ID PRAME_HUMAN Reviewed; 509 AA. AC P78395; B2R6Y7; O43481; Q8IXN8; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 25-JAN-2012, entry version 95. DE RecName: Full=Melanoma antigen preferentially expressed in tumors; DE AltName: Full=Opa-interacting protein 4; DE Short=OIP-4; DE AltName: Full=Preferentially expressed antigen of melanoma; GN Name=PRAME; Synonyms=MAPE, OIP4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX MEDLINE=97199265; PubMed=9047241; DOI=10.1016/S1074-7613(00)80426-4; RA Ikeda H., Lethe B.G., Lehmann F., van Baren N., Baurain J.-F., RA de Smet C., Chambost H., Vitale M., Moretta A., Boon T., Coulie P.G.; RT "Characterization of an antigen that is recognized on a melanoma RT showing partial HLA loss by CTL expressing an NK inhibitory RT receptor."; RL Immunity 6:199-208(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-7. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-7. RC TISSUE=Brain, Skin, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 452-509. RX MEDLINE=98125741; PubMed=9466265; RX DOI=10.1046/j.1365-2958.1998.00670.x; RA Williams J.M., Chen G.-C., Zhu L., Rest R.F.; RT "Using the yeast two-hybrid system to identify human epithelial cell RT proteins that bind gonococcal Opa proteins: intracellular gonococci RT bind pyruvate kinase via their Opa proteins and require host pyruvate RT for growth."; RL Mol. Microbiol. 27:171-186(1998). RN [7] RP FUNCTION IN RETINOIC ACID SIGNALING, INTERACTION WITH EZH2 AND RARA, RP AND MUTAGENESIS OF 470-LEU-LEU-471. RX PubMed=16179254; DOI=10.1016/j.cell.2005.07.003; RA Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R.; RT "The human tumor antigen PRAME is a dominant repressor of retinoic RT acid receptor signaling."; RL Cell 122:835-847(2005). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=16620968; DOI=10.1016/j.leukres.2006.02.031; RA Proto-Siqueira R., Figueiredo-Pontes L.L., Panepucci R.A., RA Garcia A.B., Rizzatti E.G., Nascimento F.M., Ishikawa H.C.F., RA Larson R.E., Falcao R.P., Simpson A.J., Gout I., Filonenko V., RA Rego E.M., Zago M.A.; RT "PRAME is a membrane and cytoplasmic protein aberrantly expressed in RT chronic lymphocytic leukemia and mantle cell lymphoma."; RL Leuk. Res. 30:1333-1339(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: Functions as a transcriptional repressor, inhibiting the CC signaling of retinoic acid through the retinoic acid receptors CC RARA, RARB and RARG. Prevents retinoic acid-induced cell CC proliferation arrest, differentiation and apoptosis. CC -!- SUBUNIT: Interacts with RARA (via the ligand-binding domain); the CC interaction is direct and ligand (retinoic acid)-dependent. CC Interacts with EZH2; required to repress RAR signaling. CC -!- INTERACTION: CC P49842:STK19; NbExp=1; IntAct=EBI-348325, EBI-347581; CC -!- SUBCELLULAR LOCATION: Nucleus (Probable). Cell membrane. CC -!- TISSUE SPECIFICITY: Expressed in testis. Detected in samples of CC kidney, brain and skin. CC -!- MISCELLANEOUS: Tumor antigen recognized by cytolytic T CC lymphocytes. CC -!- SIMILARITY: Belongs to the PRAME family. CC -!- SIMILARITY: Contains 4 LRR (leucine-rich) repeats. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U65011; AAC51160.1; -; mRNA. DR EMBL; CR456549; CAG30435.1; -; mRNA. DR EMBL; AK312769; BAG35634.1; -; mRNA. DR EMBL; CH471095; EAW59518.1; -; Genomic_DNA. DR EMBL; BC014074; AAH14074.1; -; mRNA. DR EMBL; BC022008; AAH22008.1; -; mRNA. DR EMBL; BC039731; AAH39731.1; -; mRNA. DR EMBL; AF025440; AAC39560.1; -; mRNA. DR IPI; IPI00019282; -. DR RefSeq; NP_006106.1; NM_006115.3. DR RefSeq; NP_996836.1; NM_206953.1. DR RefSeq; NP_996837.1; NM_206954.1. DR RefSeq; NP_996838.1; NM_206955.1. DR RefSeq; NP_996839.1; NM_206956.1. DR UniGene; Hs.30743; -. DR ProteinModelPortal; P78395; -. DR SMR; P78395; 231-443. DR IntAct; P78395; 2. DR MINT; MINT-1034364; -. DR STRING; P78395; -. DR DMDM; 6685631; -. DR PeptideAtlas; P78395; -. DR PRIDE; P78395; -. DR Ensembl; ENST00000398741; ENSP00000381726; ENSG00000185686. DR Ensembl; ENST00000398743; ENSP00000381728; ENSG00000185686. DR Ensembl; ENST00000402697; ENSP00000385198; ENSG00000185686. DR Ensembl; ENST00000405655; ENSP00000384343; ENSG00000185686. DR Ensembl; ENST00000424204; ENSP00000407342; ENSG00000185686. DR GeneID; 23532; -. DR KEGG; hsa:23532; -. DR UCSC; uc002zwf.1; human. DR CTD; 23532; -. DR GeneCards; GC22M022890; -. DR H-InvDB; HIX0016292; -. DR H-InvDB; HIX0028656; -. DR HGNC; HGNC:9336; PRAME. DR HPA; HPA045153; -. DR MIM; 606021; gene. DR neXtProt; NX_P78395; -. DR PharmGKB; PA33698; -. DR eggNOG; prNOG17547; -. DR GeneTree; ENSGT00600000084130; -. DR HOGENOM; HBG506079; -. DR InParanoid; P78395; -. DR OMA; LKIFAMP; -. DR OrthoDB; EOG4MCX07; -. DR PhylomeDB; P78395; -. DR NextBio; 46014; -. DR ArrayExpress; P78395; -. DR Bgee; P78395; -. DR CleanEx; HS_PRAME; -. DR Genevestigator; P78395; -. DR GermOnline; ENSG00000185686; Homo sapiens. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042974; F:retinoic acid receptor binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045596; P:negative regulation of cell differentiation; IDA:UniProtKB. DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB. DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. PE 1: Evidence at protein level; KW Apoptosis; Cell membrane; Complete proteome; Differentiation; KW Growth regulation; Leucine-rich repeat; Membrane; Nucleus; KW Polymorphism; Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 509 Melanoma antigen preferentially expressed FT in tumors. FT /FTId=PRO_0000156973. FT REPEAT 323 343 LRR 1. FT REPEAT 350 371 LRR 2. FT REPEAT 379 400 LRR 3. FT REPEAT 407 427 LRR 4. FT REGION 416 509 Mediates interaction with RARA. FT VARIANT 7 7 W -> R (in dbSNP:rs2266988). FT /FTId=VAR_021258. FT VARIANT 218 218 M -> V (in dbSNP:rs41277507). FT /FTId=VAR_062137. FT MUTAGEN 470 471 LL->VV: Loss of interaction with RARA and FT defective in repressing RARA signaling. FT CONFLICT 452 452 H -> D (in Ref. 6; AAC39560). SQ SEQUENCE 509 AA; 57890 MW; B5FFF3E7F7E82606 CRC64; MERRRLWGSI QSRYISMSVW TSPRRLVELA GQSLLKDEAL AIAALELLPR ELFPPLFMAA FDGRHSQTLK AMVQAWPFTC LPLGVLMKGQ HLHLETFKAV LDGLDVLLAQ EVRPRRWKLQ VLDLRKNSHQ DFWTVWSGNR ASLYSFPEPE AAQPMTKKRK VDGLSTEAEQ PFIPVEVLVD LFLKEGACDE LFSYLIEKVK RKKNVLRLCC KKLKIFAMPM QDIKMILKMV QLDSIEDLEV TCTWKLPTLA KFSPYLGQMI NLRRLLLSHI HASSYISPEK EEQYIAQFTS QFLSLQCLQA LYVDSLFFLR GRLDQLLRHV MNPLETLSIT NCRLSEGDVM HLSQSPSVSQ LSVLSLSGVM LTDVSPEPLQ ALLERASATL QDLVFDECGI TDDQLLALLP SLSHCSQLTT LSFYGNSISI SALQSLLQHL IGLSNLTHVL YPVPLESYED IHGTLHLERL AYLHARLREL LCELGRPSMV WLSANPCPHC GDRTFYDPEP ILCPCFMPN //