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Reviewed, UniProtKB/Swiss-Prot Q00975 (CAC1B_HUMAN)

Last modified January 19, 2010. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Voltage-dependent N-type calcium channel subunit alpha-1B
Alternative name(s):
    Voltage-gated calcium channel subunit alpha Cav2.2
    Calcium channel, L type, alpha-1 polypeptide isoform 5
    Brain calcium channel III
      Short name=BIII
Gene names
Name: CACNA1B
Synonyms: CACH5, CACNL1A5
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length2339 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.

Subunit structure

Multisubunit complex consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts with RIMS1 and RIMBP2 By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Isoform Alpha-1b-1 and isoform Alpha-1b-2 are expressed in the central nervous system, but not in skeletal muscle or aorta.

Domain

Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.

Post-translational modification

Phosphorylated in vitro by CaM-kinase II, PKA, PKC and CGPK By similarity. Ref.4 Ref.5

Sequence similarities

Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. [View classification]

Contains 1 EF-hand domain.

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha-1B-1 (identifier: Q00975-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Alpha-1B-2 (identifier: Q00975-2)

The sequence of this isoform differs from the canonical sequence as follows:
     2164-2339: GSGSVNGSPL...YHHPDQDHWC → AGSAVGFPNT...APPGLPTCPP

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 23392339Voltage-dependent N-type calcium channel subunit alpha-1B
PRO_0000053921

Regions

Topological domain1 – 9595Cytoplasmic Potential
Transmembrane96 – 11419S1 of repeat I Potential
Topological domain115 – 13218Extracellular Potential
Transmembrane133 – 15220S2 of repeat I Potential
Topological domain153 – 16311Cytoplasmic Potential
Transmembrane164 – 18320S3 of repeat I Potential
Topological domain184 – 1874Extracellular Potential
Transmembrane188 – 20619S4 of repeat I Potential
Topological domain207 – 22519Cytoplasmic Potential
Transmembrane226 – 24520S5 of repeat I Potential
Topological domain246 – 33186Extracellular Potential
Transmembrane332 – 35625S6 of repeat I Potential
Topological domain357 – 482126Cytoplasmic Potential
Transmembrane483 – 50119S1 of repeat II Potential
Topological domain502 – 51615Extracellular Potential
Transmembrane517 – 53620S2 of repeat II Potential
Topological domain537 – 5448Cytoplasmic Potential
Transmembrane545 – 56218S3 of repeat II Potential
Topological domain563 – 57311Extracellular Potential
Transmembrane574 – 59219S4 of repeat II Potential
Topological domain593 – 61119Cytoplasmic Potential
Transmembrane612 – 63120S5 of repeat II Potential
Topological domain632 – 68453Extracellular Potential
Transmembrane685 – 70925S6 of repeat II Potential
Topological domain710 – 1151442Cytoplasmic Potential
Transmembrane1152 – 116918S1 of repeat III Potential
Topological domain1170 – 118516Extracellular Potential
Transmembrane1186 – 120520S2 of repeat III Potential
Topological domain1206 – 121712Cytoplasmic Potential
Transmembrane1218 – 123619S3 of repeat III Potential
Topological domain1237 – 124610Extracellular Potential
Transmembrane1247 – 126519S4 of repeat III Potential
Topological domain1266 – 128419Cytoplasmic Potential
Transmembrane1285 – 130420S5 of repeat III Potential
Topological domain1305 – 139187Extracellular Potential
Transmembrane1392 – 141625S6 of repeat III Potential
Topological domain1417 – 147155Cytoplasmic Potential
Transmembrane1472 – 149019S1 of repeat IV Potential
Topological domain1491 – 150515Extracellular Potential
Transmembrane1506 – 152520S2 of repeat IV Potential
Topological domain1526 – 15338Cytoplasmic Potential
Transmembrane1534 – 155219S3 of repeat IV Potential
Topological domain1553 – 156311Extracellular Potential
Transmembrane1564 – 158219S4 of repeat IV Potential
Topological domain1583 – 160119Cytoplasmic Potential
Transmembrane1602 – 162120S5 of repeat IV Potential
Topological domain1622 – 168362Extracellular Potential
Transmembrane1684 – 170825S6 of repeat IV Potential
Topological domain1709 – 2339631Cytoplasmic Potential
Repeat82 – 359278I
Repeat468 – 712245II
Repeat1137 – 1419283III
Repeat1456 – 1711256IV
Domain1724 – 175936EF-hand
Nucleotide binding451 – 4588ATP Potential
Calcium binding1737 – 174812 By similarity
Region379 – 39618Binding to the beta subunit By similarity
Compositional bias2050 – 20545Poly-His
Compositional bias2118 – 21225Poly-Ser

