-203, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP INTERACTION WITH CBARP.
RX PubMed=24751537; DOI=10.1083/jcb.201304101;
RA Beguin P., Nagashima K., Mahalakshmi R.N., Vigot R., Matsunaga A., Miki T.,
RA Ng M.Y., Ng Y.J., Lim C.H., Tay H.S., Hwang L.A., Firsov D., Tang B.L.,
RA Inagaki N., Mori Y., Seino S., Launey T., Hunziker W.;
RT "BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked
RT exocytosis.";
RL J. Cell Biol. 205:233-249(2014).
RN [7] {ECO:0007744|PDB:1T0H, ECO:0007744|PDB:1T0J}
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 68-476 IN COMPLEX WITH CACNA1C.
RX PubMed=15141227; DOI=10.1038/nature02588;
RA Van Petegem F., Clark K.A., Chatelain F.C., Minor D.L. Jr.;
RT "Structure of a complex between a voltage-gated calcium channel beta-
RT subunit and an alpha-subunit domain.";
RL Nature 429:671-675(2004).
RN [8] {ECO:0007744|PDB:3JBR}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 68-475 IN COMPLEX WITH
RP CACNA1S; CACNG1 AND CACNA2D1, AND SUBUNIT.
RX PubMed=26680202; DOI=10.1126/science.aad2395;
RA Wu J., Yan Z., Li Z., Yan C., Lu S., Dong M., Yan N.;
RT "Structure of the voltage-gated calcium channel Cav1.1 complex.";
RL Science 350:2395-2395(2015).
CC -!- FUNCTION: The beta subunit of voltage-dependent calcium channels
CC contributes to the function of the calcium channel by increasing peak
CC calcium current, shifting the voltage dependencies of activation and
CC inactivation, modulating G protein inhibition and controlling the
CC alpha-1 subunit membrane targeting. {ECO:0000250,
CC ECO:0000269|PubMed:11604404, ECO:0000269|PubMed:12042350,
CC ECO:0000269|PubMed:1370480}.
CC -!- SUBUNIT: Component of a calcium channel complex consisting of a pore-
CC forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or
CC CACNB2, CACNG1 and CACNA2D1 (PubMed:26680202). The channel complex
CC contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e.
CC it contains either CACNB1 or CACNB2 (PubMed:26680202). Interacts with
CC CACNA1C (PubMed:15141227). Interacts with RRAD. Interaction with RRAD
CC regulates the trafficking of CACNA1C to the cell membrane (By
CC similarity). Interacts with TMIGD2 (By similarity). Interacts with
CC CAMK2D (PubMed:20194790). Interacts with CBARP (PubMed:24751537).
CC Interacts with CAMK2A (By similarity). {ECO:0000250|UniProtKB:Q08289,
CC ECO:0000269|PubMed:15141227, ECO:0000269|PubMed:20194790,
CC ECO:0000269|PubMed:24751537, ECO:0000269|PubMed:26680202}.
CC -!- INTERACTION:
CC Q8VGC3-2; Q8VGC3-2: Cacnb2; NbExp=2; IntAct=EBI-15685453, EBI-15685453;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:12042350}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12042350}; Cytoplasmic side
CC {ECO:0000269|PubMed:12042350}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8VGC3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VGC3-2; Sequence=VSP_010734;
CC Name=3; Synonyms=Beta-2c;
CC IsoId=Q8VGC3-3; Sequence=VSP_010733;
CC Name=4; Synonyms=Beta-2e;
CC IsoId=Q8VGC3-4; Sequence=VSP_010735;
CC Name=5; Synonyms=Beta-2b;
CC IsoId=Q8VGC3-5; Sequence=VSP_010736;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart and brain, and at lower
CC levels in lung. {ECO:0000269|PubMed:11604404,
CC ECO:0000269|PubMed:1370480}.
CC -!- PTM: Regulated through phosphorylation at Thr-549 by CaMK2D.
CC {ECO:0000269|PubMed:20194790}.
CC -!- SIMILARITY: Belongs to the calcium channel beta subunit family.
CC {ECO:0000305}.
