WORKLIST ENTRIES (1): LVDCCALPHA1D View alignment Voltage-dependent L-type calcium channel alpha-1D subunit signature Type of fingerprint: COMPOUND with 5 elements Links: PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1 PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1 PRINTS; PR01634 LVDCCALPHA1S; PR01635 LVDCCALPHA1C Creation date 20-DEC-2001 1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M. Structure and functional expression of an omega-conotoxin sensitive human N-type calcium channel. SCIENCE 257 389-395 (1992). 2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., IMOTO, K., TANABE, T. AND NUMA, S. Primary structure and functional expression from complementary DNA of a brain calcium channel. NATURE 350 398-402 (1991). 3. ASHCROFT, F.M. Voltage-gated Ca2+ channels. IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.161-183. 4. KOCH, W.J., ELLINOR, P.T. AND SCHWARTZ, A. cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta - evidence for the existence of alternatively spliced forms. J.BIOL.CHEM. 265(29) 17786-17791 (1990). 5. TAKIMOTO, K., LI, D., NERBONNE, J.M. AND LEVITAN, E.S. Distribution, splicing and glucocorticoid-induced expression of cardiac alpha 1C and alpha 1D voltage-gated Ca2+ channel mRNAs. J.MOL.CELL CARDIOL. 29(11) 3035-42 (1997). 6. KOSCHAK, A. REIMER, D. HUBER, I. GRABNER, M. GLOSSMANN, H. ENGEL, J. AND STRIESSNIG, J. Alpha-1D (Cav1.3) subunits can form L-type Ca2+ channels activating at negative voltages. J.BIOL.CHEM. 276(25) 22100-22106 (2001). 7. MOSER, T. AND BEUTNER, D. Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse. PROC.NATL.ACAD.SCI.U.S.A. 97 883-888 (2000). 8. MAGEE, J.C., AVERY, R.B., CHRISTIE, B.R. AND JOHNSTON, D. Dihydropyridine-sensitive, voltage-gated Ca2+ channels contribute to the resting intracellular Ca2+ concentration of hippocampal CA1 pyramidal neurons. J.NEUROPHYSIOL. 76 3460-3470 (1996). Calcium channel proteins are involved in the control of neurotransmitter release from neurons , and play an important role in the regulation of a variety of cellular functions, including membrane excitability, muscle contraction and synaptic transmission . Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels . Generally, the channel proteins are composed of 4 tightly-coupled subunits (alpha-1, alpha-2, beta and gamma), the alpha-1 subunit from each creating the pore for the import of extracellular calcium ions. The alpha-1 subunit shares sequence characteristics with all voltage-dependent cation channels, and exploits the same 6-helix bundle structural motif - in both sodium and calcium channels, this motif is repeated 4 times within the sequence to give a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM) segments (S1, S2, S3, S5, S6) are hydrophobic and one is positively charged (S4) - the latter is characterised by charged amino acids at very third position, and probably represents the voltage-sensor. Several genes encoding alpha-1 subunits have been identified, each forming a distinct electrophysiological channel . L-type calcium channels are formed from alpha-1S, alpha-1C and alpha-1D subunits. They are widely distributed and are well characterised in the heart, smooth and skeletal muscle, and some neurons. Their primary functions are in both excitation- contraction and excitation-secretion coupling. In skeletal muscle, the L-type calcium channels act as a voltage sensor for excitation-contraction coupling and, in cardiac muscle, they provide a pathway for calcium influx. Mutations affecting L-type channel subunits result in three diseases: (1) muscular dystrophy, which is characterised by a lack of functional skeletal muscle; (2) hypokalaemic periodic paralysis, which is characterised by episodic attacks of skeletal muscle weakness; and (3) malignant hyperthermia, which is the main cause of death due to anaesthesia . Alpha-1D subunits are expressed in the lung and heart, in particular the aorta and atrium. Although expressed in the same areas as the alpha-1C subunit, they are less abundant . Alpha-1D subunits allow cells to slowly inactivate voltage-gated Ca2+ influx to weak depolarisations . This property allows them to participate in important physiological functions, such as tonic neurotransmitter release in cochlear inner hair cells . In addition, these properties make them ideally suited to contribute to subthreshold Ca2+ signalling, for example in hippocampal pyramidal cells . LVDCCALPHA1D is a 5-element fingerprint that provides a signature for the voltage-dependent L-type calcium channel alpha-1D subunit. The fingerprint was derived from an initial alignment of 4 sequences: the motifs were drawn from conserved regions spanning the N-terminal portion of the alignment, focusing on those sections that characterise the alpha-1D subunit but distinguish it from other members of the alpha-1 subunit family - motifs 1 and 2 reside in the N-terminus; motif 3 lies in the cytoplasmic region between TM domains 3 and 4 of the first repeat; and motifs 4 and 5 span the cytoplasmic region between TM domain 6 of repeat II and TM domain I of repeat III. A single iteration on SPTR40_18f was required to reach convergence, no further sequences being identified beyond the starting set. A single partial match was found, Q9UDC3, a human neuronal-type voltage- gated Ca2+ channel class D alpha 1 subunit that matches motifs 4 and 5. SUMMARY INFORMATION 4 codes involving 5 elements 0 codes involving 4 elements 0 codes involving 3 elements 1 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 5| 4 4 4 4 4 4| 0 0 0 0 0 3| 0 0 0 0 0 2| 0 0 0 1 1 --+-------------------------- | 1 2 3 4 5 True positives.. CCAD_HUMAN CCAD_RAT CCAD_MESAU CCAD_CHICK Subfamily: Codes involving 2 elements Subfamily True positives.. Q9UDC3 PROTEIN TITLES CCAD_HUMAN Voltage-dependent L-type calcium channel alpha-1D subunit (C CCAD_RAT Voltage-dependent L-type calcium channel alpha-1D subunit (C CCAD_MESAU Voltage-dependent L-type calcium channel alpha-1D subunit (C CCAD_CHICK Voltage-dependent L-type calcium channel alpha-1D subunit (C Q9UDC3 NEURONAL-TYPE VOLTAGE-GATED CA2+ CHANNEL CLASS D ALPHA 1 SUB
SCAN HISTORY SPTR40_18f 1 100 NSINGLE INITIAL MOTIF SETS LVDCCALPHA1D1 Length of motif = 20 Motif number = 1 Voltage-dependent L-type calcium channel alpha-1D subunit motif I - 1 PCODE ST INT EANYARGTRLPLSGEGPTSQ CCAD_HUMAN 23 23 EANYARGTRLPISGEGPTSQ CCAD_RAT 23 23 EANYASSTRIPLPGDGPTTQ CCAD_CHICK 15 15 EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22 LVDCCALPHA1D2 Length of motif = 12 Motif number = 2 Voltage-dependent L-type calcium channel alpha-1D subunit motif II - 1 PCODE ST INT QTMSTSAPPPVG CCAD_HUMAN 67 24 QTMSTSAPPPVG CCAD_RAT 67 24 QNMNTTTAQPVG CCAD_CHICK 62 27 QTMSTSAPPPVG CCAD_MESAU 66 24 LVDCCALPHA1D3 Length of motif = 14 Motif number = 3 Voltage-dependent L-type calcium channel alpha-1D subunit motif III - 1 PCODE ST INT ETEGGNHSSGKSGG CCAD_HUMAN 220 141 ETEGGNHSSGKSGG CCAD_RAT 220 141 ETEGGSHSGGKPGG CCAD_CHICK 215 141 ETEGGNHSSGKSGG CCAD_MESAU 219 141 LVDCCALPHA1D4 Length of motif = 18 Motif number = 4 Voltage-dependent L-type calcium channel alpha-1D subunit motif IV - 1 PCODE ST INT ENKKNNKPEVNQIANSDN CCAD_HUMAN 784 550 ENKKNNKPEVNQIANSDN CCAD_RAT 843 609 ENKKSEKSEGDQKKPKDS CCAD_CHICK 805 576 ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550 LVDCCALPHA1D5 Length of motif = 16 Motif number = 5 Voltage-dependent L-type calcium channel alpha-1D subunit motif V - 1 PCODE ST INT KDPYPPCDVPVGEEEE CCAD_HUMAN 815 13 KDPYPPCDVPVGEEEE CCAD_RAT 874 13 KDPYPPCDVPVGEDEE CCAD_CHICK 837 14 KDPYPPCDVPVGEEEE CCAD_MESAU 814 13 FINAL MOTIF SETS LVDCCALPHA1D1 Length of motif = 20 Motif number = 1 Voltage-dependent L-type calcium channel alpha-1D subunit motif I - 1 PCODE ST INT EANYARGTRLPLSGEGPTSQ CCAD_HUMAN 23 23 EANYARGTRLPISGEGPTSQ CCAD_RAT 23 23 EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22 EANYASSTRIPLPGDGPTTQ CCAD_CHICK 15 15 LVDCCALPHA1D2 Length of motif = 12 Motif number = 2 Voltage-dependent L-type calcium channel alpha-1D subunit motif II - 1 PCODE ST INT QTMSTSAPPPVG CCAD_HUMAN 67 24 QTMSTSAPPPVG CCAD_RAT 67 24 QTMSTSAPPPVG CCAD_MESAU 66 24 QNMNTTTAQPVG CCAD_CHICK 62 27 LVDCCALPHA1D3 Length of motif = 14 Motif number = 3 Voltage-dependent L-type calcium channel alpha-1D subunit motif III - 1 PCODE ST INT ETEGGNHSSGKSGG CCAD_HUMAN 220 141 ETEGGNHSSGKSGG CCAD_RAT 220 141 ETEGGNHSSGKSGG CCAD_MESAU 219 141 ETEGGSHSGGKPGG CCAD_CHICK 215 141 LVDCCALPHA1D4 Length of motif = 18 Motif number = 4 Voltage-dependent L-type calcium channel alpha-1D subunit motif IV - 1 PCODE ST INT ENKKNNKPEVNQIANSDN CCAD_HUMAN 784 550 ENKKNNKPEVNQIANSDN CCAD_RAT 843 609 ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550 ENKKSEKSEGDQKKPKDS CCAD_CHICK 805 576 LVDCCALPHA1D5 Length of motif = 16 Motif number = 5 Voltage-dependent L-type calcium channel alpha-1D subunit motif V - 1 PCODE ST INT KDPYPPCDVPVGEEEE CCAD_HUMAN 815 13 KDPYPPCDVPVGEEEE CCAD_RAT 874 13 KDPYPPCDVPVGEEEE CCAD_MESAU 814 13 KDPYPPCDVPVGEDEE CCAD_CHICK 837 14
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