| Type |
Details |
Score |
| Publication |
| First Author: |
Imai A |
| Year: |
2006 |
| Journal: |
Arch Biochem Biophys |
| Title: |
Functional involvement of Noc2, a Rab27 effector, in rat parotid acinar cells. |
| Volume: |
455 |
| Issue: |
2 |
| Pages: |
127-35 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lahn M |
| Year: |
2006 |
| Journal: |
Acta Haematol |
| Title: |
The role of protein kinase C-alpha in hematologic malignancies. |
| Volume: |
115 |
| Issue: |
1-2 |
| Pages: |
1-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lahn MM |
| Year: |
2004 |
| Journal: |
Melanoma Res |
| Title: |
The role of protein kinase C-alpha (PKC-alpha) in melanoma. |
| Volume: |
14 |
| Issue: |
2 |
| Pages: |
85-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lahn M |
| Year: |
2004 |
| Journal: |
Eur J Cancer |
| Title: |
The role of protein kinase C-alpha (PKC-alpha) in malignancies of the gastrointestinal tract. |
| Volume: |
40 |
| Issue: |
1 |
| Pages: |
10-20 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Sharma GD |
| Year: |
2007 |
| Journal: |
Exp Eye Res |
| Title: |
Protein kinase C alpha and epsilon differentially modulate hepatocyte growth factor-induced epithelial proliferation and migration. |
| Volume: |
85 |
| Issue: |
2 |
| Pages: |
289-97 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Castro-Galache MD |
| Year: |
2007 |
| Journal: |
Int J Biochem Cell Biol |
| Title: |
Protein kinase C-alpha antagonizes apoptosis induction by histone deacetylase inhibitors in multidrug resistant leukaemia cells. |
| Volume: |
39 |
| Issue: |
10 |
| Pages: |
1877-85 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Tan M |
| Year: |
2006 |
| Journal: |
Oncogene |
| Title: |
Upregulation and activation of PKC alpha by ErbB2 through Src promotes breast cancer cell invasion that can be blocked by combined treatment with PKC alpha and Src inhibitors. |
| Volume: |
25 |
| Issue: |
23 |
| Pages: |
3286-95 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Herbst RS |
| Year: |
2007 |
| Journal: |
Clin Cancer Res |
| Title: |
Enzastaurin, a protein kinase Cbeta- selective inhibitor, and its potential application as an anticancer agent in lung cancer. |
| Volume: |
13 |
| Issue: |
15 Pt 2 |
| Pages: |
s4641-6 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lang GE |
| Year: |
2007 |
| Journal: |
Dev Ophthalmol |
| Title: |
Treatment of diabetic retinopathy with protein kinase C subtype Beta inhibitor. |
| Volume: |
39 |
|
| Pages: |
157-65 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Idris I |
| Year: |
2006 |
| Journal: |
Diab Vasc Dis Res |
| Title: |
Protein kinase C beta inhibition: A novel therapeutic strategy for diabetic microangiopathy. |
| Volume: |
3 |
| Issue: |
3 |
| Pages: |
172-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yan SF |
| Year: |
2006 |
| Journal: |
J Am Coll Cardiol |
| Title: |
Protein kinase C beta/early growth response-1 pathway: a key player in ischemia, atherosclerosis, and restenosis. |
| Volume: |
48 |
| Issue: |
9 Suppl 1 |
| Pages: |
A47-55 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Avignon A |
| Year: |
2006 |
| Journal: |
Diabetes Metab |
| Title: |
PKC-B inhibition: a new therapeutic approach for diabetic complications? |
| Volume: |
32 |
| Issue: |
3 |
| Pages: |
205-13 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Sledge GW Jr |
| Year: |
2006 |
| Journal: |
Semin Oncol |
| Title: |
Protein kinase C-beta as a therapeutic target in breast cancer. |
| Volume: |
33 |
| Issue: |
3 Suppl 9 |
| Pages: |
S15-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Martin PM |
| Year: |
2005 |
| Journal: |
Expert Opin Ther Targets |
| Title: |
PKC eta as a therapeutic target in glioblastoma multiforme. |
| Volume: |
9 |
| Issue: |
2 |
| Pages: |
299-313 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Steinberg SF |
| Year: |
2004 |
| Journal: |
Biochem J |
| Title: |
Distinctive activation mechanisms and functions for protein kinase Cdelta. |
| Volume: |
384 |
| Issue: |
Pt 3 |
| Pages: |
449-59 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Basu A |
| Year: |
2003 |
| Journal: |
J Cell Mol Med |
| Title: |
Involvement of protein kinase C-delta in DNA damage-induced apoptosis. |
| Volume: |
7 |
| Issue: |
4 |
| Pages: |
341-50 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Brodie C |
| Year: |
2003 |
| Journal: |
Apoptosis |
| Title: |
Regulation of cell apoptosis by protein kinase c delta. |
| Volume: |
8 |
| Issue: |
1 |
| Pages: |
19-27 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kikkawa U |
| Year: |
2002 |
| Journal: |
J Biochem |
| Title: |
Protein kinase C delta (PKC delta): activation mechanisms and functions. |
