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Protein

PAN2-PAN3 deadenylation complex catalytic subunit PAN2

Gene

PAN2

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

Functioni

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 and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation 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. Also acts as an important regulator of the HIF1A-mediated hypoxic response. Required for HIF1A mRNA stability independent of poly(A) tail length regulation.UniRule annotation3 Publications

Catalytic activityi

Exonucleolytic cleavage of poly(A) to 5'-AMP.UniRule annotation1 Publication

Cofactori

a divalent metal cationUniRule annotationNote: Binds 2 metal cations per subunit in the catalytic exonuclease domain.UniRule annotation

Activity regulationi

Positively regulated by the regulatory subunit PAN3.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi978Divalent metal cation; catalyticUniRule annotationBy similarity1
Metal bindingi980Divalent metal cation; catalyticUniRule annotationBy similarity1
Metal bindingi1087Divalent metal cation; catalyticUniRule annotationBy similarity1
Metal bindingi1139Divalent metal cation; catalyticUniRule annotationBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease
Biological processmRNA processing
LigandMetal-binding

Enzyme and pathway databases

BRENDAi3.1.13.4 2681
ReactomeiR-HSA-429947 Deadenylation of mRNA

Protein family/group databases

MEROPSiC19.978

Names & Taxonomyi

Protein namesi
Recommended name:
PAN2-PAN3 deadenylation complex catalytic subunit PAN2UniRule annotation (EC:3.1.13.4UniRule annotation)
Alternative name(s):
Inactive ubiquitin carboxyl-terminal hydrolase 52UniRule annotation
PAB1P-dependent poly(A)-specific ribonucleaseUniRule annotation
Poly(A)-nuclease deadenylation complex subunit 2UniRule annotation
Short name:
PAN deadenylation complex subunit 2UniRule annotation
Gene namesi
Name:PAN2UniRule annotation
Synonyms:KIAA0710, USP52
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000135473.14
HGNCiHGNC:20074 PAN2
MIMi617447 gene
neXtProtiNX_Q504Q3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1087D → A: Loss of exonuclease activity. 1 Publication1

Organism-specific databases

DisGeNETi9924
OpenTargetsiENSG00000135473
PharmGKBiPA162398664

Polymorphism and mutation databases

BioMutaiPAN2
DMDMi296439280

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002805211 – 1202PAN2-PAN3 deadenylation complex catalytic subunit PAN2Add BLAST1202

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei791PhosphoserineCombined sources1
Modified residuei1189PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ504Q3
MaxQBiQ504Q3
PaxDbiQ504Q3
PeptideAtlasiQ504Q3
PRIDEiQ504Q3
ProteomicsDBi62400
62401 [Q504Q3-2]
62402 [Q504Q3-3]

PTM databases

iPTMnetiQ504Q3
PhosphoSitePlusiQ504Q3

Expressioni

Gene expression databases

BgeeiENSG00000135473 Expressed in 221 organ(s), highest expression level in right lobe of thyroid gland
CleanExiHS_PAN2
ExpressionAtlasiQ504Q3 baseline and differential
GenevisibleiQ504Q3 HS

Interactioni

Subunit structurei

Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex (PubMed:14583602, PubMed:23932717). Interacts with ZFP36 (By similarity).UniRule annotation2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi115252, 369 interactors
DIPiDIP-50708N
IntActiQ504Q3, 16 interactors
STRINGi9606.ENSP00000401721

Structurei

3D structure databases

ProteinModelPortaliQ504Q3
SMRiQ504Q3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati153 – 193WD 1UniRule annotationAdd BLAST41
Repeati195 – 231WD 2UniRule annotationAdd BLAST37
Repeati244 – 280WD 3UniRule annotationAdd BLAST37
Repeati328 – 367WD 4UniRule annotationAdd BLAST40
Domaini486 – 924USPUniRule annotationAdd BLAST439
Domaini975 – 1147ExonucleaseUniRule annotationAdd BLAST173

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni368 – 485LinkerUniRule annotationAdd BLAST118

Domaini

Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.UniRule annotation
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.UniRule annotation

Sequence similaritiesi

Belongs to the peptidase C19 family. PAN2 subfamily.UniRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG1275 Eukaryota
COG0847 LUCA
GeneTreeiENSGT00390000013978
HOGENOMiHOG000230585
HOVERGENiHBG089847
InParanoidiQ504Q3
KOiK12571
OMAiIHLWGSP
OrthoDBiEOG091G01KS
PhylomeDBiQ504Q3
TreeFamiTF105657

