The SEA module: A new extracellular domain associated with <i>O</i>‐glycosylation

Bork, Peer; Patthy, László

doi:10.1002/pro.5560040716

Cited by 131 publications

(136 citation statements)

References 44 publications

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“…The present results extend these observations by demonstrating that sequences downstream of the MUC1 SEA domain G↓SVVV autocleavage site are unrelated to those found in other SEA domain containing proteins. The SEA domain has been described as a ~120 amino acid module, based on the sea urchin sperm protein, enterokinase and agrin in which it was first identified (32). A phase 1 intron at the end of a preceding module has been used to define the beginning of the SEA domain.…”

Section: Discussionmentioning

confidence: 99%

“…A phase 1 intron at the end of a preceding module has been used to define the beginning of the SEA domain. In MUC1, the SEA module extends for 122 amino acids (32). After autocleavage of MUC1, a conserved region of the SEA domain (64 amino acids) is located at the carboxy-terminus of MUC1-N (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The SEA domain is a ~120 amino acid module that is found in proteins from Caenorhabditis elegans to humans (32). SEA modules in all proteins have significant sequence similarity within the initial ~80 amino acids (32).…”

Section: Muc1 Sea Domain Contains a Divergent Carboxy-terminal Regionmentioning

confidence: 99%

“…SEA modules in all proteins have significant sequence similarity within the initial ~80 amino acids (32). An additional 40 amino acids that separate the conserved region from downstream modules have been included in SEA domain alignments (32). For example, the MUC1 SEA domain includes a 68 amino acid conserved region and an additional 54 amino acids (Fig.…”

Section: Muc1 Sea Domain Contains a Divergent Carboxy-terminal Regionmentioning

confidence: 99%

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Evolution of the human MUC1 oncoprotein

Duraisamy¹,

Kufe²,

Ramasamy³

et al. 2007

Int J Oncol

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Abstract. The mucin (MUC) family consists of secreted and membrane-bound forms. The transmembrane mucin 1 (MUC1) is a heterodimer that is aberrantly overexpressed by diverse human carcinomas and certain hematologic malignancies. The MUC1 N-terminal (MUC1-N) and C-terminal (MUC1-C) subunits are generated by autocleavage within a SEA domain. The MUC1 cytoplasmic domain (MUC1-CD) located downstream of the SEA domain is sufficient for the induction of anchorage-independent growth and tumorigenicity; however, no information is available regarding the origin of these transforming sequences. Previous work demonstrated that, except for the SEA domain, MUC1 has no sequence homology with other membrane-bound mucins. The present results demonstrate that MUC1-CD evolved from repeat regions in the MUC5B secreted mucin. We also show that MUC1 sequences upstream to the SEA domain emerged from MUC5B. These findings indicate that both the MUC1-N and MUC1-C subunits evolved from secreted gel-forming mucins and that the MUC1-CD oncogenic function emerged by diversification after evolution from MUC5B.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Muc1 Sea Domain Contains a Divergent Carboxy-terminal Regionmentioning

confidence: 99%

Section: Muc1 Sea Domain Contains a Divergent Carboxy-terminal Regionmentioning

confidence: 99%

See 2 more Smart Citations

Evolution of the human MUC1 oncoprotein

Duraisamy¹,

Kufe²,

Ramasamy³

et al. 2007

Int J Oncol

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“…A recent recombinant study with mammalian cells transiently transfected with mouse perlecan domain I, however, demonstrated substitution by both heparan and choindroitin sulfates thus supporting the first possibility (Kokenyesi and Silbert, 1995). Perlecan domain I consists of 173 residues and was predicted to contain a novel 120-residue SEA protein module (a module first identified in sperm protein, enterokinase and agrin) with a high content of secondary structure elements (Bork and Patthy, 1995). Such SEA modules are also found in other extracellular or transmembrane proteins and are often closely associated with glycosaminoglycan-rich or mucin-rich regions.…”

mentioning

confidence: 98%

Characterization of Recombinant Perlecan Domain I and Its Substitution by Glycosaminoglycans and Oligosaccharides

Costell

Manni

Yamada

et al. 1997

European Journal of Biochemistry

103

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Recombinant mouse perlecan domain I (1 73 residues) was produced in transfected embryonic kidney cells and purified from the culture medium on DEAE-cellulose. It was shown to be modified by glycosaminoglycans and could be partially separated into two protein pools which were either substituted with heparan sulfate (fragment 1A) or, to a smaller extent (20%), with chondroitiddermatan sulfate or a mixture of both glycosaminoglycans (fragment IB). The average molecular mass of the glycosaminoglycans was about 8-10 kDa and, thus, smaller than in tissue-derived perlecans. Sequence and carbohydrate analyses localized the heparan sulfate attachment site to three Ser residues within SGD consensus sequences. Furthermore, the N-terminal part of fragment IA contained six Thr/Ser residues substituted by branched galactosamine-containing oligosaccharides and an N-substituted Asn residue. Fragment I was also shown to contain unique immunological epitopes which are not dependent on glycosaminoglycans and are shared by tissue-derived perlecan. Circular dichroism demonstrated a distinct a helix (20%) and p structure (60%) in fragment TA, consistent with predictions of a novel SEA protein module located in the C-terminal part of domain I.Keywords: basement membrane; protein module ; proteoglycan : recombinant production.Perlecan consists of a 480-kDa protein core substituted by three glycosaminoglycan side chains and is known to be the most abundant basement membrane proteoglycan (Timpl, 1993 ;Iozzo et al., 1994). Electron microscopy demonstrated an elongated core protein of about 80 nm and the asymmetric attachment of the glycosaminoglycans to one end of the core (Paulsson et al., 1987). Sequence analysis of mouse and human perlecan cDNA predicted a complex modular structure for the protein core and the module arrangement was interpreted to indicate the presence of five distinct domains I-V (Noonan et al., 1991 : Kallunki andTryggvason, 1992; Murdoch et al., 1992). These domains form alternating globular and rod-like structures as shown for tissue-derived perlecan and some of its recombinant domains (Paulsson et al., 1987;Schulze et al., 1995; Chakravarti et al., 1995). Several functional properties have been localized to the core protein, including binding to nidogen and fibulin-2 (Battaglia et al., 1992;Sasaki et al., 1995), cell attachment mediated through integrin receptors (Hayashi et al., 1992;Battaglia et al., 1993; Chakravarti et al., 1995) and anti-adhesive effects for bone-marrow-derived cells (Klein et al., 1994). The heparan sulphate chains of perlecan serve different purposes, however, and bind to fibronectin, collagen IV and laminin-1 (Battaglia et al., 1993) and to basic fibroblast growth factor, thereby modulating its storage and receptor binding (Aviezer et al., 1994; Whitelock et al., 1995); they may also be involved in the control of renal filtration and proteolytic degradation (Timpl, 1993 Most perlecan forms isolated from tumor basement membranes (Hassell et al., 1985; Paulsson et al., 1987) or fibrob...

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