Human IRAK-2
AssigneesHuman Genome Sciences, Inc., The Regents of the University of Michigan
InventorsJian Ni, Ping Feng, Marta Muzio, Vishva M. Dixit
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Abstract
The present invention relates to a novel IRAK-2 protein which is a member of the IL-1 signaling pathway. In particular, isolated nucleic acid molecules are provided encoding the human IRAK-2 protein. IRAK-2 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for detecting IRAK-2 related disorders and therapeutic methods for treating IRAK-2 related disorders.
Claims88
An isolated nucleic acid molecule comprising a polynucleotide encoding an IRAK-2 polypeptide wherein, except for one to fifty conservative amino acid substitutions, said polypeptide has a sequence selected from the group consisting of:
- (a) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 590 in SEQ ID NO:2;
- (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 590 in SEQ ID NO:2;
- (c) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 625 in SEQ ID NO:4;
- (d) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 625 in SEQ ID NO:4;
- (e) a nucleotide sequence encoding a polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209340;
- and
- (f) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), or (e).
An isolated IRAK-2 polypeptide wherein, except for one to fifty conservative amino acid substitutions, said polypeptide has a sequence selected from the group consisting of:
- (a) amino acids from about 1 to about 590 in SEQ ID NO:2;
- (b) amino acids from about 2 to about 590 in SEQ ID NO:2;
- (c) amino acids from about 1 to about 625 in SEQ ID NO:4;
- (d) amino acids from about 2 to about 625 in SEQ ID NO:4;
- (e) the amino acid sequence of the IRAK-2 polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209340;
- and
- (f) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d), or (e).
An isolated nucleic acid molecule comprising a polynucleotide selected from the group consisting of:
- (a) a polynucleotide encoding amino acids 1 to 590 of SEQ ID NO:2;
- (b) a polynucleotide encoding amino acids 2 to 590 of SEQ ID NO:2;
- (c) a polynucleotide encoding amino acids 1 to 625 of SEQ ID NO:4;
- (d) a polynucleotide encoding amino acids 2 to 695 of SEQ ID NO:4;
- (e) a polynucleotide encoding amino acids 1 to 96 of SEQ ID NO:2;
- (f) a polynucleotide encoding amino acids 97 to 590 of SEQ ID NO:2;
- (g) a polynucleotide encoding human IRAK-2 having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209340;
- (h) a polynucleotide variant created by altering the polynucleotide of (a), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (a);
- (i) a polynucleotide variant created by altering the polynucleotide of (b), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (b);
- (j) a polynucleotide variant created by altering the polynucleotide of (c), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (c);
- (k) a polynucleotide variant created by altering the polynucleotide of (d), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (d);
- (l) a polynucleotide variant created by altering the polynucleotide of (e), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (e);
- (m) a polynucleotide variant created by altering the polynucleotide of (f), wherein:
- (I) said altering includes a nucleotide insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of nucleotides in (f);
- and
- (n) the complement of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k), (l) or (m).
An isolated nucleic acid molecule encoding a polypeptide comprising at least 30 contiguous amino acids of SEQ ID NO:2 or SEQ ID NO:4.
An isolated nucleic acid molecule comprising 30 contiguous nucleotides of the coding region of SEQ ID NO:1 or SEQ ID NO:3, or the complement thereof, provided that said nucleic acid molecule is not SEQ ID NO:14.
An isolated nucleic acid molecule comprising 300 contiguous nucleotides of the coding region of SEQ ID NO:1 or SEQ ID NO:3, or the complement thereof.
An isolated nucleic acid molecule comprising a first polynucleotide which hybridizes at 42.degree. C. in 50% formamide, 5.times.SSC, 50 mM sodium phosphate, 5.times.Denhardt's solution, 10% dextran sulfate, and 20 .mu.g/ml denatured, sheared salmon sperm DNA, followed by washing in 0.1.times.SSC at 65.degree. C., to a second polynucleotide having the nucleotide sequence of the coding region of SEQ ID NO:1, SEQ ID NO:3, or the complement thereof, wherein said first polynucleotide is at least 30 nucleotides long, and wherein said first polynucleotide does not have the nucleotide sequence of SEQ ID NO:14.
An isolated nucleic acid molecule comprising a polynucleotide encoding an epitope-bearing portion of human IRAK-2, wherein said epitope-bearing portion is selected from the group consisting of:
- (a) amino acids 96 to 193 in SEQ ID NO:2 or SEQ ID NO:4;
- (b) amino acids 207 to 254 in SEQ ID NO:2 or SEQ ID NO:4;
- (c) amino acids 293 to 316 in SEQ ID NO:2 or SEQ ID NO:4;
- (d) amino acids 416 to 472 in SEQ ID NO:2 or SEQ ID NO:4,
- (e) amino acids 487 to 541 in SEQ ID NO:2 or SEQ ID NO:4;
- and
- (f) amino acids 559 to 619 in SEQ ID NO:4.
An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
- (a) amino acids 1 to 590 of SEQ ID NO:2;
- (b) amino acids 2 to 590 of SEQ ID NO:2;
- (c) amino acids 1 to 625 of SEQ ID NO:4;
- (d) amino acids 2 to 625 of SEQ ID NO:4;
- (e) amino acids 1 to 96 of SEQ ID NO:2;
- (f) amino acids 97 to 590 of SEQ ID NO:2;
- (g) the amino acid sequence of the human IRAK-2 polypeptide as encoded by the cDNA clone contained in ATCC Deposit No. 209340;
- (h) an amino acid sequence variant created by altering the amino acid sequence of (a), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (a);
- (i) an amino acid sequence variant created by altering the amino acid sequence of (b), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (b);
- (j) an amino acid sequence variant created by altering the amino acid sequence of(c), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (c);
- (k) an amino acid sequence variant created by altering the amino acid sequence of (d), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (d);
- (l) an amino acid sequence variant created by altering the amino acid sequence of (e), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (e);
- and
- (m) an amino acid sequence variant created by altering the amino acid sequence of (f), wherein:
- (I) said altering includes an amino acid insertion, deletion, or substitution, or any combination thereof;
- and
- (II) the number of variations is less than or equal to 5% of the total number of amino acids in (f).
An isolated polypeptide comprising at least 30 contiguous amino acids of SEQ ID NO:2 or SEQ ID NO:4.
An isolated polypeptide comprising an epitope-bearing portion of human IRAK-2, selected from the group consisting of:
- (a) amino acids 96 to 193 in SEQ ID NO:2 or SEQ ID NO:4;
- (b) amino acids 207 to 254 in SEQ ID NO:2 or SEQ ID NO:4;
- (c) amino acids 293 to 316 in SEQ ID NO:2 or SEQ ID NO:4;
- (d) amino acids 416 to 472 in SEQ ID NO:2 or SEQ ID NO:4;
- (e) amino acids 487 to 541 in SEQ ID NO:2 or SEQ ID NO:4;
- and
- (f) amino acids 559 to 619 in SEQ ID NO:4.
Dependencies are inferred from the claim text.