| Volume: |
132 |
| Issue: |
6 |
| Pages: |
831-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Ramnath RD |
| Year: |
2010 |
| Journal: |
J Mol Med (Berl) |
| Title: |
PKC δ mediates pro-inflammatory responses in a mouse model of caerulein-induced acute pancreatitis. |
| Volume: |
88 |
| Issue: |
10 |
| Pages: |
1055-63 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Vanhaesebroeck B |
| Year: |
1997 |
| Journal: |
Trends Biochem Sci |
| Title: |
Phosphoinositide 3-kinases: a conserved family of signal transducers. |
| Volume: |
22 |
| Issue: |
7 |
| Pages: |
267-72 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hikida M |
| Year: |
2005 |
| Journal: |
Adv Immunol |
| Title: |
Regulation of phospholipase C-gamma2 networks in B lymphocytes. |
| Volume: |
88 |
|
| Pages: |
73-96 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kurosaki T |
| Year: |
2001 |
| Journal: |
Int Rev Immunol |
| Title: |
Regulation of phospholipase C-gamma2 and phosphoinositide 3-kinase pathways by adaptor proteins in B lymphocytes. |
| Volume: |
20 |
| Issue: |
6 |
| Pages: |
697-711 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Carpenter G |
| Year: |
1999 |
| Journal: |
Exp Cell Res |
| Title: |
Phospholipase C-gamma as a signal-transducing element. |
| Volume: |
253 |
| Issue: |
1 |
| Pages: |
15-24 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Patterson RL |
| Year: |
2005 |
| Journal: |
Trends Biochem Sci |
| Title: |
Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling. |
| Volume: |
30 |
| Issue: |
12 |
| Pages: |
688-97 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lawson ND |
| Year: |
2003 |
| Journal: |
Genes Dev |
| Title: |
phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development. |
| Volume: |
17 |
| Issue: |
11 |
| Pages: |
1346-51 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Choi JH |
| Year: |
2007 |
| Journal: |
Adv Enzyme Regul |
| Title: |
On/off-regulation of phospholipase C-gamma 1-mediated signal transduction. |
| Volume: |
47 |
|
| Pages: |
104-16 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Suh PG |
| Year: |
2008 |
| Journal: |
BMB Rep |
| Title: |
Multiple roles of phosphoinositide-specific phospholipase C isozymes. |
| Volume: |
41 |
| Issue: |
6 |
| Pages: |
415-34 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Wang Z |
| Year: |
2002 |
| Journal: |
Mol Interv |
| Title: |
Phospholipase C-gamma1: a phospholipase and guanine nucleotide exchange factor. |
| Volume: |
2 |
| Issue: |
6 |
| Pages: |
352-5,338 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Collazos A |
| Year: |
2011 |
| Journal: |
Biochem J |
| Title: |
Site recognition and substrate screens for PKN family proteins. |
| Volume: |
438 |
| Issue: |
3 |
| Pages: |
535-43 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Unsal-Kacmaz K |
| Year: |
2012 |
| Journal: |
Mol Oncol |
| Title: |
The interaction of PKN3 with RhoC promotes malignant growth. |
| Volume: |
6 |
| Issue: |
3 |
| Pages: |
284-98 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Manser C |
| Year: |
2008 |
| Journal: |
FEBS Lett |
| Title: |
Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport. |
| Volume: |
582 |
| Issue: |
15 |
| Pages: |
2303-2308 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kajimoto K |
| Year: |
2011 |
| Journal: |
Am J Physiol Heart Circ Physiol |
| Title: |
Hypotonic swelling-induced activation of PKN1 mediates cell survival in cardiac myocytes. |
| Volume: |
300 |
| Issue: |
1 |
| Pages: |
H191-200 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lim WG |
| Year: |
2005 |
| Journal: |
Cell Signal |
| Title: |
The last five amino acid residues at the C-terminus of PRK1/PKN is essential for full lipid responsiveness. |
| Volume: |
17 |
| Issue: |
9 |
| Pages: |
1084-97 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Sheriff S |
| Year: |
1994 |
| Journal: |
Nat Struct Biol |
| Title: |
Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil. |
| Volume: |
1 |
| Issue: |
11 |
| Pages: |
789-94 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kawasaki N |
| Year: |
1989 |
| Journal: |
J Biochem |
| Title: |
A serum lectin (mannan-binding protein) has complement-dependent bactericidal activity. |
| Volume: |
106 |
| Issue: |
3 |
| Pages: |
483-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Nauta AJ |
| Year: |
2003 |
| Journal: |
Eur J Immunol |
| Title: |
Mannose-binding lectin engagement with late apoptotic and necrotic cells. |
| Volume: |
33 |
| Issue: |
10 |
| Pages: |
2853-63 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Matsushita M |
| Year: |
1992 |
| Journal: |
J Exp Med |
| Title: |
Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. |
| Volume: |
176 |
| Issue: |
6 |
| Pages: |
1497-502 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yi SJ |
| Year: |
2009 |
| Journal: |
J Biol Chem |
| Title: |
Transglutaminase 2 regulates the GTPase-activating activity of Bcr. |
| Volume: |
284 |
| Issue: |
51 |
| Pages: |
35645-51 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yi SJ |
| Year: |
2011 |
| Journal: |
BMC Biochem |
| Title: |
Bcr is a substrate for Transglutaminase 2 cross-linking activity. |
| Volume: |
12 |
|
| Pages: |
8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Vaughan EM |
| Year: |
2011 |
| Journal: |
Curr Biol |
| Title: |
Control of local Rho GTPase crosstalk by Abr. |
| Volume: |
21 |
| Issue: |
4 |
| Pages: |
270-7 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Groffen J |
| Year: |
1997 |
| Journal: |
Baillieres Clin Haematol |
| Title: |
The chimeric BCR-ABL gene. |
| Volume: |
10 |
| Issue: |
2 |
| Pages: |
187-201 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
McWhirter JR |
| Year: |
1993 |
| Journal: |
Mol Cell Biol |
| Title: |
A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins. |
| Volume: |
13 |
| Issue: |
12 |
| Pages: |
7587-95 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Jeyabalan N |
| Year: |
2016 |
| Journal: |
Front Cell Neurosci |
| Title: |
SYNGAP1: Mind the Gap. |
| Volume: |
10 |
|
| Pages: |
32 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hamdan FF |
| Year: |
2011 |
| Journal: |
Biol Psychiatry |
| Title: |
De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. |
| Volume: |
69 |
| Issue: |
9 |
| Pages: |
898-901 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Siao W |
| Year: |
2016 |
| Journal: |
J Exp Bot |
| Title: |
Arabidopsis SYT1 maintains stability of cortical endoplasmic reticulum networks and VAP27-1-enriched endoplasmic reticulum-plasma membrane contact sites. |
| Volume: |
67 |
| Issue: |
21 |
| Pages: |
6161-6171 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Suzuki M |
| Year: |
2012 |
| Journal: |
Acta Crystallogr D Biol Crystallogr |
| Title: |
The structure of L-amino-acid ligase from Bacillus licheniformis. |
| Volume: |
68 |
| Issue: |
Pt 11 |
| Pages: |
1535-40 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Gerber SH |
| Year: |
2001 |
| Journal: |
EMBO J |
| Title: |
An unusual C(2)-domain in the active-zone protein piccolo: implications for Ca(2+) regulation of neurotransmitter release. |
| Volume: |
20 |
| Issue: |
7 |
| Pages: |
1605-19 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lewis JD |
| Year: |
2010 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Arabidopsis synaptotagmin SYTA regulates endocytosis and virus movement protein cell-to-cell transport. |
| Volume: |
107 |
| Issue: |
6 |
| Pages: |
2491-6 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Chapman ER |
| Year: |
2008 |
| Journal: |
Annu Rev Biochem |
| Title: |
How does synaptotagmin trigger neurotransmitter release? |
| Volume: |
77 |
|
| Pages: |
615-41 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Eckardt NA |
| Year: |
2008 |
| Journal: |
Plant Cell |
| Title: |
Arabidopsis synaptotagmin1 maintains plasma membrane integrity. |
| Volume: |
20 |
| Issue: |
12 |
| Pages: |
3182 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yamazaki T |
| Year: |
2008 |
| Journal: |
Plant Cell |
| Title: |
Calcium-dependent freezing tolerance in Arabidopsis involves membrane resealing via synaptotagmin SYT1. |
| Volume: |
20 |
| Issue: |
12 |
| Pages: |
3389-404 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a β-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerises to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell [].This entry represents the SMP domain found in plant synaptotagmins []and extended synaptotagmins from metazoa. The extended synaptotagmins transport glycerolipids between the two bilayers via their lipid-harboring SMP domains and Ca2 + regulates their membrane tethering and lipid transport function []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Synaptotagmin-like protein 5 (SYTL5 or Slp5) is a novel Rab27A-specific effector that is highly expressed in placenta and liver. Slp5 specifically interacted with the GTP-bound form of Rab27A and is involved in Rab27A-dependent membrane trafficking in specific tissues. Slp5 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp5 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif [].This entry represents the FYVE-related domain found in SYTL5. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway [, ]. Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound []. Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration [].Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Synaptotagmin-4 (SYT4) belongs to the synaptotagmin family, which is a group of membrane-trafficking proteins that contain two C-terminal C2 domains. Most of the synaptotagmins have a unique N-terminal domain that is involved in membrane anchoring or specific ligand binding. This entry represents SYT4 from chordates. SYT4 is a Ca2+-sensor in the fly but not in the rat []. Like all synaptotagmins, SYT4 contains the highly conserved C2A and C2B calcium-binding domains, but an amino acid substitution found in the C2A domain decreases SYT4's affinity for calcium under some conditions [, ]. In adult hypothalamic oxytocin neurons, SYT4 is specifically induced by high-fat diet, and this negatively regulates oxytocin exocytosis, which is associated with obesity []. In humans the SYT4 gene is localised to a locus linked to schizophrenia and bipolar disorder []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome [].One of the subunits of the APC that is required for its ubiquitination activity is Doc1/Apc10, a protein composed of a Doc1 homology domain that has been identified in a number of diverse putative E3 ubiquitin ligases []. The Doc1 homology domain forms a β-sandwich structure that is related in architecture to the galactose-binding domain of galactose oxidase, the coagulation factor C2 domain and a domain of XRCC1. This group represents a subgroup of subunit 10. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Synaptotagmin-17 (SYT17) belongs to the synaptotagmin family, which is a group of membrane-trafficking proteins that contain two C-terminal C2 domains. Although synaptotagmins have been found to have a unique N-terminal domain that is involved in membrane anchoring (e.g., synaptotagmin) or specific ligand binding (e.g., rabphilin-3A and Doc2, ), SYT17 does not contain this domain. SYT17 is highly expressed in brain and kidney (B/K) []. However, despite the lack of a transmembrane domain, it is tightly bound to the membrane fraction after treatment with high concentration of salt or high pH. Deletion and mutation analyses indicate that the cysteine cluster at the N terminus is essential for membrane localisation of SYT17. When wild-type SYT17 is expressed in PC12 cells, SYT17 proteins are localised mainly to the perinuclear region (trans-Golgi network), whereas mutant SYT17 carrying Cys-to-Ala substitutions are cytosolic []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway [, ]. Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound []. Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration [].Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras [].This entry represents the N-terminal SH2 domain. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Ras GTPase-activating protein 1 (also known as p120-RasGAP) is an inhibitory regulator of the Ras-cyclic AMP pathway [, ]. Its C-terminal catalytic domain promotes GTP hydrolysis and plays a key role in the regulation of Ras-GTP bound []. Its N-terminal part contains two SH2, SH3, PH (pleckstrin homology) and CaLB/C2 (calcium-dependent phospholipid-binding domain) domains, which allow various functions such as anti-/pro-apoptosis, proliferation and cell migration [].Alternative splicing results in two isoforms. The shorter isoform which lacksthe N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains two SH2 domains, an SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras [].This entry represents the C-terminal SH2 domain. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
NADH:ubiquinone oxidoreductase (complex I) () is a respiratory-chain enzyme that catalyses the transfer of two electrons from NADH to ubiquinone in a reaction that is associated with proton translocation across the membrane (NADH + ubiquinone = NAD+ + ubiquinol) []. Complex I is a major source of reactive oxygen species (ROS) that are predominantly formed by electron transfer from FMNH(2). Complex I is found in bacteria, cyanobacteria (as a NADH-plastoquinone oxidoreductase), archaea [], mitochondria, and in the hydrogenosome, a mitochondria-derived organelle. In general, the bacterial complex consists of 14 different subunits, while the mitochondrial complex contains homologues to these subunits in addition to approximately 31 additional proteins [].This family consists of several NADH dehydrogenase [ubiquinone]1 subunit C2 (NDUC2 or NDUFC2, also known as NADH-ubiquinone oxidoreductase subunit b14.5b) proteins. It is an accessory protein, not involved in catalysis [, ]. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs) [, , ], that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis []. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminal and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DOCKER domain () is a GEF catalytic domain organised into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe C, which form an antiparallel four α-helical bundle and contains a loop known as the nucleotide sensor characterised by a conserved valine residue essential for catalytic activity [, ]. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents a conserved region within a number of eukaryotic dedicator of cytokinesis proteins (DOCK), which are guanine nucleotide exchange factors (GEFs) [, , ], that activate some small GTPases by exchanging bound GDP for free GTP such as Rac. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis []. These proteins have a DOCK-homology region 1 (DHR-1, also known as DOCK-type C2 domain) at the N-terminal and a DHR-2 (also known as DOCKER domain) at the C-terminal. The DOCKER domain () is a GEF catalytic domain organised into three lobes, A, B and C, with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. This entry represents Lobe A, formed from an antiparallel array of α-helices that adopts a tetratricopeptide repeat-like fold, which through extensive contacts with lobe B, stabilises DHR-2 domain [, ]. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain [, ]. Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium []. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types [, , ]. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses [, ]. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Protein kinases C (PKCs) constitute a family ofSer/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain [, ]. Conventional PKCs (cPKCs) have functional C1A and C1B domains, and a C2 domain. PKCs undergo three phosphorylations in order to take mature forms [, ]. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine for activation. There are three conventional PKC isoenzymes (alpha, beta, and gamma).PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility [, ]. It plays a role in the signalling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumours [, , , ]. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain [, ]. Conventional PKCs (cPKCs) have functional C1A and C1B domains, and a C2 domain. PKCs undergo three phosphorylations in order to take mature forms [, ]. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine for activation. There are three conventional PKC isoenzymes (alpha, beta, and gamma).The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function [, , , ]. PKC-beta is also being explored as a therapeutic target in cancer [, ]. It contributes to tumour formation and is involved in the tumour host mechanisms of inflammation and angiogenesis []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Protein kinases C (PKCs) constitute a family of Ser/Thr kinases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain [, ]. Novel PKCs (nPKCs) comprise delta, epsilon, eta, and theta isoforms, which have tandem C1 domains and a C2 domain that does not bind calcium []. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation []. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development []. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This represents a conserved region approximately 180 residues long within eukaryotic copines. Copines are Ca2+-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth []. They were originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes []. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding [, ]. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
The active zone is the presynaptic region in the nerve terminals that mediates neurotransmitter release and is composed a dense collection of proteins called the cytomatrix at the active zone (CAZ). The CAZ proteins are thought to mediate synapse formation and regulate neurotransmitter release [, ].RIM proteins are scaffolding proteins at the active zone which bind to several other presynaptic proteins. The long isoforms of RIM proteins, which contain N-terminal Rab3 and Munc13 interacting domains, as well as a central PDZ domain and two C-terminal C2 domains, are encoded by two genes, Rim1 and Rim2 []. They have multiple isoforms (alpha, beta, gamma) diverging in their structural composition, which mediate overlapping and distinct functions [, ]. These isoforms are involved in determining Ca2+ channel density and vesicle docking at the presynaptic active zone []. This entry represents regulating synaptic membrane exocytosis protein 2 (RIM2). RIM2alpha plays a critical role in insulin granule exocytosis []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Synaptotagmin-12 (Syt12) belongs to the synaptotagmin family, which is a group of membrane-trafficking proteins that contain two C-terminal C2 domains (known as C2A and C2B domains). Most of the synaptotagmins have a unique N-terminal domain that is involved in membrane anchoring or specific ligand binding. Mammals contain 16 synaptotagmins; eight of these bind Ca2+ via their C2-domains (Syt1-Syt3, Syt5-7, Syt9, and Syt10), whereas the other eight, including Syt12, do not [].Syt12 colocalises with and binds Syt1 on synaptic vesicles, but regulates spontaneous release independently from Syt1. Syt12 is phosphorylated by cAMP-dependent protein kinase A (PKA) at a single site, and mutation of this site blocks the effect of Syt12 on spontaneous release []. Syt12 is not essential for basal synaptic transmission, but is required for cAMP-dependent mossy fibre long-term potentiation (LTP), a presynaptic form of long-term plasticity that is induced by PKA activation []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Protein piccolo, also known as aczonin, is a neuron-specific presynaptic active zone scaffolding protein that mainly interacts with a detergent-resistant cytoskeletal-like subcellular fraction and is involved in the organization of the interplay between neurotransmitter vesicles, the cytoskeleton, and the plasma membrane at synaptic active zones []. It binds profilin, an actin-binding protein implicated in actin cytoskeletal dynamics []. It also functions as a presynaptic low-affinity Ca2 sensor and has been implicated in Ca2 regulation of neurotransmitter release []. Piccolo is a multi-domain protein containing two N-terminal FYVE zinc fingers, a polyproline tract, and a PDZ domain and two C-terminal C2 domains. This entry represents the first FYVE domain, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Synaptotagmins are synaptic vesicle membrane proteins found in abundance in nerve cells and some endocrine cells [, ]. The amino acid sequence of synaptotagmin comprises a single transmembrane region with a short vesicular N-terminal region, and a cytoplasmic C-terminal region containing 2 internal repeats similar to the C2 regulatory domain of protein kinase C. The protein is believed to be important in the docking and fusion of synaptic vesicles with the plasma membrane, i.e. with neurotransmitter release [, ].Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and also functions as a vesicular Ca2+-sensor [, ]. It is distinguished from the other synaptotagmins by having over 12 splice forms []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Proteins in this family contain an MD-2-related lipid-recognition (ML) domain, which is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like β-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins:NPC intracellular cholesterol transporter 2 (NPC2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes [].Phosphatidylglycerol/phosphatidylinositol transfer protein (Npc2) from yeasts, which catalyzes the intermembrane transfer of phosphatidylglycerol and phosphatidylinositol [].House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents the EF-hand domain found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLC-delta3).PLC-delta-3 is essential for trophoblast and placental development []. It locates at the cleavage furrow where it may participate in cytokinesis []. PI-PLC-delta3 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
PLCgamma2 (phospholipase C-gamma-2 or 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2) is primarily expressed in haematopoietic cells, specifically in B cells []. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells []. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2]to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC [, ]. PLCgamma2 contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by an SH3 domain and C2 domain. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
PLCgamma1 (phospholipase C-II or 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1) is widely expressed and is essential in growth and development []. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation []. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2]to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC []. PLCgamma contains a pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF) [, ]. It also interacts with Cbl, inhibiting its phosphorylation and activity.This entry represents the SH3 domain of PLCgamma1. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction []. It plays a role in clathrin-coated pit (CCP) formation []. It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation []. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. This entry represents the first SH3 domain of ITSN2. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction []. It plays a role in clathrin-coated pit(CCP) formation []. It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation []. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. This entry represents the second SH3 domain of ITSN2. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction []. It plays a role in clathrin-coated pit (CCP) formation []. It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation []. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. This entry represents the third SH3 domain of ITSN2. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction []. It plays a role in clathrin-coated pit (CCP) formation []. It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation []. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. This entry represents the fourth SH3 domain of ITSN2. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction []. It plays a role in clathrin-coated pit (CCP) formation []. It binds to many proteins through its multidomain structure and facilitates the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation []. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. This entry represents the fifth SH3 domain of ITSN2. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
PKN1 is a serine/threonine protein kinase activated by the Rho family of small GTPases, and by fatty acids such as arachidonic and linoleic acids [, ]. It is expressed ubiquitously and is the most abundant PKN isoform in neurons []. PKN1 is implicated in a variety of functions including cytoskeletal reorganization, cardiac cell survival, cell adhesion, and glucose transport, among others [, ]. PKN1 contains three HR1 domains, a C2 domain, and a kinase domain.This entry represents the second HR1 domain of PKN1. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family; PKN1 binds the GTPases RhoA, RhoB, and RhoC, and can also interact weakly with Rac []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
PKN, also called Protein-kinase C-related kinase (PRK), is a serine/threonine protein kinase that can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytoskeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis []. In some vertebrates, there are three PKN isoforms from different genes (designated PKN1, PKN2, and PKN3), which show different enzymatic properties, tissue distribution, and varied functions [, ]. PKN proteins contain three HR1 domains, a C2 domain, and a kinase domain. This entry represents the first HR1 domain of PKN. HR1 domains are anti-parallel coiled-coil (ACC) domains that bind small GTPases from the Rho family []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Mannose-binding protein C (MBL2) is a calcium-dependent lectin involved in innate immune defence. It binds to oligosaccharides (mannose, fucose and N-acetylglucosamine) on the surface of micro-organisms and initiates complement activation of the lectin pathway []. It also binds to late apoptotic cells, enabling their uptake by macrophages []. MBL2 forms a homotrimer []which then binds to mannan-binding lectin-associated serine peptidases, leading to their activation and cleavage of complement components C2 and C4 to form the C3/C5 convertase [, ]. MBL2 expressed on the brush border epithelial cells of kidney-proximal tubules interacts with meprin precursors, preventing activation []. The tertiary structure of MBL2 has been solved, and the protein contains a collagen-like and a C-typelectin domain []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
RasSynGAP family members include SynGAP, DOC-2/DAB2-interacting protein (DAB2IP) and neuronal growth-associated protein (nGAP/RASAL2). They contain the PH domain, C2 domain and the RasGAP domain.SynGAP (also known as SYNGAP1) is a negative regulator of Ras and Rap GTPases [, ]. It is s primarily expressed in the excitatory neurons in the brain. It has several isoforms, SYNGAP A, B and C, differing in their N-termini. A and B isoforms contain unique peptide sequence and a complete PH domain, whereas isoform C is a shorter, truncated protein with no unique peptide sequence and no PH domain []. Mutations in the SynGAP gene cause mental retardation, autosomal dominant 5 [].This entry represents the PH domain of SynGAP. