C2

Protein kinase C conserved region 2 (CalB)

• SMART accession number: SM00239
• Description: Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.
• Interpro abstract (IPR000008):

  The C2 domain is a Ca ²⁺ -dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. C2 domains are unique among membrane targeting domains in that they show wide range of lipid selectivity for the major components of cell membranes, including phosphatidylserine and phosphatidylcholine. This C2 domain is about 116 amino-acid residues and is located between the two copies of the C1 domain in Protein Kinase C and the protein kinase catalytic domain [ (PUBMED:22453964) ]. Regions with significant homology [ (PUBMED:7559667) ] to the C2-domain have been found in many proteins. The C2 domain is thought to be involved in calcium-dependent phospholipid binding [ (PUBMED:8253763) ] and in membrane targetting processes such as subcellular localisation.

  The 3D structure of the C2 domain of synaptotagmin has been reported [ (PUBMED:7697723) ], the domain forms an eight-stranded beta sandwich constructed around a conserved 4-stranded motif, designated a C2 key [ (PUBMED:7697723) ]. Calcium binds in a cup-shaped depression formed by the N- and C-terminal loops of the C2-key motif. Structural analyses of several C2 domains have shown them to consist of similar ternary structures in which three Ca ²⁺ -binding loops are located at the end of an 8 stranded antiparallel beta sandwich.

There are 169765 C2 domains in 106000 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling
Binding / catalysis: calcium-binding, phospholipid-binding, inositol polyphosphate-binding, membrane-binding

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Rizo J, Sudhof TC
• C2-domains, structure and function of a universal Ca2+-binding domain.
• J Biol Chem. 1998; 273: 15879-82

• Hurley JH, Newton AC, Parker PJ, Blumberg PM, Nishizuka Y
• Taxonomy and function of C1 protein kinase C homology domains.
• Protein Sci. 1997; 6: 477-80

C1 domains are compact alpha/beta structural units of about 50 amino acids which tightly bind two zinc ions. These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain 2 C1 domains (C1A and C1B) in their N-terminal regulatory regions. We present a comprehensive list of 54 C1 domains occurring singly or doubly in 34 different proteins. Many C1 domains and C1 domain-containing proteins bind phorbol esters, but many others do not. By combining analysis of 54 C1 domain sequences with information from previously reported solution and crystal structure determinations and site-directed mutagenesis, profiles are derived and used to classify C1 domains. Twenty-six C1 domains fit the profile for phorbol-ester binding and are termed "typical." Twenty-eight other domains fit the profile for the overall C1 domain fold but do not fit the profile for phorbol ester binding, and are termed "atypical." Proteins containing typical C1 domains are predicted to be regulated by diacylglycerol, whereas those containing only atypical domains are not.

• Puls A, Schmidt S, Grawe F, Stabel S
• Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein.
• Proc Natl Acad Sci U S A. 1997; 94: 6191-6

The atypical protein kinase C (PKC) member PKC-zeta has been implicated in several signal transduction pathways regulating differentiation, proliferation or apoptosis of mammalian cells. We report here the identification of a cytoplasmic and membrane-associated protein that we name zeta-interacting protein (ZIP) and that interacts with the regulatory domain of PKC-zeta but not classic PKCs. The structural motifs in ZIP include a recently defined ZZ zinc finger as a potential protein binding module, two PEST sequences and a novel putative protein binding motif with the consensus sequence YXDEDX5SDEE/D. ZIP binds to the pseudosubstrate region in the regulatory domain of PKC-zeta and is phosphorylated by PKC-zeta in vitro. ZIP dimerizes via the same region that promotes binding to PKC-zeta suggesting a competitive situation between ZIP:ZIP and ZIP:PKC-zeta complexes. In the absence of PKC-zeta proper subcellular localization of ZIP is impaired and we show that intracellular targeting of ZIP is dependent on a balanced interaction with PKC-zeta. Taking into account the recent isolation of ZIP by others in different contexts we propose that ZIP may function as a scaffold protein linking PKC-zeta to protein tyrosine kinases and cytokine receptors.

