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Protein

Melanoma antigen preferentially expressed in tumors

Gene

PRAME

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • retinoic acid receptor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell differentiation Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of retinoic acid receptor signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Apoptosis, Differentiation, Growth regulation, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
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 namesi
Name:PRAME
Synonyms:MAPE, OIP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:9336. PRAME.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi470 – 4712LL → VV: Loss of interaction with RARA and defective in repressing RARA signaling. 1 Publication

Organism-specific databases

PharmGKBiPA33698.

Polymorphism and mutation databases

BioMutaiPRAME.
DMDMi6685631.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 509509Melanoma antigen preferentially expressed in tumorsPRO_0000156973Add
BLAST

Proteomic databases

EPDiP78395.
MaxQBiP78395.
PaxDbiP78395.
PeptideAtlasiP78395.
PRIDEiP78395.

PTM databases

iPTMnetiP78395.
PhosphoSiteiP78395.

Expressioni

Tissue specificityi

Expressed in testis. Detected in samples of kidney, brain and skin.1 Publication

Gene expression databases

BgeeiP78395.
CleanExiHS_PRAME.
ExpressionAtlasiP78395. baseline and differential.
GenevisibleiP78395. HS.

Organism-specific databases

HPAiHPA045153.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
STK19P498421EBI-348325,EBI-347581

GO - Molecular functioni

  • retinoic acid receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi117078. 48 interactions.
IntActiP78395. 16 interactions.
MINTiMINT-1034364.
STRINGi9606.ENSP00000381726.

Structurei

3D structure databases

ProteinModelPortaliP78395.
SMRiP78395. Positions 258-439.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati323 – 34321LRR 1Add
BLAST
Repeati350 – 37122LRR 2Add
BLAST
Repeati379 – 40022LRR 3Add
BLAST
Repeati407 – 42721LRR 4Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni416 – 50994Mediates interaction with RARAAdd
BLAST

Sequence similaritiesi

Belongs to the PRAME family.Curated
Contains 4 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410J8VX. Eukaryota.
ENOG411194M. LUCA.
GeneTreeiENSGT00760000119028.
HOGENOMiHOG000231112.
InParanoidiP78395.
OMAiDLRKNAH.
OrthoDBiEOG7KSX88.
PhylomeDBiP78395.
TreeFamiTF332708.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR026271. PRAME_family.
[Graphical view]
PIRSFiPIRSF038286. PRAME. 1 hit.

Sequencei

Sequence statusi: Complete.

P78395-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERRRLWGSI QSRYISMSVW TSPRRLVELA GQSLLKDEAL AIAALELLPR
60 70 80 90 100
ELFPPLFMAA FDGRHSQTLK AMVQAWPFTC LPLGVLMKGQ HLHLETFKAV
110 120 130 140 150
LDGLDVLLAQ EVRPRRWKLQ VLDLRKNSHQ DFWTVWSGNR ASLYSFPEPE
160 170 180 190 200
AAQPMTKKRK VDGLSTEAEQ PFIPVEVLVD LFLKEGACDE LFSYLIEKVK
210 220 230 240 250
RKKNVLRLCC KKLKIFAMPM QDIKMILKMV QLDSIEDLEV TCTWKLPTLA
260 270 280 290 300
KFSPYLGQMI NLRRLLLSHI HASSYISPEK EEQYIAQFTS QFLSLQCLQA
310 320 330 340 350
LYVDSLFFLR GRLDQLLRHV MNPLETLSIT NCRLSEGDVM HLSQSPSVSQ
360 370 380 390 400
LSVLSLSGVM LTDVSPEPLQ ALLERASATL QDLVFDECGI TDDQLLALLP
410 420 430 440 450
SLSHCSQLTT LSFYGNSISI SALQSLLQHL IGLSNLTHVL YPVPLESYED
460 470 480 490 500
IHGTLHLERL AYLHARLREL LCELGRPSMV WLSANPCPHC GDRTFYDPEP

ILCPCFMPN
Length:509
Mass (Da):57,890
Last modified:May 1, 1997 - v1
Checksum:iB5FFF3E7F7E82606
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti452 – 4521H → D in AAC39560 (PubMed:9466265).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71W → R.2 Publications
Corresponds to variant rs2266988 [ dbSNP | Ensembl ].
VAR_021258
Natural varianti218 – 2181M → V.
Corresponds to variant rs41277507 [ dbSNP | Ensembl ].
VAR_062137

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13801.1.
RefSeqiNP_001278644.1. NM_001291715.1.
NP_001278645.1. NM_001291716.1.
NP_001278646.1. NM_001291717.1.
NP_001278648.1. NM_001291719.1.
NP_001305055.1. NM_001318126.1.
NP_001305056.1. NM_001318127.1.
NP_006106.1. NM_006115.4.
NP_996836.1. NM_206953.2.
NP_996837.1. NM_206954.2.
NP_996838.1. NM_206955.2.
NP_996839.1. NM_206956.2.
UniGeneiHs.30743.

