Biomedical subjects

L Birnbaumer

Publications and source records attributed to L Birnbaumer.

At least 55 records · Page 3Linked to original sources

PubMed1997

Feedback inhibition of Ca2+ channels by Ca2+ depends on a short sequence of the C terminus that does not include the Ca2+ -binding function of a motif with similarity to Ca2+ -binding domains.

alpha(1C)- and alpha(1E)-based Ca2+ channels differ in that the former are inhibited by Ca2+ entering through its pore, while the latter are not. It has been proposed on the basis of analysis of alpha(1E)/alpha(1C) chimeras that the molecular determinants responsible for Ca2+ inhibition involve both a conserved Ca2+-binding motif (EF hand) plus additional sequences located C-terminal to the EF hand. Through construction of similar alpha(1E)/alpha(1C) chimeras, we transferred Ca2+ inhibition from alpha(1C) to alpha(1E) by replacing a 134-aa segment of alpha(1E) with the homologous 142-aa segment of alpha(1C). This segment is located immediately after the proposed Ca2+ -binding EF hand motif. Replacement of the alpha(1C) EF hand with the corresponding EF hand of alpha(1E) did not interfere with inhibition of alpha(1C) by Ca2+, and a triple mutant of alpha(1C), alpha(1C)[D1535A,E1537A,D1546A], that disrupts the potential Ca2+-coordinating ability of the EF hand continued to be inhibited by Ca2+. These results indicate that a small portion of the alpha(1C) C terminus is essential for inhibition by Ca2+ and place the Ca2+ -binding site anywhere in alpha(1C), with the exception of its EF hand-like motif.

Amino Acid Sequence↗

PubMed1997

A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit.

Two closely related beta subunit mRNAs (xo28 and xo32) were identified in Xenopus oocytes by molecular cloning. One or both appear to be expressed as active proteins, because: (i) injection of Xenopus beta antisense oligonucleotides, but not of sense or unrelated oligonucleotides, significantly reduced endogenous oocyte voltage-gated Ca2+ channel (VGCC) currents and obliterated VGCC currents that arise after injection of mammalian alpha1 cRNAs (alpha(1C) and alpha(1E)); (ii) coinjection of a Xenopus beta antisense oligonucleotide and excess rat beta cRNA rescued expression of alpha1 Ca2+ channel currents; and (iii) coinjection of mammalian alpha1 cRNA with cRNA encoding either of the two Xenopus beta subunits facilitated both activation and inactivation of Ca2+ channel currents by voltage, as happens with most mammalian beta subunits. The Xenopus beta subunit cDNAs (beta3xo cDNAs) predict proteins of 484 aa that differ in only 22 aa and resemble most closely the sequence of the mammalian type 3 beta subunit. We propose that "alpha1 alone" channels are in fact tightly associated alpha1beta3xo channels, and that effects of exogenous beta subunits are due to formation of higher-order [alpha1beta]beta(n) complexes with an unknown contribution of beta3xo. It is thus possible that functional mammalian VGCCs, rather than having subunit composition alpha1beta, are [alpha1beta]beta(n) complexes that associate with alpha2delta and, as appropriate, other tissue-specific accessory proteins. In support of this hypothesis, we discovered that the last 277-aa of alpha(1E) have a beta subunit binding domain. This beta binding domain is distinct from the previously known interaction domain located between repeats I and II of calcium channel alpha1 subunits.

Amino Acid Sequence↗

PubMed1997

G(alpha)i2-deficient mice with colitis exhibit a local increase in memory CD4+ T cells and proinflammatory Th1-type cytokines.

Mice with targeted deletion of the G protein G(alpha)i2 develop an inflammatory bowel disease closely resembling ulcerative colitis. To better define disease pathogenesis, the mucosal immune system in G(alpha)i2-deficient mice was studied. Phenotypic analysis of large intestine lamina propria lymphocytes revealed a large increase in memory CD4+ T cells (CD44high, CD45RBlow, CD62Llow). Furthermore, expression of the mucosal homing receptor integrin beta7 was increased on mucosal, but not systemic, CD4+ T cells. Analysis of cytokine production revealed a marked increase in proinflammatory Th1-type cytokines in inflamed colons, as compared with wild-type mice or G(alpha)i2-deficient mice without colitis. Thus, IFN-gamma and IL-1beta levels were increased 13-fold and 30-fold, respectively, with more modest increases in IL-6 levels (5-fold) and TNF levels (2-fold). Inflamed colons of G(alpha)i2-deficient mice also demonstrated increased IL-12 p40 mRNA levels. No increase in IL-2, IL-4, IL-5, and IL-10 was seen. Large intestinal epithelial cells in G(alpha)i2-deficient mice with colitis were found by immunohistochemistry to express increased levels of both MHC class I and class II Ags. Colitis was associated with increased IgG levels (60-fold increase), predominantly IgG2a (135-fold increase), in large but not small intestinal secretions. This was shown by ELISPOT analysis to result from local production within the lamina propria.