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Abr (active breakpoint cluster region-related protein) and Bcr (breakpoint cluster region protein) are homologous proteins containing a C-terminal domain with GTPase-activating protein (GAP) activity specific for Rac. They control multiple cellular functions of murine macrophages []. They contain several domains, including tandem DH-PH, C2 and GAP domains. Bcr has an extra N-terminal oligomerization domain []. Bcr has been shown to fused to Abl tyrosine kinase in leukemia. The fusion of Bcr to Abl deregulates the tyrosine kinase activity of Abl []. The N-terminal oligomerization domain is thought to be the most critical component that allows the formation of homo-tetramer Bcr/Abl complexes and deregulates the Abl tyrosine kinase [, ]. The GTPase-activating activity of Bcr has been shown to be regulated by transglutaminase 2 (TG2), a multifunctional protein that has been implicated in numerous pathologies including that of neurodegeneration and celiac disease [, ].Abr is a critical regulator of Rho and Cdc42 during the single cell wound healing []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
This entry represents a group of plant synaptotagmins and related proteins. In Arabodopsis, there are five members, SYT1-5. Structurally, they have a short uncleaved N-terminal signal peptide that overlaps a transmembrane (TM) domain, followed by a cytosolic variable region and two C-terminal C2 domains, C2A and C2B. Whereas C2A and C2B each bind phospholipids in a Ca2+-dependent manner, fold independently and act synergistically, C2B is essential for activity []. Arabidopsis SYT1, also known as SYTA, plays an important role in maintaining plasma membrane integrity during freezing and osmotic stresses [, ]. It also serves as a virus movement protein that transports its cargos to plasmodesmata for cell-to-cell spread via an endocytic recycling pathway []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| Description: |
This entry represents a domain found at the C terminus of some GTPase-activating proteins (also known as GAP) found in animals, including Disabled homologue 2-interacting protein (DAB2P) and Ras/Rap GTPase-activating protein SynGAP (SYGP1). DAB2P functions as a tumour suppressor that is also involved in several processes such as innate immune response and inflammation and plays a key role in brain development and function [, , ]. SYGP1 is essential for postsynaptic signalling and has been related to brain injury, leading to long-term learning and memory deficits [, ].This domain, which is found associated with the RasGAP domain () and the C2 domain (), includes a coiled-coil domain that forms a parallel trimer in solution []. |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kuroda TS |
| Year: |
2004 |
| Journal: |
Nat Cell Biol |
| Title: |
Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. |
| Volume: |
6 |
| Issue: |
12 |
| Pages: |
1195-203 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yu M |
| Year: |
2007 |
| Journal: |
Mol Biol Cell |
| Title: |
Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique Ca2+-inhibitory phospholipid-binding activity of the C2A domain. |
| Volume: |
18 |
| Issue: |
2 |
| Pages: |
688-96 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
211
 |
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
352
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
326
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
78
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
77
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Essen LO |
| Year: |
1997 |
| Journal: |
Biochemistry |
| Title: |
Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C. |
| Volume: |
36 |
| Issue: |
7 |
| Pages: |
1704-18 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kadamur G |
| Year: |
2013 |
| Journal: |
Annu Rev Physiol |
| Title: |
Mammalian phospholipase C. |
| Volume: |
75 |
|
| Pages: |
127-54 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Liu J |
| Year: |
2014 |
| Journal: |
Chem Rev |
| Title: |
Metalloproteins containing cytochrome, iron-sulfur, or copper redox centers. |
| Volume: |
114 |
| Issue: |
8 |
| Pages: |
4366-469 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Bhattacharya AA |
| Year: |
2004 |
| Journal: |
Structure |
| Title: |
Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation. |
| Volume: |
12 |
| Issue: |
3 |
| Pages: |
371-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Jing H |
| Year: |
2000 |
| Journal: |
EMBO J |
| Title: |
New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. |
| Volume: |
19 |
| Issue: |
2 |
| Pages: |
164-73 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Ménasché G |
| Year: |
2008 |
| Journal: |
Blood |
| Title: |
A newly identified isoform of Slp2a associates with Rab27a in cytotoxic T cells and participates to cytotoxic granule secretion. |
| Volume: |
112 |
| Issue: |
13 |
| Pages: |
5052-62 |
|
•
•
•
•
•
|