• Nalefski EA, Falke JJ
• The C2 domain calcium-binding motif: structural and functional diversity.
• Protein Sci. 1996; 5: 2375-90

The C2 domain is a Ca(2+)-binding motif of approximately 130 residues in length originally identified in the Ca(2+)-dependent isoforms of protein kinase C. Single and multiple copies of C2 domains have been identified in a growing number of eukaryotic signalling proteins that interact with cellular membranes and mediate a broad array of critical intracellular processes, including membrane trafficking, the generation of lipid-second messengers, activation of GTPases, and the control of protein phosphorylation. As a group, C2 domains display the remarkable property of binding a variety of different ligands and substrates, including Ca2+, phospholipids, inositol polyphosphates, and intracellular proteins. Expanding this functional diversity is the fact that not all proteins containing C2 domains are regulated by Ca2+, suggesting that some C2 domains may play a purely structural role or may have lost the ability to bind Ca2+. The present review summarizes the information currently available regarding the structure and function of the C2 domain and provides a novel sequence alignment of 65 C2 domain primary structures. This alignment predicts that C2 domains form two distinct topological folds, illustrated by the recent crystal structures of C2 domains from synaptotagmin 1 and phosphoinositide-specific phospholipase C-delta 1, respectively. The alignment highlights residues that may be critical to the C2 domain fold or required for Ca2+ binding and regulation.

• Ponting CP, Parker PJ
• Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin.
• Protein Sci. 1996; 5: 162-6

Various membrane lipid metabolites, generated by phospholipases C and D (PLCs, PLDs), are known to regulate the activities of protein kinases C (PKCs) and GTP-ase activating proteins (GAPs) in a range of cellular processes. Conventional Ca(2+)-dependent PKCs (alpha, beta I, beta II, and gamma), PLCs and various GAPs are all known to contain copies of a phospholipid-binding domain, termed C2 or CalB. Here we recognize that C2 domains are also present in "new" Ca(2+)-independent PKCs (delta, epsilon, eta, and theta), other kinases, a eukaryotic PLD, the breakpoint cluster region (BCR) gene product, and two further GAPS. Twenty-two previously unrecognized C2 domain sequences are presented, which include a single copy in the mammalian poreforming proteins, perforin.

• Shao X, Davletov BA, Sutton RB, Sudhof TC, Rizo J
• Bipartite Ca2+-binding motif in C2 domains of synaptotagmin and protein kinase C.
• Science. 1996; 273: 248-51

C2 domains are found in many proteins involved in membrane traffic or signal transduction. Although C2 domains are thought to bind calcium ions, the structural basis for calcium binding is unclear. Analysis of calcium binding to C2 domains of synaptotagmin I and protein kinase C-beta by nuclear magnetic resonance spectroscopy revealed a bipartite calcium-binding motif that involves the coordination of two calcium ions by five aspartate residues located on two separate loops. Sequence comparisons indicated that this may be a widely used calcium-binding motif, designated here as the C2 motif.

• Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Sudhof TC
• Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins.
• Nature. 1995; 375: 594-9

Synaptotagmins (Syts) are brain-specific Ca2+/phospholipid-binding proteins. In hippocampal synapses, Syt I is essential for fast Ca(2+)-dependent synaptic vesicle exocytosis but not for Ca(2+)-independent exocytosis. In vertebrates and invertebrates, Syt may therefore participate in Ca(2+)-dependent synaptic membrane fusion, either by serving as the Ca2+ sensor in the last step of fast Ca(2+)-triggered neurotransmitter release, or by collaborating with an additional Ca2+ sensor. While Syt I binds Ca2+ (refs 10, 11), its phospholipid binding is triggered at lower calcium concentrations (EC50 = 3-6 microM) than those required for exocytosis. Furthermore, Syts bind clathrin-AP2 with high affinity, indicating that they may play a general role in endocytosis rather than being confined to a specialized function in regulated exocytosis. Here we resolve this apparent contradiction by describing four Syts, three of which (Syt VI, VII and VIII) are widely expressed in non-neural tissues. All Syts tested share a common domain structure, with a cytoplasmic region composed of two C2 domains that interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins. The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids with a similar Ca(2+)-concentration dependence (EC50 = 3-6 microM). The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs from that of Syt III and VII (< 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