Family and domain databases

Gene3Di2.130.10.10, 1 hit
3.30.420.10, 1 hit
HAMAPiMF_03182 PAN2, 1 hit
InterProiView protein in InterPro
IPR013520 Exonuclease_RNaseT/DNA_pol3
IPR030843 PAN2
IPR028881 PAN2_dom
IPR038765 Papain_like_cys_pep_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR028889 USP_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00929 RNase_T, 1 hit
PF13423 UCH_1, 1 hit
SMARTiView protein in SMART
SM00479 EXOIII, 1 hit
SUPFAMiSSF50978 SSF50978, 1 hit
SSF53098 SSF53098, 1 hit
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS50235 USP_3, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q504Q3-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MNFEGLDPGL AEYAPAMHSA LDPVLDAHLN PSLLQNVELD PEGVALEALP
60 70 80 90 100
VQESVHIMEG VYSELHSVVA EVGVPVSVSH FDLHEEMLWV GSHGGHATSF
110 120 130 140 150
FGPALERYSS FQVNGSDDIR QIQSLENGIL FLTKNNLKYM ARGGLIIFDY
160 170 180 190 200
LLDENEDMHS LLLTDSSTLL VGGLQNHIIE IDLNTVQETQ KYAVETPGVT
210 220 230 240 250
IMRQTNRFFF CGHTSGKVSL RDLRTFKVEH EFDAFSGSLS DFDVHGNLLA
260 270 280 290 300
ACGFSSRLTG LACDRFLKVY DLRMMRAITP LQVHVDPAFL RFIPTYTSRL
310 320 330 340 350
AIISQSGQCQ FCEPTGLANP ADIFHVNPVG PLLMTFDVSA SKQALAFGDS
360 370 380 390 400
EGCVHLWTDS PEPSFNPYSR ETEFALPCLV DSLPPLDWSQ DLLPLSLIPV
410 420 430 440 450
PLTTDTLLSD WPAANSAPAP RRAPPVDAEI LRTMKKVGFI GYAPNPRTRL
460 470 480 490 500
RNQIPYRLKE SDSEFDSFSQ VTESPVGREE EPHLHMVSKK YRKVTIKYSK
510 520 530 540 550
LGLEDFDFKH YNKTLFAGLE PHIPNAYCNC MIQVLYFLEP VRCLIQNHLC
560 570 580 590 600
QKEFCLACEL GFLFHMLDLS RGDPCQGNNF LRAFRTIPEA SALGLILADS
610 620 630 640 650
DEASGKGNLA RLIQRWNRFI LTQLHQDMQE LEIPQAYRGA GGSSFCSSGD
660 670 680 690 700
SVIGQLFSCE MENCSLCRCG SETVRASSTL LFTLSYPDGS KSDKTGKNYD
710 720 730 740 750
FAQVLKRSIC LDQNTQAWCD TCEKYQPTIQ TRNIRHLPDI LVINCEVNSS
760 770 780 790 800
KEADFWRMQA EVAFKMAVKK HGGEISKNKE FALADWKELG SPEGVLVCPS
810 820 830 840 850
IEELKNVWLP FSIRMKMTKN KGLDVCNWTD GDEMQWGPAR AEEEHGVYVY
860 870 880 890 900
DLMATVVHIL DSRTGGSLVA HIKVGETYHQ RKEGVTHQQW YLFNDFLIEP
910 920 930 940 950
IDKHEAVQFD MNWKVPAILY YVKRNLNSRY NLNIKNPIEA SVLLAEASLA
960 970 980 990 1000
RKQRKTHTTF IPLMLNEMPQ IGDLVGLDAE FVTLNEEEAE LRSDGTKSTI
1010 1020 1030 1040 1050
KPSQMSVARI TCVRGQGPNE GIPFIDDYIS TQEQVVDYLT QYSGIKPGDL
1060 1070 1080 1090 1100
DAKISSKHLT TLKSTYLKLR FLIDIGVKFV GHGLQKDFRV INLMVPKDQV
1110 1120 1130 1140 1150
LDTVYLFHMP RKRMISLRFL AWYFLDLKIQ GETHDSIEDA RTALQLYRKY
1160 1170 1180 1190 1200
LELSKNGTEP ESFHKVLKGL YEKGRKMDWK VPEPEGQTSP KNAAVFSSVL

AL
Length:1,202
Mass (Da):135,368
Last modified:May 18, 2010 - v3
Checksum:i579194C102FCA019
GO
Isoform 2 (identifier: Q504Q3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     689-692: Missing.

Show »
Length:1,198
Mass (Da):135,008
Checksum:i9F0D327BE78EC7D7
GO
Isoform 3 (identifier: Q504Q3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     643-643: Missing.

Note: No experimental confirmation available.
Show »
Length:1,201
Mass (Da):135,281
Checksum:iE185DC887D382DC1
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VXK8F8VXK8_HUMAN
PAN2-PAN3 deadenylation complex cat...
PAN2
111Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9G → E in AAH94885 (PubMed:15489334).Curated1
Sequence conflicti1091I → V in AAH94885 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03116232S → N1 PublicationCorresponds to variant dbSNP:rs11558139Ensembl.1
Natural variantiVAR_031163179I → L3 PublicationsCorresponds to variant dbSNP:rs1918496Ensembl.1
Natural variantiVAR_0363591201A → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1330054285Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023748643Missing in isoform 3. 1 Publication1
Alternative sequenceiVSP_023749689 – 692Missing in isoform 2. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB107585 mRNA Translation: BAD02263.1
AB014610 mRNA Translation: BAA31685.2 Different initiation.
BC024043 mRNA Translation: AAH24043.1
BC094885 mRNA Translation: AAH94885.1
CCDSiCCDS44922.1 [Q504Q3-1]
CCDS53802.1 [Q504Q3-3]
CCDS8915.1 [Q504Q3-2]
RefSeqiNP_001120932.1, NM_001127460.2
NP_001159751.1, NM_001166279.1
NP_055686.3, NM_014871.4
UniGeneiHs.273397