Animals↗

PubMed1997

Inactivation of the G alpha i2 and G alpha o genes by homologous recombination.

G proteins couple receptors to effectors and thus regulate multiple biological processes. Here we report on the phenotypes of G alpha i2-deficient and G alpha o-deficient mice. G alpha i2-deficient mice display a blunted inhibitory regulation of adenylyl cyclase, alterations in T cell maturation and function, a growth retardation and also develop a lethal diffuse colitis with clinical and histopathological features closely resembling ulcerative colitis in humans, including the development of adenocarcinoma of the colon. G alpha o-deficient mice are also viable, but significantly smaller than wild-type controls.

Animals↗

PubMed1996

On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins.

During the last 2 years, our laboratory has worked on the elucidation of the molecular basis of capacitative calcium entry (CCE) into cells. Specifically, we tested the hypothesis that CCE channels are formed of subunits encoded in genes related to the Drosophila trp gene. The first step in this pursuit was to search for mammalian trp genes. We found not one but six mammalian genes and cloned several of their cDNAs, some in their full length. As assayed in mammalian cells, overexpression of some mammalian Trps increases CCE, while expression of partial trp cDNAs in antisense orientation can interfere with endogenous CCE. These findings provided a firm connection between CCE and mammalian Trps. This article reviews the known forms of CCE and highlights unanswered questions in our understanding of intracellular Ca2+ homeostasis and the physiological roles of CCE.

Animals↗

PubMed1996

Coupling between charge movement and pore opening in vertebrate neuronal alpha 1E calcium channels.

1. Neuronal alpha 1E Ca2+ channels were expressed alone and in combination with the beta 2a subunit in Xenopus laevis oocytes. 2. The properties of ionic and gating currents of alpha 1E were investigated: ionic currents were measured in 10 mM external Ba2+; gating currents were isolated in 2 mM external Co2+. 3. Charge movement preceded channel opening. The charge movement voltage curve (Q(V)) preceded the ionic conductance voltage dependence (G(V)) by approximately 20 mV. 4. Coexpression of alpha 1E with the beta 2a subunit did not modify the voltage dependence of charge movement but shifted the G(V) curve to more negative potentials. The voltage gap between Q(V) and G(V) curves was reduced by the beta 2a subunit and both curves overlapped at potentials near 0 mV. 5. The coupling efficiency between the charge movement and pore opening was estimated by the ration between limiting conductance and maximum charge movement (Gmax/Qmax). Coexpression of the beta 2a subunit increased the Gmax/Qmax ratio from 9.2 x 10(5) +/- 1.4 x 10(5) to 21.9 x 10(5) +/- 2.8 X 10(5) S C-1 for alpha 1E and alpha 1E + beta 2a, respectively. 6. We conclude that in the neuronal alpha 1E the charge movement is tightly coupled with the pore opening and that the beta 2a subunit coexpression further improves this coupling.

Animals↗

PubMed1996

trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry.

SUMMARY: Capacitative calcium entry (CCE) describes CA2+ influx into cells that replenishes CA2+ stores emptied through the action of IP3 and other agents. It is an essential component of cellular responses to many hormones and growth factors. The molecular basis of this form of Ca2+ entry is complex and may involve more than one type of channel. Studies on visual signal transduction in Drosophila led to the hypothesis that a protein encoded in trp may be a component of CCE channels. We reported the existence of six trp-related genes in the mouse genome. Expression in L cells of small portions of these genes in antisense orientation suppressed CCE. Expression in COS cells of two full-length cDNAs encoding human trp homologs, Htrp1 and Htrp3, increased CCE. This identifies mammalian gene products that participate in CCE. We propose that trp homologs are subunits of CCE channels, not unlike those of classical voltage-gated ion channels.

