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   03-NOV-2009, entry version 75.
DE   RecName: Full=Melanoma antigen preferentially expressed in tumors;
DE   AltName: Full=Preferentially expressed antigen of melanoma;
DE   AltName: Full=OPA-interacting protein 4;
DE            Short=OIP4;
GN   Name=PRAME; Synonyms=MAPE;
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:RESEARCH84.1-RESEARCH84.11(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 [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
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 7 LRR (leucine-rich) repeats.
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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; -.
DR   RefSeq; NP_996836.1; -.
DR   RefSeq; NP_996837.1; -.
DR   RefSeq; NP_996838.1; -.
DR   RefSeq; NP_996839.1; -.
DR   UniGene; Hs.30743; -.
DR   IntAct; P78395; 2.
DR   STRING; P78395; -.
DR   PeptideAtlas; P78395; -.
DR   PRIDE; P78395; -.
DR   Ensembl; ENST00000358617; ENSP00000351432; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000398741; ENSP00000381726; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000398743; ENSP00000381728; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000402697; ENSP00000385198; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000403441; ENSP00000385091; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000405655; ENSP00000384343; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000406503; ENSP00000384058; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000420709; ENSP00000412318; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000424204; ENSP00000407342; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000438888; ENSP00000407121; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000439106; ENSP00000407320; ENSG00000185686; Homo sapiens.
DR   Ensembl; ENST00000442481; ENSP00000399816; ENSG00000185686; Homo sapiens.
DR   GeneID; 23532; -.
DR   KEGG; hsa:23532; -.
DR   UCSC; uc002zwf.1; human.
DR   CTD; 23532; -.
DR   GeneCards; GC22M021214; -.
DR   H-InvDB; HIX0016292; -.
DR   H-InvDB; HIX0023687; -.
DR   H-InvDB; HIX0028656; -.
DR   H-InvDB; HIX0029617; -.
DR   H-InvDB; HIX0029716; -.
DR   H-InvDB; HIX0056767; -.
DR   H-InvDB; HIX0056782; -.
DR   H-InvDB; HIX0056783; -.
DR   H-InvDB; HIX0056892; -.
DR   HGNC; HGNC:9336; PRAME.
DR   MIM; 606021; gene.
DR   PharmGKB; PA33698; -.
DR   HOGENOM; P78395; -.
DR   HOVERGEN; P78395; -.
DR   OMA; IFAMPMQ; -.
DR   NextBio; 46014; -.
DR   ArrayExpress; P78395; -.
DR   Bgee; P78395; -.
DR   CleanEx; HS_PRAME; -.
DR   Genevestigator; P78395; -.
DR   GermOnline; ENSG00000185686; Homo sapiens.
DR   GO; GO:0042974; F:retinoic acid receptor binding; IDA:UniProtKB.
DR   GO; GO:0016564; F:transcription repressor activity; IDA:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptosis; IDA:UniProtKB.
DR   GO; GO:0045596; P:negative regulation of cell differentiation; IDA:UniProtKB.
DR   GO; GO:0048387; P:negative regulation of retinoic acid recept...; IDA:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Apoptosis; Cell membrane; Complete proteome; Differentiation;
KW   Growth regulation; Leucine-rich repeat; Membrane; Nucleus;
KW   Polymorphism; Repeat; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN         1    509       Melanoma antigen preferentially expressed
FT                                in tumors.
FT                                /FTId=PRO_0000156973.
FT   REPEAT       32     55       LRR 1.
FT   REPEAT      116    138       LRR 2.
FT   REPEAT      259    283       LRR 3.
FT   REPEAT      321    344       LRR 4.
FT   REPEAT      348    371       LRR 5.
FT   REPEAT      405    429       LRR 6.
FT   REPEAT      454    477       LRR 7.
FT   REGION      416    509       Mediates interaction with RARA.
FT   VARIANT       7      7       W -> R (in dbSNP:rs2266988).
FT                                /FTId=VAR_021258.
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
//