Cav2.2

Description: calcium channel, voltage-dependent, N type, alpha 1B subunit
Gene: Cacna1b
Alias: ca2.2, BIII, CACNN, Cav2.2, CACNL1A5, CACNA1B

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Introduction

The N-type calcium channels, also known as a1B or Cav2.2, are high voltage activated (HCA) calcium channels found presynaptically. For a longer introduction, see page 502 in the review [477]. See also the Channelpedia entry for Cav2.1, as this subunit is similar in many respects.

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Gene

GeneID: 257648 Cacna1b calcium channel, voltage-dependent, N type, alpha 1B subunit [ Rattus norvegicus ]

Species	NCBI gene ID	Chromosome	Position
Human	774	9	246837
Mouse	12287	2	159338
Rat	257648	3	165212

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_000718.4	9792
Mouse	NM_001042528.2	9772
Rat	NM_001195199.1	7065

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q00975	2339
Mouse	O55017	2327
Rat	Q02294	2336

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_007579.3

9655

NP_031605.2

2288

transcript variant 2

isoform 2

NM_001042528.2

9772

NP_001035993.1

2327

transcript variant 1

isoform 1

Predicted

XR_003950091.2

9820

transcript variant X18

XR_374052.4

5700

transcript variant X16

XM_006497635.4

9687

XP_006497698.1

2276

transcript variant X13

isoform X13

XM_006497634.3

9830

XP_006497697.1

2324

transcript variant X12

isoform X12

XM_006497632.3

9833

XP_006497695.1

2325

transcript variant X10

isoform X10

XM_017315156.1

9890

XP_017170645.1

2344

transcript variant X20

isoform X18

XM_017315140.1

9908

XP_017170629.1

2350

transcript variant X3

isoform X3

XM_017315146.1

9845

XP_017170635.1

2329

transcript variant X9

isoform X9

XM_006497633.3

9830

XP_006497696.1

2324

transcript variant X11

isoform X11

XM_006497631.3

9848

XP_006497694.1

2330

transcript variant X8

isoform X8

XM_006497629.3

9896

XP_006497692.1

2346

transcript variant X6

isoform X6

XM_006497627.3

9908

XP_006497690.1

2350

transcript variant X2

isoform X2

XM_006497630.3

9893

XP_006497693.1

2345

transcript variant X7

isoform X7

XM_006497628.3

9899

XP_006497691.1

2347

transcript variant X5

isoform X5

XM_017315141.1

9905

XP_017170630.1

2349

transcript variant X4

isoform X4

XM_006497626.3

9911

XP_006497689.1

2351

transcript variant X1

isoform X1

XM_011239014.2

6890

XP_011237316.1

1242

transcript variant X19

isoform X17

XM_006497637.5

5677

XP_006497700.1

1808

transcript variant X14

isoform X14

XM_017315155.2

6708

XP_017170644.1

1790

transcript variant X17

isoform X16

XM_006497638.4

6726

XP_006497701.1

1796

transcript variant X15

isoform X15

Known

NM_147141.2

9683

NP_671482.1

2333

transcript variant 2

isoform 2

NM_001195199.1

7065

NP_001182128.1

2354

transcript variant 1

isoform 1

NM_001413253.1

9729

NP_001400182.1

2336

isoform 3

Predicted

XR_005501788.1

5655

transcript variant X13

XM_017591505.2

9832

XP_017446994.1

2352

transcript variant X16

isoform X15

XM_017591500.2

9850

XP_017446989.1

2358

transcript variant X3

isoform X3

XM_006233576.4

9787

XP_006233638.1

2337

transcript variant X8

isoform X8

XM_006233575.4

9790

XP_006233637.1

2338

transcript variant X7

isoform X7

XM_006233570.4

9850

XP_006233632.1

2358

transcript variant X2

isoform X2

XM_006233574.4

9835

XP_006233636.1

2353

transcript variant X6

isoform X6

XM_006233573.4

9841

XP_006233635.1

2355

transcript variant X5

isoform X5

XM_006233569.4

9853

XP_006233631.1

2359

transcript variant X1

isoform X1

XM_017591502.2

9626

XP_017446991.1

2332

transcript variant X12

isoform X12

XM_039104391.1

6666

XP_038960319.1

1211

transcript variant X15

isoform X14

XM_039104389.1

7151

XP_038960317.1

2334

transcript variant X11

isoform X11

XM_006233572.4

7220

XP_006233634.1

2357

transcript variant X4

isoform X4

XM_006233578.4

7008

XP_006233640.1

2335

transcript variant X10

isoform X10

XM_006233577.4

7011

XP_006233639.1

2336

transcript variant X9

isoform X9

XM_039104390.1

5287

XP_038960318.1

1518

transcript variant X14

isoform X13

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Post-Translational Modifications