Genome annotation databases

EnsembliENST00000257931; ENSP00000257931; ENSG00000135473 [Q504Q3-3]
ENST00000425394; ENSP00000401721; ENSG00000135473 [Q504Q3-1]
ENST00000440411; ENSP00000388231; ENSG00000135473 [Q504Q3-2]
ENST00000548043; ENSP00000449861; ENSG00000135473 [Q504Q3-1]
ENST00000610546; ENSP00000481859; ENSG00000135473 [Q504Q3-1]
GeneIDi9924
KEGGihsa:9924
UCSCiuc001skx.3 human [Q504Q3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB107585 mRNA Translation: BAD02263.1
AB014610 mRNA Translation: BAA31685.2 Different initiation.
BC024043 mRNA Translation: AAH24043.1
BC094885 mRNA Translation: AAH94885.1
CCDSiCCDS44922.1 [Q504Q3-1]
CCDS53802.1 [Q504Q3-3]
CCDS8915.1 [Q504Q3-2]
RefSeqiNP_001120932.1, NM_001127460.2
NP_001159751.1, NM_001166279.1
NP_055686.3, NM_014871.4
UniGeneiHs.273397

3D structure databases

ProteinModelPortaliQ504Q3
SMRiQ504Q3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115252, 369 interactors
DIPiDIP-50708N
IntActiQ504Q3, 16 interactors
STRINGi9606.ENSP00000401721

Protein family/group databases

MEROPSiC19.978

PTM databases

iPTMnetiQ504Q3
PhosphoSitePlusiQ504Q3

Polymorphism and mutation databases

BioMutaiPAN2
DMDMi296439280

Proteomic databases

EPDiQ504Q3
MaxQBiQ504Q3
PaxDbiQ504Q3
PeptideAtlasiQ504Q3
PRIDEiQ504Q3
ProteomicsDBi62400
62401 [Q504Q3-2]
62402 [Q504Q3-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257931; ENSP00000257931; ENSG00000135473 [Q504Q3-3]
ENST00000425394; ENSP00000401721; ENSG00000135473 [Q504Q3-1]
ENST00000440411; ENSP00000388231; ENSG00000135473 [Q504Q3-2]
ENST00000548043; ENSP00000449861; ENSG00000135473 [Q504Q3-1]
ENST00000610546; ENSP00000481859; ENSG00000135473 [Q504Q3-1]
GeneIDi9924
KEGGihsa:9924
UCSCiuc001skx.3 human [Q504Q3-1]

Organism-specific databases

CTDi9924
DisGeNETi9924
EuPathDBiHostDB:ENSG00000135473.14
GeneCardsiPAN2
HGNCiHGNC:20074 PAN2
MIMi617447 gene
neXtProtiNX_Q504Q3
OpenTargetsiENSG00000135473
PharmGKBiPA162398664
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1275 Eukaryota
COG0847 LUCA
GeneTreeiENSGT00390000013978
HOGENOMiHOG000230585
HOVERGENiHBG089847
InParanoidiQ504Q3
KOiK12571
OMAiIHLWGSP
OrthoDBiEOG091G01KS
PhylomeDBiQ504Q3
TreeFamiTF105657

Enzyme and pathway databases

BRENDAi3.1.13.4 2681
ReactomeiR-HSA-429947 Deadenylation of mRNA

Miscellaneous databases

ChiTaRSiPAN2 human
GeneWikiiUSP52
GenomeRNAii9924
PROiPR:Q504Q3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135473 Expressed in 221 organ(s), highest expression level in right lobe of thyroid gland
CleanExiHS_PAN2
ExpressionAtlasiQ504Q3 baseline and differential
GenevisibleiQ504Q3 HS

Family and domain databases

Gene3Di2.130.10.10, 1 hit
3.30.420.10, 1 hit
HAMAPiMF_03182 PAN2, 1 hit
InterProiView protein in InterPro
IPR013520 Exonuclease_RNaseT/DNA_pol3
IPR030843 PAN2
IPR028881 PAN2_dom
IPR038765 Papain_like_cys_pep_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR028889 USP_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00929 RNase_T, 1 hit
PF13423 UCH_1, 1 hit
SMARTiView protein in SMART
SM00479 EXOIII, 1 hit
SUPFAMiSSF50978 SSF50978, 1 hit
SSF53098 SSF53098, 1 hit
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS50235 USP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPAN2_HUMAN
AccessioniPrimary (citable) accession number: Q504Q3
Secondary accession number(s): O75189, Q76E12, Q8IVE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: May 18, 2010
Last modified: October 10, 2018
This is version 139 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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