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DR EMBL; AF394941; AAL47074.1; -; mRNA.
DR EMBL; M80545; AAK14821.1; -; mRNA.
DR EMBL; AF423193; AAL16952.1; -; mRNA.
DR EMBL; AY190119; AAO38996.1; -; mRNA.
DR EMBL; AY190120; AAO38997.1; -; mRNA.
DR PIR; A42044; A42044.
DR RefSeq; NP_446303.1; NM_053851.1.
DR RefSeq; XP_006254360.1; XM_006254298.3.
DR RefSeq; XP_006254365.1; XM_006254303.3. [Q8VGC3-5]
DR PDB; 1T0H; X-ray; 1.97 A; A=68-196, B=254-476.
DR PDB; 1T0J; X-ray; 2.00 A; A=68-196, B=254-476.
DR PDB; 3JBR; EM; 4.20 A; B=68-196, B=254-475.
DR PDB; 5V2P; X-ray; 2.00 A; A=68-189, A=254-476.
DR PDB; 5V2Q; X-ray; 1.70 A; A=68-189, A=254-476.
DR PDBsum; 1T0H; -.
DR PDBsum; 1T0J; -.
DR PDBsum; 3JBR; -.
DR PDBsum; 5V2P; -.
DR PDBsum; 5V2Q; -.
DR AlphaFoldDB; Q8VGC3; -.
DR SMR; Q8VGC3; -.
DR DIP; DIP-29590N; -.
DR IntAct; Q8VGC3; 5.
DR MINT; Q8VGC3; -.
DR STRING; 10116.ENSRNOP00000037354; -.
DR CarbonylDB; Q8VGC3; -.
DR iPTMnet; Q8VGC3; -.
DR PhosphoSitePlus; Q8VGC3; -.
DR SwissPalm; Q8VGC3; -.
DR PaxDb; Q8VGC3; -.
DR PRIDE; Q8VGC3; -.
DR ABCD; Q8VGC3; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000066826; ENSRNOP00000063474; ENSRNOG00000018378. [Q8VGC3-5]
DR GeneID; 116600; -.
DR KEGG; rno:116600; -.
DR UCSC; RGD:67385; rat. [Q8VGC3-1]
DR CTD; 783; -.
DR RGD; 67385; Cacnb2.
DR eggNOG; KOG3812; Eukaryota.
DR GeneTree; ENSGT00950000182837; -.
DR InParanoid; Q8VGC3; -.
DR OrthoDB; 926074at2759; -.
DR PhylomeDB; Q8VGC3; -.
DR BRENDA; 2.7.4.8; 5301.
DR Reactome; R-RNO-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-RNO-422356; Regulation of insulin secretion.
DR Reactome; R-RNO-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-RNO-5576893; Phase 2 - plateau phase.
DR EvolutionaryTrace; Q8VGC3; -.
DR PRO; PR:Q8VGC3; -.
DR Proteomes; UP000002494; Chromosome 17.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; ISO:RGD.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:RGD.
DR GO; GO:0051015; F:actin filament binding; IDA:BHF-UCL.
DR GO; GO:0005246; F:calcium channel regulator activity; IDA:RGD.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; IDA:RGD.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:RGD.
DR GO; GO:0099635; F:voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels; ISO:RGD.
DR GO; GO:0070509; P:calcium ion import; ISO:RGD.
DR GO; GO:0006816; P:calcium ion transport; TAS:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0007528; P:neuromuscular junction development; IBA:GO_Central.
DR GO; GO:1904879; P:positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:RGD.
DR GO; GO:1901843; P:positive regulation of high voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL.
DR GO; GO:1901385; P:regulation of voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:0007601; P:visual perception; ISO:RGD.
DR CDD; cd12040; SH3_CACNB2; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR035605; CACNB2_SH3.
DR InterPro; IPR008145; GK/Ca_channel_bsu.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR005444; VDCC_L_b2su.
DR InterPro; IPR000584; VDCC_L_bsu.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF12052; VGCC_beta4Aa_N; 1.
DR PRINTS; PR01626; LCACHANNELB.
