Q504Q3 (PAN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PAB-dependent poly(A)-specific ribonuclease subunit 2
Short name=hPan2
EC=3.1.13.4

Alternative name(s):
Inactive ubiquitin carboxyl-terminal hydrolase 52

Gene names

Name:	PAN2
Synonyms:	KIAA0710, USP52

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1202 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions in cytoplasmic mRNA decay. As part of the Pan nuclease complex, shortens poly(A) tails of RNA when the poly(A) stretch is bound by polyadenylate-binding protein. Ref.1 Ref.6
Catalytic activity	Exonucleolytic cleavage of poly(A) to 5'-AMP. Ref.1
Subunit structure	Interacts with PAN3 to form the Pan nuclease complex which in turn interacts with the polyadenylate-binding protein through PAN3. Ref.1
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between nucleus and cytoplasm. Ref.1 Ref.6
Sequence similarities	Belongs to the peptidase C19 family. PAN2 subfamily. Contains 1 exonuclease domain.
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 process	Nonsense-mediated mRNA decay
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Exonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Inferred from electronic annotation. Source: UniProtKB-KW nuclear-transcribed mRNA poly(A) tail shortening Traceable author statement. Source: Reactome ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasmic mRNA processing body Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro poly(A)-specific ribonuclease activity Traceable author statement. Source: Reactome ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1202	1202	PAB-dependent poly(A)-specific ribonuclease subunit 2		PRO_0000280521
Regions
	Domain	974 – 1147	174	Exonuclease
Amino acid modifications
	Modified residue	791	1	Phosphoserine Ref.8
	Modified residue	1189	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	643	1	Missing in isoform 3.		VSP_023748
	Alternative sequence	689 – 692	4	Missing in isoform 2.		VSP_023749
	Natural variant	32	1	S → N. Ref.4 Corresponds to variant rs11558139 [ dbSNP | Ensembl ].		VAR_031162
	Natural variant	179	1	I → L. Ref.1 Ref.2 Ref.4 Corresponds to variant rs1918496 [ dbSNP | Ensembl ].		VAR_031163
	Natural variant	1201	1	A → V in a colorectal cancer sample; somatic mutation. Ref.10		VAR_036359
Experimental info
	Mutagenesis	1087	1	D → A: Loss of exonuclease activity. Ref.1
	Sequence conflict	9	1	G → E in AAH94885. Ref.4
	Sequence conflict	1091	1	I → V in AAH94885. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 579194C102FCA019	FASTA	1,202	135,368
	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
	Isoform 2 [UniParc]. Checksum: 9F0D327BE78EC7D7	FASTA	1,198	135,008
	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 LFTLSYPDDK TGKNYDFAQV LKRSICLDQN TQAWCDTCEK 730 740 750 760 770 780 YQPTIQTRNI RHLPDILVIN CEVNSSKEAD FWRMQAEVAF KMAVKKHGGE ISKNKEFALA 790 800 810 820 830 840 DWKELGSPEG VLVCPSIEEL KNVWLPFSIR MKMTKNKGLD VCNWTDGDEM QWGPARAEEE 850 860 870 880 890 900 HGVYVYDLMA TVVHILDSRT GGSLVAHIKV GETYHQRKEG VTHQQWYLFN DFLIEPIDKH 910 920 930 940 950 960 EAVQFDMNWK VPAILYYVKR NLNSRYNLNI KNPIEASVLL AEASLARKQR KTHTTFIPLM 970 980 990 1000 1010 1020 LNEMPQIGDL VGLDAEFVTL NEEEAELRSD GTKSTIKPSQ MSVARITCVR GQGPNEGIPF 1030 1040 1050 1060 1070 1080 IDDYISTQEQ VVDYLTQYSG IKPGDLDAKI SSKHLTTLKS TYLKLRFLID IGVKFVGHGL 1090 1100 1110 1120 1130 1140 QKDFRVINLM VPKDQVLDTV YLFHMPRKRM ISLRFLAWYF LDLKIQGETH DSIEDARTAL 1150 1160 1170 1180 1190 QLYRKYLELS KNGTEPESFH KVLKGLYEKG RKMDWKVPEP EGQTSPKNAA VFSSVLAL
	Isoform 3 [UniParc]. Checksum: E185DC887D382DC1	FASTA	1,201	135,281
	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 GGSFCSSGDS VIGQLFSCEM 670 680 690 700 710 720 ENCSLCRCGS ETVRASSTLL FTLSYPDGSK SDKTGKNYDF AQVLKRSICL DQNTQAWCDT 730 740 750 760 770 780 CEKYQPTIQT RNIRHLPDIL VINCEVNSSK EADFWRMQAE VAFKMAVKKH GGEISKNKEF 790 800 810 820 830 840 ALADWKELGS PEGVLVCPSI EELKNVWLPF SIRMKMTKNK GLDVCNWTDG DEMQWGPARA 850 860 870 880 890 900 EEEHGVYVYD LMATVVHILD SRTGGSLVAH IKVGETYHQR KEGVTHQQWY LFNDFLIEPI 910 920 930 940 950 960 DKHEAVQFDM NWKVPAILYY VKRNLNSRYN LNIKNPIEAS VLLAEASLAR KQRKTHTTFI 970 980 990 1000 1010 1020 PLMLNEMPQI GDLVGLDAEF VTLNEEEAEL RSDGTKSTIK PSQMSVARIT CVRGQGPNEG 1030 1040 1050 1060 1070 1080 IPFIDDYIST QEQVVDYLTQ YSGIKPGDLD AKISSKHLTT LKSTYLKLRF LIDIGVKFVG 1090 1100 1110 1120 1130 1140 HGLQKDFRVI NLMVPKDQVL DTVYLFHMPR KRMISLRFLA WYFLDLKIQG ETHDSIEDAR 1150 1160 1170 1180 1190 1200 TALQLYRKYL ELSKNGTEPE SFHKVLKGLY EKGRKMDWKV PEPEGQTSPK NAAVFSSVLA L

