Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
2  structures 121  species 0  interactions 179  sequences 2  architectures

Family: Sep15_SelM (PF08806)

Summary: Sep15/SelM redox domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "SEP15". More...

SEP15 Edit Wikipedia article

15 kDa selenoprotein
Identifiers
Symbol SEP15
External IDs OMIM606254 MGI1927947 HomoloGene3145 GeneCards: SEP15 Gene
Orthologs
Species Human Mouse
Entrez 9403 93684
Ensembl ENSG00000183291 ENSMUSG00000037072
UniProt O60613 Q9ERR7
RefSeq (mRNA) NM_004261 NM_053102
RefSeq (protein) NP_004252 NP_444332
Location (UCSC) Chr 1:
87.33 – 87.38 Mb
Chr 3:
144.23 – 144.26 Mb
PubMed search [1] [2]

15 kDa selenoprotein is a protein that in humans is encoded by the SEP15 gene.[1] Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Function[edit]

This gene encodes a selenoprotein, which contains a selenocysteine (Sec) residue at its active site. The selenocysteine is encoded by the UGA codon that normally signals translation termination. The 3' UTR of selenoprotein genes have a common stem-loop structure, the sec insertion sequence (SECIS), that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Studies in mouse suggest that this selenoprotein may have redox function and may be involved in the quality control of protein folding.[1]

Clinical significance[edit]

This gene is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.[1]

Protein domain[edit]

Sep15
PDB 2a2p EBI.jpg
Solution structure of SelM from Mus musculus
Identifiers
Symbol Sep15_SelM
Pfam PF08806
InterPro IPR014912

The protein this gene encodes for is often called Sep15 however in the case of mice, it is named SelM. This protein is an selenoprotein only found in eukaryotes. This domain has a thioredoxin-like domain and a surface accessible active site redox motif.[2] This suggests that they function as thiol-disulfide isomerases involved in disulfide bond formation in the endoplasmic reticulum.[2]

Function[edit]

Recent studies have shown in mice, where the SEP15 gene has been silenced the mice subsequently became deficient in SEP15 and were able to inhibit the development of colorectal cancer.[3]

Structure[edit]

The particular structure has an alpha/beta central domain which is actually made up of three alpha helices and a mixed parallel/anti-parallel four-stranded beta-sheet.[2]

References[edit]

  1. ^ a b c "Entrez Gene: SEP15 15 kDa selenoprotein". 
  2. ^ a b c Ferguson AD, Labunskyy VM, Fomenko DE, Araç D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J (February 2006). "NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family". J. Biol. Chem. 281 (6): 3536–43. doi:10.1074/jbc.M511386200. PMID 16319061. 
  3. ^ Tsuji PA, Naranjo-Suarez S, Carlson BA, Tobe R, Yoo MH, Davis CD (2011). "Deficiency in the 15 kDa selenoprotein inhibits human colon cancer cell growth.". Nutrients 3 (9): 805–17. doi:10.3390/nu3090805. PMC 3257736. PMID 22254125. 

Further reading[edit]


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Thioredoxin fold". More...

Thioredoxin fold Edit Wikipedia article

Thioredoxin
Thioredoxin-fold-1ert.png
One molecule of human thioredoxin (PDB ID 1ERT), a canonical example of the thioredoxin fold class.
Identifiers
Symbol Thioredoxin
Pfam PF00085
Pfam clan CL0172
InterPro IPR013766
PROSITE PDOC00172
SCOP 3trx
SUPERFAMILY 3trx
CDD cd01659

The thioredoxin fold is a protein fold common to enzymes that catalyze disulfide bond formation and isomerization. The fold is named for the canonical example thioredoxin and is found in both prokaryotic and eukaryotic proteins. It is an example of an alpha/beta protein fold that has oxidoreductase activity. The fold's spatial topology consists of a four-stranded antiparallel beta sheet sandwiched between three alpha helices. The strand topology is 2134 with 3 antiparallel to the rest.

Sequence conservation[edit]

Despite sequence variability in many regions of the fold, thioredoxin proteins share a common active site sequence with two reactive cysteine residues: Cys-X-Y-Cys, where X and Y are often but not necessarily hydrophobic amino acids. The reduced form of the protein contains two free thiol groups at the cysteine residues, whereas the oxidized form contains a disulfide bond between them.

Disulfide bond formation[edit]

Different thioredoxin fold-containing proteins vary greatly in their reactivity and in the pKa of their free thiols, which derives from the ability of the overall protein structure to stabilize the activated thiolate. Although the structure is fairly consistent among proteins containing the thioredoxin fold, the pKa is extremely sensitive to small variations in structure, especially in the placement of protein backbone atoms near the first cysteine.

Examples[edit]

Human proteins containing this domain include:

References[edit]

  • Creighton TE. (2000). Protein folding coupled to disulphide-bond formation. In Mechanisms of Protein Folding 2nd ed. Editor RH Pain. Oxford University Press.

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Sep15/SelM redox domain Provide feedback

Sep15 and SelM are eukaryotic selenoproteins that have a thioredoxin-like domain and a surface accessible active site redox motif [1]. This suggests that they function as thiol-disulphide isomerases involved in disulphide bond formation in the endoplasmic reticulum [1].

Literature references

  1. Ferguson AD, Labunskyy VM, Fomenko DE, Arac D, Chelliah Y, Amezcua CA, Rizo J, Gladyshev VN, Deisenhofer J; , J Biol Chem. 2006;281:3536-3543.: NMR structures of the selenoproteins Sep15 and SelM reveal redox activity of a new thioredoxin-like family. PUBMED:16319061 EPMC:16319061


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR014912

Sep15 and SelM are eukaryotic selenoproteins that have a thioredoxin-like domain and a surface accessible active site redox motif [PUBMED:16319061]. This suggests that they function as thiol-disulphide isomerases involved in disulphide bond formation in the endoplasmic reticulum [PUBMED:16319061].

Domain organisation

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

Loading domain graphics...

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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.

  Seed
(12)
Full
(179)
Representative proteomes NCBI
(204)
Meta
(1)
RP15
(44)
RP35
(62)
RP55
(91)
RP75
(112)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(12)
Full
(179)
Representative proteomes NCBI
(204)
Meta
(1)
RP15
(44)
RP35
(62)
RP55
(91)
RP75
(112)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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.

  Seed
(12)
Full
(179)
Representative proteomes NCBI
(204)
Meta
(1)
RP15
(44)
RP35
(62)
RP55
(91)
RP75
(112)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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

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 HMMER3.

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'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: pdb_2a4h
Previous IDs: none
Type: Domain
Author: Mistry J
Number in seed: 12
Number in full: 179
Average length of the domain: 73.00 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 48.92 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.2 21.2
Trusted cut-off 21.4 21.7
Noise cut-off 21.0 20.6
Model length: 78
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

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...

Loading sunburst data...

Tree controls

Hide

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

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

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 Sep15_SelM domain has been found. There are 2 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...