ID   CACB2_HUMAN             Reviewed;         660 AA.
AC   Q08289; A6PVM5; A6PVM7; A6PVM8; O00304; Q5QJ99; Q5QJA0; Q5VVG9; Q5VVH0;
AC   Q5VWV6; Q6TME1; Q6TME2; Q6TME3; Q8WX81; Q96NZ3; Q96NZ4; Q96NZ5; Q9BWU2;
AC   Q9HD32; Q9Y340; Q9Y341;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 3.
DT   24-JAN-2024, entry version 217.
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;
DE   AltName: Full=Lambert-Eaton myasthenic syndrome antigen B;
DE            Short=MYSB;
GN   Name=CACNB2; Synonyms=CACNLB2, MYSB;
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] (ISOFORMS 2A; 2G AND 2H).
RC   TISSUE=Fetal brain;
RX   PubMed=8494331; DOI=10.1002/ana.410330126;
RA   Rosenfeld M.R., Wong E., Dalmau J., Manley G., Posner J.B., Sher E.,
RA   Furneaux H.M.;
RT   "Cloning and characterization of a Lambert-Eaton myasthenic syndrome
RT   antigen.";
RL   Ann. Neurol. 33:113-120(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2A).
RC   TISSUE=Brain;
RX   PubMed=9254841; DOI=10.1007/pl00008704;
RA   Taviaux S., Williams M.E., Harpold M.M., Nargeot J., Lory P.;
RT   "Assignment of human genes for beta 2 and beta 4 subunits of voltage-
RT   dependent Ca2+ channels to chromosomes 10p12 and 2q22-q23.";
RL   Hum. Genet. 100:151-154(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A; 2B; 2C; 2D AND 2E).
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   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2B; 2C; 2H; 2CN2 AND 2CN4),
RP   ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RC   TISSUE=Heart;
RX   PubMed=14762176; DOI=10.1152/physiolgenomics.00207.2003;
RA   Foell J.D., Balijepalli R.C., Delisle B.P., Yunker A.M.R., Robia S.L.,
RA   Walker J.W., McEnery M.W., January C.T., Kamp T.J.;
RT   "Molecular heterogeneity of calcium channel beta-subunits in canine and
RT   human heart: evidence for differential subcellular localization.";
RL   Physiol. Genomics 17:183-200(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2A AND 2D).
RA   Mikala G., Yamaguchi H., Schwartz A.;
RT   "Cooperative effects of alpha2delta and beta2a subunits on surface
RT   expression of calcium channel alpha1c subunits.";
RL   Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2A).
RA   Li D., Roberts R.;
RT   "The beta 2 subunit of the voltage-dependent calcium channel (CACNB2):
RT   genomic structure and mutational analysis as a candidate gene for ARVD6.";
RL   Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2F).
RC   TISSUE=Jejunum;
RA   Lyford G.L., Strege P., Shepard A., Miller S., Rae J., Gibbons S.,
RA   Szurszewski J., Farrugia G.;
RT   "Human jejunum voltage-gated calcium channel subunits.";
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [9]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [11]
RP   INTERACTION WITH RRAD.
RX   PubMed=17525370; DOI=10.1161/circresaha.106.146399;
RA   Yada H., Murata M., Shimoda K., Yuasa S., Kawaguchi H., Ieda M., Adachi T.,
RA   Murata M., Ogawa S., Fukuda K.;
RT   "Dominant negative suppression of Rad leads to QT prolongation and causes
RT   ventricular arrhythmias via modulation of L-type Ca2+ channels in the
RT   heart.";
RL   Circ. Res. 101:69-77(2007).
RN   [12]
RP   INTERACTION WITH TMIGD2.
RX   PubMed=22419821; DOI=10.1091/mbc.e11-11-0934;
RA   Rahimi N., Rezazadeh K., Mahoney J.E., Hartsough E., Meyer R.D.;
RT   "Identification of IGPR-1 as a novel adhesion molecule involved in
RT   angiogenesis.";
RL   Mol. Biol. Cell 23:1646-1656(2012).
RN   [13]
RP   INTERACTION WITH CAMK2A.
RX   PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017;
RA   Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C.,
RA   Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.;
RT   "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and
RT   Causes ASD-Related Behaviors.";
RL   J. Neurosci. 37:2216-2233(2017).
