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0  structures 1342  species 0  interactions 5986  sequences 70  architectures

Family: NT-C2 (PF10358)

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

  1. 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

  2. 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

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 YEATS


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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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
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Representative proteomes UniProt

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_7857 (release 21.0)
Previous IDs: Eeig1;
Type: Domain
Sequence Ontology: SO:0000417
Author: Wood V , Coggill P , Zhang D , Aravind L
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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.2 25.2
Trusted cut-off 25.2 25.2
Noise cut-off 25.1 25.1
Model length: 147
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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.

Protein Predicted structure External Information
A0A044SSR4 View 3D Structure Click here
A0A044U4W3 View 3D Structure Click here
A0A077YXD6 View 3D Structure Click here
A0A077YYD2 View 3D Structure Click here
A0A0D2GI37 View 3D Structure Click here
A0A0G2K6R8 View 3D Structure Click here
A0A0K0EHC1 View 3D Structure Click here
A0A0K0ERD5 View 3D Structure Click here
A0A0K0J858 View 3D Structure Click here
A0A0N4UBV4 View 3D Structure Click here
A0A0P0Y8Q6 View 3D Structure Click here
A0A0R0GDN0 View 3D Structure Click here
A0A0R0HYA9 View 3D Structure Click here
A0A0R4ISQ6 View 3D Structure Click here
A0A175W468 View 3D Structure Click here
A0A1C1CYZ1 View 3D Structure Click here
A0A1D6GNH1 View 3D Structure Click here
A0A1D6IAR4 View 3D Structure Click here
A0A1D6JKD7 View 3D Structure Click here
A0A1D6K7M3 View 3D Structure Click here
A0A1D6KR95 View 3D Structure Click here
A0A1D6KRC7 View 3D Structure Click here
A0A1D6KZE0 View 3D Structure Click here
A0A1D6MVE3 View 3D Structure Click here
A0A1D6N0L5 View 3D Structure Click here
A0A1D6P7D7 View 3D Structure Click here
A0A1D6PLU5 View 3D Structure Click here
A0A1P8B2L4 View 3D Structure Click here
A0A2R8QKL4 View 3D Structure Click here
A0A368UGA6 View 3D Structure Click here
A0A3P7EPJ5 View 3D Structure Click here
A0A3Q0KI13 View 3D Structure Click here
A0A3Q0KRR4 View 3D Structure Click here
A0A5K4ETN4 View 3D Structure Click here
A0A5K4ETY2 View 3D Structure Click here
A0A5K4EUQ0 View 3D Structure Click here
A2CEP8 View 3D Structure Click here
A4UZL3 View 3D Structure Click here
C0NUC4 View 3D Structure Click here
C1GTD5 View 3D Structure Click here