HCC-2, a human chemokine: gene structure, expression pattern, and biological activity.
Cloning and sequencing of the upstream region of the gene of the CC chemokine HCC-1 led to the discovery of an adjacent gene coding for a CC chemokine that was named "HCC-2." The two genes are separated by 12-kbp and reside in a head-to-tail orientation on chromosome 17. At variance with the genes for HCC-1 and other human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene consists of four exons and three introns. Expression of HCC-2 and HCC-1 as studied by Northern analysis revealed, in addition to the regular, monocistronic mRNAs, a common, bicistronic transcript. In contrast to HCC-1, which is expressed constitutively in numerous human tissues, HCC-2 is expressed only in the gut and the liver. HCC-2 shares significant sequence homology with CKbeta8 and the murine chemokines C10, CCF18/MRP-2, and macrophage inflammatory protein 1gamma, which all contain six instead of four conserved cysteines. The two additional cysteines of HCC-2 form a third disulfide bond, which anchors the COOH-terminal domain to the core of the molecule. Highly purified recombinant HCC-2 was tested on neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit marked functional similarities to macrophage inflammatory protein 1alpha. It is a potent chemoattractant and inducer of enzyme release in monocytes and a moderately active attractant for eosinophils. Desensitization studies indicate that HCC-2 acts mainly via CC chemokine receptor CCR1.
Pardigol
A
A
Lower Saxony Institute for Peptide Research, D-30625 Hannover, Germany.
Forssmann
U
U
Zucht
H D
HD
Loetscher
P
P
Schulz-Knappe
P
P
Baggiolini
M
M
Forssmann
W G
WG
Mägert
H J
HJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D019742:Chemokines, CC / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D015846:Monokines; D000089762:Multidrug Resistance-Associated Protein 2; D016415:Sequence Alignment; D017421:Sequence Analysis
C000715087:ABCC2 protein, human; C097720:CCL14 protein, human; C108814:CCL15 protein, human; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D000089762:Multidrug Resistance-Associated Protein 2