PNDC1_HUMAN
ID PNDC1_HUMAN Reviewed; 520 AA.
AC Q8NA58; Q5TAP7; Q8N7X5;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Poly(A)-specific ribonuclease PNLDC1 {ECO:0000305};
DE EC=3.1.13.4 {ECO:0000269|PubMed:27515512};
DE AltName: Full=PARN-like domain-containing protein 1 {ECO:0000312|HGNC:HGNC:21185};
DE AltName: Full=Poly(A)-specific ribonuclease domain-containing protein 1 {ECO:0000312|HGNC:HGNC:21185};
DE Short=HsPNLDC1 {ECO:0000303|PubMed:27515512};
GN Name=PNLDC1 {ECO:0000312|HGNC:HGNC:21185};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=27515512; DOI=10.1093/nar/gkw709;
RA Anastasakis D., Skeparnias I., Shaukat A.N., Grafanaki K., Kanellou A.,
RA Taraviras S., Papachristou D.J., Papakyriakou A., Stathopoulos C.;
RT "Mammalian PNLDC1 is a novel poly(A) specific exonuclease with discrete
RT expression during early development.";
RL Nucleic Acids Res. 44:8908-8920(2016).
RN [6]
RP FUNCTION, INVOLVEMENT IN SPGF57, AND VARIANTS SPGF57 SER-84; THR-259 AND
RP 452-ARG--THR-520 DEL.
RX PubMed=34347949; DOI=10.1056/nejmoa2028973;
RA Nagirnaja L., Moerup N., Nielsen J.E., Stakaitis R., Golubickaite I.,
RA Oud M.S., Winge S.B., Carvalho F., Aston K.I., Khani F.,
RA van der Heijden G.W., Marques C.J., Skakkebaek N.E., Rajpert-De Meyts E.,
RA Schlegel P.N., Joergensen N., Veltman J.A., Lopes A.M., Conrad D.F.,
RA Almstrup K.;
RT "Variant PNLDC1, defective piRNA processing, and azoospermia.";
RL N. Engl. J. Med. 385:707-719(2021).
CC -!- FUNCTION: 3'-exoribonuclease that has a preference for poly(A) tails of
CC mRNAs, thereby efficiently degrading poly(A) tails (PubMed:27515512).
CC Exonucleolytic degradation of the poly(A) tail is often the first step
CC in the decay of eukaryotic mRNAs and is also used to silence certain
CC maternal mRNAs translationally during oocyte maturation and early
CC embryonic development (PubMed:27515512). May act as a regulator of
CC multipotency in embryonic stem cells (By similarity). Is a critical
CC factor for proper spermatogenesis, involved in pre-piRNAs processing to
CC generate mature piRNAs (PubMed:34347949).
CC {ECO:0000250|UniProtKB:B2RXZ1, ECO:0000269|PubMed:27515512,
CC ECO:0000269|PubMed:34347949}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000269|PubMed:27515512};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:27515512};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:27515512}; Single-pass membrane protein
CC {ECO:0000305}. Note=Localizes mainly in the endoplasmic reticulum
CC (PubMed:27515512). {ECO:0000269|PubMed:27515512}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NA58-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NA58-2; Sequence=VSP_029552;
CC -!- DISEASE: Spermatogenic failure 57 (SPGF57) [MIM:619528]: An autosomal
CC recessive male infertility disorder characterized by non-obstructive
CC azoospermia, due to error-prone meiosis and spermatogenic arrest at the
CC late pachytene stage. {ECO:0000269|PubMed:34347949}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CAF1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK093139; BAC04070.1; -; mRNA.
DR EMBL; AK097559; BAC05101.1; -; mRNA.
DR EMBL; AL139045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47612.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47613.1; -; Genomic_DNA.
DR EMBL; BC112246; AAI12247.1; -; mRNA.
DR CCDS; CCDS5271.2; -. [Q8NA58-2]
DR CCDS; CCDS64561.1; -. [Q8NA58-1]
DR RefSeq; NP_001258791.1; NM_001271862.1. [Q8NA58-2]
DR RefSeq; NP_775787.1; NM_173516.2. [Q8NA58-1]
DR RefSeq; XP_011533793.1; XM_011535491.2. [Q8NA58-1]
DR AlphaFoldDB; Q8NA58; -.
DR SMR; Q8NA58; -.
DR BioGRID; 127539; 17.
DR IntAct; Q8NA58; 12.
DR STRING; 9606.ENSP00000376007; -.
DR iPTMnet; Q8NA58; -.
DR PhosphoSitePlus; Q8NA58; -.
DR BioMuta; PNLDC1; -.
DR DMDM; 160419239; -.
DR MassIVE; Q8NA58; -.
DR PaxDb; Q8NA58; -.
DR PeptideAtlas; Q8NA58; -.
DR PRIDE; Q8NA58; -.
DR ProteomicsDB; 72643; -. [Q8NA58-1]
DR ProteomicsDB; 72644; -. [Q8NA58-2]
DR TopDownProteomics; Q8NA58-2; -. [Q8NA58-2]
DR Antibodypedia; 64136; 74 antibodies from 18 providers.
