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Q504Q3 (PAN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
PAB-dependent poly(A)-specific ribonuclease subunit PAN2

Short name=hPan2
EC=3.1.13.4
Alternative name(s):
Inactive ubiquitin carboxyl-terminal hydrolase 52
PAB1P-dependent poly(A)-nuclease
PAN deadenylation complex catalytic subunit 2
Gene names
Name:PAN2
Synonyms:KIAA0710, USP52
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1202 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA when the poly(A) stretch is bound by poly(A)-binding protein (PABP), which is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. Ref.1 Ref.6

Catalytic activity

Exonucleolytic cleavage of poly(A) to 5'-AMP. Ref.1

Enzyme regulation

Positively regulated by the regulatory subunit PAN3 By similarity. HAMAP-Rule MF_03182

Subunit structure

Interacts with the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex. Ref.1 Ref.12

Subcellular location

CytoplasmP-body. Nucleus. Note: Shuttles between nucleus and cytoplasm. Ref.1 Ref.6 Ref.8

Sequence similarities

Belongs to the peptidase C19 family. PAN2 subfamily.

Contains 1 exonuclease domain.

Contains 1 USP domain.

Contains 4 WD repeats.

Caution

Has no ubiquitin carboxyl terminal hydrolase activity since it lacks a conserved catalytic Cys at position 525.

Sequence caution

The sequence BAA31685.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processmRNA processing
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
WD repeat
   Molecular functionExonuclease
Hydrolase
Nuclease
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA metabolic process

Traceable author statement. Source: Reactome

RNA phosphodiester bond hydrolysis, exonucleolytic

Inferred from direct assay Ref.1. Source: GOC

gene expression

Traceable author statement. Source: Reactome

mRNA metabolic process

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA poly(A) tail shortening

Traceable author statement. Source: Reactome

   Cellular_componentPAN complex

Inferred from direct assay Ref.1. Source: UniProtKB

cytoplasmic mRNA processing body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_function3'-5'-exoribonuclease activity

Inferred from direct assay Ref.1. Source: UniProtKB

nucleic acid binding

Inferred from electronic annotation. Source: InterPro

poly(A)-specific ribonuclease activity

Inferred from direct assay Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.1PubMed 19615732. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PAN3Q58A456EBI-1058976,EBI-2513054

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q504Q3-1)

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: Q504Q3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     689-692: Missing.
Isoform 3 (identifier: Q504Q3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     643-643: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12021202PAB-dependent poly(A)-specific ribonuclease subunit PAN2 HAMAP-Rule MF_03182
PRO_0000280521

Regions

Repeat153 – 19341WD 1 HAMAP-Rule MF_03182
Repeat195 – 23137WD 2 HAMAP-Rule MF_03182
Repeat244 – 28037WD 3 HAMAP-Rule MF_03182
Repeat328 – 36740WD 4 HAMAP-Rule MF_03182
Domain517 – 924408USP
Domain975 – 1147173Exonuclease

Amino acid modifications

Modified residue7911Phosphoserine Ref.9
Modified residue11891Phosphoserine Ref.7

Natural variations

Alternative sequence6431Missing in isoform 3.
VSP_023748
Alternative sequence689 – 6924Missing in isoform 2.
VSP_023749
Natural variant321S → N. Ref.4
Corresponds to variant rs11558139 [ dbSNP | Ensembl ].
VAR_031162
Natural variant1791I → L. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1918496 [ dbSNP | Ensembl ].
VAR_031163
Natural variant12011A → V in a colorectal cancer sample; somatic mutation. Ref.13
VAR_036359

Experimental info

Mutagenesis10871D → A: Loss of exonuclease activity. Ref.1
Sequence conflict91G → E in AAH94885. Ref.4
Sequence conflict10911I → V in AAH94885. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 579194C102FCA019

FASTA1,202135,368
        10         20         30         40         50         60 
MNFEGLDPGL AEYAPAMHSA LDPVLDAHLN PSLLQNVELD PEGVALEALP VQESVHIMEG 

        70         80         90        100        110        120 
VYSELHSVVA EVGVPVSVSH FDLHEEMLWV GSHGGHATSF FGPALERYSS FQVNGSDDIR 