• Sutton RB, Davletov BA, Berghuis AM, Sudhof TC, Sprang SR
• Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
• Cell. 1995; 80: 929-38

C2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca2+ regulation of exocytosis, contains two C2 domains, the first of which acts as a Ca2+ sensor. We now describe the three-dimensional structure of this C2 domain at 1.9 A resolution in both the Ca(2+)-bound and Ca(2+)-free forms. The C2 polypeptide forms an eight-stranded beta sandwich constructed around a conserved four-stranded motif designated as a C2 key. Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C2-key motif.

• Brose N, Petrenko AG, Sudhof TC, Jahn R
• Synaptotagmin: a calcium sensor on the synaptic vesicle surface.
• Science. 1992; 256: 1021-5

Neurons release neurotransmitters by calcium-dependent exocytosis of synaptic vesicles. However, the molecular steps transducing the calcium signal into membrane fusion are still an enigma. It is reported here that synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids. This binding is specific for calcium and involves the cytoplasmic domain of synaptotagmin. Calcium binding is dependent on the intact oligomeric structure of synaptotagmin (it is abolished by proteolytic cleavage at a single site). These results suggest that synaptotagmin acts as a cooperative calcium receptor in exocytosis.

• Perin MS, Fried VA, Mignery GA, Jahn R, Sudhof TC
• Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C.
• Nature. 1990; 345: 260-3

Neurotransmitters are released at synapses by the Ca2(+)-regulated exocytosis of synaptic vesicles, which are specialized secretory organelles that store high concentrations of neurotransmitters. The rapid Ca2(+)-triggered fusion of synaptic vesicles is presumably mediated by specific proteins that must interact with Ca2+ and the phospholipid bilayer. We now report that the cytoplasmic domain of p65, a synaptic vesicle-specific protein that binds calmodulin contains an internally repeated sequence that is homologous to the regulatory C2-region of protein kinase C (PKC). The cytoplasmic domain of recombinant p65 binds acidic phospholipids with a specificity indicating an interaction of p65 with the hydrophobic core as well as the headgroups of the phospholipids. The binding specificity resembles PKC, except that p65 also binds calmodulin, placing the C2-regions in a context of potential Ca2(+)-regulation that is different from PKC. This is a novel homology between a cellular protein and the regulatory domain of protein kinase C. The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the C2 domain.