DR DNASU; 154197; -.
DR Ensembl; ENST00000392167.4; ENSP00000376007.3; ENSG00000146453.13. [Q8NA58-2]
DR Ensembl; ENST00000610273.5; ENSP00000476448.1; ENSG00000146453.13. [Q8NA58-1]
DR GeneID; 154197; -.
DR KEGG; hsa:154197; -.
DR MANE-Select; ENST00000392167.4; ENSP00000376007.3; NM_001271862.2; NP_001258791.1. [Q8NA58-2]
DR UCSC; uc003qsx.3; human. [Q8NA58-1]
DR CTD; 154197; -.
DR DisGeNET; 154197; -.
DR GeneCards; PNLDC1; -.
DR HGNC; HGNC:21185; PNLDC1.
DR HPA; ENSG00000146453; Group enriched (brain, testis).
DR MIM; 619528; phenotype.
DR MIM; 619529; gene.
DR neXtProt; NX_Q8NA58; -.
DR OpenTargets; ENSG00000146453; -.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA134892245; -.
DR VEuPathDB; HostDB:ENSG00000146453; -.
DR eggNOG; KOG1990; Eukaryota.
DR GeneTree; ENSGT00940000153167; -.
DR HOGENOM; CLU_018030_3_0_1; -.
DR InParanoid; Q8NA58; -.
DR OMA; HRWYLEH; -.
DR OrthoDB; 1402758at2759; -.
DR PhylomeDB; Q8NA58; -.
DR TreeFam; TF314502; -.
DR BRENDA; 3.1.13.4; 2681.
DR PathwayCommons; Q8NA58; -.
DR SignaLink; Q8NA58; -.
DR BioGRID-ORCS; 154197; 7 hits in 970 CRISPR screens.
DR ChiTaRS; PNLDC1; human.
DR GenomeRNAi; 154197; -.
DR Pharos; Q8NA58; Tbio.
DR PRO; PR:Q8NA58; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8NA58; protein.
DR Bgee; ENSG00000146453; Expressed in oocyte and 96 other tissues.
DR ExpressionAtlas; Q8NA58; baseline and differential.
DR Genevisible; Q8NA58; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IDA:UniProtKB.
DR GO; GO:1990511; P:piRNA biosynthetic process; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 3.30.420.10; -; 2.
DR InterPro; IPR006941; RNase_CAF1.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF04857; CAF1; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Endoplasmic reticulum; Exonuclease;
KW Hydrolase; Magnesium; Membrane; Metal-binding;
KW Nonsense-mediated mRNA decay; Nuclease; Reference proteome; RNA-binding;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..520
FT /note="Poly(A)-specific ribonuclease PNLDC1"
FT /id="PRO_0000311365"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 17
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453"
FT BINDING 19
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453"
FT BINDING 260
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453"
FT BINDING 354
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453"
FT SITE 294
FT /note="Interaction with poly(A)"
FT /evidence="ECO:0000250|UniProtKB:O95453"
FT VAR_SEQ 1..14
FT /note="MFCTRGLLFFAFLA -> MDVGADEFEESLPLLQELVQEADFV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029552"
FT VARIANT 84
FT /note="P -> S (in SPGF57)"
FT /evidence="ECO:0000269|PubMed:34347949"
FT /id="VAR_085807"
FT VARIANT 259
FT /note="M -> T (in SPGF57; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:34347949"
FT /id="VAR_085808"
FT VARIANT 452..520
FT /note="Missing (in SPGF57)"
FT /evidence="ECO:0000269|PubMed:34347949"
FT /id="VAR_085809"
SQ SEQUENCE 520 AA; 60124 MW; 02DEB5953BE88448 CRC64;
MFCTRGLLFF AFLAGLDIEF TGLRSNLSGP QQISLFDLPS EWYLKTRQSV QQFTVCQIGL
SVFSAIEGEA NKYIAHSCNF YLFPTTFGIL DSEFSFQASS VQFLNQYGFN YNKFLKNGIP
YMNEEQEKKI RHDILTGNWR VRSSPDKDQI KVVIDEVTRW LELAKEGDWM TLPGITGFQA
FEVQLVLRQA LPNIWTVLKD EGVVVKKVSK QHRWYLQNTS CDRESCWKEN ILLSARGFSV
FFQMLVKAQK PLVGHNMMMD LLHLHEKFFR PLPESYDQFK QNIHSLFPVL IDTKSVTKDI
WKEMNFPRVS NLSEVYEVLN SDLNPTKNSG PEIVHASRCE KYVETKCPHE AAYDAFLCGS
VLLKVAHLLL QKIYHIDPVP ESSFPQYLDV LAPYVNQVNL IRAGVPKINF SGPDYPSIRP
PILILSVKRW PGVSEQQVYH KFQNLCKFDV RRLTRSQFLL LTNKFKDARN ILKEYRDHPT
LCISLYRYWR HSPNVNCLLQ VCGIVTAWAL LAFILGRSGT