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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].
[10]	"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. , 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.
IPI	IPI00328254. IPI00747362. IPI00796020.
RefSeq	NP_001120932.1. NM_001127460.2. NP_001159751.1. NM_001166279.1. NP_055686.3. NM_014871.4.
UniGene	Hs.273397.
3D structure databases
ProteinModelPortal	Q504Q3.
SMR	Q504Q3. Positions 332-360.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-50708N.
IntAct	Q504Q3. 16 interactions.
STRING	9606.ENSP00000368809.
Protein family/group databases
MEROPS	C19.978.
PTM databases
PhosphoSite	Q504Q3.
Polymorphism databases
DMDM	296439280.
Proteomic databases
PaxDb	Q504Q3.
PRIDE	Q504Q3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257931; ENSP00000257931; ENSG00000135473. ENST00000425394; ENSP00000401721; ENSG00000135473. ENST00000440411; ENSP00000388231; ENSG00000135473. ENST00000548043; ENSP00000449861; ENSG00000135473.
GeneID	9924.
KEGG	hsa:9924.
UCSC	uc001skx.3. human. uc001sky.3. human. uc001skz.3. human.
Organism-specific databases
CTD	9924.
GeneCards	GC12M056710.
HGNC	HGNC:20074. PAN2.
neXtProt	NX_Q504Q3.
PharmGKB	PA162398664.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0847.
HOGENOM	HOG000230585.
HOVERGEN	HBG089847.
InParanoid	Q504Q3.
KO	K12571.
OMA	TQLHQDM.
OrthoDB	EOG4HQDHH.
Enzyme and pathway databases
Reactome	REACT_21257. Metabolism of RNA. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q504Q3.
Bgee	Q504Q3.
CleanEx	HS_PAN2.
Genevestigator	Q504Q3.
Family and domain databases
Gene3D	2.130.10.10. 1 hit.
InterPro	IPR006055. Exonuclease. IPR013520. Exonuclease_RNaseT/DNA_pol3. IPR001394. Peptidase_C19. IPR012337. RNaseH-like_dom. IPR015943. WD40/YVTN_repeat-like_dom. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00929. RNase_T. 1 hit. [Graphical view]
SMART	SM00479. EXOIII. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit. SSF50978. WD40_like. 1 hit.
PROSITE	PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9924.
NextBio	37442.

Entry information

Entry name

PAN2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 88 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.