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2  structures 391  species 0  interactions 537  sequences 18  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

Aliases SEP15
External IDs MGI: 1927947 HomoloGene: 3145 GeneCards: SEP15
Gene location (Human)
Chromosome 1 (human)
Chr. Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for SEP15
Genomic location for SEP15
Band n/a Start 86,862,445 bp[1]
End 86,914,424 bp[1]
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 1: 86.86 – 86.91 Mb Chr 1: 144.57 – 144.6 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

15 kDa selenoprotein is a protein that in humans is encoded by the SEP15 gene.[5] Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.


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.[5]

Clinical significance

This gene is localized on chromosome 1p31, a genetic locus commonly mutated or deleted in human cancers.[5]

Protein domain

PDB 2a2p EBI.jpg
Solution structure of SelM from Mus musculus
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.[6] This suggests that they function as thiol-disulfide isomerases involved in disulfide bond formation in the endoplasmic reticulum.[6]


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.[7]


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.[6]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000183291 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037072 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ a b c "Entrez Gene: SEP15 15 kDa selenoprotein". 
  6. ^ 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". The Journal of Biological Chemistry. 281 (6): 3536–43. PMID 16319061. doi:10.1074/jbc.M511386200. 
  7. ^ Tsuji PA, Naranjo-Suarez S, Carlson BA, Tobe R, Yoo MH, Davis CD (September 2011). "Deficiency in the 15 kDa selenoprotein inhibits human colon cancer cell growth". Nutrients. 3 (9): 805–17. PMC 3257736Freely accessible. PMID 22254125. doi:10.3390/nu3090805. 

Further reading

  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1-2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149–56. PMID 9373149. doi:10.1016/S0378-1119(97)00411-3. 
  • Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL (April 1998). "A new human selenium-containing protein. Purification, characterization, and cDNA sequence". The Journal of Biological Chemistry. 273 (15): 8910–5. PMID 9535873. doi:10.1074/jbc.273.15.8910. 
  • Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN (November 2000). "Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology". The Journal of Biological Chemistry. 275 (45): 35540–7. PMID 10945981. doi:10.1074/jbc.M004014200. 
  • Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. PMC 311072Freely accessible. PMID 11230166. doi:10.1101/gr.GR1547R. 
  • Korotkov KV, Kumaraswamy E, Zhou Y, Hatfield DL, Gladyshev VN (May 2001). "Association between the 15-kDa selenoprotein and UDP-glucose:glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells". The Journal of Biological Chemistry. 276 (18): 15330–6. PMID 11278576. doi:10.1074/jbc.M009861200. 
  • Kumaraswamy E, Korotkov KV, Diamond AM, Gladyshev VN, Hatfield DL (2002). "Genetic and functional analysis of mammalian Sep15 selenoprotein". Methods in Enzymology. Methods in Enzymology. 347: 187–97. ISBN 978-0-12-182248-4. PMID 11898406. doi:10.1016/S0076-6879(02)47017-6. 
  • Wu HJ, Lin C, Zha YY, Yang JG, Zhang MC, Zhang XY, Liang X, Fu M, Wu M (February 2003). "[Redox reactions of Sep15 and its relationship with tumor development]". Ai Zheng = Aizheng = Chinese Journal of Cancer. 22 (2): 119–22. PMID 12600282. 
  • Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. PMID 12665801. doi:10.1038/nbt810. 
  • Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR (June 2004). "Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype". Oncogene. 23 (29): 5032–40. PMID 15107826. doi:10.1038/sj.onc.1207683. 
  • Wellenreuther R, Schupp I, Poustka A, Wiemann S (June 2004). "SMART amplification combined with cDNA size fractionation in order to obtain large full-length clones". BMC Genomics. 5 (1): 36. PMC 436056Freely accessible. PMID 15198809. doi:10.1186/1471-2164-5-36. 

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

Thioredoxin fold Edit Wikipedia article

One molecule of human thioredoxin (PDB ID 1ERT), a canonical example of the thioredoxin fold class.
Symbol Thioredoxin, Trx
Pfam PF00085
Pfam clan CL0172
InterPro IPR013766
SCOP 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

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

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.


Human proteins containing this domain include:


  • 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

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]. Structurally it resembles the thioredoxin-fold.

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

This tab holds annotation information from the InterPro database.

InterPro entry IPR014912

Selenoprotein F (Sep15) and selenoprotein M (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].

The core of SelM and Sep15 consists of a central alpha/beta domain. SelM has a short N-terminal extension, whereas Sep15 has an elongated cysteine-rich N-terminal extension highly conserved among Sep15 homologues [PUBMED:16319061].

Domain organisation

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Pfam Clan

This family is a member of clan Thioredoxin (CL0172), which has the following description:

This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.

The clan contains the following 62 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF836 DUF899 DUF953 ERp29_N GILT Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 GST_N_5 HyaE KaiB L51_S25_CI-B8 MRP-S23 MRP-S25 OST3_OST6 Phe_hydrox_dim Phosducin QSOX_Trx1 Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_11 Thioredoxin_12 Thioredoxin_13 Thioredoxin_14 Thioredoxin_15 Thioredoxin_16 Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045


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Curation and family details

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Seed source: pdb_2a4h
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Mistry J
Number in seed: 40
Number in full: 537
Average length of the domain: 69.50 aa
Average identity of full alignment: 33 %
Average coverage of the sequence by the domain: 41.15 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.2 21.2
Trusted cut-off 21.4 21.2
Noise cut-off 21.1 20.9
Model length: 76
Family (HMM) version: 11
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Species distribution

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


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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 sequence.

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