©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
The Human COL11A2 Gene Structure Indicates that the Gene Has Not Evolved with the Genes for the Major Fibrillar Collagens (*)

(Received for publication, May 22, 1995 )

Mirka M. Vuoristo Tero Pihlajamaa Philipp Vandenberg Darwin J. Prockop (§) Leena Ala-Kokko

From the Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES

ABSTRACT

The human COL11A2 gene was analyzed from two overlapping cosmid clones that were previously isolated in the course of searching the human major histocompatibility region (Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H.(1992) Immunogenetics 35, 272-278). Nucleotide sequencing defined over 28,000 base pairs of the gene. It was shown to contain 66 exons. As with most genes for fibrillar collagens, the first intron was among the largest, and the introns at the 5`-end of the gene were in general larger than the introns at the 3`-end. Analysis of the exons coding for the major triple helical domain indicated that the gene structure had not evolved with the genes for the major fibrillar collagens in that there were marked differences in the number of exons, the exon sizes, and codon usage. The gene was located close to the gene for the retinoic X receptor beta in a head-to-tail arrangement similar to that previously seen with the two mouse genes (P. Vandenberg and D. J. Prockop, submitted for publication). Also, there was marked interspecies homology in the intergenic sequences. The amino acid sequences and the pattern of charged amino acids in the major triple helix of the alpha2(XI) chain suggested that the chain can be incorporated into the same molecule as alpha1(XI) and alpha1(V) chains but not into the same molecule as the alpha3(XI)/alpha1(II) chain. The structure of the carboxyl-terminal propeptide was similar to the carboxyl-terminal propeptides of the proalpha1(XI) chain and proalpha chains of other fibrillar collagens, but it was shorter because of internal deletions of about 30 amino acids.


INTRODUCTION

Over 19 types of collagens are known, each with an apparently unique biological function(1, 2, 3) . A major subclass is the fibrillar collagens that form ordered extracellular fibrils and that include type I, type II, type III, type V, and type XI collagens. Type I and type III collagens are found in most non-cartilaginous tissues. Type II is found primarily in cartilage where it is the most abundant protein, but it is also present in the vitreous humor and several other tissues in early embryonic development. Type XI collagen was originally recognized as a minor fibrillar collagen in cartilage that was similar to type II collagen. The protein was considered to consist of three alpha chains referred to as alpha1(XI), alpha2(XI), and alpha3(XI)(4, 5, 6) . The alpha3(XI) chain was subsequently shown to be derived from the same gene as the alpha1(II) chain of type II collagen that, by an unknown mechanism, was assembled with the alpha1(XI) and alpha2(XI) chain to form a unique procollagen molecule(4, 5, 6, 7, 8, 9) . In further analyses, type XI collagen was found to be closely related in structure to type V collagen, and both type V and type XI collagens were found in small amounts in a variety of cartilaginous and non-cartilaginous connective tissues(10, 11) . Amino acid sequencing of fragments of collagen fibrils from mammalian vitreous humor demonstrated that fibrils were assembled from molecules containing alpha1(XI) and alpha2(V) chains(12) . Also, during the maturation of articular cartilage, isolated fractions rich in type XI collagen were found to contain an increasing proportion of the alpha1(V) chain and a decreasing proportion of alpha1(XI) chains(7) . These observations and others (13, 14, 15, 16, 17) led to the suggestion (2) that type V and type XI collagens are a heterogeneous class of collagens comprised of five or six different alpha chains, i.e. the alpha1(V), alpha2(V), alpha3(V), alpha1(XI), and alpha2(XI) together with the alpha3(XI) chain, which apparently has the same primary structure as the alpha1(II) chain.