PTM

Position

Type

Modified residue

Omega-N-methylarginine

Modified residue

411

Phosphoserine

Modified residue

745

Phosphoserine

Modified residue

748

Phosphoserine

Modified residue

783

Phosphoserine

Modified residue

1069

Phosphoserine

Modified residue

2066

Phosphoserine

Modified residue

2224

Phosphoserine

Modified residue

2233

Phosphoserine

Modified residue

2256

Phosphoserine

Glycosylation

256

N-linked (GlcNAc...) asparagine

Glycosylation

1563

N-linked (GlcNAc...) asparagine

Glycosylation

1675

N-linked (GlcNAc...) asparagine

Modified residue

Omega-N-methylarginine

Modified residue

411

Phosphoserine

Modified residue

745

Phosphoserine

Modified residue

748

Phosphoserine

Modified residue

783

Phosphoserine

Modified residue

1058

Phosphoserine

Modified residue

2056

Phosphoserine

Modified residue

2212

Phosphoserine

Modified residue

2221

Phosphoserine

Modified residue

2244

Phosphoserine

Glycosylation

256

N-linked (GlcNAc...) asparagine

Glycosylation

1554

N-linked (GlcNAc...) asparagine

Glycosylation

1666

N-linked (GlcNAc...) asparagine

Modified residue

Omega-N-methylarginine

Modified residue

411

Phosphoserine

Modified residue

746

Phosphoserine

Modified residue

749

Phosphoserine

Modified residue

784

Phosphoserine

Modified residue

1067

Phosphoserine

Modified residue

2065

Phosphoserine

Modified residue

2221

Phosphoserine

Modified residue

2230

Phosphoserine

Modified residue

2253

Phosphoserine

Glycosylation

256

N-linked (GlcNAc...) asparagine

Glycosylation

1563

N-linked (GlcNAc...) asparagine

Glycosylation

1675

N-linked (GlcNAc...) asparagine

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Structure

The Cav2.2 subunit consists of four homologous domains (I–IV), each consisting of six trans- membrane (TM) segments. The domains are linked by intracellular loops and have intracellular N and C termini. (see Fig. 1A) in [88]

See also figure 7 in [90] for a structural connection between Cav2.1 and Cav2.2.

Cav2.2 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	9301.02	source
Mouse	9704.08	source
Rat	9682.18	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Biophysics

The most detailed model can be found in [250]. It is from hippocampal mossy fiber boutons.

For a Hodgkin Huxley rate equation for the Ca2.2 (= N-type) current, see [260].

Model CaN (ID=6)

Animal	Cat
CellType	RGC
Age	34 Days
Temperature	36.0°C
Reversal	135.0 mV
Ion	Ca +
Ligand ion
Reference	[259] S J Huang et. al; Neuroscience 1998 Jul
mpower	2.0
m Alpha	(0.1*(v-20)/(1-exp(-(v-20)/10))) If v neq 20
m Beta	0.4*exp(-(v+25)/18)
hpower	1.0
h Alpha	0.01*exp(-(v+50)/10)
h Beta	0.1/(1+exp(-(v+17)/17))

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Expression and Distribution

Cav2.2 can be found in retinal ganglion cells. [259]

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Function

Cav2.2 control the excitability in retinal ganglion cells and thus are crucial for the development of the visual system. [250]

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Interaction

G proteins

See figure 10 in [94] for the mechanism of G protein modulation in calcium channels and the effect of palmitoylation on the interaction of Cav-beta subunits with the I–II linker.

Neurokinin 1 Receptor

Unlike R-type channels encoded by CaV2.3, L-type (CaV1.3), N- type (CaV2.2), and P/Q-type (CaV2.1) channels are inhibited, but not stimulated, through Neurokinin 1 receptors. [89]

Beta 3 Subunit

Overexpressed beta 3 subunit (12.5 ng/cell cRNA) significantly suppressed N- and R-type, but not L-type calcium channel currents at holding potentials of 60 and 80 mV.[92]

Roscovitine

Roscovitine, a potent inhibitor of cyclin-dependent kinases 1, 2, and 5, slows the deactivation of P/Q (Cav2.1) and N-type (Cav2.2) calcium channels. [93]

References

Page KM et al. N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2.
J. Biol. Chem., 2010 Jan 8 , 285 (835-44).

Meza U et al. Neurokinin 1 receptors trigger overlapping stimulation and inhibition of CaV2.3 (R-type) calcium channels.
Mol. Pharmacol., 2007 Jan , 71 (284-93).

Vitko I et al. Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.
PLoS ONE, 2008 , 3 (e3560).

Yasuda T et al. Overexpressed Ca(v)beta3 inhibits N-type (Cav2.2) calcium channel currents through a hyperpolarizing shift of ultra-slow and closed-state inactivation.
J. Gen. Physiol., 2004 Apr , 123 (401-16).

Buraei Z et al. Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent kinase inhibitor roscovitine.
Biophys. J., 2005 Sep , 89 (1681-91).

Leroy J et al. Interaction via a key tryptophan in the I-II linker of N-type calcium channels is required for beta1 but not for palmitoylated beta2, implicating an additional binding site in the regulation of channel voltage-dependent properties.
J. Neurosci., 2005 Jul 27 , 25 (6984-96).

Helton TD et al. Neuronal L-type calcium channels open quickly and are inhibited slowly.
J. Neurosci., 2005 Nov 2 , 25 (10247-51).

Raghib A et al. Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs.
J. Neurosci., 2001 Nov 1 , 21 (8495-504).

250

Li L et al. Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons.
J. Neurosci., 2007 Dec 5 , 27 (13420-9).

259

Huang SJ et al. Activation and inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells.
Neuroscience, 1998 Jul , 85 (239-47).

260

Benison G et al. Modeling temporal behavior of postnatal cat retinal ganglion cells.
J. Theor. Biol., 2001 May 21 , 210 (187-99).

477

Catterall WA Structure and regulation of voltage-gated Ca2+ channels.
Annu. Rev. Cell Dev. Biol., 2000 , 16 (521-55).

478

Black JL The voltage-gated calcium channel gamma subunits: a review of the literature.
J. Bioenerg. Biomembr., 2003 Dec , 35 (649-60).

555

Mintz IM et al. Block of calcium channels in rat neurons by synthetic omega-Aga-IVA.
Neuropharmacology, 1993 Nov , 32 (1161-9).

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Credits

Contributors: Rajnish Ranjan, Michael Schartner

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/79/ , accessed on 2024 Apr 16

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