Reviewed, UniProtKB/Swiss-Prot O00541 (PESC_HUMAN)

Names and origin

Protein names

Recommended name:
    Pescadillo homolog

Gene names

Name:

PES1

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	588 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome. Ref.10 Ref.12 Ref.13
Subunit structure	Interacts with IRS1 and UBTF. May interact with MAP1B By similarity. Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. Within the PeBoW complex BOP1 interacts directly with PES1 and WDR12. The PeBoW complex also associates with the 66S pre-ribosome.
Subcellular location	Nucleus › nucleolus. Nucleus › nucleoplasm. Note: Appears to localize to the periphery of metaphase chromosomes during mitosis and to the prenucleolar bodies that form in mitotic cells prior to the actual nucleoli By similarity.
Tissue specificity	Significant levels are detected in a variety of cancer cell lines, including glioblastoma, breast carcinoma, colon carcinoma and cervical carcinoma cells. Levels are abnormally elevated in malignant tumors of astrocytic origin.
Induction	By MYC. Ref.9
Post-translational modification	Sumoylated.
Sequence similarities	Belongs to the pescadillo family. Contains 1 BRCT domain.

Ontologies

Keywords
Biological process	Ribosome biogenesis rRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.9 Ref.10 Inferred from mutant phenotype. Source: UniProtKB maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Ref.10 Inferred from mutant phenotype. Source: UniProtKB maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Ref.10 Ref.12 Inferred from mutant phenotype. Source: UniProtKB regulation of cell cycle Ref.10 Inferred from mutant phenotype. Source: UniProtKB ribosomal large subunit biogenesis Ref.10 Ref.12 Inferred by curator. Source: UniProtKB
Cellular component	PeBoW complex Ref.9 Ref.10 Ref.12 Inferred from direct assay. Source: UniProtKB nucleoplasm Ref.10 Inferred from direct assay. Source: UniProtKB preribosome, large subunit precursor Ref.10 Ref.12 Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Ref.9 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	1	EBI-1053271,EBI-743313
ARRB2	P32121	1	EBI-1053271,EBI-714559

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00541-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O00541-2)

The sequence of this isoform differs from the canonical sequence as follows:
     306-310: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 588

588

Pescadillo homolog

PRO_0000186188

Regions

Domain

322 – 415

94

BRCT

Region

1 – 257

257

Sufficient for nucleolar localization

Region

1 – 54

54

Required for 28S ribosomal RNA processing

Region

306 – 415

110

Sufficient for interaction with MAP1B By similarity

Region

539 – 588

50

Required for 28S ribosomal RNA processing

Compositional bias

456 – 531

76

Glu-rich

Amino acid modifications

Modified residue

457

1

Phosphoserine Ref.14

Modified residue

488

1

Phosphoserine Ref.14

Modified residue

548

1

Phosphotyrosine Ref.11

Natural variations

Alternative sequence

306 – 310

5

Missing in isoform 2.

VSP_013023

Natural variant

264

1

T → S: dbSNP rs42942.

VAR_034375

Natural variant

370

1

D → H: dbSNP rs11541876.

VAR_053570

Natural variant

411

1

A → T: dbSNP rs34123894.

VAR_053571

Experimental info

Mutagenesis

327

1

F → R: Reduces incorporation into the PeBoW complex and nucleolar localization and impairs maturation of 28S ribosomal RNA. Ref.13

Mutagenesis

347

1

I → R: Reduces incorporation into the PeBoW complex and nucleolar localization and impairs maturation of 28S ribosomal RNA. Ref.13

Mutagenesis

380

1

R → W: Slightly impairs nucleolar localization. Ref.13

Mutagenesis

397

1

W → R: Reduces incorporation into the PeBoW complex and nucleolar localization and impairs maturation of 28S ribosomal RNA. Ref.13

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

588

Helix Strand Turn

Details...