Here, we report the complete structure of the human gene for the alpha2(XI) chain of type XI collagen. The results demonstrate that (a) the gene structure did not evolve with the genes for the major fibrillar collagens in that there were marked differences in the number of exons, the exon sizes, and the codon usage(1, 3) ; (b) the gene was located close to the gene for the retinoic X receptor beta in a head-to-tail arrangement similar to that seen previously with the two mouse genes, and there was marked interspecies homology in the intergenic sequences; (^1)(c) the amino acid sequences and the pattern of charged amino acids in the major triple helix of both the alpha1(XI) chain (11) and alpha2(XI) chain (18, 19) as well as the alpha1(V) chain (20) differed from the charged amino acid pattern seen with the alpha3(XI)/alpha1(II) chain(21) , an observation suggesting that the alpha3(XI)/alpha1(II) chain is not incorporated into the same molecule; and (d) the structure of the C-propeptide (^2)was similar to the C-propeptides of the proalpha1(XI) chain and proalpha chains of other fibrillar collagens, but it was shorter because of internal deletions of about 30 amino acids.


MATERIALS AND METHODS

Characterization of Cosmid Clones for the Human COL11A2 Gene

The human COL11A2 gene was obtained from two overlapping cosmid clones, 505-1 and 515, that were isolated in the course of searching the human major histocompatibility complex region (22) . The presence of the COL11A2 gene in the clones was confirmed by Southern blot hybridization with mouse and human probes for the same gene(18, 19) .^1

Nucleotide Sequencing of the Cosmid Clones

Nucleotide sequencing was carried out either directly with the cosmid clones or with the subclones in a plasmid vector (pBluescript, Stratagene) using the dideoxynucleotide sequencing method (23) and modified T7 DNA polymerase (Sequenase 2.0, U. S. Biochemical Corp.). Some of the nucleotide sequencing was carried out by cycle sequencing of PCR products (dsDNA Cycle Sequencing System, Life Technologies, Inc.). For cycle sequencing, the 5`-primer was labeled with T4 polynucleotide kinase (U. S. Biochemical Corp.) and [-P]ATP (DuPont NEN). To isolate cosmids or plasmid subclones for sequencing, alkaline lysis and CsCl centrifugation was used(24) . Alternatively, the cosmids or plasmids were purified by alkaline lysis and absorption to a commercial column of coated silica gel (Qiagen Plasmid Maxi kit, Qiagen Inc.). The RNaseI treatment step was omitted.

To prepare templates for sequencing, 3-5 µg of a cosmid clone or plasmid subclone in 10 mM Tris-HCl buffer (pH 8) and 1 mM EDTA was denatured with 0.2 M NaOH for 5 min at room temperature in a total volume of 20 µl. The sample was precipitated by adding 2 µl of 5 M NaCl and 55 µl of 100% ethanol and then incubating the sample on dry ice for 10 min. The sample was centrifuged for 10 min, and the pellet was washed with 200 µl of 70% ethanol, dried, and dissolved in 7 µl of distilled water. For annealing, 25 ng of a 17- or 18-mer primer was used in a reaction volume of 10 µl. The samples were annealed at 37 °C for over 30 min. For the initial DNA sequencing, primers were designed based on published sequences of the COL11A2 gene by Kimura et al.(18) and Zhidkova et al.(19) . Primers for the retinoic X receptor beta gene were designed from the published sequences by Fleischhauer et al.(25) and Epplen and Epplen(26) . Additional primers were developed based on the sequences derived during the progress of the work. Nucleotide sequence analysis was carried out using the Wisconsin Sequence Analysis Package (GCG) Version 8.0-UNIX (Genetics Computer Group).