Amino Acid Sequence↗

PubMed1996

The IVS6 segment of the L-type calcium channel is critical for the action of dihydropyridines and phenylalkylamines.

The current through the L-type calcium channel is inhibited and stimulated by distinct dihydropyridines at very low concentrations. The molecular determinants for the high affinity block and stimulation were investigated using chimeras between the class C and E calcium channels. Mutation of three amino acids in the last putative transmembrane segment (IVS6) of the alpha1C subunit decreased the affinity for (+)isradipine 100-fold without significantly affecting the basic properties of the expressed channel. Mutation of two of these three amino acids completely abolished the stimulatory effect of the calcium channel agonist Bay K 8644. These mutations only slightly affected the blocking efficacy of mibefradil and the phenylalkylamine devapamil. Three distinct but adjacently located amino acids mediated the high affinity block by devapamil. These results suggest that the IVS6 segment of the alpha1C subunit is critical for the high affinity interaction between the L-type calcium channel and the calcium channel agonist Bay K 8644 and the two antagonists isradipine and devapamil.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1996

Adenylyl cyclase inhibition and altered G protein subunit expression and ADP-ribosylation patterns in tissues and cells from Gi2 alpha-/-mice.

The inhibition of alpha i2-/- mouse cardiac isoproterenol-stimulated adenylyl cyclase (AC; EC 4.6.1.1) activity by carbachol and that of alpha i2-/- adipocyte AC by phenylisopropyladenosine (PIA), prostaglandin E2, and nicotinic acid were partially, but not completely, inhibited. While the inhibition of cardiac AC was affected in all alpha i2-/- animals tested, only 50% of the alpha i2-/- animals showed an impaired inhibition of adipocyte AC, indicative of a partial penetrance of this phenotype. In agreement with previous results, the data show that Gi2 mediates hormonal inhibition of AC and that Gi3 and/or Gi1 is capable of doing the same but with a lower efficacy. Disruption of the alpha i2 gene affected about equally the actions of all the receptors studied, indicating that none of them exhibits a striking specificity for one type of Gi over another and that receptors are likely to he selective rather than specific in their interaction with functionally homologous G proteins (e.g., Gi1, Gi2, Gi3). Western analysis of G protein subunit levels in simian virus 40-transformed primary embryonic fibroblasts from alpha i2+/+ and alpha i2-/- animals showed that alpha i2 accounts for about 50% of the immunopositive G protein alpha subunits and that loss of the alpha i2 is accompanied by a parallel reduction in G beta 35 and G beta 36 subunits and by a 30-50% increase in alpha i3. This suggests that G beta-gamma levels may be regulated passively through differential rates of turnover in their free vs. trimeric states. The existence of compensatory increase(s) in alpha i subunit expression raises the possibility that the lack of effect of a missing alpha i2 on AC inhibition in adipocytes of some alpha i2-/- animals may be the reflection of a more pronounced compensatory expression of alpha i3 and/or alpha i1.

Adenosine Diphosphate Ribose↗

PubMed1996

G protein subunits and the stimulation of phospholipase C by Gs-and Gi-coupled receptors: Lack of receptor selectivity of Galpha(16) and evidence for a synergic interaction between Gbeta gamma and the alpha subunit of a receptor activated G protein.