RN   [14]
RP   FUNCTION, INTERACTION WITH RRAD, AND MUTAGENESIS OF ASP-298; ASP-374 AND
RP   ASP-376.
RX   PubMed=36424916; DOI=10.1038/s44161-022-00157-y;
RA   Papa A., Zakharov S.I., Katchman A.N., Kushner J.S., Chen B.X., Yang L.,
RA   Liu G., Jimenez A.S., Eisert R.J., Bradshaw G.A., Dun W., Ali S.R.,
RA   Rodriques A., Zhou K., Topkara V., Yang M., Morrow J.P., Tsai E.J.,
RA   Karlin A., Wan E., Kalocsay M., Pitt G.S., Colecraft H.M., Ben-Johny M.,
RA   Marx S.O.;
RT   "Rad regulation of CaV1.2 channels controls cardiac fight-or-flight
RT   response.";
RL   Nat. Cardiovasc. Res. 1:1022-1038(2022).
RN   [15]
RP   VARIANT [LARGE SCALE ANALYSIS] GLY-99.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [16]
RP   VARIANT BRGDA4 LEU-535, AND CHARACTERIZATION OF VARIANT BRGDA4 LEU-535.
RX   PubMed=17224476; DOI=10.1161/circulationaha.106.668392;
RA   Antzelevitch C., Pollevick G.D., Cordeiro J.M., Casis O., Sanguinetti M.C.,
RA   Aizawa Y., Guerchicoff A., Pfeiffer R., Oliva A., Wollnik B., Gelber P.,
RA   Bonaros E.P. Jr., Burashnikov E., Wu Y., Sargent J.D., Schickel S.,
RA   Oberheiden R., Bhatia A., Hsu L.F., Haissaguerre M., Schimpf R.,
RA   Borggrefe M., Wolpert C.;
RT   "Loss-of-function mutations in the cardiac calcium channel underlie a new
RT   clinical entity characterized by ST-segment elevation, short QT intervals,
RT   and sudden cardiac death.";
RL   Circulation 115:442-449(2007).
CC   -!- FUNCTION: Beta subunit of voltage-dependent calcium channels which
CC       contributes to the function of the calcium channel by increasing peak
CC       calcium current (By similarity). Plays a role in shifting voltage
CC       dependencies of activation and inactivation of the channel (By
CC       similarity). May modulate G protein inhibition (By similarity). May
CC       contribute to beta-adrenergic augmentation of Ca(2+) influx in
CC       cardiomyocytes, thereby regulating increases in heart rate and
CC       contractile force (PubMed:36424916). Involved in membrane targeting of
CC       the alpha-1 subunit CACNA1C (PubMed:17525370).
CC       {ECO:0000250|UniProtKB:Q8CC27, ECO:0000250|UniProtKB:Q8VGC3,
CC       ECO:0000269|PubMed:17525370, ECO:0000269|PubMed:36424916}.
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 (By similarity). 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 (By similarity). Interacts with
CC       CACNA1C (By similarity). Interacts with RRAD; interaction may be
CC       involved in beta-adrenergic regulation of heart rate and contractile
CC       force (PubMed:17525370, PubMed:36424916). Interaction with RRAD
CC       regulates the trafficking of CACNA1C to the cell membrane
CC       (PubMed:17525370). Interacts with TMIGD2 (PubMed:22419821). Interacts
CC       with CAMK2D (By similarity). Interacts with CBARP (By similarity).
CC       Interacts with CAMK2A (PubMed:28130356). {ECO:0000250|UniProtKB:Q8VGC3,
CC       ECO:0000269|PubMed:17525370, ECO:0000269|PubMed:22419821,
CC       ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:36424916}.