3`-RACE Analysis

To define the 3`-end of the gene, a reverse transcriptase-PCR reaction was carried out. About 0.4 µg of total RNA from human fetal cartilage (21) was reverse transcribed (GeneAmp RNA PCR kit, Perkin Elmer Corp.) using an oligo(dT) primer linked to a random sequence 5`-GACTGATCAGCGAATTCTACGTCGC(T). The single-stranded cDNA was amplified with three sequential PCRs with nested forward primers designed to hybridize to the 3`-end of the cDNA, i.e. TP-1 (5`-GGTGTGGTCCAGCTCACCTTC), TP-2 (5`-GAGCTGAGCCCGGAGACTA), and TP-3 (5`-GAATTCAGAGATGGCTGCCAG). The reverse primer for each PCR was identical with the random sequence at the 5`-end of the oligo(dT) primer. The first PCR was in a volume of 25 µl with 10 pmol of reverse primer and 10 pmol of TP-1 at 94.5 °C for 55 s, 62 °C for 45 s, and 72 °C for 90 s for 40 cycles. About 2 µl of 25 µl were taken for a second PCR with 20 pmol of reverse primer and 20 pmol of TP-2 in a final volume of 50 µl. The conditions were 94.5 °C for 55 s, 58 °C for 45 s, and 72 °C for 90 s for 35 cycles. The products from the second PCR were separated by agarose gel electrophoresis, and a gel plug was used for a third PCR reaction with 20 pmol of reverse primer and 20 pmol of TP-3 in a reaction volume of 50 µl. The conditions were 94.5 °C for 55 s, 62 °C for 45 s, and 72 °C for 90 s for 30 cycles. The products of the third PCR were separated by agarose gel electrophoresis and extracted with a commercial resin (Qiaex Extraction Kit; Qiagen, Inc.). The extracted DNA was cloned into a plasmid vector (pT7 Blue T-Vector kit, Novagen). DNA from positive clones was sequenced using primers designed to the vector sequences (T7 Promoter Primer and -40 Primer, U. S. Biochemical Corp.).


RESULTS

Characterization of Cosmid Clones

Two cosmid clones previously shown to contain the human COL11A2 gene (22) were characterized here by restriction mapping. Sites for selected restriction enzymes are shown in Fig. 1. Nucleotide sequencing of the human COL11A2 gene was carried out in part by direct sequencing of the cosmid clones and in part by sequencing of subclones in plasmids. A total of over 28,000 base pairs were defined. The gene was shown to contain 66 exons ( Fig. 1and Fig. 2). The data provided about 200 codons not previously obtained for the human gene(18, 19) , including the structures of exons 1, 2, 6, 8, and 66. As with most genes for fibrillar collagens(1, 3) , the first intron was among the largest. However, intron 8 was also large. Exons 6, 7, and 8 were recently shown to be alternatively spliced in mouse(27) .


Figure 1: Schematic diagram of the two cosmid clones 515 and 505-1 containing the human COL11A2 gene(22) . Exons and introns are drawn to scale. Sites for cleavage by selected restriction enzymes are shown. The size of exon 1 is not defined.




Figure 2: Nucleotide sequences of the exon-intron boundaries and the sizes of the exons and the introns of the human COL11A2 gene. Intron sequences are in lowercase, and exon sequences are in uppercase. Amino acids are numbered by the first glycine in the major triple helix defined as position 1. Numbers indicate the first amino acid in each exon.



The 5`-End of the COL11A2 Gene

One of the cosmid clones) extended beyond the 5`-end of the COL11A2 gene. Therefore, it was searched for the presence of the retinoic X receptor beta gene (25, 26) that was found 5` to the mouse COL11A2 gene.^1 The same head-to-tail arrangement of the two genes found in the mouse genome was also found in the human genome. Also, a large degree of identity was found between the mouse and the human intergenic sequences (Fig. 3). The distance from the potential poly(A) addition site of the retinoic X receptor beta gene to the start of translation of the COL11A2 gene was 1,362 bp. The separation of the two genes was, therefore, essentially the same in the human and mouse genomes. Four MAZ sequences (28) were found at the 3`-end of the retinoic X receptor beta gene. The sequences were largely conserved in the mouse.


Figure 3: Nucleotide sequences between the retinoic X receptor beta gene and the COL11A2 gene in the human (top line) and mouse (bottom line) genomes. Rectangle, putative poly(A) addition signal for the retinoic X receptor beta gene; four successive openboxes, putative MAZ binding sites for the termination of transcription(28) ; capitalletters and openrectangle, coding sequences for the COL11A2 gene; ellipses, gaps created to align sequences; lines, conserved SpI sites.