Beta strand

331 – 333

3

Beta strand

336 – 338

3

Helix

340 – 349

10

Beta strand

353 – 355

3

Turn

358 – 360

3

Beta strand

375 – 377

3

Turn

381 – 383

3

Beta strand

390 – 393

4

Helix

396 – 404

9

Turn

410 – 412

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: CB6201D6E34D82B1	FASTA	588	68,003
	10 20 30 40 50 60 MGGLEKKKYE RGSATNYITR NKARKKLQLS LADFRRLCIL KGIYPHEPKH KKKVNKGSTA 70 80 90 100 110 120 ARTFYLIKDI RFLLHEPIVN KFREYKVFVR KLRKAYGKSE WNTVERLKDN KPNYKLDHII 130 140 150 160 170 180 KERYPTFIDA LRDLDDALSM CFLFSTFPRT GKCHVQTIQL CRRLTVEFMH YIIAARALRK 190 200 210 220 230 240 VFLSIKGIYY QAEVLGQPIV WITPYAFSHD HPTDVDYRVM ATFTEFYTTL LGFVNFRLYQ 250 260 270 280 290 300 LLNLHYPPKL EGQAQAEAKA GEGTYALDSE SCMEKLAALS ASLARVVVPA TEEEAEVDEF 310 320 330 340 350 360 PTDGEMSAQE EDRRKELEAQ EKHKKLFEGL KFFLNREVPR EALAFIIRSF GGEVSWDKSL 370 380 390 400 410 420 CIGATYDVTD SRITHQIVDR PGQQTSVIGR CYVQPQWVFD SVNARLLLPV AEYFSGVQLP 430 440 450 460 470 480 PHLSPFVTEK EGDYVPPEKL KLLALQRGED PGNLNESEEE EEEDDNNEGD GDEEGENEEE 490 500 510 520 530 540 EEDAEAGSEK EEEARLAALE EQRMEGKKPR VMAGTLKLED KQRLAQEEES EAKRLAIMMM 550 560 570 580 KKREKYLYQK IMFGKRRKIR EANKLAEKRK AHDEAVRSEK KAKKARPE
	Isoform 2. Checksum: 89BEC8BB4328F707	FASTA	583	67,456
	10 20 30 40 50 60 MGGLEKKKYE RGSATNYITR NKARKKLQLS LADFRRLCIL KGIYPHEPKH KKKVNKGSTA 70 80 90 100 110 120 ARTFYLIKDI RFLLHEPIVN KFREYKVFVR KLRKAYGKSE WNTVERLKDN KPNYKLDHII 130 140 150 160 170 180 KERYPTFIDA LRDLDDALSM CFLFSTFPRT GKCHVQTIQL CRRLTVEFMH YIIAARALRK 190 200 210 220 230 240 VFLSIKGIYY QAEVLGQPIV WITPYAFSHD HPTDVDYRVM ATFTEFYTTL LGFVNFRLYQ 250 260 270 280 290 300 LLNLHYPPKL EGQAQAEAKA GEGTYALDSE SCMEKLAALS ASLARVVVPA TEEEAEVDEF 310 320 330 340 350 360 PTDGEEDRRK ELEAQEKHKK LFEGLKFFLN REVPREALAF IIRSFGGEVS WDKSLCIGAT 370 380 390 400 410 420 YDVTDSRITH QIVDRPGQQT SVIGRCYVQP QWVFDSVNAR LLLPVAEYFS GVQLPPHLSP 430 440 450 460 470 480 FVTEKEGDYV PPEKLKLLAL QRGEDPGNLN ESEEEEEEDD NNEGDGDEEG ENEEEEEDAE 490 500 510 520 530 540 AGSEKEEEAR LAALEEQRME GKKPRVMAGT LKLEDKQRLA QEEESEAKRL AIMMMKKREK 550 560 570 580 YLYQKIMFGK RRKIREANKL AEKRKAHDEA VRSEKKAKKA RPE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and dead eye, essential for embryonic development." Allende M.L., Amsterdam A., Becker T., Kawakami K., Gaiano N., Hopkins N. Genes Dev. 10:3141-3155(1996) [PubMed: 8985183] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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:RESEARCH84.1-RESEARCH84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1). Tissue: Mammary gland.
[5]	"Pescadillo, a novel cell cycle regulatory protein abnormally expressed in malignant cells." Kinoshita Y., Jarell A.D., Flaman J.-M., Foltz G., Schuster J., Sopher B.L., Irvin D.K., Kanning K., Kornblum H.I., Nelson P.S., Hieter P., Morrison R.S. J. Biol. Chem. 276:6656-6665(2001) [PubMed: 11071894] [Abstract] Cited for: CHARACTERIZATION.
[6]	"Yeast Pescadillo is required for multiple activities during 60S ribosomal subunit synthesis." Oeffinger M., Leung A., Lamond A., Tollervey D. RNA 8:626-636(2002) [PubMed: 12022229] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	Erratum Oeffinger M., Leung A., Lamond A., Tollervey D. RNA 8:851-851(2002)
[8]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed: 12429849] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation." Hoelzel M., Rohrmoser M., Schlee M., Grimm T., Harasim T., Malamoussi A., Gruber-Eber A., Kremmer E., Hiddemann W., Bornkamm G.W., Eick D. J. Cell Biol. 170:367-378(2005) [PubMed: 16043514] [Abstract] Cited for: INTERACTION WITH BOP1 AND WDR12, INDUCTION.
[10]	"Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex." Grimm T., Hoelzel M., Rohrmoser M., Harasim T., Malamoussi A., Gruber-Eber A., Kremmer E., Eick D. Nucleic Acids Res. 34:3030-3043(2006) [PubMed: 16738141] [Abstract] Cited for: FUNCTION, INTERACTION WITH BOP1 AND WDR12, SUBCELLULAR LOCATION.
[11]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-548, MASS SPECTROMETRY.
[12]	"Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit." Rohrmoser M., Hoelzel M., Grimm T., Malamoussi A., Harasim T., Orban M., Pfisterer I., Gruber-Eber A., Kremmer E., Eick D. Mol. Cell. Biol. 27:3682-3694(2007) [PubMed: 17353269] [Abstract] Cited for: FUNCTION, INTERACTION WITH BOP1 AND WDR12.
[13]	"The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing." Hoelzel M., Grimm T., Rohrmoser M., Malamoussi A., Harasim T., Gruber-Eber A., Kremmer E., Eick D. Nucleic Acids Res. 35:789-800(2007) [PubMed: 17189298] [Abstract] Cited for: FUNCTION, INTERACTION WITH BOP1 AND WDR12, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-327; ILE-347; ARG-380 AND TRP-397.
[14]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457 AND SER-488, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Solution structure of the BRCT domain from human pescadillo homolog 1." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 322-414.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U78310 mRNA. Translation: AAB61140.1.
CR456539 mRNA. Translation: CAG30425.1.
AC005006 Genomic DNA. No translation available.
BC032489 mRNA. Translation: AAH32489.1.