CC   -!- INTERACTION:
CC       Q08289; P56545-3: CTBP2; NbExp=5; IntAct=EBI-2874501, EBI-10171902;
CC       Q08289; Q96MH2: HEXIM2; NbExp=3; IntAct=EBI-2874501, EBI-5460660;
CC       Q08289; O14744: PRMT5; NbExp=3; IntAct=EBI-2874501, EBI-351098;
CC       Q08289; Q8WUU8: TMEM174; NbExp=3; IntAct=EBI-2874501, EBI-10276729;
CC       Q08289-1; Q13936: CACNA1C; NbExp=4; IntAct=EBI-15707999, EBI-1038838;
CC   -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=10;
CC       Name=2d; Synonyms=CACNB2d;
CC         IsoId=Q08289-1; Sequence=Displayed;
CC       Name=2a; Synonyms=CACNB2a;
CC         IsoId=Q08289-2; Sequence=VSP_000627;
CC       Name=2b; Synonyms=CACNB2b, 2aN4;
CC         IsoId=Q08289-3; Sequence=VSP_000628;
CC       Name=2c; Synonyms=CACNB2c, 2aN2;
CC         IsoId=Q08289-4; Sequence=VSP_000626;
CC       Name=2e; Synonyms=CACNB2e;
CC         IsoId=Q08289-5; Sequence=VSP_000629;
CC       Name=2f;
CC         IsoId=Q08289-6; Sequence=VSP_000627, VSP_000630;
CC       Name=2g;
CC         IsoId=Q08289-7; Sequence=VSP_000630;
CC       Name=2h; Synonyms=2cN1;
CC         IsoId=Q08289-8; Sequence=VSP_000631;
CC       Name=2cN2;
CC         IsoId=Q08289-9; Sequence=VSP_000626, VSP_000631;
CC       Name=2cN4;
CC         IsoId=Q08289-10; Sequence=VSP_000628, VSP_000631;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues.
CC   -!- PTM: Regulated through phosphorylation at Thr-554 by CaMK2D.
CC       {ECO:0000250}.
CC   -!- DISEASE: Brugada syndrome 4 (BRGDA4) [MIM:611876]: A heart disease
CC       characterized by the association of Brugada syndrome with shortened QT
CC       intervals. Brugada syndrome is a tachyarrhythmia characterized by right
CC       bundle branch block and ST segment elevation on an electrocardiogram
CC       (ECG). It can cause the ventricles to beat so fast that the blood is
CC       prevented from circulating efficiently in the body. When this situation
CC       occurs, the individual will faint and may die in a few minutes if the
CC       heart is not reset. {ECO:0000269|PubMed:17224476}. Note=The gene
CC       represented in this entry may be involved in disease pathogenesis.
CC   -!- SIMILARITY: Belongs to the calcium channel beta subunit family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB51370.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; S60415; AAB51370.1; ALT_FRAME; mRNA.
DR   EMBL; U95019; AAB53332.1; -; mRNA.
DR   EMBL; AF423189; AAL16948.1; -; mRNA.
DR   EMBL; AF423190; AAL16949.1; -; mRNA.
DR   EMBL; AF423191; AAL16950.1; -; mRNA.
DR   EMBL; AF423192; AAL16951.1; -; mRNA.
DR   EMBL; AF285239; AAG01473.2; -; mRNA.
DR   EMBL; AY393858; AAQ97606.1; -; mRNA.
DR   EMBL; AY393859; AAQ97607.1; -; mRNA.
DR   EMBL; AY393860; AAQ97608.1; -; mRNA.
DR   EMBL; AY393861; AAQ97609.1; -; mRNA.
DR   EMBL; AY393862; AAQ97610.1; -; mRNA.
DR   EMBL; AF137376; AAD33729.1; -; mRNA.
DR   EMBL; AF137377; AAD33730.1; -; mRNA.
DR   EMBL; AY027898; AAK16994.1; -; Genomic_DNA.
DR   EMBL; AY027893; AAK16994.1; JOINED; Genomic_DNA.
DR   EMBL; AY027894; AAK16994.1; JOINED; Genomic_DNA.
DR   EMBL; AY027895; AAK16994.1; JOINED; Genomic_DNA.
DR   EMBL; AY027896; AAK16994.1; JOINED; Genomic_DNA.
DR   EMBL; AY027897; AAK16994.1; JOINED; Genomic_DNA.
DR   EMBL; AF465485; AAL73495.1; -; mRNA.
DR   EMBL; AL139814; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL360231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL390783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL450364; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL450384; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL353603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471072; EAW86196.1; -; Genomic_DNA.
DR   EMBL; CH471072; EAW86197.1; -; Genomic_DNA.
DR   EMBL; BC136409; AAI36410.1; -; mRNA.