The first 11 exons of the mouse COL11A2 gene were previously defined.^1 Comparison of the mouse gene with the human gene here established that the sizes of the first 11 exons were identical (Table 1). Also, the sizes of the first 10 introns were similar.



The Major Triple Helical Domain

The junction exon separating the N-telopeptide from the major triple helical domain was exon 14, and the junction exon separating the 3`-end of the major triple helical domain from the C-telopeptide was exon 63 (Fig. 4). Therefore, the triple helical domain was encoded by 48 exons and part of the two junction exons. The exons for the major triple helical domain all began with a complete codon for glycine and, therefore, were similar to the exons for other fibrillar collagens(1, 3) .


Figure 4: Schematic of the exon sizes for the major triple helical domain of the human COL11A2 gene and the human COL2A1 gene. As indicated, the junction exons in the COL11A2 gene are exons 14 and 63 and in the COL2A1 gene exons 6 and 49. The exons are drawn to scale. The exon sizes for the human COL2A1 gene are from Ala-Kokko and Prockop(29) .



As indicated in Fig. 4, the coding region for the major triple helical domain of the alpha2(XI) chain had a large number of 54-bp exons. The remaining exons appeared to maintain a 54-bp motif in that seven exons were twice 54 bp (or 108 bp). Also, seven exons were 45 bp or the equivalent of 54 bp with a 9-bp deletion. These exons were similar in size, therefore, to many of the exons found in the major fibrillar collagens(1, 3) . However, there was no exon of 162 bp as is found in each of the major fibrillar collagens. Also, there were no exons of 99 bp, the size of five exons in the COL2A1 gene. In addition, there were two exons of unusual size in that one exon was 90 bp (exon 40) and the other was 36 bp (exon 61). As indicated in Fig. 4, the number of exons and the pattern of exon sizes in the COL11A2 gene was different from the COL2A1 gene(29) . Despite these differences, the number of amino acids for the major triple helical domain was 1,014, the same number as in major fibrillar collagens.

The differences between the COL11A2 gene and other genes for fibrillar collagens were also emphasized by comparison of a third base used in codons for glycine, proline, and alanine (Table 2). The four bases were more uniformly used for glycine codons in the alpha2(XI) chain than in the alpha1(I) and alpha1(II) chains. In addition, the pattern of third base usage in codons for alanine appear to be different between the alpha2(XI) chain and the alpha1(I), alpha1(II), and alpha1(XI) chains. Overall, the pattern of codon usage for glycine, proline, and alanine in the alpha2(XI) chain was most similar to the pattern of codon usage for the alpha1(V) chain.



Differences in Amino Acid Sequences of the Triple Helical Domain between the alpha2(XI) Chain and Other alpha Chains for Fibrillar Collagens

Homotrimeric molecules of collagen of necessity have identical amino acid sequences, and the different alpha1(I) and alpha2(I) chains of the heterotrimeric type I collagen have a high degree of identity in amino acid sequence(32) . They also have an almost identical pattern of distribution of positively and negatively charged amino acids. Therefore, if alpha1(XI), alpha2(XI), and alpha3(XI)/alpha1(II) chains are assembled into the same procollagen and collagen molecules, their amino acid sequences should be very similar. Here, a high degree of homology was found in the amino acids of the triple helical domain of the alpha2(XI), alpha1(XI), and alpha1(V) chains (Fig. 5). In contrast, there were marked differences between the amino acid sequences of these three chains and the sequences of the alpha3(XI)/alpha1(II) chain. In addition, it was apparent that the distribution of positively charged amino acids was essentially the same in the alpha2(XI), alpha1(XI), and alpha1(V) chains, but the pattern of positively charged amino acids in all three of these chains differed markedly from the pattern of the alpha1(II) chain (Fig. 6). Similar results were obtained when the patterns of negatively charged residues were compared (not shown).


Figure 5: Comparison of amino acid sequences for the major triple helical domains of alpha2(XI), alpha1(XI), alpha1(V), and alpha1(II) chains. The residues identical with those found in the alpha2(XI) chain are indicated by a dash. The sequences for the alpha1(XI) chain are from Bernard et al.(11) , sequences for the alpha1(V) chain are from Takahara et al.(20) , and sequences for the alpha1(II) chain are from Baldwin et al.(21) .