Sites

Site3141Calcium ion selectivity and permeability By similarity
Site6631Calcium ion selectivity and permeability By similarity
Site13651Calcium ion selectivity and permeability By similarity
Site16551Calcium ion selectivity and permeability By similarity

Amino acid modifications

Modified residue4551Phosphoserine Ref.4
Modified residue7451Phosphoserine By similarity
Modified residue7831Phosphoserine By similarity
Modified residue17191Phosphoserine; by PKA Potential
Modified residue19681Phosphoserine Ref.5
Modified residue22561Phosphoserine By similarity
Glycosylation2561N-linked (GlcNAc...) Potential
Glycosylation15631N-linked (GlcNAc...) Potential
Glycosylation16751N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence2164 – 2339176GSGSV…QDHWC → AGSAVGFPNTTPCCRETPSA SPWPLALELALTLTWGSVWT VRPLSTPCLRTRSLSRRLWP PTRAAPPGLPTCPP in isoform Alpha-1B-2.
VSP_000882
Natural variant1671N → K: dbSNP rs4422842.
VAR_048741
Natural variant8621A → S: dbSNP rs7873074.
VAR_061100
Natural variant9961T → A: dbSNP rs11137342.
VAR_061101
Natural variant14361E → K: dbSNP rs12377346.
VAR_048742
Natural variant15001E → K: dbSNP rs12377346.
VAR_048743

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Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha-1B-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 17A45C6D1E76B39D

FASTA2,339262,496
        10         20         30         40         50         60 
MVRFGDELGG RYGGPGGGER ARGGGAGGAG GPGPGGLQPG QRVLYKQSIA QRARTMALYN 

        70         80         90        100        110        120 
PIPVKQNCFT VNRSLFVFSE DNVVRKYAKR ITEWPPFEYM ILATIIANCI VLALEQHLPD 

       130        140        150        160        170        180 
GDKTPMSERL DDTEPYFIGI FCFEAGIKII ALGFVFHKGS YLRNGWNVMD FVVVLTGILA 

       190        200        210        220        230        240 
TAGTDFDLRT LRAVRVLRPL KLVSGIPSLQ VVLKSIMKAM VPLLQIGLLL FFAILMFAII 

       250        260        270        280        290        300 
GLEFYMGKFH KACFPNSTDA EPVGDFPCGK EAPARLCEGD TECREYWPGP NFGITNFDNI 

       310        320        330        340        350        360 
LFAILTVFQC ITMEGWTDIL YNTNDAAGNT WNWLYFIPLI IIGSFFMLNL VLGVLSGEFA 

       370        380        390        400        410        420 
KERERVENRR AFLKLRRQQQ IERELNGYLE WIFKAEEVML AEEDRNAEEK SPLDVLKRAA 

       430        440        450        460        470        480 
TKKSRNDLIH AEEGEDRFAD LCAVGSPFAR ASLKSGKTES SSYFRRKEKM FRFFIRRMVK 

       490        500        510        520        530        540 
AQSFYWVVLC VVALNTLCVA MVHYNQPRRL TTTLYFAEFV FLGLFLTEMS LKMYGLGPRS 

       550        560        570        580        590        600 
YFRSSFNCFD FGVIVGSVFE VVWAAIKPGS SFGISVLRAL RLLRIFKVTK YWSSLRNLVV 

       610        620        630        640        650        660 
SLLNSMKSII SLLFLLFLFI VVFALLGMQL FGGQFNFQDE TPTTNFDTFP AAILTVFQIL 

       670        680        690        700        710        720 
TGEDWNAVMY HGIESQGGVS KGMFSSFYFI VLTLFGNYTL LNVFLAIAVD NLANAQELTK 

       730        740        750        760        770        780 
DEEEMEEAAN QKLALQKAKE VAEVSPMSAA NISIAARQQN SAKARSVWEQ RASQLRLQNL 

       790        800        810        820        830        840 
RASCEALYSE MDPEERLRFA TTRHLRPDMK THLDRPLVVE LGRDGARGPV GGKARPEAAE 

       850        860        870        880        890        900 
APEGVDPPRR HHRHRDKDKT PAAGDQDRAE APKAESGEPG AREERPRPHR SHSKEAAGPP 

       910        920        930        940        950        960 
EARSERGRGP GPEGGRRHHR RGSPEEAAER EPRRHRAHRH QDPSKECAGA KGERRARHRG 

       970        980        990       1000       1010       1020 
GPRAGPREAE SGEEPARRHR ARHKAQPAHE AVEKETTEKE ATEKEAEIVE ADKEKELRNH 

      1030       1040       1050       1060       1070       1080 
QPREPHCDLE TSGTVTVGPM HTLPSTCLQK VEEQPEDADN QRNVTRMGSQ PPDPNTIVHI 

      1090       1100       1110       1120       1130       1140 
PVMLTGPLGE ATVVPSGNVD LESQAEGKKE VEADDVMRSG PRPIVPYSSM FCLSPTNLLR 

      1150       1160       1170       1180       1190       1200 
RFCHYIVTMR YFEVVILVVI ALSSIALAAE DPVRTDSPRN NALKYLDYIF TGVFTFEMVI 

      1210       1220       1230       1240       1250       1260 
KMIDLGLLLH PGAYFRDLWN ILDFIVVSGA LVAFAFSGSK GKDINTIKSL RVLRVLRPLK 

      1270       1280       1290       1300       1310       1320 
TIKRLPKLKA VFDCVVNSLK NVLNILIVYM LFMFIFAVIA VQLFKGKFFY CTDESKELER 

      1330       1340       1350       1360       1370       1380 
DCRGQYLDYE KEEVEAQPRQ WKKYDFHYDN VLWALLTLFT VSTGEGWPMV LKHSVDATYE 

      1390       1400       1410       1420       1430       1440 
EQGPSPGYRM ELSIFYVVYF VVFPFFFVNI FVALIIITFQ EQGDKVMSEC SLEKNERACI 

      1450       1460       1470       1480       1490       1500 
DFAISAKPLT RYMPQNRQSF QYKTWTFVVS PPFEYFIMAM IALNTVVLMM KFYDAPYEYE 

      1510       1520       1530       1540       1550       1560 
LMLKCLNIVF TSMFSMECVL KIIAFGVLNY FRDAWNVFDF VTVLGSITDI LVTEIAETNN 

      1570       1580       1590       1600       1610       1620 
FINLSFLRLF RAARLIKLLR QGYTIRILLW TFVQSFKALP YVCLLIAMLF FIYAIIGMQV 

      1630       1640       1650       1660       1670       1680 
FGNIALDDDT SINRHNNFRT FLQALMLLFR SATGEAWHEI MLSCLSNQAC DEQANATECG 

      1690       1700       1710       1720       1730       1740 
SDFAYFYFVS FIFLCSFLML NLFVAVIMDN FEYLTRDSSI LGPHHLDEFI RVWAEYDPAA 

      1750       1760       1770       1780       1790       1800 
CGRISYNDMF EMLKHMSPPL GLGKKCPARV AYKRLVRMNM PISNEDMTVH FTSTLMALIR 

      1810       1820       1830       1840       1850       1860 
TALEIKLAPA GTKQHQCDAE LRKEISVVWA NLPQKTLDLL VPPHKPDEMT VGKVYAALMI 

      1870       1880       1890       1900       1910       1920 
FDFYKQNKTT RDQMQQAPGG LSQMGPVSLF HPLKATLEQT QPAVLRGARV FLRQKSSTSL 

      1930       1940       1950       1960       1970       1980 
SNGGAIQNQE SGIKESVSWG TQRTQDAPHE ARPPLERGHS TEIPVGRSGA LAVDVQMQSI 

      1990       2000       2010       2020       2030       2040 
TRRGPDGEPQ PGLESQGRAA SMPRLAAETQ PVTDASPMKR SISTLAQRPR GTHLCSTTPD 