Stimulatory guanine nucleotide binding protein (Gs)-coupled receptors activated by luteinizing hormone, vasopressin, and the catecholamine isoproterenol (luteinizing hormone receptor, type 2 vasopressin receptor, and types 1 and 2 beta-adrenergic receptors) and the Gi-coupled M2 muscarinic receptor (M2R) were expressed transiently in COS cells, alone and in combination with Gbeta gamma dimers, their corresponding Galphas (Galpha(s), or Galpha(i3)) and either Galpha(q) or Galpha(16). Phospholipase C (PLC) activity, assessed by inositol phosphate production from preincorporated myo[3H]inositol, was then determined to gain insight into differential coupling preferences among receptors and G proteins. The following were observed: (i) All receptors tested were able to stimulate PLC activity in response to agonist occupation. The effect of the M2R was pertussis toxin sensitive. (ii) While, as expected, expression of Galpha(q) facilitated an agonist-induced activation of PLC that varied widely from receptor to receptor (400% with type 2 vasopressin receptor and only 30% with M2R), expression of Galpha(16) facilitated about equally well the activation of PLC by any of the tested receptors and thus showed little if any discrimination for one receptor over another. (iii) Gbeta gamma elevated basal (agonist independent) PLC activity between 2- and 4-fold, confirming the proven ability of Gbeta gamma to stimulate PLCbeta. (iv) Activation of expressed receptors by their respective ligands in cells coexpressing excess Gbeta gamma elicited agonist stimulated PLC activities, which, in the case of the M2R, was not blocked by pertussis toxin (PTX), suggesting mediation by a PTX-insensitive PLC-stimulating Galpha subunit, presumably, but not necessarily, of the Gq family. (v) The effects of Gbeta gamma and the PTX-insensitive Galpha elicited by M2R were synergistic, suggesting the possibility that one or more forms of PLC are under conditional or dual regulation of G protein subunits such that stimulation by one sensitizes to the stimulation by the other.

Animals↗

PubMed1996

Separate roles for N- and C-termini of the STE4 (beta) subunit of the Saccharomyces cerevisiae G protein in the mediation of the growth arrest. Lack of growth-arresting activity of mammalian beta gamma complexes.

Mating pheromone signal transduction in Saccharomyces cerevisiae involves a G protein composed to Scg1p (Gpa1p), Ste4p and Ste18p subunits, homologous to the alpha, beta and gamma subunits of mammalian G protein. Growth arrest in G1 phase is activated by the Ste4p/Ste18p complex via a downstream pathway and it is negatively controlled by the Scg1p subunit. Here we explored whether mammalian beta or gamma subunits could functionally substitute for their yeast homologues. While no evidence was obtained for functional replacement of Ste4p and Ste18p, we found that overexpression of Ste18p potentiated the effect of hybrid proteins in which the N terminus of the Ste4p subunit was replaced by that of the mammalian beta. ste4 mutants having deletions in the N terminus showed a decreased activity in signalling to the downstream effector of the pheromone response. This defect was totally cured by overexpression of Ste18p, indicating that the truncated forms of Ste4p have retained their ability to form an active complex with Ste18p. Removal of six amino acids from the C terminus of Ste4p rendered a completely inactive subunit and this defect persisted in hybrids where the C terminus was placed by that of the beta subunit, indicating that the C terminus of Ste4p is essential to trigger the effector of the yeast pheromone response pathway.

Amino Acid Sequence↗

PubMed1996

Effective gating charges per channel in voltage-dependent K+ and Ca2+ channels.

In voltage-dependent ion channels, the gating of the channels is determined by the movement of the voltage sensor. This movement reflects the rearrangement of the protein in response to a voltage stimulus, and it can be thought of as a net displacement of elementary charges (e0) through the membrane (z: effective number of elementary charges). In this paper, we measured z in Shaker IR (inactivation removed) K+ channels, neuronal alpha 1E and alpha 1A, and cardiac alpha 1C Ca2+ channels using two methods: (a) limiting slope analysis of the conductance-voltage relationship and (b) variance analysis, to evaluate the number of active channels in a patch, combined with the measurement of charge movement in the same patch. We found that in Shaker IR K+ channels the two methods agreed with a z congruent to 13. This suggests that all the channels that gate can open and that all the measured charge is coupled to pore opening in a strictly sequential kinetic model. For all Ca2+ channels the limiting slope method gave consistent results regardless of the presence or type of beta subunit tested (z = 8.6). However, as seen with alpha 1E, the variance analysis gave different results depending on the beta subunit used. alpha 1E and alpha 1E beta 1a gave higher z values (z = 14.77 and z = 15.13 respectively) than alpha 1E beta 2a (z = 9.50, which is similar to the limiting slope results). Both the beta 1a and beta 2a subunits, coexpressed with alpha 1E Ca2+ channels facilitated channel opening by shifting the activation curve to more negative potentials, but only the beta 2a subunit increased the maximum open probability. The higher z using variance analysis in alpha 1E and alpha 1E beta 1a can be explained by a set of charges not coupled to pore opening. This set of charges moves in transitions leading to nulls thus not contributing to the ionic current fluctuations but eliciting gating currents. Coexpression of the beta 2a subunit would minimize the fraction of nulls leading to the correct estimation of the number of channels and z.