Figure 6: Schematic for the distribution of positively charged amino acid residues in the alpha2(XI), alpha1(XI), alpha1(V), and alpha1(II) chains. As indicated, there is a large identical pattern distribution of positively charged amino acids between the first three chains, but the pattern in the alpha1(II) chain is different. The sequences for the alpha1(XI) chain are from Bernard et al.(11) , sequences for the alpha1(V) chain are from Takahara et al.(20) , and sequences for the alpha1(II) chain are from Baldwin et al.(21) .



Identification of the 3`-End of the Gene

Previous analyses of the COL11A2 gene did not identify the 3`-end of the gene(18) . Here, reverse transcriptase-PCR followed by 3`-RACE with three nested forward primers defined the last exon (Fig. 7). One major band of about 600 bp was seen in all three nested PCR reactions (not shown). The sequences obtained provided additional in-frame codons for 47 amino acids, the stop codon, and 283 bp of the 3`-non-translated region (Fig. 7). The same sequences were found in all eight independent plasmid clones of PCR products that were analyzed. The 283 bp of 3`-non-translated region included a potential poly(A) addition signal sequence of ATTTAA. The ATTTAA is an unusual poly(A) addition signal sequence but is homologous to signal sequences seen in other genes, e.g. the AATAAA, AATTAA, and ATTAAA found in the mouse opsin gene(33) . Also, the ATTTAA sequence found here was 24 bp upstream of a carboxyl-terminal nucleotide at the 5`-end of the poly(A) tail, a typical arrangement of a poly(A) signal and an RNA cleavage site(34) . The 3`-end of the cosmid clone 515 included some of the sequences of the 3`-non-translated region. Therefore, a reverse primer to sequences in the vector was used to sequence the 3`-end of the cosmid insert. The results provided the coding sequences of the last exon (exon 66) and intron 65.


Figure 7: The 3`-end of the human COL11A2 gene. The nucleotide sequences of exon 65, intron 65, and exon 66 are indicated. Underlinedsequences are the three nested forward primers used in the 3`-RACE assay. The box indicates the unusual ATTTAA sequence that is probably a poly(A) signal sequence.



The Structure of the C-propeptide

The sequences encoding the C-propeptide indicated that the structure in the proalpha2(XI) chain was about 30 amino acids shorter than the C-propeptides for proalpha1(I), proalpha1(II), proalpha1(V), proalpha2(V), and proalpha1(XI) chains because of internal deletions (Fig. 8). One major internal deletion consisted of 23-27 amino acids compared to the other five chains. Another deletion consisted of 9 amino acids that were present in the C-propeptides of the other five chains. The deletion of 23-27 amino acids included a region that was homologous in the other C-propeptides. As previously noted(18) , the carbohydrate attachment sequence of Asn-X-(Ser/Thr) found in the other fibrillar procollagens was not present in the C-propeptide for alpha2(XI) at the same site, but an additional potential carbohydrate site of Asn-Tyr-Thr was found more amino-terminal in the sequence of the alpha2(XI), alpha1(XI), and the alpha1(V) chains. Cysteine residues were conserved among the six C-propeptides except that the alpha2(V) chain lacked one of the eight cysteines and the alpha1(XI) chain lacked another.


Figure 8: Comparison of the amino acid sequences of the C-propeptides of proalpha2(XI), proalpha1(XI), proalpha1(V), proalpha2(V), proalpha1(II), and proalpha1(I) chains. Homologous amino acid sequences are indicated by boxes. Darkverticalrectangles indicate conserved cysteine residues. Dashes indicate gaps created to align sequences. Homologous amino acids are defined as suggested by Dayhoff et al.(35) . The data for proalpha1(XI) are from Bernard et al.(11) , for proalpha1(V) from Takahara et al.(20) , for proalpha2(V) from Weil et al.(36) , for proalpha1(II) from Cheah et al.(37) , and for proalpha1(I) from Bernard et al.(30) .