DR PRINTS; PR01628; LCACHANNELB2.
DR SMART; SM00072; GuKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; SH3 domain; Transport;
KW Voltage-gated channel.
FT CHAIN 1..655
FT /note="Voltage-dependent L-type calcium channel subunit
FT beta-2"
FT /id="PRO_0000144054"
FT DOMAIN 110..179
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 34..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 186..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..103
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..548
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..595
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 603..632
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 544
FT /note="Required for CaMK2D-binding"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CC27"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CC27"
FT MOD_RES 549
FT /note="Phosphothreonine; by CaMK2D"
FT /evidence="ECO:0000269|PubMed:20194790"
FT VAR_SEQ 1..67
FT /note="MVQSDTSKSPPIAAVAQESQMELLESAAPAGALGAQSYGKGARRKNRFKGSD
FT DSTSSDTTSNSFVRQ -> MQCCGLVHRRRVRVSR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1370480"
FT /id="VSP_010734"
FT VAR_SEQ 1..67
FT /note="MVQSDTSKSPPIAAVAQESQMELLESAAPAGALGAQSYGKGARRKNRFKGSD
FT DSTSSDTTSNSFVRQ -> MKATWIRLLKRAKGERLKDSDIC (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12042350"
FT /id="VSP_010735"
FT VAR_SEQ 1..67
FT /note="MVQSDTSKSPPIAAVAQESQMELLESAAPAGALGAQSYGKGARRKNRFKGSD
FT DSTSSDTTSNSFVRQ -> MLDRQLVSSQTQSSIPG (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12042350"
FT /id="VSP_010736"
FT VAR_SEQ 1..36
FT /note="MVQSDTSKSPPIAAVAQESQMELLESAAPAGALGAQ -> MDQASGLDRLKI
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12042350"
FT /id="VSP_010733"
FT CONFLICT 53
FT /note="D -> G (in Ref. 3; AAO38996)"
FT /evidence="ECO:0000305"
FT HELIX 91..106
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 172..186
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 270..274
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 291..307
FT /evidence="ECO:0007829|PDB:5V2Q"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 311..317
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 344..361
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 366..371
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:5V2Q"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 388..392
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 397..406
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 409..412
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 415..427
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 430..433
FT /evidence="ECO:0007829|PDB:5V2Q"
FT STRAND 435..438
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 443..461
FT /evidence="ECO:0007829|PDB:5V2Q"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:5V2Q"
SQ SEQUENCE 655 AA; 73226 MW; 0BD9B42FD4CDF52A CRC64;
MVQSDTSKSP PIAAVAQESQ MELLESAAPA GALGAQSYGK GARRKNRFKG SDDSTSSDTT
SNSFVRQGSA DSYTSRPSDS DVSLEEDREA VRREAERQAQ AQLEKAKTKP VAFAVRTNVR
YSAAQEDDVP VPGMAISFEA KDFLHVKEKF NNDWWIGRLV KEGCEIGFIP SPVKLENMRL
QHEQRAKQGK FYSSKSGGNS SSSLGDIVPS SRKSTPPSSA IDIDATGLDA EENDIPANHR
SPKPSANSVT SPHSKEKRMP FFKKTEHTPP YDVVPSMRPV VLVGPSLKGY EVTDMMQKAL
FDFLKHRFEG RISITRVTAD ISLAKRSVLN NPSKHAIIER SNTRSSLAEV QSEIERIFEL
ARTLQLVVLD ADTINHPAQL SKTSLAPIIV YVKISSPKVL QRLIKSRGKS QAKHLNVQMV
AADKLAQCPP QESFDVILDE NQLEDACEHL ADYLEAYWKA THPPSSNLPN PLLSRTLATS
TLPLSPTLAS NSQGSQGDQR TDRSAPRSAS QAEEEPCLEP VKKSQHRSSS ATHQNHRSGT
GRGLSRQETF DSETQESRDS AYVEPKEDYS HEHVDRYVPH REHNHREESH SSNGHRHREP
RHRTRDMGRD QDHNECSKQR SRHKSKDRYC DKEGEVISKR RSEAGEWNRD VYIRQ
