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14  structures 571  species 2  interactions 1145  sequences 14  architectures

Family: Cupin_3 (PF05899)

Summary: Protein of unknown function (DUF861)

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 "Cupin superfamily". More...

Cupin superfamily Edit Wikipedia article

PDB 1l3j EBI.jpg
crystal structure of oxalate decarboxylase formate complex
Symbol Cupin_1
Pfam PF00190
Pfam clan CL0029
InterPro IPR006045
SCOP 2phl
PDB 1y3t EBI.jpg
crystal structure of yxag, a dioxygenase from Bacillus subtilis
Symbol Cupin_2
Pfam PF07883
Pfam clan CL0029
InterPro IPR013096
SCOP 1vj2
PDB 1rc6 EBI.jpg
crystal structure of protein ylba from E. coli, pfam duf861
Symbol Cupin_3
Pfam PF05899
Pfam clan CL0029
InterPro IPR008579
SCOP 1o5u
Symbol Cupin_4
Pfam PF08007
Pfam clan CL0029
PDB 1yud EBI.jpg
x-ray crystal structure of protein so0799 from Shewanella oneidensis. northeast structural genomics consortium target sor12.
Symbol Cupin_5
Pfam PF06172
Pfam clan CL0029
InterPro IPR009327
Symbol Cupin_6
Pfam PF12852
Pfam clan CL0029
Symbol Cupin_7
Pfam PF12973
Pfam clan CL0029

The cupin superfamily is a diverse superfamily of proteins named after its conserved barrel domain (cupa being the Latin term for a small barrel). The superfamily includes a wide variety of enzymes as well as non-enzymatic seed storage proteins.[1][2]

Members of the superfamily plays a role in allergy, specifically the 11 S globulins (found in legumins) and the 7S members (found in vicilins). These can be found as seed storage proteins and may be a component of normal human diet.

Sclerotinia sclerotiorum (Lib.) deBary was the first oxalic acid (oxalate), secreting organism to be described as early as 1886 in Botan. Z. by A. de Barry. However, since oxalate secreting fungi are not a major threat to crop cereals no studies of this interaction were made for almost 100 years. In the early 1980s a protein dubbed 'germin' was identified in germinating wheat embryos; and in the early 1990s (1992) it was found to be an enzyme having oxalate oxidase (OXO) activity converting an oxalate substrate into carbon dioxide and hydrogen peroxide.

S. sclerotiorum, better known as "white mold", is a fungal disease of many economically valuable crops such as (legumes) beans, soybeans, peanuts, etc., potato, lettuce, sunflower. 400 plant species are susceptible including stone fruits.[3][4]

Thomas Burr Osborne at the end of the 19th century was the first person to systematically study seed storage proteins by their solubility characteristics. He established 4 classes of proteins: water-soluble albumins; salt soluble globulins: vicilin—typically having sedimentation coefficients, S values (a measure of the protein mass determined by sedimentation equilibrium ultracentrifugation) of about 7 Svedberg units (hence the common name 7S globulin) and legumin (11S); alcohol/water-soluble—cereal—prolamines; and a fourth class, glutelins, of difficultly soluble proteins no longer recognized and now considered low solubility prolamin or globulin storage proteins . Gluten consists of a mixture of prolamins: 'glutenin' and 'gliadin'. Osborne and his Yale colleague Lafayette Mendel are considered the 'founders' of the modern science of nutrition.

Legumin and vicilin share a common evolutionary ancestor, namely, a vicilin-like protein in a fern-spore which also exhibits some characteristics of legumin. Each of these proteins contains equivalent 'subunits' indicating an evolution from a single-gene ancestor which has been duplicated during evolution. It was suggested that "germin" , {first found and only known to occur in the "true cereals": barley, corn, oat, rice, and wheat} a plant enzyme, oxalate oxidase 'one-very-tough-little- protein' as such an ancestor. This hypothesis stimulated a search for the evolutionary roots of the seed storage globulins which include such food proteins as the legume soy protein—the gold standard for plant-based proteins—due to its balanced content of 7S and 11S globulin protein, other beans, the pseudocereals buckwheat, & quinoa, pumpkin seeds, cocoa, coffee, nuts, and the two cereals oats and rice.

This search turned up a new realm: that seed storage globulin proteins (7S & 11S), as well as many other non-storage plant proteins {notably germins (G-OXOs), germin-like proteins (GLPs)} and microbial proteins belong to a vast superfamily of proteins dubbed the 'cupin superfamily' of proteins, named on the basis of a conserved beta-barrel fold (cupa the Latin term for a small barrel) originally discovered within germin and germin-like proteins from higher plants. Germin is a monocupin and 7S & 11S are each bicupins. It is a large and functionally immensely diverse 'superfamily' of proteins, numbering in the thousands, that have a common origin and whose evolution can be followed from bacteria to eukaryotes including animals and higher plants. "Cupins" are the most functionally diverse protein superfamily occurring in all spermatophytes (seed bearing plants). " GLPs, moreover, are now known to be ubiquitous plant proteins, no longer linked only to cereal germination, but involved in plant responses to biotic and abiotic stress.[5] "G-OXOs and GLPs are plant do-all proteins."[6]

Germin of the "true cereals" is known as the 'archetypal' member of the cupin superfamily, however it is not to be considered an empty cask or barrel but a 'jellyroll' in which six monomer subunits are wrapped in three dimensions to form a barrel shape. This structure accounts for its astonishing 'refractory' nature toward various 'denaturing' agents: all germins share a remarkable stability when subjected to heat, detergents, extreme pH and resistance to broad specificity proteolytic (digestive) enzymes. Ironically, seed storage proteins of grasses and cereals belong to the eponymous prolamin superfamily which also includes plant albumins(2S). Prolamin seed storage proteins so characteristic of cereals and grasses is not considered very nutritious because of its high content of the amino acid proline which it shares with gelatin and its low content of lysine, a vital amino acid.