DISCUSSION

Initial analyses of the genes for the major fibrillar collagens revealed a striking pattern in the exons encoding for the major triple helical domains of the proteins (see (1) and (3) ). All the exons began with a complete codon for glycine. Also, the sizes had a 54-bp motif in that most exons were 54 bp or simple multiples thereof. In addition, the bases used for the third position in codons for glycine, proline, and alanine were similar among the genes. Therefore, the results suggested that the genes for the fibrillar collagens evolved from a 54-bp exon that was duplicated during evolution. The suggestion was supported by the further observation that these features of the exons were conserved among man, rodents, and chick. Also, with one exception, the exon sizes were conserved among the four genes for type I collagen, type II collagen, and type III collagen. Analysis of the genes for type IV collagen demonstrated a different pattern in that many of the exons began with split codons for glycine, and the exon sizes did not show a consistent 54-bp motif. The genes for other non-fibrillar collagens also varied in exon structures, but it was generally assumed that all fibrillar collagens maintained the same gene structure through long periods of evolution. The results here present the first complete structure of a gene for a minor fibrillar collagen. The exon structure does not fit the pattern found in the genes for the major fibrillar collagens. Also, the codon usage differs. Therefore, the results demonstrate that the COL11A2 gene has not evolved with the genes for the major fibrillar collagens. Previous reports demonstrated that the codon usage for the alpha1(V) chain of type V collagen differed from that of other fibrillar collagens(20) . Also, the distribution of charged amino acids in the alpha2(V) chain appeared to differ from the distribution in the major fibrillar collagens(38) . Therefore, the genes for alpha1(V) and alpha2(V) chains of type V collagen may also have evolved differently from the genes for the major fibrillar collagens.

Considerable evidence has suggested that the alpha1(XI) and alpha2(XI) chains are incorporated into the same procollagen molecules as the alpha3(XI)/alpha1(II) chain and the alpha1(V) chain(4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17) . If this conclusion is correct, there should be a similarity in the amino acid sequences and in the distribution of charged amino acids among the alpha chains (see (32) ). The results here demonstrated that a high degree of homology in the sequences and in the pattern of charged amino acids was in fact found between the alpha2(XI) chain and the alpha1(XI) and alpha1(V) chains. Therefore, the results were consistent with the chemical data indicating that heterotrimeric molecules can be comprised of varying combinations of alpha1(XI), alpha2(XI), and type V collagen chains. However, there was relatively little conservation of sequence and of distribution of charged amino acids with the alpha3(XI)/alpha1(II) chain. Therefore, if the alpha3(XI)/alpha1(II) chain is incorporated into the same molecule as alpha1(XI) and alpha2(XI) chains, the resulting triple helical molecule must be far more heterogeneous in the distribution of amino acid side chains that are on the surface of the molecule and that direct fibril assembly than any better characterized molecule of a fibrillar collagen (see (32) ). Because of the differences among the alpha chains observed here, it appears that further documentation of the chemical structure of the molecules containing alpha3(XI)/alpha1(II) chains is now warranted.

The C-propeptide of the proalpha2(XI) chain showed a relatively high degree of homology with the C-propeptides of other fibrillar collagens (39) . However, there was a series of internal deletions that made the chain shorter by about 30 amino acids. Apparently, the deleted 30 or so amino acids are not critical for directing chain association and chain selection.

Recent analyses on the mouse COL11A2 gene demonstrated that the gene was located at the 3`-end of the gene for the retinoic X receptor beta and that the two genes were close together.^1 The results here demonstrate that a similar arrangement of the two genes is maintained in the human genome. In addition, there is a high degree of conservation of the intergenic sequences. Therefore, the results suggest that there may be some functional consequences of this unusual arrangement of genes. The presence of four MAZ sequences at the 3`-end of retinoic X receptor beta gene apparently prevents continuous transcription of the two genes, much as has been found in at least three other pairs of genes that are in a similar head-to-tail arrangement (see (28) ).


FOOTNOTES

*
This work was supported in part by National Institutes of Health Grant AR-39740 and a grant from the Lucille P. Markey Charitable Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) U32169[GenBank].

§
To whom correspondence should be addressed. Tel.: 215-955-4830; Fax: 215-955-5393.

(^1)
P. Vandenberg and D. J. Prockop, submitted for publication.

(^2)
The abbreviations used are: C-propeptide, carboxyl-terminal propeptide; RACE, rapid amplification of cDNA ends; PCR, polymerase chain reaction; bp, base pair(s).


ACKNOWLEDGEMENTS

We thank Drs. M. Janatipour, Y. Naumov, A. Ando, K. Sugimura, N. Okamoto, K. Tsuji, K. Abe, and H. Inoko for the two cosmid clones containing the human COL11A2 gene. The clones were provided by Dr. Ando.


REFERENCES

  1. Vuorio, E., and de Crombrugghe, B. (1990) Annu. Rev. Biochem. 59,837-872 [CrossRef][Medline] [Order article via Infotrieve]
  2. van der Rest, M., Garrone, R., and Herbage, D. (1993) Adv. Mol. Cell Biol. 6,1-67
  3. Prockop, D. J., and Kivirikko, K. I. (1995) Annu. Rev. Biochem. , in press
  4. Burgeson, R. E., and Hollister, D. W. (1979) Biochem. Biophys. Res. Commun. 87,1124-1131 [Medline] [Order article via Infotrieve]
  5. Reese, C. A., and Mayne, R. (1981) Biochemistry 20,5443-5448 [Medline] [Order article via Infotrieve]
  6. Burgeson, R. E., Hebda, P. A., Morris, N. P., and Hollister, D. W. (1982) J. Biol. Chem. 257,7852-7856 [Abstract/Free Full Text]
  7. Eyre, D., and Wu, J. (1987) in Structure and Function of Collagen Types (Mayne, R., and Burgeson, R. E., eds) pp. 261-281, Academic Press, New York
  8. Morris, N. P., and Bächinger, H.-P. (1987) J. Biol. Chem. 262,11345-11350 [Abstract/Free Full Text]
  9. Morris, N. P., Watt, S. L., Davis, J. M., and Bächinger, H.-P. (1990) J. Biol. Chem. 265,10081-10087 [Abstract/Free Full Text]
  10. Fessler, J. H., and Fessler, L. I. (1987) in Structure and Function of Collagen Types (Mayne, R., and Burgeson, R. E., eds) pp. 81-103, Academic Press, New York
  11. Bernard, M., Yoshioka, H., Rodriguez, E., van der Rest, M., Kimura, T., Ninomiya, Y., Olsen, B. R., and Ramirez, F. (1988) J. Biol. Chem. 263,17159-17166 [Abstract/Free Full Text]
  12. Mayne, R., Brewton, R. G., Mayne, P. M., and Baker, J. R. (1993) J. Biol. Chem. 268,9381-9386 [Abstract/Free Full Text]
  13. Kleman, J.-P., Hartmann, D. J., Ramirez, F., and van der Rest, M. (1992) Eur. J. Biochem. 210,329-335 [Abstract]
  14. Eyre, D. R. (1991) Semin. Arthritis Rheum. 21,2-11 [Medline] [Order article via Infotrieve]
  15. Brown, K. E., Lawrence, R., and Sonenshein, G. E. (1991) J. Biol. Chem. 266,23268-23273 [Abstract/Free Full Text]
  16. Yoshioka, H., and Ramirez, F. (1990) J. Biol. Chem. 265,6423-6426 [Abstract/Free Full Text]
  17. Mendler, M., Eich Bender, S. G., Vaughan, L., Winterhalter, K. H., and Bruckner, P. (1989) J. Cell Biol. 108,191-197 [Abstract]
  18. Kimura, T., Cheah, K. S. E., Chan, S. D. H., Lui, V. C. H., Mattei, M.-G., van der Rest, M., Ono, K., Solomon, E., Ninomiya, Y., and Olsen, B. R. (1989) J. Biol. Chem. 264,13910-13916 [Abstract/Free Full Text]
  19. Zhidkova, N. I., Brewton, R. G., and Mayne, R. (1993) FEBS Lett. 326,25-28 [CrossRef][Medline] [Order article via Infotrieve]
  20. Takahara, K., Sato, Y., Okazawa, K., Okamoto, N., Noda, A., Yaoi, Y., and Kato, I. (1991) J. Biol. Chem. 266,13124-13129 [Abstract/Free Full Text]
  21. Baldwin, C. T., Reginato, A. M., Smith, C., Jimenez, S. A., and Prockop, D. J. (1989) Biochem. J. 262,521-528 [Medline] [Order article via Infotrieve]
  22. Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. (1992) Immunogenetics 35,272-278 [Medline] [Order article via Infotrieve]
  23. Sanger, F., Nicklen, S., and Coulson, A. R. (1977) Proc. Natl. Acad. Sci. U. S. A. 74,5463-5467 [Abstract]
  24. Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual , 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
  25. Fleischhauer, K., Park, J. H., DiSanto, J. P., Marks, M., Ozato, K., and Yang, S. Y. (1992) Nucleic Acids Res. 20,1801 [Medline] [Order article via Infotrieve]
  26. Epplen, C., and Epplen, J. T. (1992) Mamm. Genome 3,472-475 [CrossRef][Medline] [Order article via Infotrieve]
  27. Tsumaki, N., and Kimura, T. (1994) Matrix Biol. 14,364
  28. Ashfield, R., Patel, A. J., Bossone, S. A., Brown, H., Campbell, R. D., Marcu, K. B., and Proudfoot, N. J. (1994) EMBOJ. 13,5656-5667 [Abstract]
  29. Ala-Kokko, L., and Prockop, D. J. (1990) Genomics 8,454-460 [Medline] [Order article via Infotrieve]
  30. Bernard, M. P., Chu, M.-L., Myers, J. C., Ramirez, F., Eikenberry, E. F., and Prockop, D. J. (1983) Biochemistry 22,5213-5223 [Medline] [Order article via Infotrieve]
  31. Tromp, G., Kuivaniemi, H., Stacey, A., Shikata, H., Baldwin, C. T., Jaenisch, R., and Prockop, D. J. (1988) Biochem. J. 253,919-922 [Medline] [Order article via Infotrieve]
  32. Chapman, J. (1984) in Connective Tissue Matrix (Hukins, D. W. L., ed) pp. 89-132, Verlag Chemie, Basel
  33. Al-Ubaidi, M. R., Pittler, S. J., Champagne, M. S., Triantafyllos, J. T., McGinnis, J. F., and Baehr, W. (1990) J. Biol. Chem. 265,20563-20569 [Abstract/Free Full Text]
  34. Sheets, M. D., Ogg, S. C., and Wickens, M. P. (1990) Nucleic Acids Res. 18,5799-5805 [Abstract]
  35. Dayhoff, M. O., Schwartz, R. M., and Orcutt, B. C. (1978) in Atlas of Protein Sequence and Structure (Dayhoff, M. O., ed) Vol. 5, Suppl. 3, pp. 345-352, National Biomedical Research Foundation, Silver Spring, MD
  36. Weil, D., Bernard, M., Gargano, S., and Ramirez, F. (1987) Nucleic Acids Res. 15,181-198 [Abstract]
  37. Cheah, K. S. E., Stoker, N. G., Griffin, J. R., Grosveld, F. G., and Solomon, E. (1985) Proc. Natl. Acad. Sci. U. S. A. 82,2555-2559 [Abstract]
  38. Myers, J. C., Loidl, H. R., Stolle, C. A., and Seyer, J. M. (1985) J. Biol. Chem. 260,5533-5541 [Abstract]
  39. Dion, A. S., and Myers, J. C. (1987) J. Mol. Biol. 193,127-143 [Medline] [Order article via Infotrieve]

©1995 by The American Society for Biochemistry and Molecular Biology, Inc.