DR   CCDS; CCDS41493.1; -. [Q08289-9]
DR   CCDS; CCDS41494.1; -. [Q08289-3]
DR   CCDS; CCDS7125.1; -. [Q08289-1]
DR   CCDS; CCDS7126.1; -. [Q08289-8]
DR   CCDS; CCDS7127.1; -. [Q08289-4]
DR   CCDS; CCDS7128.1; -. [Q08289-2]
DR   CCDS; CCDS7129.1; -. [Q08289-5]
DR   CCDS; CCDS81442.1; -. [Q08289-6]
DR   PIR; A48895; A48895.
DR   RefSeq; NP_000715.2; NM_000724.3. [Q08289-2]
DR   RefSeq; NP_001316989.1; NM_001330060.1. [Q08289-6]
DR   RefSeq; NP_963864.1; NM_201570.2. [Q08289-5]
DR   RefSeq; NP_963865.2; NM_201571.3. [Q08289-4]
DR   RefSeq; NP_963866.2; NM_201572.3. [Q08289-9]
DR   RefSeq; NP_963884.2; NM_201590.2. [Q08289-3]
DR   RefSeq; NP_963887.2; NM_201593.2. [Q08289-7]
DR   RefSeq; NP_963890.2; NM_201596.2. [Q08289-1]
DR   RefSeq; NP_963891.1; NM_201597.2. [Q08289-8]
DR   RefSeq; XP_011517961.1; XM_011519659.2. [Q08289-10]
DR   AlphaFoldDB; Q08289; -.
DR   SMR; Q08289; -.
DR   BioGRID; 107237; 9.
DR   ComplexPortal; CPX-3195; Cardiac muscle voltage-gated calcium channel complex.
DR   IntAct; Q08289; 9.
DR   MINT; Q08289; -.
DR   STRING; 9606.ENSP00000320025; -.
DR   BindingDB; Q08289; -.
DR   ChEMBL; CHEMBL3317336; -.
DR   DrugBank; DB01118; Amiodarone.
DR   DrugBank; DB09231; Benidipine.
DR   DrugBank; DB13746; Bioallethrin.
DR   DrugBank; DB11148; Butamben.
DR   DrugBank; DB11093; Calcium citrate.
DR   DrugBank; DB11348; Calcium Phosphate.
DR   DrugBank; DB14481; Calcium phosphate dihydrate.
DR   DrugBank; DB09232; Cilnidipine.
DR   DrugBank; DB04855; Dronedarone.
DR   DrugBank; DB06751; Drotaverine.
DR   DrugBank; DB09235; Efonidipine.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB00153; Ergocalciferol.
DR   DrugBank; DB01023; Felodipine.
DR   DrugBank; DB13961; Fish oil.
DR   DrugBank; DB00270; Isradipine.
DR   DrugBank; DB09236; Lacidipine.
DR   DrugBank; DB00825; Levomenthol.
DR   DrugBank; DB00653; Magnesium sulfate.
DR   DrugBank; DB09238; Manidipine.
DR   DrugBank; DB01388; Mibefradil.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB00622; Nicardipine.
DR   DrugBank; DB01115; Nifedipine.
DR   DrugBank; DB06712; Nilvadipine.
DR   DrugBank; DB00393; Nimodipine.
DR   DrugBank; DB00401; Nisoldipine.
DR   DrugBank; DB01054; Nitrendipine.
DR   DrugBank; DB00252; Phenytoin.
DR   DrugBank; DB00243; Ranolazine.
DR   DrugBank; DB00421; Spironolactone.
DR   DrugBank; DB00273; Topiramate.
DR   DrugBank; DB09089; Trimebutine.
DR   DrugBank; DB00661; Verapamil.
DR   TCDB; 8.A.22.1.2; the ca(2+) channel auxiliary subunit Beta types 1-4 (cca-Beta) family.
DR   GlyGen; Q08289; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q08289; -.
DR   PhosphoSitePlus; Q08289; -.
DR   BioMuta; CACNB2; -.
DR   DMDM; 145559447; -.
DR   EPD; Q08289; -.
DR   jPOST; Q08289; -.
DR   MassIVE; Q08289; -.
DR   MaxQB; Q08289; -.
DR   PaxDb; 9606-ENSP00000320025; -.
DR   PeptideAtlas; Q08289; -.
DR   ProteomicsDB; 1694; -.