Protein	Disease
Perforin-1 (P14222) (SMART)	OMIM:170280: Hemophagocytic lymphohistiocytosis, familial, 2 OMIM:603553:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
10.12	map04070	Phosphatidylinositol signaling system
7.26	map00562	Inositol phosphate metabolism
7.19	map04020	Calcium signaling pathway
4.46	map04730	Long-term depression
3.93	map04370	VEGF signaling pathway
3.93	map04650	Natural killer cell mediated cytotoxicity
3.86	map04310	Wnt signaling pathway
3.86	map04720	Long-term potentiation
3.86	map04916	Melanogenesis
3.86	map04540	Gap junction
3.60	map04010	MAPK signaling pathway
3.33	map04670	Leukocyte transendothelial migration
3.33	map05214	Glioma
3.33	map05223	Non-small cell lung cancer
3.33	map04012	ErbB signaling pathway
3.13	map04530	Tight junction
2.93	map04912	GnRH signaling pathway
2.33	map04510	Focal adhesion
2.00	map04664	Fc epsilon RI signaling pathway
1.60	map04120	Ubiquitin mediated proteolysis
1.53	map00564	Glycerophospholipid metabolism
1.13	map04620	Toll-like receptor signaling pathway
1.00	map05120	Epithelial cell signaling in Helicobacter pylori infection
1.00	map00565	Ether lipid metabolism
0.87	map05050	Dentatorubropallidoluysian atrophy (DRPLA)
0.80	map05220	Chronic myeloid leukemia
0.73	map04350	TGF-beta signaling pathway
0.73	map04360	Axon guidance
0.60	map04140	Regulation of autophagy
0.60	map00590	Arachidonic acid metabolism
0.60	map00592	alpha-Linolenic acid metabolism
0.60	map04940	Type I diabetes mellitus
0.60	map00591	Linoleic acid metabolism
0.53	map05040	Huntington's disease
0.47	map00260	Glycine, serine and threonine metabolism
0.40	map05222	Small cell lung cancer
0.40	map05213	Endometrial cancer
0.40	map04662	B cell receptor signaling pathway
0.40	map05212	Pancreatic cancer
0.40	map04630	Jak-STAT signaling pathway
0.40	map04810	Regulation of actin cytoskeleton
0.40	map05210	Colorectal cancer
0.40	map04210	Apoptosis
0.40	map04910	Insulin signaling pathway
0.40	map05215	Prostate cancer
0.40	map04150	mTOR signaling pathway
0.40	map04660	T cell receptor signaling pathway
0.40	map05211	Renal cell carcinoma
0.40	map05221	Acute myeloid leukemia
0.40	map04930	Type II diabetes mellitus
0.40	map05218	Melanoma
0.40	map04914	Progesterone-mediated oocyte maturation
0.13	map00380	Tryptophan metabolism
0.07	map00632	Benzoate degradation via CoA ligation

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with C2 domain which could be assigned to a KEGG orthologous group, and not all proteins containing C2 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of C2 domains in PDB