Genome annotation databases

EnsembliENST00000398741; ENSP00000381726; ENSG00000185686.
ENST00000398743; ENSP00000381728; ENSG00000185686.
ENST00000402697; ENSP00000385198; ENSG00000185686.
ENST00000405655; ENSP00000384343; ENSG00000185686.
ENST00000539862; ENSP00000445097; ENSG00000275013.
ENST00000543184; ENSP00000445675; ENSG00000185686.
ENST00000617728; ENSP00000484066; ENSG00000275013.
ENST00000626503; ENSP00000486485; ENSG00000275013.
ENST00000628830; ENSP00000486330; ENSG00000275013.
GeneIDi23532.
KEGGihsa:23532.
UCSCiuc032qia.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13801.1.
RefSeqiNP_001278644.1. NM_001291715.1.
NP_001278645.1. NM_001291716.1.
NP_001278646.1. NM_001291717.1.
NP_001278648.1. NM_001291719.1.
NP_001305055.1. NM_001318126.1.
NP_001305056.1. NM_001318127.1.
NP_006106.1. NM_006115.4.
NP_996836.1. NM_206953.2.
NP_996837.1. NM_206954.2.
NP_996838.1. NM_206955.2.
NP_996839.1. NM_206956.2.
UniGeneiHs.30743.

3D structure databases

ProteinModelPortaliP78395.
SMRiP78395. Positions 258-439.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117078. 48 interactions.
IntActiP78395. 16 interactions.
MINTiMINT-1034364.
STRINGi9606.ENSP00000381726.

PTM databases

iPTMnetiP78395.
PhosphoSiteiP78395.

Polymorphism and mutation databases

BioMutaiPRAME.
DMDMi6685631.

Proteomic databases

EPDiP78395.
MaxQBiP78395.
PaxDbiP78395.
PeptideAtlasiP78395.
PRIDEiP78395.

Protocols and materials databases

DNASUi23532.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000398741; ENSP00000381726; ENSG00000185686.
ENST00000398743; ENSP00000381728; ENSG00000185686.
ENST00000402697; ENSP00000385198; ENSG00000185686.
ENST00000405655; ENSP00000384343; ENSG00000185686.
ENST00000539862; ENSP00000445097; ENSG00000275013.
ENST00000543184; ENSP00000445675; ENSG00000185686.
ENST00000617728; ENSP00000484066; ENSG00000275013.
ENST00000626503; ENSP00000486485; ENSG00000275013.
ENST00000628830; ENSP00000486330; ENSG00000275013.
GeneIDi23532.
KEGGihsa:23532.
UCSCiuc032qia.2. human.

Organism-specific databases

CTDi23532.
GeneCardsiPRAME.
HGNCiHGNC:9336. PRAME.
HPAiHPA045153.
MIMi606021. gene.
neXtProtiNX_P78395.
PharmGKBiPA33698.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J8VX. Eukaryota.
ENOG411194M. LUCA.
GeneTreeiENSGT00760000119028.
HOGENOMiHOG000231112.
InParanoidiP78395.
OMAiDLRKNAH.
OrthoDBiEOG7KSX88.
PhylomeDBiP78395.
TreeFamiTF332708.

Miscellaneous databases

GeneWikiiPRAME.
GenomeRNAii23532.
NextBioi46014.
PROiP78395.
SOURCEiSearch...

Gene expression databases

BgeeiP78395.
CleanExiHS_PRAME.
ExpressionAtlasiP78395. baseline and differential.
GenevisibleiP78395. HS.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR026271. PRAME_family.
[Graphical view]
PIRSFiPIRSF038286. PRAME. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  4. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPRAME_HUMAN
AccessioniPrimary (citable) accession number: P78395
Secondary accession number(s): B2R6Y7, O43481, Q8IXN8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: March 16, 2016
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

Tumor antigen recognized by cytolytic T lymphocytes.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.