P78395 (PRAME_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Melanoma antigen preferentially expressed in tumors

Alternative name(s):
Opa-interacting protein 4
Short name=OIP-4
Preferentially expressed antigen of melanoma

Gene names

Name:	PRAME
Synonyms:	MAPE, OIP4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptors RARA, RARB and RARG. Prevents retinoic acid-induced cell proliferation arrest, differentiation and apoptosis. Ref.7
Subunit structure	Interacts with RARA (via the ligand-binding domain); the interaction is direct and ligand (retinoic acid)-dependent. Interacts with EZH2; required to repress RAR signaling. Ref.7
Subcellular location	Nucleus Probable. Cell membrane Ref.8.
Tissue specificity	Expressed in testis. Detected in samples of kidney, brain and skin. Ref.1
Miscellaneous	Tumor antigen recognized by cytolytic T lymphocytes.
Sequence similarities	Belongs to the PRAME family. Contains 4 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	Apoptosis Differentiation Growth regulation Transcription Transcription regulation
Cellular component	Cell membrane Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat
Molecular function	Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of cell differentiation Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of retinoic acid receptor signaling pathway Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.7. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay Ref.7. Source: UniProtKB regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	retinoic acid receptor binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
STK19	P49842	1	EBI-348325,EBI-347581

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 509	509	Melanoma antigen preferentially expressed in tumors		PRO_0000156973
Regions
	Repeat	323 – 343	21	LRR 1
	Repeat	350 – 371	22	LRR 2
	Repeat	379 – 400	22	LRR 3
	Repeat	407 – 427	21	LRR 4
	Region	416 – 509	94	Mediates interaction with RARA
Natural variations
	Natural variant	7	1	W → R. Ref.2 Ref.5 Corresponds to variant rs2266988 [ dbSNP | Ensembl ].		VAR_021258
	Natural variant	218	1	M → V. Corresponds to variant rs41277507 [ dbSNP | Ensembl ].		VAR_062137
Experimental info
	Mutagenesis	470 – 471	2	LL → VV: Loss of interaction with RARA and defective in repressing RARA signaling. Ref.7
	Sequence conflict	452	1	H → D in AAC39560. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P78395 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: B5FFF3E7F7E82606	FASTA	509	57,890
	10 20 30 40 50 60 MERRRLWGSI QSRYISMSVW TSPRRLVELA GQSLLKDEAL AIAALELLPR ELFPPLFMAA 70 80 90 100 110 120 FDGRHSQTLK AMVQAWPFTC LPLGVLMKGQ HLHLETFKAV LDGLDVLLAQ EVRPRRWKLQ 130 140 150 160 170 180 VLDLRKNSHQ DFWTVWSGNR ASLYSFPEPE AAQPMTKKRK VDGLSTEAEQ PFIPVEVLVD 190 200 210 220 230 240 LFLKEGACDE LFSYLIEKVK RKKNVLRLCC KKLKIFAMPM QDIKMILKMV QLDSIEDLEV 250 260 270 280 290 300 TCTWKLPTLA KFSPYLGQMI NLRRLLLSHI HASSYISPEK EEQYIAQFTS QFLSLQCLQA 310 320 330 340 350 360 LYVDSLFFLR GRLDQLLRHV MNPLETLSIT NCRLSEGDVM HLSQSPSVSQ LSVLSLSGVM 370 380 390 400 410 420 LTDVSPEPLQ ALLERASATL QDLVFDECGI TDDQLLALLP SLSHCSQLTT LSFYGNSISI 430 440 450 460 470 480 SALQSLLQHL IGLSNLTHVL YPVPLESYED IHGTLHLERL AYLHARLREL LCELGRPSMV 490 500 WLSANPCPHC GDRTFYDPEP ILCPCFMPN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor." Ikeda H., Lethe B.G., Lehmann F., van Baren N., Baurain J.-F., de Smet C., Chambost H., Vitale M., Moretta A., Boon T., Coulie P.G. Immunity 6:199-208(1997) [PubMed: 9047241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-7.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-7. Tissue: Brain, Skin and Testis.
[6]	"Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth." Williams J.M., Chen G.-C., Zhu L., Rest R.F. Mol. Microbiol. 27:171-186(1998) [PubMed: 9466265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 452-509.
[7]	"The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling." Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R. Cell 122:835-847(2005) [PubMed: 16179254] [Abstract] Cited for: FUNCTION IN RETINOIC ACID SIGNALING, INTERACTION WITH EZH2 AND RARA, MUTAGENESIS OF 470-LEU-LEU-471.
[8]	"PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma." Proto-Siqueira R., Figueiredo-Pontes L.L., Panepucci R.A., Garcia A.B., Rizzatti E.G., Nascimento F.M., Ishikawa H.C.F., Larson R.E., Falcao R.P., Simpson A.J., Gout I., Filonenko V., Rego E.M., Zago M.A. Leuk. Res. 30:1333-1339(2006) [PubMed: 16620968] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U65011 mRNA. Translation: AAC51160.1. CR456549 mRNA. Translation: CAG30435.1. AK312769 mRNA. Translation: BAG35634.1. CH471095 Genomic DNA. Translation: EAW59518.1. BC014074 mRNA. Translation: AAH14074.1. BC022008 mRNA. Translation: AAH22008.1. BC039731 mRNA. Translation: AAH39731.1. AF025440 mRNA. Translation: AAC39560.1.
IPI	IPI00019282.
RefSeq	NP_006106.1. NM_006115.3. NP_996836.1. NM_206953.1. NP_996837.1. NM_206954.1. NP_996838.1. NM_206955.1. NP_996839.1. NM_206956.1.
UniGene	Hs.30743.
3D structure databases
ProteinModelPortal	P78395.
SMR	P78395. Positions 231-443.
ModBase	Search...
Protein-protein interaction databases
IntAct	P78395. 2 interactions.
MINT	MINT-1034364.
STRING	P78395.
Polymorphism databases
DMDM	6685631.
Proteomic databases
PeptideAtlas	P78395.
PRIDE	P78395.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398741; ENSP00000381726; ENSG00000185686. ENST00000398743; ENSP00000381728; ENSG00000185686. ENST00000402697; ENSP00000385198; ENSG00000185686. ENST00000405655; ENSP00000384343; ENSG00000185686. ENST00000424204; ENSP00000407342; ENSG00000185686.
GeneID	23532.
KEGG	hsa:23532.
UCSC	uc002zwf.1. human.
Organism-specific databases
CTD	23532.
GeneCards	GC22M022890.
H-InvDB	HIX0016292. HIX0028656.
HGNC	HGNC:9336. PRAME.
HPA	HPA045153.
MIM	606021. gene.
neXtProt	NX_P78395.
PharmGKB	PA33698.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17547.
GeneTree	ENSGT00600000084130.
HOGENOM	HBG506079.
InParanoid	P78395.
OMA	LKIFAMP.
OrthoDB	EOG4MCX07.
PhylomeDB	P78395.
Gene expression databases
ArrayExpress	P78395.
Bgee	P78395.
CleanEx	HS_PRAME.
Genevestigator	P78395.
GermOnline	ENSG00000185686. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	46014.
SOURCE	Search...

Entry information

Entry name

PRAME_HUMAN

Accession

Primary (citable) accession number: P78395
Secondary accession number(s): B2R6Y7, O43481, Q8IXN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.