A surprising new protein superfamily containing ovalbumin, antithrombin-III, and alpha1-proteinase inhibitor

Hunt, Lois T.; Dayhoff, M. O.

doi:10.1016/0006-291x(80)90867-0

Cited by 408 publications

(187 citation statements)

References 13 publications

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“…Numerous protein families based on more or less distinct homologies have been reported, inter alia: albumin and cu-fetoprotein [9]; tonin, nerve growth factor a-subunit, epidermal growth factor-binding protein and serine proteases [lo]; streptokinase and serine proteases [l 11; 'superfamily' of ovalbumin, antithrombin III and ar-proteinase inhibitor [12]. During identification of,&turns in regions of polypeptide chain reversals in Hp, some analogies with Con A emerged [ 11.…”

Section: Discussionmentioning

confidence: 99%

Structural similarities among concanavalin A, haptoglobin, and trypsin

Dobryszycka

Przysiecki

1984

FEBS Letters

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Comparison of the primary structure of concanavalin A with those of trypsin and fl (heavy) chain of haptoglobin revealed a significant degree of chemical similarity. The amino acid sequence of concanavalin A was found to be 53.6% related to trypsin and haptoglobin. Certain analogy in the tertiary structure was shown by the use of thionine binding to the specific active site, characteristic for serine proteases. Concanavalin A Haptoglobin TrypsinStructural similarity

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Section: Discussionmentioning

confidence: 99%

Structural similarities among concanavalin A, haptoglobin, and trypsin

Dobryszycka

Przysiecki

1984

FEBS Letters

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“…The proteins that showed the greatest similarity to the 38-kDa protein were those belonging to a proposed superfamily of proteins, each related to the extent of -30% sequence identity. Several members of this family are plasma proteins that are inhibitors of serine proteases; these include human antithrombin III (22), human a1-antichymotrypsin (23), mouse and human a1-proteinase inhibitor (22,24), human heparin cofactor II (25), baboon a1-antitrypsin (26), and mouse contrapsin (24). Fig.…”

Section: G D Y S N M C N S D V S V D a M I B K T Y I D V N E E Y T E mentioning

confidence: 99%

Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases.

Pickup¹,

Ink²,

Hu³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

175

112

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Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, between 31 and 32 kilobases from the end of the genome. This position corresponds well with that predicted from analyses of the DNA structures of spontaneously generated deletion mutants. The gene responsible for hemorrhage encodes a 38-kDa protein that is one of the most abundant early gene products. The 11-basepair sequence GAAAATATATT present 84 base pairs upstream of its coding region is also present upstream of three other early genes of vaccinia virus; therefore, this sequence may be involved in the regulation of transcription. There is extensive similarity between the predicted amino acid sequence of the 38-kDa protein and the amino acid sequences of several plasma proteins that are inhibitors of various serine proteases involved in blood coagulation pathways. This suggests that the viral protein may possess a similar biological activity, which may enable it to effect hemorrhage by inhibiting one or more of the serine proteases involved in the host's normal processes of blood coagulation and wound containment.The inoculation of cowpox virus (CPV) into the skin of various mammals (guinea pigs, rabbits, humans) results in lesions that exhibit edema, hypertrophy ofthe epidermis, and hemorrhage. Similar effects are produced in CPV lesions (pocks) in the chorioallantoic membrane of developing chicken embryos; there is extensive proliferation of ectodermal and mesodermal cells, edema, and localized hemorrhage that gives the pocks a deep red color (1).CPV variants that do not produce hemorrhage have been isolated from the white pocks that usually comprise up to 1% of the pocks present on chorioallantoic membranes infected with wild-type CPV (2, 3). The existence of these white-pock variants demonstrates that a viral function controls the production of the hemorrhage.Studies of the structures of the DNAs of these white-pock variants have shown that their genomes are generated from the genome of the wild-type virus by large deletions and duplications of sequences (4, 5). Similar results have been obtained from studies of the DNAs of white-pock variants of rabbitpox virus and monkeypox virus (6-8). The rearrangements of DNA that generate the white-pock variants of CPV typically involve the replacement of up to 39 kilobases (kb) of one end of the genome with an inverted copy of up to 50 kb of DNA from the other end (4, 5). The mechanisms by which these rearrangements proceed are unknown; but it is clear that there are no identifiable homologous sequence elements at the sites of the duplication/deletion end points (5). This result suggests that it is the location of essential genes rather than DNA sequence content that limits where rearrangements may occur. The position ofgenes that encode markers, such as production of hemorrhage, will place a further cons...

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“…The serpins (serine protease inhibitors) are a superfamily of proteins comprising over 60 members from a wide range of organisms, and includes well-characterised plasma proteins such as ~-antitrypsin and antithrombin III [1,2]. The inhibitory specificity of serpins is largely determined by residues at the P~-P~' positions within the reactive site loop region which acts as a pseudo-substrate for the target protease [3].…”

Section: Introductionmentioning

confidence: 99%