We have used the recently developed technique of differential display polymerase chain reaction to seek for new genes modulated by tumor necrosis factor-alpha (TNF-alpha) in cultured synoviocytes. One PCR fragment was shown to correspond to a new gene that was mapped by high-resolution fluorescence in situ hybridization to band 6p21.33. The cDNA of this gene was cloned, and the deduced amino acid sequence revealed consensus motifs for the nucleotide binding folds of the ATP-binding cassette (ABC) family of proteins. However, a hydropathy curve showed that the polypeptide does not contain the transmembrane domains that are typical of the subfamily of ABC transporters and are associated with transporter/channel functions. The new gene, called ABC50, is the first human and mammalian ABC protein found to lack transmembrane domains. Homology with some yeast ABC proteins suggests that ABC50 codes for a new human ribosomal protein involved in translation of mRNA. It could therefore play a role in the enhancement of protein synthesis that follows TNF-alpha treatment of synoviocytes and thus participate in the inflammatory processes mediated by this cytokine. Furthermore, since TNF-alpha also modulates the expression of MHC class I genes, and these genes are known to map to 6p21.33, it is hypothesized that ABC50 and MHC class I are part of the same chromatin expression domain.

>sp|Q8NE71|ABCF1_HUMAN ATP-binding cassette sub-family F member 1 OS=Homo sapiens OX=9606 GN=ABCF1 PE=1 SV=2
MPKAPKQQPPEPEWIGDGESTSPSDKVVKKGKKDKKIKKTFFEELAVEDKQAGEEEKVLKEKEQQQQQQQQQQKKKRDTR
KGRRKKDVDDDGEEKELMERLKKLSVPTSDEEDEVPAPKPRGGKKTKGGNVFAALIQDQSEEEEEEEKHPPKPAKPEKNR
INKAVSEEQQPALKGKKGKEEKSKGKAKPQNKFAALDNEEEDKEEEIIKEKEPPKQGKEKAKKAEQGSEEEGEGEEEEEE
GGESKADDPYAHLSKKEKKKLKKQMEYERQVASLKAANAAENDFSVSQAEMSSRQAMLENASDIKLEKFSISAHGKELFV
NADLYIVAGRRYGLVGPNGKGKTTLLKHIANRALSIPPNIDVLLCEQEVVADETPAVQAVLRADTKRLKLLEEERRLQGQ
LEQGDDTAAERLEKVYEELRATGAAAAEAKARRILAGLGFDPEMQNRPTQKFSGGWRMRVSLARALFMEPTLLMLDEPTN
HLDLNAVIWLNNYLQGWRKTLLIVSHDQGFLDDVCTDIIHLDAQRLHYYRGNYMTFKKMYQQKQKELLKQYEKQEKKLKE
LKAGGKSTKQAEKQTKEALTRKQQKCRRKNQDEESQEAPELLKRPKEYTVRFTFPDPPPLSPPVLGLHGVTFGYQGQKPL
FKNLDFGIDMDSRICIVGPNGVGKSTLLLLLTGKLTPTHGEMRKNHRLKIGFFNQQYAEQLRMEETPTEYLQRGFNLPYQ
DARKCLGRFGLESHAHTIQICKLSGGQKARVVFAELACREPDVLILDEPTNNLDIESIDALGEAINEYKGAVIVVSHDAR
LITETNCQLWVVEEQSVSQIDGDFEDYKREVLEALGEVMVSRPRE