DR   ProteomicsDB; 58586; -. [Q08289-1]
DR   ProteomicsDB; 58587; -. [Q08289-2]
DR   ProteomicsDB; 58588; -. [Q08289-3]
DR   ProteomicsDB; 58589; -. [Q08289-4]
DR   ProteomicsDB; 58590; -. [Q08289-5]
DR   ProteomicsDB; 58591; -. [Q08289-6]
DR   ProteomicsDB; 58592; -. [Q08289-7]
DR   ProteomicsDB; 58593; -. [Q08289-8]
DR   ABCD; Q08289; 1 sequenced antibody.
DR   Antibodypedia; 12067; 619 antibodies from 35 providers.
DR   DNASU; 783; -.
DR   Ensembl; ENST00000282343.13; ENSP00000282343.8; ENSG00000165995.24. [Q08289-4]
DR   Ensembl; ENST00000324631.13; ENSP00000320025.8; ENSG00000165995.24. [Q08289-1]
DR   Ensembl; ENST00000352115.10; ENSP00000344474.6; ENSG00000165995.24. [Q08289-8]
DR   Ensembl; ENST00000377315.6; ENSP00000366532.4; ENSG00000165995.24. [Q08289-5]
DR   Ensembl; ENST00000377319.9; ENSP00000366536.3; ENSG00000165995.24. [Q08289-6]
DR   Ensembl; ENST00000377329.10; ENSP00000366546.4; ENSG00000165995.24. [Q08289-3]
DR   Ensembl; ENST00000396576.6; ENSP00000379821.2; ENSG00000165995.24. [Q08289-2]
DR   Ensembl; ENST00000645287.2; ENSP00000496203.1; ENSG00000165995.24. [Q08289-9]
DR   GeneID; 783; -.
DR   KEGG; hsa:783; -.
DR   MANE-Select; ENST00000324631.13; ENSP00000320025.8; NM_201596.3; NP_963890.2.
DR   UCSC; uc001ipr.3; human. [Q08289-1]
DR   AGR; HGNC:1402; -.
DR   CTD; 783; -.
DR   DisGeNET; 783; -.
DR   GeneCards; CACNB2; -.
DR   GeneReviews; CACNB2; -.
DR   HGNC; HGNC:1402; CACNB2.
DR   HPA; ENSG00000165995; Low tissue specificity.
DR   MalaCards; CACNB2; -.
DR   MIM; 600003; gene.
DR   MIM; 611876; phenotype.
DR   neXtProt; NX_Q08289; -.
DR   OpenTargets; ENSG00000165995; -.
DR   Orphanet; 130; Brugada syndrome.
DR   PharmGKB; PA88; -.
DR   VEuPathDB; HostDB:ENSG00000165995; -.
DR   eggNOG; KOG3812; Eukaryota.
DR   GeneTree; ENSGT00950000182837; -.
DR   HOGENOM; CLU_021995_3_0_1; -.
DR   InParanoid; Q08289; -.
DR   OMA; XELFDVI; -.
DR   OrthoDB; 2953516at2759; -.
DR   PhylomeDB; Q08289; -.
DR   TreeFam; TF316195; -.
DR   PathwayCommons; Q08289; -.
DR   Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
DR   Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR   Reactome; R-HSA-419037; NCAM1 interactions.
DR   Reactome; R-HSA-422356; Regulation of insulin secretion.
DR   Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR   Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR   Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR   SignaLink; Q08289; -.
DR   SIGNOR; Q08289; -.
DR   BioGRID-ORCS; 783; 10 hits in 1156 CRISPR screens.
DR   ChiTaRS; CACNB2; human.
DR   GeneWiki; CACNB2; -.
DR   GenomeRNAi; 783; -.
DR   Pharos; Q08289; Tbio.
DR   PRO; PR:Q08289; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q08289; Protein.
DR   Bgee; ENSG00000165995; Expressed in adrenal tissue and 159 other cell types or tissues.
DR   ExpressionAtlas; Q08289; baseline and differential.
DR   GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:BHF-UCL.
DR   GO; GO:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0098793; C:presynapse; IEA:GOC.
DR   GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:BHF-UCL.
DR   GO; GO:0051015; F:actin filament binding; ISS:BHF-UCL.
DR   GO; GO:0005262; F:calcium channel activity; NAS:UniProtKB.
DR   GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:BHF-UCL.
