TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.50.1.1









Phospholamban (PLB) pentameric Ca2+/K+ channel (Kovacs et al., 1988; Smeazzetto et al. 2013; Smeazzetto et al. 2014).  In spite of extensive experimental evidence, suggesting a pore size of 2.2 Å, the conclusion of ion channel activity for phospholamban has been questioned (Maffeo and Aksimentiev 2009).  Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca2+ ATPase (SERCA). This cyclic mechanism constitutes the driving force for calcium reuptake from the cytoplasm into the myocite lumen, regulating cardiac contractility. PLN undergoes a conformational transition between a relaxed (R) and tense (T) state, an equilibrium perturbed by the addition of SERCA. Phosphoryl transfer to Ser16 induces a conformational switch to the R state. The binding affinity of PLN to SERCA is not affected ((Kd ~ 60 microM). However, the binding surface and dynamics in domain Ib (residues 22-31) change substantially upon phosphorylation. Since PLN can be singly or doubly phosphorylated at Ser16 and Thr17, these sites may remotely control the conformation of domain Ib (Traaseth et al. 2006).

Eukaryota
Metazoa
PLB of Homo sapiens (P26678)
*1.A.50.1.2









Cardiac phospholamban-like protein of 131 aas and 1 TMS.

Eukaryota
Metazoa
Phospholamban of Scleropages formosus
*1.A.50.1.3









Cardiac phospholamban of 55 aas and 1 TMS.

Eukaryota
Metazoa
Phospholamban of Esox lucius (northern pike)
*1.A.50.2.1









Sarcolipin (SLN). Oligomeric interactions of sarcolipin and the Ca-ATPase have been documented (Autry et al., 2011).  Sarcolipin, but not phospholamban, promotes uncoupling of the SERCA pump (3.A.3.2.7; Sahoo et al. 2013).  Forms a pentameric pore that can transport water, Na+, Ca2+ and Cl-.  Leu21 serves as the gate (Cao et al. 2015).   In the channel, water molecules near the Leu21 pore demonstrated a clear hydrated-dehydrated transition (Cao et al. 2016). Small ankyrin 1 (sAnk1; TC#8.A.28.1.2) and SLN interact with each other in their transmembrane domains to regulate SERCA (TC# 3.A.3.2.7) (Desmond et al. 2017).

Eukaryota
Metazoa
SLN of Homo sapiens (O00631)
*1.A.50.2.2









sarcolipin-like protein of 32 aas and 1 TMS.

Eukaryota
Metazoa
Sarcolipin of Esox lucius (northern pike)
*1.A.50.2.3









Sarcolipin-like protein (SLN) of 31 aas and 1 TMS

Eukaryota
Metazoa
SLN of Ovis aries (Sheep)
*1.A.50.3.1









Myoregulin of 46 aas (Anderson et al. 2015).

Eukaryota
Metazoa
Myoregulin of Homo sapiens
*1.A.50.3.2









Myoregulin of 43 aas

Eukaryota
Metazoa
Myoregulin of Echinops telfairi
*1.A.50.3.3









Myoregulin of 105 aas

Eukaryota
Metazoa
Myoregulin of Sarcophilus harrisii (Tasmanian devil) (Sarcophilus laniarius)
*1.A.50.4.1









DWORF of 34 aas; synthetic construct (Nelson et al. 2016).  Counteracts the inhibitory effects of single transmembrane peptides, phospholamban (TC# 1.A.50.1), sarcolipin (1.A.50.2) and myoregulin (1.A.50.3), on SERCA (TC# 3.A.3.2).  Homology with the inhibitory peptides has not been established although all of these peptides have about the same size with a single C-terminal TMS. 

DWORF, made synthetically, probably copied from DWORF of Mus musculus
*1.A.50.5.1









Endoregulin, ELN, also called small integral membrane protein-6, SMIM6, is of 62 aas and 1 TMS.  This protein and the other members of the phospholamban family have been designated "micropeptides". Micropeptides function as regulators of calcium-dependent signaling in muscle. The sarco/endoplasmic reticulum Ca2+ ATPase (SERCA TC# 3.A.3.2.7), is the membrane pump that promotes muscle relaxation by taking up Ca2+ into the sarcoplasmic reticulum. It is directly inhibited by three known muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN) and sarcolipin (SLN). In non muscle cells, there are two other such micopeptides, endoregulin (ELN) and "another-regulin (ALN) (Anderson et al. 2016).  Endoregulin is also known as "small integral membrane protein-6" (SMIM6) while ALN is also known as Protein C4 orf3 (C4orf3).  These proteins share key amino acids with their muscle-specific counterparts and function as direct inhibitors of SERCA pump activity. The distribution of transcripts encoding ELN and ALN mirrored that of SERCA isoform-encoding transcripts in nonmuscle cell types. Thus, these two proteins are additional members of the SERCA-inhibitory micropeptide family, revealing a conserved mechanism for the control of intracellular Ca2+ dynamics in both muscle and nonmuscle cell types (Anderson et al. 2016).

Eukaryota
Metazoa
Endoregulin of Homo sapiens
*1.A.50.5.2









ELN homologue of 78 aas and 1 TMS.

Eukaryota
Metazoa
ELN homologue of Nothobranchius furzeri
*1.A.50.5.3









ELN homologue of 75 aas and 1 TMS.

Eukaryota
Metazoa
ELN of Larimichthys crocea (large yellow croaker)
*1.A.50.5.4









Bacterial ELN homologue of unknown function with 101 aas and 1 TMS

Bacteria
Proteobacteria
ELN homologue of Desulfobacteraceae bacterium
*1.A.50.5.5









ELN homologue of 85 aas and 1 TMS

Bacteria
Thermotogae
ELN homologue of Thermotoga sp.
*1.A.50.6.1









"Another-regulin", ALN, of 66 aas and 1 TMS.  Also called Protein C4orf3. This protein and the other members of the phospholamban family have been designated "micropeptides". Micropeptides function as regulators of calcium-dependent signaling in muscle. The sarco/endoplasmic reticulum Ca2+ ATPase (SERCA, TC# 3.A.3.2.7), is the membrane pump that promotes muscle relaxation by taking up Ca2+ into the sarcoplasmic reticulum. It is directly inhibited by three known muscle-specific micropeptides: myoregulin (MLN), phospholamban (PLN) and sarcolipin (SLN). In non muscle cells, there are two other such micopeptides, endoregulin (ELN) and "another-regulin" (ALN) (Anderson et al. 2016). These proteins share key amino acids with their muscle-specific counterparts and function as direct inhibitors of SERCA pump activity. The distribution of transcripts encoding ELN and ALN mirror that of SERCA isoform-encoding transcripts in nonmuscle cell types. Thus, these two proteins are additional members of the SERCA-inhibitory micropeptide family, revealing a conserved mechanism for the control of intracellular Ca2+ dynamics in both muscle and nonmuscle cell types (Anderson et al. 2016).

Eukaryota
Metazoa
ALN in Homo sapiens
*1.A.50.6.2









Uncharacterized protein of 93 aas and 1 TMS.

Eukaryota
Metazoa
UP of Larimichthys crocea (large yellow croaker)
*1.A.50.6.3









Uncharacterized protein of 104 aas and 1 TMS

Eukaryota
Metazoa
UP of Xenopus laevis (African clawed frog)
*1.A.50.6.4









Uncharacterized C4orf3 homologue of77 aas and 1 TMS

Eukaryota
Metazoa
UP of Monodelphis domestica (Gray short-tailed opossum)