Animals↗

PubMed1996

Identification of a second region of the beta-subunit involved in regulation of calcium channel inactivation.

Previous studies have shown that NH2 termini of the type 1 and 2 beta-subunits modulate the rate at which the neuronal alpha 1E calcium channel inactivates in response to voltage and that they do so independently of their common effect to stimulate activation by voltage (R. Olcese, N. Qin, T. Schneider, A. Neely, X. Wei, E. Stefani, and L. Birnbaumer, Neuron 13: 1433-1438, 1994). By constructing NH2-terminal deletions of several splice variants of beta-subunits, we have now found differences in the way they affect the rate of alpha 1E inactivation that lead us to identify a second domain that also regulates the rate of voltage-induced inactivation of the Ca2+ channel. This second domain, named segment 3, lies between two regions of high-sequence identity between all known beta-subunits and exists in two lengths (long and short), each encoded in a separate exon. Beta-Subunits with the longer 45- to 53-amino acid version cause the channel to inactivate more slowly than subunits with the shorter 7-amino acid version. As is the case for the NH2 terminus, the segment 3 does not affect the regulation of channel activation by the beta-subunit. In addition, the effect of the NH2-terminal segment prevails over that of the internal segment. This raises the possibility that phosphorylation, other types of posttranslational modification, or interaction with other auxiliary calcium channel subunits may be necessary to unmask the regulatory effect of the internal segment.

Alternative Splicing↗

PubMed1996

Subunit composition is a major determinant in high affinity binding of a Ca2+ channel blocker.

Skeletal muscle L-type channels are the pharmacological receptors for Ca2+ channel antagonists, including dihydropyridines (DHPs). High affinity DHP binding to these channels in skeletal muscle membranes has been reported to be independent of Ca2+ addition and to become dependent on Ca2+ after solubilization. The channel is a multimeric complex composed of alpha 1, beta, gamma, and alpha 2 delta, of which alpha 1 is the pore-forming and DHP-binding component. In this study we coexpressed non-alpha 1 components with alpha 1 in L and COS cells and investigated their roles in the regulation of high affinity DHP binding by Mg2+ and Ca2+. No DHP binding to membranes of cells expressing alpha 1 beta alone was detected in the absence of Ca2+ or Mg2+. Addition of Mg2+ revealed the presence of (+)-PN200-110 (DHP) binding sites with a Kd of 1 nM. This affinity was 4-fold lower than that of skeletal muscle membrane binding sites (Kd = 0.25 nM). Addition of Ca2+ increased the affinity for DHP in membranes from alpha 1 beta-expressing cells to that seen in skeletal muscle membranes (Kd = 0.2-0.3 nM; EC50 of 0.2 microM). Ca2+ did not affect DHP binding to skeletal muscle membranes. Coexpression of all of the subunits completely recapitulated the high affinity DHP binding seen with skeletal muscle membranes in the absence of Ca2+ and Mg2+ (Kd = 0.15 nM). This affinity was unaffected by addition of Ca2+ or Mg2+. Coexpression of alpha 1 beta with either alpha 2 delta or gamma alone resulted in DHP binding intermediate between levels seen with alpha 1 beta and alpha 1 beta alpha 2 delta gamma. Thus, this study demonstrates that alpha 2 delta and gamma are essential for full reconstitution of the DHP binding characteristics of the skeletal muscle L-type Ca2+ channel/DHP receptor.

Aniline Compounds↗

PubMed1996

Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac alpha 1C subunit.

The alpha 1 subunit of the cardiac L-type Ca2+ channel (alpha 1C) is one of the many alternatively spliced products of a single gene that is expressed in a number of excitable tissues. Sequence comparison indicates that the amino terminus is a site of significant structural diversity. To explore the role of the amino terminus of alpha 1C in expression and function of Ca2+ channels, we constructed a series of deletion mutants of the rabbit cardiac alpha 1C subunit and expressed them in Xenopus oocytes. Deletions of up to 120 amino acids from the amino terminus increased both ionic and gating currents by 5- to 8-fold. Ca2+ currents induced by these mutants had voltage-dependent activation, inactivation, modulation by beta subunits, and single channel conductance similar to the wild type cardiac alpha 1C (wt alpha 1C). Thus, deletion of a major portion of the amino terminus of alpha 1C did not alter the three dimensional conformation essential for channel function, but enhanced the expression of Ca2+ channels in Xenopus oocytes. A deletion mutant lacking the first 171 amino acids did not yield any measurable current.

Amino Acid Sequence↗

PubMed1996

Reconstitution of the skeletal muscle dihydropyridine receptor. Functional interaction among alpha 1, beta, gamma and alpha 2 delta subunits.

The L-type voltage-dependent Ca2+ channel purified from skeletal muscle by virtue of its dihydropyridine (DHP) binding activity, is composed of alpha 1, alpha 2 delta, beta and gamma subunits. The alpha 1 subunit has the ability to function alone as a Ca2+ channel and a receptor for DHP and other Ca2+ channel antagonists. In this study, the non-alpha 1 components coexpressed with alpha 1 in COS cells were investigated for their effects on DHP binding and suppression of an anomalous allosteric regulation of the phenylalkylamine (-)D600 in complexes lacking one or more subunits. (-)D600 increased DHP binding to membranes of COS cells expressing alpha 1 beta while it did not affect DHP binding to skeletal muscle membranes. Coexpression of gamma or alpha 2 delta with alpha 1 beta partially suppressed this effect. Coexpression of all the subunits completely eliminated the stimulatory effect of (-)D600, while at the same time increasing the affinity of the complex for DHP to that stabilized in partial complexes by the phenylalkylamine. These results demonstrate that all of the components that co-purify are required for the formation of a functional DHP receptor having the properties of the native skeletal muscle DHP receptor.

Animals↗

PubMed1995

Molecular determinants of cardiac Ca2+ channel pharmacology. Subunit requirement for the high affinity and allosteric regulation of dihydropyridine binding.

Cardiac L-type Ca2+ channels are multisubunit complexes composed of alpha 1C, alpha 2 delta, and beta 2 subunits. We tested the roles of these subunits in forming a functional complex by characterizing the effects of subunit composition on dihydropyridine binding, its allosteric regulation, and the ability of dihydropyridines to inhibit channel activity. Transfection of COS.M6 cells with cardiac alpha 1C-a (alpha 1) led to the appearance of dihydropyridine ([3H]PN200-110) binding which was increased by coexpression of cardiac beta 2a (beta), alpha 2 delta a (alpha 2), and the skeletal muscle gamma. Maximum binding was achieved when cells expressed alpha 1, beta, and alpha 2. Cells transfected with alpha 1 and beta had a binding affinity that was 5-10-fold lower than that observed in cardiac membranes. Coexpression of alpha 2 normalized this affinity. (-)-D600 and diltiazem both partially inhibited PN200-100 binding to cardiac microsomes, but stimulated binding in cells transfected with alpha 1 and beta. Again, coexpression of alpha 2 normalized this allosteric regulation. Therefore coexpression of alpha 1 beta and alpha 2 completely reconstituted high affinity dihydropyridine binding and its allosteric regulation as observed in cardiac membranes. Skeletal muscle gamma was not required for this reconstitution. Expression in Xenopus oocytes demonstrated that coexpression of alpha 2 with alpha 1 beta increased the potency and maximum extent of block of Ca2+ channel currents by nisoldipine, a dihydropyridine Ca2+ channel antagonist. Our results demonstrate that alpha 2 subunits are essential components of the cardiac L-type Ca2+ channel and predict a minimum subunit composition of alpha 1C beta 2 alpha 2 delta for this channel.

Allosteric Regulation↗

PubMed1995

Molecular cloning of a widely expressed human homologue for the Drosophila trp gene.

The Drosophila transient receptor potential (trp) gene and its homologue, trpl, have been suggested to mediate calcium entry during the insect's phototransduction process. We isolated a human cDNA, human trp-1 (Htrp-1), encoding a polypeptide of 793 amino acids that is 37% identical (62% similar) to Drosophila trp and trpl. Northern analysis showed that the Htrp-1 transcript is approximately 5.5 kb and expressed in most human tissues, with higher amounts in ovary, testis, heart, and brain. Isolation of Htrp-1 suggests that a trp-type protein is present in mammals and should provide a useful tool in studying calcium-depletion induced calcium influx processes.

Amino Acid Sequence↗