IPI

IPI00003768.
IPI00554461.

RefSeq

NP_055118.1.

UniGene

Hs.517543

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EP8	NMR	-	A	322-414	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O00541. 2 interactions.

PTM databases

PhosphoSite

O00541.

2-D gel databases

SWISS-2DPAGE

O00541.

Proteomic databases

PRIDE

O00541.

Genome annotation databases

Ensembl

ENSG00000100029. Homo sapiens. [Contig view]

GeneID

23481.

KEGG

hsa:23481.

Organism-specific databases

GeneCards

GC22M029297.

H-InvDB

HIX0016375.
HIX0031675.

HGNC

HGNC:8848. PES1.

MIM

605819. gene.

PharmGKB

PA33190.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O00541.

HOVERGEN

O00541.

OMA

O00541. GIYPREP.

Gene expression databases

ArrayExpress

O00541.

Bgee

O00541.

CleanEx

HS_PES1.

GermOnline

ENSG00000100029. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT.
IPR010613. Pescadillo_N.
[Graphical view]

Pfam

PF00533. BRCT. 1 hit.
PF06732. Pescadillo_N. 1 hit.
[Graphical view]

SMART

SM00292. BRCT. 1 hit.
[Graphical view]

PROSITE

PS50172. BRCT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

45839.

SOURCE

Search...

Entry information

Entry name

PESC_HUMAN

Accession

Primary (citable) accession number: O00541
Secondary accession number(s): Q6IC29

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2002
Last sequence update:	July 1, 1997
Last modified:	June 16, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)