       130        140        150        160        170        180 
QIQSLENGIL FLTKNNLKYM ARGGLIIFDY LLDENEDMHS LLLTDSSTLL VGGLQNHIIE 

       190        200        210        220        230        240 
IDLNTVQETQ KYAVETPGVT IMRQTNRFFF CGHTSGKVSL RDLRTFKVEH EFDAFSGSLS 

       250        260        270        280        290        300 
DFDVHGNLLA ACGFSSRLTG LACDRFLKVY DLRMMRAITP LQVHVDPAFL RFIPTYTSRL 

       310        320        330        340        350        360 
AIISQSGQCQ FCEPTGLANP ADIFHVNPVG PLLMTFDVSA SKQALAFGDS EGCVHLWTDS 

       370        380        390        400        410        420 
PEPSFNPYSR ETEFALPCLV DSLPPLDWSQ DLLPLSLIPV PLTTDTLLSD WPAANSAPAP 

       430        440        450        460        470        480 
RRAPPVDAEI LRTMKKVGFI GYAPNPRTRL RNQIPYRLKE SDSEFDSFSQ VTESPVGREE 

       490        500        510        520        530        540 
EPHLHMVSKK YRKVTIKYSK LGLEDFDFKH YNKTLFAGLE PHIPNAYCNC MIQVLYFLEP 

       550        560        570        580        590        600 
VRCLIQNHLC QKEFCLACEL GFLFHMLDLS RGDPCQGNNF LRAFRTIPEA SALGLILADS 

       610        620        630        640        650        660 
DEASGKGNLA RLIQRWNRFI LTQLHQDMQE LEIPQAYRGA GGSSFCSSGD SVIGQLFSCE 

       670        680        690        700        710        720 
MENCSLCRCG SETVRASSTL LFTLSYPDGS KSDKTGKNYD FAQVLKRSIC LDQNTQAWCD 

       730        740        750        760        770        780 
TCEKYQPTIQ TRNIRHLPDI LVINCEVNSS KEADFWRMQA EVAFKMAVKK HGGEISKNKE 

       790        800        810        820        830        840 
FALADWKELG SPEGVLVCPS IEELKNVWLP FSIRMKMTKN KGLDVCNWTD GDEMQWGPAR 

       850        860        870        880        890        900 
AEEEHGVYVY DLMATVVHIL DSRTGGSLVA HIKVGETYHQ RKEGVTHQQW YLFNDFLIEP 

       910        920        930        940        950        960 
IDKHEAVQFD MNWKVPAILY YVKRNLNSRY NLNIKNPIEA SVLLAEASLA RKQRKTHTTF 

       970        980        990       1000       1010       1020 
IPLMLNEMPQ IGDLVGLDAE FVTLNEEEAE LRSDGTKSTI KPSQMSVARI TCVRGQGPNE 

      1030       1040       1050       1060       1070       1080 
GIPFIDDYIS TQEQVVDYLT QYSGIKPGDL DAKISSKHLT TLKSTYLKLR FLIDIGVKFV 

      1090       1100       1110       1120       1130       1140 
GHGLQKDFRV INLMVPKDQV LDTVYLFHMP RKRMISLRFL AWYFLDLKIQ GETHDSIEDA 

      1150       1160       1170       1180       1190       1200 
RTALQLYRKY LELSKNGTEP ESFHKVLKGL YEKGRKMDWK VPEPEGQTSP KNAAVFSSVL 


AL 

« Hide

Isoform 2 [UniParc].

Checksum: 9F0D327BE78EC7D7
Show »

FASTA1,198135,008
Isoform 3 [UniParc].

