CMD1/YBR109C Summary Help

Standard Name CMD1 1
Systematic Name YBR109C
Feature Type ORF, Verified
Description Calmodulin; Ca++ binding protein that regulates Ca++ independent processes (mitosis, bud growth, actin organization, endocytosis, etc.) and Ca++ dependent processes (stress-activated pathways), targets include Nuf1p, Myo2p and calcineurin (2, 3, 4, 5, 6, 7, 8, 9 and see Summary Paragraph)
Also known as: CaM 10
Name Description CalMoDulin
Chromosomal Location
ChrII:458362 to 457919 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 53 cM
Gene Ontology Annotations All CMD1 GO evidence and references
  View Computational GO annotations for CMD1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 5 genes
Classical genetics
Large-scale survey
reduction of function
289 total interaction(s) for 196 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 92
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 20
  • Biochemical Activity: 4
  • Co-crystal Structure: 1
  • Co-fractionation: 1
  • Co-purification: 1
  • Far Western: 1
  • FRET: 5
  • PCA: 1
  • Protein-peptide: 6
  • Reconstituted Complex: 41
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 18
  • Negative Genetic: 71
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Positive Genetic: 4
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 6
  • Synthetic Rescue: 3

Expression Summary
Length (a.a.) 147
Molecular Weight (Da) 16,135
Isoelectric Point (pI) 4.01
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrII:458362 to 457919 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 53 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..444 458362..457919 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000313

Calmodulin (also referred to as CaM) is a small, essential Ca2+ binding protein encoded by CMD1 that regulates many processes including response to various stress conditions, mating, budding, and actin-based processes (7). This wide range of roles is possible because calmodulin undergoes a conformational change upon calcium binding. The apo-calcium form has a very different structure than the calcium bound form and thus binds to a different set of protein targets (7). Although calmodulin is essential (3, 4), the essential functions mediated by calmodulin do not require calcium-binding, as cells with mutant forms of calmodulin which lack the ability to bind Ca2+ are viable and have only minor defects in growth and morphology in standard laboratory conditions (11). Some of the Ca2+-dependent targets of calmodulin only become essential in response to various stress conditions (7). Thus calmodulin has many targets, both Ca2+-dependent and Ca2+-independent.

Ca2+-independent roles of Calmodulin

Ca2+-independent targets of calmodulin, some of which are essential genes, play roles in the organization and formation of the spindle pole body (SPB), karyogamy, actin cytoskeletal organization and bud emergence, endocytosis, and microautophagy. Calmodulin localizes to the central plaque of the spindle pole body through its interaction with Spc110p (12, 13). Binding by calmodulin is required for correct localization of the essential Spc110p component to the SPB and thus the formation of the SPB (7, 14) and also for karyogamy (15). Calmodulin also interacts with Myo2p, one of two type V myosin heavy chains (16). Through its interaction with Myo2p, calmodulin is required for polarized growth of yeast cells and inheritance of the vacuole by daughter cells (7). Calmodulin may also interact with the other type V heavy chain encoded by Myo4p (7). Through interactions with both the unconventional type I myosin, encoded by MYO5, and Arc35p, a component of the Arp2/3 complex, calmodulin is also required for receptor-mediated endocytosis (17, 2, 7). Calmodulin is also involved in microautophagy, a role which may be mediated by Vtc2p and Vtc3p (18).

Ca2+-dedependent roles of Calmodulin

Calmodulin also has multiple Ca2+-dependent targets, including calcineurin and calmodulin-stimulated protein kinases. Calcineurin, or PP2B, is a Ca2+ and calmodulin dependent phosphatase that is highly conserved amongst eukaryotic organisms and regulates many different processes. Calcineurin is composed of a heterodimer of a catalytic A subunit, encoded by CMP2 and CNA1, and a regulatory B subunit, encoded by CNB1, which is an EF-hand domain protein related to calmodulin. When stimulatory levels of Ca2+ are present, calcium-bound calmodulin binds to the A subunit, displacing an autoinhibitory domain of the A subunit. In yeast, calcineurin regulates at least three different processes: a stress-activated transcriptional pathway, calcium homeostasis, and the G2 to M transition of the cell cycle. Calmodulin also regulates calcium and calmodulin dependent kinases, of which there are two in S. cerevisiae, encoded by CMK1 and CMK2. In the presense of calcium and calmodulin, they become autophosphorylated and can phosphorylate many different substrates. The calmodulin-dependent kinases regulate a number of different stress responses, including response to mating pheromone, response to organic acids, and tolerance to heat stress (7).

Other roles of Calmodulin

Calmodulin plays additional roles in the cell, and it is not yet clear whether these processes are dependent on or independent of calcium. Calmodulin plays a role in vacuole fusion. Some calmodulin mutants display abnormal vacuolar morphologies, calmodulin binds to vacuoles in a Ca2+-dependent manner, and in vitro assays indicate that calmodulin is required for a post-docking step in vacuole fusion (6). However, it is not clear whether this process requires calcium as a non-calcium binding mutant shows normal vacuolar morphology in vivo (7) and variable results have been obtained in assays testing whether the non-calcium binding mutant protein supports vacuolar fusion in vitro (9). The effect of calmodulin on vacuolar fusion may be due to its affects on remodelling of the actin cytoskeleton (19). Overexpression of Mss4p, a phosphatidylinositol-4-phosphate 5-kinase involved in the organization of the actin cytoskeleton, suppresses the actin cytoskeleton defects of a particular calmodulin mutation, which also causes reduced levels of phosphatidylinositol (4,5)-bisphosphate (8).

Structure of calmodulin and comparison with those from other organims

Calmodulin is a highly conserved protein found in all eukaryotes, including animals, plants, and fungi. While the amino acid sequences of calmodulins from multicellular organisms are more than 90% identical, that from S. cerevisiae is significantly diverged, with only 60% identity to vertebrate calmodulins. Calmodulin contains four EF-hand domains; in most species, including S. pombe, each motif chelates one Ca2+ ion. However, in calmodulin from S. cerevisiae, the fourth motif is divergent and does not bind calcium, making it the only yet characterized calmodulin to bind less than four Ca2+ ions. Despite these structural differences between calmodulin of S. cerevisiae and other organisms, its basic functions appear to be conserved (7).

Last updated: 2007-07-24 Contact SGD

References cited on this page View Complete Literature Guide for CMD1
1) Davis, T.  (1992) Personal Communication, Mortimer Map Edition 11
2) Kubler E, et al.  (1994) Calcium-independent calmodulin requirement for endocytosis in yeast. EMBO J 13(23):5539-46
3) Davis TN, et al.  (1986) Isolation of the yeast calmodulin gene: calmodulin is an essential protein. Cell 47(3):423-31
4) Ohya Y and Botstein D  (1994) Diverse essential functions revealed by complementing yeast calmodulin mutants. Science 263(5149):963-6
5) Starovasnik MA, et al.  (1993) Similarities and differences between yeast and vertebrate calmodulin: an examination of the calcium-binding and structural properties of calmodulin from the yeast Saccharomyces cerevisiae. Biochemistry 32(13):3261-70
6) Peters C and Mayer A  (1998) Ca2+/calmodulin signals the completion of docking and triggers a late step of vacuole fusion. Nature 396(6711):575-80
7) Cyert MS  (2001) Genetic analysis of calmodulin and its targets in Saccharomyces cerevisiae. Annu Rev Genet 35:647-72
8) Desrivieres S, et al.  (2002) Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae. Biochem J 366(Pt 3):945-51
9) Starai VJ, et al.  (2005) Ion regulation of homotypic vacuole fusion in Saccharomyces cerevisiae. J Biol Chem 280(17):16754-62
10) Spang A, et al.  (1996) The spacer protein Spc110p targets calmodulin to the central plaque of the yeast spindle pole body. J Cell Sci 109 ( Pt 9)():2229-37
11) Geiser JR, et al.  (1991) Can calmodulin function without binding calcium? Cell 65(6):949-59
12) Stirling DA, et al.  (1994) Interaction with calmodulin is required for the function of Spc110p, an essential component of the yeast spindle pole body. EMBO J 13(18):4329-42
13) Geiser JR, et al.  (1993) The essential mitotic target of calmodulin is the 110-kilodalton component of the spindle pole body in Saccharomyces cerevisiae. Mol Cell Biol 13(12):7913-24
14) Sun GH, et al.  (1992) Mutations in yeast calmodulin cause defects in spindle pole body functions and nuclear integrity. J Cell Biol 119(6):1625-39
15) Okano H and Ohya Y  (2003) Binding of calmodulin to Nuf1p is required for karyogamy in Saccharomyces cerevisiae. Mol Genet Genomics 269(5):649-57
16) Brockerhoff SE and Davis TN  (1992) Calmodulin concentrates at regions of cell growth in Saccharomyces cerevisiae. J Cell Biol 118(3):619-29
17) Geli MI, et al.  (1998) Distinct functions of calmodulin are required for the uptake step of receptor-mediated endocytosis in yeast: the type I myosin Myo5p is one of the calmodulin targets. EMBO J 17(3):635-47
18) Uttenweiler A, et al.  (2005) Microautophagic vacuole invagination requires calmodulin in a Ca2+-independent function. J Biol Chem 280(39):33289-97
19) Eitzen G, et al.  (2002) Remodeling of organelle-bound actin is required for yeast vacuole fusion. J Cell Biol 158(4):669-79