Summary: N-terminal C2 in EEIG1 and EHBP1 proteins
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N-terminal C2 in EEIG1 and EHBP1 proteins Provide feedback
This version of the C2 domain was initally identified in the vertebrate estrogen early-induced gene 1 (EEIG1) [1] and its Drosophila ortholog required for uptake of dsRNA via the endocytotic machinery to induce RNAi silencing [2]. It is also in C.elegans ortholog Sym-3 (SYnthetic lethal with Mec-3) and the mammalian protein EHBP1 (EH domain Binding Protein-1) that regulates endocytotic recycling and two plant proteins, RPG that regulates Rhizobium-directed polar growth and PMI1 (Plastid Movement Impaired 1) that is essential for intracellular movement of chloroplasts in response to blue light [2].
Literature references
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Wang DY, Fulthorpe R, Liss SN, Edwards EA; , Mol Endocrinol. 2004;18:402-411.: Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. PUBMED:14605097 EPMC:14605097
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Zhang D, Aravind L;, Gene. 2010;469:18-30.: Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes. PUBMED:20713135 EPMC:20713135
Internal database links
SCOOP: | C2 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR019448
The C2 domain is one of the most prevalent eukaryotic lipid-binding domains deployed in diverse functional contexts. Many C2 domains bind directly to membrane lipids and display a wide range of lipid selectivity, with preference for anionic phosphatidylserine (PS) and phosphatidylinositol-phosphates (PIPs).
Despite their limited sequence similarity, all C2 domains contain at their core a compact beta-sandwich composed of two four-stranded beta sheets with highly variable inter-strand regions that might contain one or more alpha- helices.
The NT-type C2 domain shows a diverse range of domain architectures but it is nearly always found at the N-termini of proteins that contain it. Hence, it has been named the N-terminal C2 (NT-C2) family. It is typically coupled with a coiled-coil domain, that could mediate di/oligo-merization and the DIL (Dilute) domain. It is also coupled with the Calponin homology (CH) domain in EHBP1 proteins, Filamin/ABP280 repeats and Mg2+ transporter MgtE N-terminal domain in proteins from chlorophyte algae such as Micromonas and Ostreococcus tauri. Thus, a common theme across the NT-type C2 domain proteins is the combination to several different domains with microfilament-binding or actin-related roles (i.e. such as CH, DIL, and Filamin). Other conserved groups of the NT-type C2 proteins prototyped by EEIG1, PMI1, and SYNC1 have their own distinct C- terminal conserved extensions that are restricted to these groups and might mediate specific interactions. The primary function of the NT-type C2 domain appears to be the linking of actin/microfilament-binding adaptors to the membrane and to act as a link that tethers endosomal vesicles to the cytoskeleton in course of their intracellular trafficking [ PUBMED:20713135 , PUBMED:27272733 ].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan C2 (CL0154), which has the following description:
This superfamily includes C2 domains and C2-like domains.
The clan contains the following 18 members:
Aida_C2 Anillin B9-C2 C2 C2-C2_1 CC2D2AN-C2 CEP76-C2 DOCK-C2 IcmF_C MNNL NT-C2 PI3K_C2 PTEN_C2 pYEATS RPGR1_C SPATA6 Spond_N YEATSAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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Seed (55) |
Full (5986) |
Representative proteomes | UniProt (9084) |
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RP15 (912) |
RP35 (2630) |
RP55 (4702) |
RP75 (6324) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (55) |
Full (5986) |
Representative proteomes | UniProt (9084) |
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RP15 (912) |
RP35 (2630) |
RP55 (4702) |
RP75 (6324) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Curation and family details
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Curation
Seed source: | Pfam-B_7857 (release 21.0) |
Previous IDs: | Eeig1; |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Wood V |
Number in seed: | 55 |
Number in full: | 5986 |
Average length of the domain: | 146.9 aa |
Average identity of full alignment: | 20 % |
Average coverage of the sequence by the domain: | 16.49 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 147 | ||||||||||||
Family (HMM) version: | 12 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.