Checksum: E185DC887D382DC1
Show »

FASTA1,201135,281

References

« Hide 'large scale' references
[1]"Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein."
Uchida N., Hoshino S., Katada T.
J. Biol. Chem. 279:1383-1391(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PAN3 AND POLYADENYLATE-BINDING PROTEIN, MUTAGENESIS OF ASP-1087, VARIANT LEU-179.
Tissue: Cervix carcinoma.
[2]"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT LEU-179.
Tissue: Brain.
[3]Ohara O., Suyama M., Nagase T., Ishikawa K.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ASN-32 AND LEU-179.
Tissue: Eye and Testis.
[5]"Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases."
Quesada V., Diaz-Perales A., Gutierrez-Fernandez A., Garabaya C., Cal S., Lopez-Otin C.
Biochem. Biophys. Res. Commun. 314:54-62(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: LACK OF UBIQUITIN CARBOXYL TERMINAL HYDROLASE ACTIVITY.
[6]"Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover."
Yamashita A., Chang T.-C., Yamashita Y., Zhu W., Zhong Z., Chen C.-Y.A., Shyu A.-B.
Nat. Struct. Mol. Biol. 12:1054-1063(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1189, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells."
Zheng D., Ezzeddine N., Chen C.Y., Zhu W., He X., Shyu A.B.
J. Cell Biol. 182:89-101(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Structure of the PAN3 pseudokinase reveals the basis for interactions with the PAN2 deadenylase and the GW182 proteins."
Christie M., Boland A., Huntzinger E., Weichenrieder O., Izaurralde E.
Mol. Cell 51:360-373(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PAN3.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-1201.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB107585 mRNA. Translation: BAD02263.1.
AB014610 mRNA. Translation: BAA31685.2. Different initiation.
BC024043 mRNA. Translation: AAH24043.1.
BC094885 mRNA. Translation: AAH94885.1.
CCDSCCDS44922.1. [Q504Q3-1]
CCDS53802.1. [Q504Q3-3]
CCDS8915.1. [Q504Q3-2]
RefSeqNP_001120932.1. NM_001127460.2.
NP_001159751.1. NM_001166279.1.
NP_055686.3. NM_014871.4.
UniGeneHs.273397.

3D structure databases

ProteinModelPortalQ504Q3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115252. 341 interactions.
DIPDIP-50708N.
IntActQ504Q3. 16 interactions.
STRING9606.ENSP00000368809.

Protein family/group databases

MEROPSC19.978.

PTM databases

PhosphoSiteQ504Q3.

Polymorphism databases

DMDM296439280.

Proteomic databases

MaxQBQ504Q3.
PaxDbQ504Q3.
PRIDEQ504Q3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257931; ENSP00000257931; ENSG00000135473. [Q504Q3-3]
ENST00000425394; ENSP00000401721; ENSG00000135473. [Q504Q3-1]
ENST00000440411; ENSP00000388231; ENSG00000135473. [Q504Q3-2]
ENST00000548043; ENSP00000449861; ENSG00000135473. [Q504Q3-1]
GeneID9924.
KEGGhsa:9924.
UCSCuc001skx.3. human. [Q504Q3-1]
uc001sky.3. human. [Q504Q3-2]
uc001skz.3. human. [Q504Q3-3]

Organism-specific databases

CTD9924.
GeneCardsGC12M056710.
HGNCHGNC:20074. PAN2.
neXtProtNX_Q504Q3.
PharmGKBPA162398664.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0847.
HOGENOMHOG000230585.
HOVERGENHBG089847.
InParanoidQ504Q3.
KOK12571.
OMAMEADWDE.
OrthoDBEOG7JHM4K.
PhylomeDBQ504Q3.
TreeFamTF105657.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ504Q3.
BgeeQ504Q3.
CleanExHS_PAN2.
GenevestigatorQ504Q3.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
3.30.420.10. 1 hit.
HAMAPMF_03182. PAN2.
InterProIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR028881. PAN2.
IPR012337. RNaseH-like_dom.
IPR028889. UCH/PAN2.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00929. RNase_T. 1 hit.
PF13423. UCH_1. 1 hit.
[Graphical view]
SMARTSM00479. EXOIII. 1 hit.
[Graphical view]
SUPFAMSSF50978. SSF50978. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEPS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUSP52.
GenomeRNAi9924.
NextBio37442.
PROQ504Q3.

Entry information

Entry namePAN2_HUMAN
AccessionPrimary (citable) accession number: Q504Q3
Secondary accession number(s): O75189, Q76E12, Q8IVE1
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 100 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM