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Protein

PAN2-PAN3 deadenylation complex catalytic subunit PAN2

Gene

PAN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • nucleic acid binding Source: InterPro
  • poly(A)-specific ribonuclease activity Source: UniProtKB

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.

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.

PTM databases

iPTMnetiQ504Q3.
PhosphoSitePlusiQ504Q3.

Expressioni

Gene expression databases

BgeeiENSG00000135473.
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

WithEntry#Exp.IntActNotes
PAN3Q58A456EBI-1058976,EBI-2513054

Protein-protein interaction databases

BioGridi115252. 349 interactors.
DIPiDIP-50708N.
IntActiQ504Q3. 36 interactors.
STRINGi9606.ENSP00000401721.

Structurei

3D structure databases

ProteinModelPortaliQ504Q3.
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.
OMAiMVYDLRM.
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.
IPR012337. RNaseH-like_dom.
IPR028889. USP_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR017986. WD40_repeat_dom.
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.
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

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

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 Publication1

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

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: September 27, 2017
This is version 130 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. Human chromosome 12
    Human chromosome 12: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families