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8  structures 387  species 0  interactions 6495  sequences 559  architectures

Family: SEA (PF01390)

Summary: SEA domain

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SEA domain Provide feedback

Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed function of regulating or binding carbohydrate side chains. Recently a proteolytic activity has been shown for a SEA domain [4].

Literature references

  1. Bork P, Patthy L; , Protein Sci 1995;4:1421-1425.: The SEA module: a new extracellular domain associated with O-glycosylation. PUBMED:7670383 EPMC:7670383

  2. Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE; , Proc Natl Acad Sci U S A 1994;91:7588-7592.: Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains. PUBMED:8052624 EPMC:8052624

  3. Maeda T, Inoue M, Koshiba S, Yabuki T, Aoki M, Nunokawa E, Seki E, Matsuda T, Motoda Y, Kobayashi A, Hiroyasu F, Shirouzu M, Terada T, Hayami N, Ishizuka Y, Shinya N, Tatsuguchi A, Yoshida M, Hirota H, Matsuo Y, Tani K, Arakawa T, Carninci P, Kawai J, Hay, J Biol Chem 2004;279:13174-13182.: Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16). PUBMED:14764598 EPMC:14764598

  4. Akhavan A, Crivelli SN, Singh M, Lingappa VR, Muschler JL; , FASEB J. 2008;22:612-621.: SEA domain proteolysis determines the functional composition of dystroglycan. PUBMED:17905726 EPMC:17905726

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000082

The SEA domain has been named after the first three proteins in which it was identified (Sperm protein, Enterokinase and Agrin). The SEA domain has around 120 residues, it is an extracellular domain whose function is not known. It is found in one or two copies in mosaic extracellular or transmembrane proteins. The SEA domain is closely associated with regions receiving extensive O-glycosylation. It has been proposed that carbohydrates are required to stabilise SEA domains and protect them against proteolytic degradation and that the extent of substitution may control proteolytic processing [ PUBMED:7670383 , PUBMED:9762901 ].

The SEA domain contains an about 80-residue conserved region and an about 40-residue segment that separates the conserved region from the subsequent C-terminal domains. Secondary structure predictions and circular dichroism suggest an alternating conformation of beta sheets and alpha helices for the SEA domain [ PUBMED:7670383 , PUBMED:9030729 ].

Some proteins known to contain a SEA domain include:

  • Vertebrate agrin, an heparan sulfate proteoglycan of the basal lamina of the neuromuscular junction. It is responsible for the clustering of acetylcholine receptors (AChRs) and other proteins at the neuromuscular junction.
  • Mammalian enterokinase. It catalyses the conversion of trypsinogen to trypsin which in turn activates other proenzymes, including chymotrypsinogen, procarboxypeptidases, and proelastases.
  • 63kDa sea urchin sperm protein (SP63). It might mediate sperm-egg or sperm-matrix interactions.
  • Animal perlecan, a heparan sulfate containing proteoglycan found in all basement membranes. It interacts with other basement membrane components such as laminin and collagen type IV and serves as an attachment substrate for cells.
  • Some vertebrate epithelial mucins. They form a family of secreted and cell surface glycoproteins expressed by epithelial tissues and implicated in epithelial cell protection, adhesion modulation and signaling.
  • Mammalian cell surface antigen 114/A10, an integral transmembrane protein that is highly expressed in hematopoietic progenitor cells and IL-3-dependent cell lines.

Domain organisation

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

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

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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.

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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: [1]
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Ponting CP
Number in seed: 188
Number in full: 6495
Average length of the domain: 100.10 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 12.26 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.4 22.0
Trusted cut-off 26.4 22.0
Noise cut-off 26.3 21.9
Model length: 106
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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 SEA domain has been found. There are 8 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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