DR   GO; GO:0099626; F:voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels; IEA:Ensembl.
DR   GO; GO:0070509; P:calcium ion import; IDA:BHF-UCL.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR   GO; GO:0086045; P:membrane depolarization during AV node cell action potential; IMP: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; ISS:BHF-UCL.
DR   GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:BHF-UCL.
DR   GO; GO:1901843; P:positive regulation of high voltage-gated calcium channel activity; ISS:BHF-UCL.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISS:BHF-UCL.
DR   GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR   GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR   CDD; cd12040; SH3_CACNB2; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   InterPro; IPR046937; CAB1-4_N_A-dom.
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   PANTHER; PTHR11824; VOLTAGE-DEPENDENT CALCIUM CHANNEL BETA SUBUNIT; 1.
DR   PANTHER; PTHR11824:SF9; VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL SUBUNIT BETA-2; 1.
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   SMART; SM00326; SH3; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS50002; SH3; 1.
DR   Genevisible; Q08289; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Brugada syndrome; Calcium; Calcium channel;
KW   Calcium transport; Cell membrane; Disease variant; Ion channel;
KW   Ion transport; Membrane; Phosphoprotein; Reference proteome; SH3 domain;
KW   Transport; Voltage-gated channel.
FT   CHAIN           1..660
FT                   /note="Voltage-dependent L-type calcium channel subunit
FT                   beta-2"
FT                   /id="PRO_0000144051"
FT   DOMAIN          114..183
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REGION          39..101
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          190..261
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          486..641
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        56..83
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        84..101
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        194..225
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        244..258
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        486..511
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        538..553
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        554..641
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            549
FT                   /note="Required for CaMK2D-binding"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         204
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VGC3"
FT   MOD_RES         207
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CC27"
FT   MOD_RES         218
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CC27"
FT   MOD_RES         550
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CC27"
FT   MOD_RES         554
FT                   /note="Phosphothreonine; by CaMK2D"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VGC3"
FT   VAR_SEQ         1..71
FT                   /note="MVQRDMSKSPPTAAAAVAQEIQMELLENVAPAGALGAAAQSYGKGARRKNRF
FT                   KGSDGSTSSDTTSNSFVRQ -> MQCCGLVHRRRVRVSY (in isoform 2a and
FT                   isoform 2f)"
FT                   /evidence="ECO:0000303|PubMed:12042350,
FT                   ECO:0000303|PubMed:8494331, ECO:0000303|PubMed:9254841,
FT                   ECO:0000303|Ref.5, ECO:0000303|Ref.7"
FT                   /id="VSP_000627"
FT   VAR_SEQ         1..71
FT                   /note="MVQRDMSKSPPTAAAAVAQEIQMELLENVAPAGALGAAAQSYGKGARRKNRF
FT                   KGSDGSTSSDTTSNSFVRQ -> MLDRRLIAPQTKYIIPG (in isoform 2b and
FT                   isoform 2cN4)"
FT                   /evidence="ECO:0000303|PubMed:12042350,
FT                   ECO:0000303|PubMed:14762176"
FT                   /id="VSP_000628"
FT   VAR_SEQ         1..71
FT                   /note="MVQRDMSKSPPTAAAAVAQEIQMELLENVAPAGALGAAAQSYGKGARRKNRF
FT                   KGSDGSTSSDTTSNSFVRQ -> MKATWIRLLKRAKGGRLKNSDIC (in isoform
FT                   2e)"
FT                   /evidence="ECO:0000303|PubMed:12042350"
FT                   /id="VSP_000629"
FT   VAR_SEQ         1..40
FT                   /note="MVQRDMSKSPPTAAAAVAQEIQMELLENVAPAGALGAAAQ -> MNQGSGLD
FT                   LLKI (in isoform 2c and isoform 2cN2)"
FT                   /evidence="ECO:0000303|PubMed:12042350,
FT                   ECO:0000303|PubMed:14762176"
FT                   /id="VSP_000626"
FT   VAR_SEQ         224..268
FT                   /note="AIDIDATGLDAEENDIPANHRSPKPSANSVTSPHSKEKRMPFFKK -> AKQ
FT                   KQKS (in isoform 2f and isoform 2g)"
FT                   /evidence="ECO:0000303|PubMed:8494331, ECO:0000303|Ref.7"
FT                   /id="VSP_000630"
FT   VAR_SEQ         224..268
FT                   /note="AIDIDATGLDAEENDIPANHRSPKPSANSVTSPHSKEKRMPFFKK -> GAK
FT                   SADEQDQWKTAGLFWRFT (in isoform 2h, isoform 2cN2 and isoform
FT                   2cN4)"
FT                   /evidence="ECO:0000303|PubMed:14762176,
FT                   ECO:0000303|PubMed:8494331"
FT                   /id="VSP_000631"
FT   VARIANT         99
FT                   /note="A -> G (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs745502425)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036350"
FT   VARIANT         535
FT                   /note="S -> L (in BRGDA4; uncertain significance; affects
FT                   channel activity; dbSNP:rs121917812)"
FT                   /evidence="ECO:0000269|PubMed:17224476"
FT                   /id="VAR_044041"
FT   MUTAGEN         298
FT                   /note="D->A: Reduces binding to RRAD; when associated with
FT                   A-374 and A-376."
