Summary

Calcipressin

Calcipressin is also known as calcineurin-binding protein, since it inhibits calcineurin-mediated transcriptional modulation by binding to calcineurin's catalytic domain [1].

Literature references

Ermak G, Harris CD, Davies KJ; , FASEB J 2002;16:814-824.: The DSCR1 (Adapt78) isoform 1 protein calcipressin 1 inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress. PUBMED:12039863

InterPro entry IPR006931

Calcipressin 1 negatively regulates calcineurin () by direct binding and is essential for the survival of T helper type 1 cells. Calcipressin 1 is a phosphoprotein that increases its capacity to inhibit calcineurin when phosphorylated at the FLISPP motif, and this phosphorylation also controls the half-life of calcipressin 1 by accelerating its degradation PUBMED:12809556.

Calcineurin is a calcium-responsive enzyme that dephosphorylates the nuclear factor of activated T cells (NFAT). In so doing it promotes its nuclear translocation and uniquely links calcium signalling to transcriptional regulation PUBMED:12942079. Calcipressins are a family of proteins derived from three genes. Calcipressin 1 is also known as modulatory calcineurin-interacting protein 1 (MCIP1), Adapt78 and Down syndrome critical region 1 (DSCR1). Calcipressin 2 is variously known as MCIP2, ZAKI-4 and DSCR1-like 1. Calcipressin 3 is also called MCIP3 and DSCR1-like 2 PUBMED:12942079. DSCR1 (Adapt78) is associated with successful adaptation to oxidative stress and calcium stress as well as with diseases like Alzheimer's and Down syndrome.

The DSCR1 (Adapt78) isoform 1 protein, calcipressin 1, inhibits calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress PUBMED:12039863. Calcipressin 1 is encoded by DSCR1, a gene on human chromosome 21. Calcipressin 1 isoform 1 has an N-terminal coding region, which generates a new polypeptide of 252 amino acids. Endogenous calcipressin 1 exists as a complex together with the calcineurin A and B heterodimer PUBMED:12809556.

Clan

This family is a member of clan RRM (CL0221), which contains the following 11 members:

BRAP2 Calcipressin DUF1866 Limkain-b1 MPPN Ribosomal_L23 RNA_bind RRM_1 RRM_2 RRM_3 Smg4_UPF3

Gene Ontology

Biological process

calcium-mediated signaling (GO:0019722)

External database links

PANDIT:	PF04847
SYSTERS:	Calcipressin

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (9) Full (145) NCBI (268) Metagenomics
Viewer:

Formatting options

Alignment:	Seed (9) Full (145)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (9) Full (145) NCBI (268) Metagenomics
Full length sequences	Full-sequences (145)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

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...

Trees

This page displays the phylogenetic tree for this family. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

Pfam-B_4547 (release 7.6)

Previous IDs:

none

Type:

Family

Author:

Mifsud W

Number in seed:

9

Number in full:

145

Average length of the domain:

178.10 aa

Average identity of full alignment:

33 %

Average coverage of the sequence by the domain:

75.14 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.1	21.1
Trusted cut-off	21.1	21.4
Noise cut-off	21.0	20.6

Model length:

185

Family (HMM) version:

5

Download:

download the raw HMM for this family

Species distribution

Tree controls

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The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Calcipressin domain has been found.

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Family: Calcipressin (PF04847)

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