Germin was initially identified in the early stages of wheat seed germination, thus its name. Interestingly, domesticated cereals most notably 'hexaploid' bread wheat ( pasta wheat is tetraploid) was selected by humans for its resistance to fungal pathogens. Many years later it was found to have oxalate oxidase activity generating 'antimicrobial' hydrogen peroxide from a substrate of the double-acid, oxalic acid, secreted by an invading fungus or other microbe. A reaction between oxalate and the calcium cation makes calcium oxalate, a type of 'kidney stone' in humans. Amazingly, oxalate is a metabolite of ascorbate (vitamin C), and it is worth emphasizing that ascorbate is a direct precursor of oxalate in plants.

The 'sweetest' outcome from our knowledge of germin biochemistry is that the wheat-germin gene is the obvious candidate for insertion into the American chestnut for producing a transgenic American chestnut. This tree called the "perfect tree" has no resistance to Cryphonectria parasitica, the chestnut blight fungus.[7] The fungal mycelium produce oxalic acid which eats away at the tree's bark giving it a portal into the underlying growing tissue. The xylem vessels carrying water become plugged through the chelation of calcium cations by oxalate just as in the kidney. Death is by strangulation as a canker encircles and girdles the trunk.

Transgenic American chestnut seedlings have been produced and field tested carrying the wheat germin gene for oxalate oxidase which breaks down oxalic acid the caustic chemical excreted by the invasive chestnut blight fungus.

Soybean Protein Nomenclature: Aprogress.[8] Effects of ionic strength on the ultracentrifuge pattern for water-extractable soybean proteins at pH 7.6. The terminology used most extensively in the past.


  1. ^ Dunwell JM (1998). "Cupins: a new superfamily of functionally diverse proteins that include germins and plant storage proteins". Biotechnol. Genet. Eng. Rev. 15: 1–32. doi:10.1080/02648725.1998.10647950. PMID 9573603. 
  2. ^ Dunwell, J. M.; Purvis, A.; Khuri, S. (2004). "Cupins: The most functionally diverse protein superfamily?". Phytochemistry. 65 (1): 7–17. doi:10.1016/j.phytochem.2003.08.016. PMID 14697267. 
  3. ^ "Sclerotinia sclerotiorum Genome Project | Broad Institute". Retrieved 2016-12-17. 
  4. ^ "White mold (Sclerotinia)". Retrieved 2016-12-17. 
  5. ^ Dunwell, Jim; Gibbings, J. George; Mahmood, Tariq; Saqlan Naqvi, S.M. (2008-09-01). "Germin and Germin-like Proteins: Evolution, Structure, and Function". Critical Reviews in Plant Sciences. 27 (5): 342–375. doi:10.1080/07352680802333938. 
  6. ^ "Germins and germin-like proteins: Plant do-all proteins. But what do they do exactly?". Plant Physiology and Biochemistry. 39: 545–554. doi:10.1016/S0981-9428(01)01285-2. 
  7. ^ "American Chestnut". Retrieved 2016-12-17. 
  8. ^ "Download from National Agricultural Library Digital Collections". Retrieved 2016-12-17. 

This article incorporates text from the public domain Pfam and InterPro IPR013096

This article incorporates text from the public domain Pfam and InterPro IPR006045

This article incorporates text from the public domain Pfam and InterPro IPR009327

This article incorporates text from the public domain Pfam and InterPro IPR008579

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.

Protein of unknown function (DUF861) Provide feedback

This family consists of several proteins which seem to be specific to plants and bacteria. The function of this family is unknown.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008579

The function of the proteins in this entry are unknown. They contain the conserved barrel domain of the 'cupin' superfamily and members are specific to plants and bacteria.

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 Cupin (CL0029), which has the following description:

This clan represents the conserved barrel domain of the 'cupin' superfamily [1] ('cupa' is the Latin term for a small barrel). The cupin fold is found in a wide variety of enzymes, but notably contains the non-enzymatic seed storage proteins also.

The clan contains the following 57 members:

2OG-Fe_Oxy_2 2OG-FeII_Oxy 2OG-FeII_Oxy_2 2OG-FeII_Oxy_3 2OG-FeII_Oxy_4 2OG-FeII_Oxy_5 3-HAO AraC_binding AraC_binding_2 AraC_N ARD Asp_Arg_Hydrox Auxin_BP CDO_I CENP-C_C CsiD Cupin_1 Cupin_2 Cupin_3 Cupin_4 Cupin_5 Cupin_6 Cupin_7 Cupin_8 DMSP_lyase dTDP_sugar_isom DUF1255 DUF1479 DUF1498 DUF1971 DUF386 DUF4437 DUF4867 Ectoine_synth EutQ FdtA FTO_NTD GPI HgmA HutD JmjC KduI MannoseP_isomer Ofd1_CTDD Oxygenase-NA PCO_ADO PhyH Pirin Pirin_C PMI_typeI Popeye Pox_C4_C10 TauD Tet_JBP Ureidogly_lyase VIT VIT_2


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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_2000 (release 8.0)
Previous IDs: DUF861;
Type: Domain
Author: Moxon SJ
Number in seed: 32
Number in full: 1145
Average length of the domain: 74.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 53.29 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.5 23.5
Noise cut-off 23.4 23.4
Model length: 74
Family (HMM) version: 10
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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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There are 2 interactions for this family. More...

Cupin_2 Cupin_3


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 Cupin_3 domain has been found. There are 14 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.

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