FT                   /evidence="ECO:0000269|PubMed:36424916"
FT   MUTAGEN         374
FT                   /note="D->A: Reduces binding to RRAD; when associated with
FT                   A-298 and A-376."
FT                   /evidence="ECO:0000269|PubMed:36424916"
FT   MUTAGEN         376
FT                   /note="D->A: Reduces binding to RRAD; when associated with
FT                   A-298 and A-374."
FT                   /evidence="ECO:0000269|PubMed:36424916"
FT   CONFLICT        56
FT                   /note="D -> N (in Ref. 4; AAQ97608)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        69
FT                   /note="V -> L (in Ref. 5; AAD33729)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        100..101
FT                   /note="ER -> Q (in Ref. 5; AAD33729)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        122
FT                   /note="N -> D (in Ref. 5; AAD33729)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        364
FT                   /note="L -> V (in Ref. 5; AAD33729/AAD33730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        406
FT                   /note="R -> T (in Ref. 5; AAD33729/AAD33730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        501
FT                   /note="D -> H (in Ref. 5; AAD33729/AAD33730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        524
FT                   /note="P -> G (in Ref. 5; AAD33729/AAD33730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        624
FT                   /note="Q -> QQ (in Ref. 5; AAD33729/AAD33730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        659
FT                   /note="R -> P (in Ref. 2; AAB53332, 3;
FT                   AAG01473/AAL16948/AAL16951/AAL16950, 4;
FT                   AAQ97606/AAQ97607/AAQ97608/AAQ97609/AAQ97610 and 6;
FT                   AAL73495)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   660 AA;  73581 MW;  4A08B141EE66404E CRC64;
     MVQRDMSKSP PTAAAAVAQE IQMELLENVA PAGALGAAAQ SYGKGARRKN RFKGSDGSTS
     SDTTSNSFVR QGSADSYTSR PSDSDVSLEE DREAVRREAE RQAQAQLEKA KTKPVAFAVR
     TNVSYSAAHE DDVPVPGMAI SFEAKDFLHV KEKFNNDWWI GRLVKEGCEI GFIPSPVKLE
     NMRLQHEQRA KQGKFYSSKS GGNSSSSLGD IVPSSRKSTP PSSAIDIDAT GLDAEENDIP
     ANHRSPKPSA NSVTSPHSKE KRMPFFKKTE HTPPYDVVPS MRPVVLVGPS LKGYEVTDMM
     QKALFDFLKH RFEGRISITR VTADISLAKR SVLNNPSKHA IIERSNTRSS LAEVQSEIER
     IFELARTLQL VVLDADTINH PAQLSKTSLA PIIVYVKISS PKVLQRLIKS RGKSQAKHLN
     VQMVAADKLA QCPPELFDVI LDENQLEDAC EHLADYLEAY WKATHPPSSS LPNPLLSRTL
     ATSSLPLSPT LASNSQGSQG DQRTDRSAPI RSASQAEEEP SVEPVKKSQH RSSSSAPHHN
     HRSGTSRGLS RQETFDSETQ ESRDSAYVEP KEDYSHDHVD HYASHRDHNH RDETHGSSDH
     RHRESRHRSR DVDREQDHNE CNKQRSRHKS KDRYCEKDGE VISKKRNEAG EWNRDVYIRQ
//