      2050       2060       2070       2080       2090       2100 
RPPPSQASSH HHHHRCHRRR DRKQRSLEKG PSLSADMDGA PSSAVGPGLP PGEGPTGCRR 

      2110       2120       2130       2140       2150       2160 
ERERRQERGR SQERRQPSSS SSEKQRFYSC DRFGGREPPK PKPSLSSHPT SPTAGQEPGP 

      2170       2180       2190       2200       2210       2220 
HPQGSGSVNG SPLLSTSGAS TPGRGGRRQL PQTPLTPRPS ITYKTANSSP IHFAGAQTSL 

      2230       2240       2250       2260       2270       2280 
PAFSPGRLSR GLSEHNALLQ RDPLSQPLAP GSRIGSDPYL GQRLDSEASV HALPEDTLTF 

      2290       2300       2310       2320       2330 
EEAVATNSGR SSRTSYVSSL TSQSHPLRRV PNGYHCTLGL SSGGRARHSY HHPDQDHWC

« Hide

Isoform Alpha-1B-2.

Checksum: C6804E510F1E60F0
Show »

FASTA2,237251,759

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References

« Hide 'large scale' references
[1]"Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel."
Williams M.E., Brust P.F., Feldman D.H., Patthi S., Simerson S., Maroufi A., McCue A.F., Velicelebi G., Ellis S.B., Harpold M.M.
Science 257:389-395(1992) [PubMed: 1321501] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1B-1 AND ALPHA-1B-2).
Tissue: Brain.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed: 15164053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Isolation and characterization of the 5'-upstream region of the human N-type calcium channel alpha1B subunit gene. Chromosomal localization and promoter analysis."
Kim D.S., Jung H.-H., Park S.-H., Chin H.
J. Biol. Chem. 272:5098-5104(1997) [PubMed: 9030575] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-94.
Tissue: Lung fibroblast.
[4]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, MASS SPECTROMETRY.
Tissue: Epithelium.
[5]"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column."
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.
Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1968, MASS SPECTROMETRY.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M94172 mRNA. Translation: AAA51897.1.
M94173 mRNA. Translation: AAA51898.1.
AL591424, AL772363 Genomic DNA. Translation: CAI40687.1.
AL772363, AL591424 Genomic DNA. Translation: CAI17144.1.
U76666 Genomic DNA. Translation: AAC51138.1.
IPIIPI00025477.
IPI00220431.
PIRA42566.
T45115.
RefSeqNP_000709.1.
UniGeneHs.495522

3D structure databases

SMRQ00975. Positions 1147-1227, 1465-1541.
ModBaseSearch...

Protein-protein interaction databases

IntActQ00975. 1 interaction.
STRINGQ00975.

PTM databases

PhosphoSiteQ00975.

Proteomic databases

PRIDEQ00975.

Genome annotation databases

EnsemblENST00000371372; ENSP00000360423; ENSG00000148408; Homo sapiens. [Genome view]
GeneID774.
KEGGhsa:774.
UCSCuc004cog.1. human.

Organism-specific databases

CTD774.
GeneCardsGC09P139892.
H-InvDBHIX0034816.
HGNCHGNC:1389. CACNA1B.
MIM601012. gene.
PharmGKBPA26008.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG07061.
HOVERGENQ00975.
OrthoDBEOG9DBWZW.

Enzyme and pathway databases

ReactomeREACT_13685. Synaptic Transmission.

Gene expression databases

ArrayExpressQ00975.
BgeeQ00975.
CleanExHS_CACNA1B.
GenevestigatorQ00975.
GermOnlineENSG00000148408. Homo sapiens.

Family and domain databases

InterProIPR018249. EF_HAND_2.
IPR005821. Ion_trans.
IPR014873. VDCC_a1su_IQ.
IPR005447. VDCC_N_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
PANTHERPTHR10037:SF58. NVDCCAlpha1. 1 hit.
PfamPF08763. Ca_chan_IQ. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]
PRINTSPR00167. CACHANNEL.
PR01631. NVDCCALPHA1.
PROSITEPS50222. EF_HAND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00381. Amlodipine.
DB00996. Gabapentin.
NextBio3128.
SOURCESearch...

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Entry information

Entry nameCAC1B_HUMAN
AccessionPrimary (citable) accession number: Q00975
Secondary accession number(s): B1AQK5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: January 19, 2010
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents