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









Phospholamban (PLB or PLN) 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 myocyte 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 μM). 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). Phospholamban interests with SERCA with conformational memory (Smeazzetto et al. 2017). Under physiological conditions, PLB phosphorylation induces little or no change in the interaction of the TMS with SERCA, so relief of inhibition is predominantly due to the  structural shift in the cytoplasmic domain (Martin et al. 2018). The phospholamban pentamer alters the function of the sarcoplasmic reticulum calcium pump, SERCA (Glaves et al. 2019). PLB phosphorylation serves as an allosteric molecular switch that releases inhibitory contacts and strings together the catalytic elements required for SERCA activation (Aguayo-Ortiz and Espinoza-Fonseca 2020).

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 isoform X1 of 55 aas and 1 TMS.

Eukaryota
Metazoa
Phospholamban of Esox lucius (northern pike)
1.A.50.1.4









Uncharacterized protein of 101 aas and 1 C-terminal TMS.

Eukaryota
Opisthokonta
UP of Acipenser ruthenus (sterlet)
1.A.50.2.1









Sarcolipin (SLN) anion pore-forming protein of 31 aas and 1 TMS, with selectivity for Cl- and H2PO4-. 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).  SNL forms pentameric pores that can transport water, H+, 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). The TM voltage has a positive effect on the permeability of water molecules and ions (Cao et al. 2020). The conserved C-terminus is an essential element required for the dynamic control of SLN regulatory function (Aguayo-Ortiz et al. 2020).

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









Sarcolipin 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. This protein is homologous to a region of several proteins in the DMT family (e.g., TC# 2.A.7.24.10).

Eukaryota
Metazoa
SLN of Ovis aries (Sheep)
1.A.50.2.4









Uncharacterized protein of 205 aas and 2 C-terminal TMSs

Eukaryota
Opisthokonta
UP of Etheostoma spectabile (orangethroat darter)
1.A.50.2.5









Sarcoplipin of 119 aas and 1 C-terminal TMS

Eukaryota
Opisthokonta
Sarcolipin of Equus asinus (ass)
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 and 1 TMS (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). DWORF also activates SERCA in the absence of PLM (Li et al. 2021). Homology with the inhibitory peptides has been established for these peptides, all of which have about the same size with a single C-terminal TMS (D. Tyler & M. Saier, unpublished results). 

Eukaryota
Metazoa
DWORF of Homo sapiens
1.A.50.4.2









Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator, DWORF-like protein, of 37 aas and 1 TMS.

Eukaryota
Metazoa
DWORF of Esox lucius
1.A.50.4.3









DWARF open reading frameof 82 aas and 1 C-terminal TMS.

Eukaryota
Metazoa
DWARF of Oreochromis niloticus
1.A.50.4.4









DWARF open reading frame isoform X1 of 99 aas and 1 C-terminal TMS.

Eukaryota
Metazoa
DWARF of Athene cunicularia
1.A.50.4.5









Dwarf homolog, isoform X2, of 123 aas and 1 C-terminal TMS.

Eukaryota
Metazoa
DWARF of Paramormyrops kingsleyae
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 of 77 aas and 1 TMS

Eukaryota
Metazoa
UP of Monodelphis domestica (Gray short-tailed opossum)
1.A.50.6.5









Uncharacterized protein of 139 aas and one C-terminal TMS.

Eukaryota
Opisthokonta
UP of Oryzias melastigma (Indian medaka)
1.A.50.6.6









Uncharacterized protein of 82 aas and 1 C-terminal TMS.

Eukaryota
Opisthokonta
UP of Platysternon megacephalum (big-headed turtle)