PDB code	Title
1a25	C2 DOMAIN FROM PROTEIN KINASE C (BETA)
1bci	C2 DOMAIN OF CYTOSOLIC PHOSPHOLIPASE A2, NMR, MINIMIZED AVERAGE STRUCTURE
1bdy	C2 DOMAIN FROM PROTEIN KINASE C DELTA
1byn	SOLUTION STRUCTURE OF THE CALCIUM-BOUND FIRST C2-DOMAIN OF SYNAPTOTAGMIN I
1cjy	HUMAN CYTOSOLIC PHOSPHOLIPASE A2
1djg	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH LANTHANUM
1djh	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH BARIUM
1dji	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH CALCIUM
1djw	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH INOSITOL-2-METHYLENE-1,2-CYCLIC-MONOPHOSPHONATE
1djx	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH INOSITOL-1,4,5-TRISPHOSPHATE
1djy	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH INOSITOL-2,4,5-TRISPHOSPHATE
1djz	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH INOSITOL-4,5-BISPHOSPHATE
1dqv	CRYSTAL STRUCTURE OF SYNAPTOTAGMIN III C2A/C2B
1dsy	C2 DOMAIN FROM PROTEIN KINASE C (ALPHA) COMPLEXED WITH CA2+ AND PHOSPHATIDYLSERINE
1gmi	Structure of the c2 domain from novel protein kinase C epsilon
1k5w	THREE-DIMENSIONAL STRUCTURE OF THE SYNAPTOTAGMIN 1 C2B-DOMAIN: SYNAPTOTAGMIN 1 AS A PHOSPHOLIPID BINDING MACHINE
1qas	1-PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHODIESTERASE DELTA 1
1qat	1-PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHODIESTERASE DELTA COMPLEX WITH SAMARIUM (III) CHLORIDE
1rh8	Three-dimensional structure of the calcium-free Piccolo C2A-domain
1rlw	CALCIUM-PHOSPHOLIPID BINDING DOMAIN FROM CYTOSOLIC PHOSPHOLIPASE A2
1rsy	STRUCTURE OF THE FIRST C2-DOMAIN OF SYNAPTOTAGMIN I: A NOVEL CA2+(SLASH)PHOSPHOLIPID BINDING FOLD
1tjm	Crystallographic Identification of Sr2+ Coordination Site in Synaptotagmin I C2B Domain
1tjx	Crystallographic Identification of Ca2+ Coordination Sites in Synaptotagmin I C2B Domain
1ugk	Solution structure of the first C2 domain of synaptotagmin IV from human fetal brain (KIAA1342)
1uov	Calcium binding domain C2B
1uow	Calcium binding domain C2B
1v27	Solution structure of the first C2 domain of RIM2
1w15	rat synaptotagmin 4 C2B domain in the presence of calcium
1w16	rat synaptotagmin 4 C2B domain in the absence of calcium
1wfj	C2 domain-containing protein from putative elicitor-responsive gene
1yrk	The C2 Domain of PKC is a new Phospho-Tyrosine Binding Domain
2b3r	Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2
2bwq	Crystal Structure of the RIM2 C2A-domain at 1.4 angstrom Resolution
2chd	Crystal structure of the C2A domain of Rabphilin-3A
2cjs	Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules
2cjt	Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules
2cm5	crystal structure of the C2B domain of rabphilin
2cm6	crystal structure of the C2B domain of rabphilin3A
2d8k	Solution structure of the first C2 domain of synaptotagmin VII
2dmg	Solution structure of the third C2 domain of KIAA1228 protein
2dmh	Solution structure of the first C2 domain of human myoferlin
2enp	Solution structure of the first C2 domain from human B/K protein
2enq	Solution structure of the C2 domain from human PI3-kinase p110 subunit alpha
2ep6	Solution structure of the second C2 domain from human MCTP2 protein
2fju	Activated Rac1 bound to its effector phospholipase C beta 2
2fk9	Human protein kinase C, eta
2isd	PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT
2jqz	Solution Structure of the C2 domain of human Smurf2
2k3h	Structural determinants for Ca2+ and PIP2 binding by the C2A domain of rabphilin-3A
2k45	C2A domain of synaptototagmin I solution structure in the FGF-1-C2A binary complex: key component in the fibroblast growthfactor non-classical pathway
2k4a	FGF-1-C2A binary complex structure: a key component in the fibroblast growthfactor non-classical pathway
2k8m	S100A13-C2A binary complex structure
2ki6	The FGF1-S100A13-C2A hetero-hexameric complex structure: A component in the non-classical pathway for FGF1 secretion
2lha	Solution structure of C2B with IP6
2n1t	2N1T
2nq3	Crystal structure of the C2 Domain of Human Itchy Homolog E3 Ubiquitin Protein Ligase
2nsq	Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein
2q3x	The RIM1alpha C2B domain
2r83	Crystal structure analysis of human synaptotagmin 1 C2A-C2B
2rd0	Structure of a human p110alpha/p85alpha complex
2uzp	Crystal structure of the C2 domain of human protein kinase C gamma.
2yoa	Synaptotagmin-1 C2B domain with phosphoserine
2zkm	Crystal Structure of Phospholipase C Beta 2
3b7y	Crystal structure of the C2 Domain of the E3 Ubiquitin-Protein Ligase NEDD4
3bxj	Crystal Structure of the C2-GAP Fragment of synGAP
3f00	Crystal Structure of Synaptotagmin I C2A domain with Cu(II)
3f01	Crystal Structure of Synaptotagmin I C2A domain with Cu(II)
3f04	Crystal Structure of Synaptotagmin I C2A domain
3f05	Crystal Structure of Synaptotagmin I C2A domain with Mn(II)
3fbk	Crystal structure of the C2 domain of the human regulator of G-protein signaling 3 isoform 6 (RGP3), Northeast Structural Genomics Consortium Target HR5550A
3fdw	Crystal structure of a C2 domain from human synaptotagmin-like protein 4
3gpe	Crystal Structure Analysis of PKC (alpha)-C2 domain complexed with Ca2+ and PtdIns(4,5)P2
3hhm	Crystal structure of p110alpha H1047R mutant in complex with niSH2 of p85alpha and the drug wortmannin
3hiz	Crystal structure of p110alpha H1047R mutant in complex with niSH2 of p85alpha
3hn8	Crystal structure of synaptotagmin
3jzy	Crystal structure of human Intersectin 2 C2 domain
3kwt	Munc13-1 C2B-domain, calcium-free
3kwu	Munc13-1 C2B-domain, calcium bound
3l9b	Crystal Structure of Rat Otoferlin C2A
3m7f	Crystal structure of the Nedd4 C2/Grb10 SH2 complex
3n5a	Synaptotagmin-7, C2B-domain, calcium bound
3nsj	The X-ray crystal structure of lymphocyte perforin
3ohm	Crystal structure of activated G alpha Q bound to its effector phospholipase C beta 3
3pfq	Crystal Structure and Allosteric Activation of Protein Kinase C beta II
3pyc	Crystal structure of human SMURF1 C2 domain
3qr0	Crystal Structure of S. officinalis PLC21
3qr1	Crystal Structure of L. pealei PLC21
3rdj	Rat PKC C2 domain Apo
3rpb	THE C2B-DOMAIN OF RABPHILIN: STRUCTURAL VARIATIONS IN A JANUS-FACED DOMAIN
3twy	RAT PKC C2 DOMAIN BOUND TO PB
3w56	Structure of a C2 domain
3w57	Structure of a C2 domain
3zim	Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase PI3Kalpha
4a55	Crystal structure of p110alpha in complex with iSH2 of p85alpha and the inhibitor PIK-108
4dnl	Crystal structure of a C2 domain of a protein kinase C alpha (PRKCA) from Homo sapiens at 1.90 A resolution
4gnk	Crystal structure of Galphaq in complex with full-length human PLCbeta3
4icw	4ICW
4icx	4ICX
4ihb	X-RAY STRUCTURE OF THE canonical C2A DOMAIN FROM HUMAN DYSFERLIN
4iqh	Crystal Structure Analysis of Dysferlin C2A variant 1 (C2Av1)
4jps	Co-crystal Structures of the Lipid Kinase PI3K alpha with Pan and Isoform Selective Inhibitors
4l1b	Crystal Structure of p110alpha complexed with niSH2 of p85alpha
4l1l	Rat PKC C2 domain bound to CD
4l23	Crystal Structure of p110alpha complexed with niSH2 of p85alpha and PI-103
4l2y	Crystal Structure of p110alpha complexed with niSH2 of p85alpha and compound 9d
4lcv	Crystal Structure of DOC2B C2A domain
4ldc	Crystal Structure of DOC2B C2B domain
4lt7	Crystal structure of the c2a domain of rabphilin-3a in complex with a calcium
4mjj	Crystal structure of the C2A domain of DOC2A
4np9	Structure of Rabphilin C2A domain bound to IP3
4npj	Extended-Synaptotagmin 2, C2A- and C2B-domains
4npk	Extended-Synaptotagmin 2, C2A- and C2B-domains, calcium bound
4ns0	The C2A domain of Rabphilin 3A in complex with PI(4,5)P2
4ovu	4OVU
4ovv	4OVV
4p42	Extended-Synaptotagmin 2, SMP - C2A - C2B Domains
4qj3	4QJ3
4qj4	4QJ4
4qj5	4QJ5
4rj9	4RJ9
4ts6	4TS6
4tuu	4TUU
4tv3	4TV3
4v11	4V11
4v29	4V29
4waf	4WAF
4wee	4WEE
4y1s	4Y1S
4y1t	4Y1T
4ykn	4YKN
4zop	4ZOP
5a4x	5A4X
5a50	5A50
5a51	5A51
5a52	5A52
5ccg	5CCG
5cch	5CCH
5cci	5CCI
5ccj	5CCJ
5dxh	5DXH
5dxt	5DXT
5fi4	5FI4
5h4y	5H4Y
5h4z	5H4Z
5itd	5ITD
5ixc	5IXC
5iz5	5IZ5
5izr	5IZR
5kj7	5KJ7
5kj8	5KJ8

Links (links to other resources describing this domain)

• PROSITE: C2_DOMAIN_2
• INTERPRO: IPR000008
• PFAM: C2