PLD4_HUMAN
ID PLD4_HUMAN Reviewed; 506 AA.
AC Q96BZ4; Q6UWD2;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=5'-3' exonuclease PLD4 {ECO:0000305};
DE EC=3.1.16.1 {ECO:0000250|UniProtKB:Q8BG07};
DE AltName: Full=Choline phosphatase 4;
DE AltName: Full=Phosphatidylcholine-hydrolyzing phospholipase D4;
DE AltName: Full=Phospholipase D family member 4 {ECO:0000312|HGNC:HGNC:23792};
DE AltName: Full=Phospholipase D4;
DE Short=PLD 4;
GN Name=PLD4; Synonyms=C14orf175; ORFNames=UNQ2488/PRO5775;
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].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell;
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).
CC -!- FUNCTION: 5'->3' DNA exonuclease which digests single-stranded DNA
CC (ssDNA). Regulates inflammatory cytokine responses via the degradation
CC of nucleic acids, by reducing the concentration of ssDNA able to
CC stimulate TLR9, a nucleotide-sensing receptor. Involved in phagocytosis
CC of activated microglia. {ECO:0000250|UniProtKB:Q8BG07}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 5'- to 3'-direction to yield
CC nucleoside 3'-phosphates.; EC=3.1.16.1;
CC Evidence={ECO:0000250|UniProtKB:Q8BG07};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8BG07}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q8BG07}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000250|UniProtKB:Q8BG07}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:Q8BG07}. Nucleus
CC {ECO:0000250|UniProtKB:Q8BG07}. Early endosome
CC {ECO:0000250|UniProtKB:Q8BG07}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q8BG07}. Note=Activation of microglia induces
CC translocation of PLD4 from the nucleus to the phagosomes.
CC {ECO:0000250|UniProtKB:Q8BG07}.
CC -!- PTM: Highly N-glycosylated. {ECO:0000250|UniProtKB:Q8BG07}.
CC -!- SIMILARITY: Belongs to the phospholipase D family. {ECO:0000305}.
CC -!- CAUTION: Exhibits no phospholipase activity, despite two HKD motifs.
CC {ECO:0000250|UniProtKB:Q8BG07}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89202.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY358843; AAQ89202.1; ALT_INIT; mRNA.
DR EMBL; BC015003; AAH15003.2; -; mRNA.
DR CCDS; CCDS9995.2; -.
DR RefSeq; NP_620145.2; NM_138790.3.
DR AlphaFoldDB; Q96BZ4; -.
DR SMR; Q96BZ4; -.
DR BioGRID; 125782; 1.
DR STRING; 9606.ENSP00000376372; -.
DR GlyConnect; 1605; 8 N-Linked glycans (5 sites).
DR GlyGen; Q96BZ4; 10 sites, 8 N-linked glycans (5 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q96BZ4; -.
DR PhosphoSitePlus; Q96BZ4; -.
DR BioMuta; PLD4; -.
DR DMDM; 121944492; -.
DR jPOST; Q96BZ4; -.
DR MassIVE; Q96BZ4; -.
DR MaxQB; Q96BZ4; -.
DR PaxDb; Q96BZ4; -.
DR PeptideAtlas; Q96BZ4; -.
DR PRIDE; Q96BZ4; -.
DR ProteomicsDB; 76132; -.
DR Antibodypedia; 28277; 190 antibodies from 26 providers.
DR DNASU; 122618; -.
DR Ensembl; ENST00000392593.9; ENSP00000376372.5; ENSG00000166428.14.
DR GeneID; 122618; -.
DR KEGG; hsa:122618; -.
DR MANE-Select; ENST00000392593.9; ENSP00000376372.5; NM_138790.5; NP_620145.2.
DR UCSC; uc001ypu.2; human.
DR CTD; 122618; -.
DR DisGeNET; 122618; -.
DR GeneCards; PLD4; -.
DR HGNC; HGNC:23792; PLD4.
DR HPA; ENSG00000166428; Tissue enhanced (bone marrow, brain, lymphoid tissue).
DR MIM; 618488; gene.
DR neXtProt; NX_Q96BZ4; -.
DR OpenTargets; ENSG00000166428; -.
DR PharmGKB; PA134861676; -.
DR VEuPathDB; HostDB:ENSG00000166428; -.
DR eggNOG; KOG3603; Eukaryota.
DR GeneTree; ENSGT00950000183059; -.
DR HOGENOM; CLU_027021_0_0_1; -.
DR InParanoid; Q96BZ4; -.
DR OrthoDB; 1057467at2759; -.
DR PhylomeDB; Q96BZ4; -.
DR TreeFam; TF313378; -.
DR PathwayCommons; Q96BZ4; -.
DR Reactome; R-HSA-1483148; Synthesis of PG.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR BioGRID-ORCS; 122618; 11 hits in 1069 CRISPR screens.
DR ChiTaRS; PLD4; human.
DR GenomeRNAi; 122618; -.
DR Pharos; Q96BZ4; Tbio.
DR PRO; PR:Q96BZ4; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96BZ4; protein.
DR Bgee; ENSG00000166428; Expressed in granulocyte and 105 other tissues.
DR ExpressionAtlas; Q96BZ4; baseline and differential.
DR Genevisible; Q96BZ4; HS.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR InterPro; IPR032803; PLDc_3.
DR InterPro; IPR001736; PLipase_D/transphosphatidylase.
DR Pfam; PF00614; PLDc; 1.
DR Pfam; PF13918; PLDc_3; 1.
DR SMART; SM00155; PLDc; 2.
DR PROSITE; PS50035; PLD; 2.
PE 2: Evidence at transcript level;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Exonuclease;
KW Glycoprotein; Golgi apparatus; Hydrolase; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Nuclease; Nucleus; Reference proteome; Repeat;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..506
FT /note="5'-3' exonuclease PLD4"
FT /id="PRO_0000280333"
FT TRANSMEM 31..51
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 209..236
FT /note="PLD phosphodiesterase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT DOMAIN 423..449
FT /note="PLD phosphodiesterase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 214
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 216
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT ACT_SITE 221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00153"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 403
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 427
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VARIANT 16
FT /note="C -> R (in dbSNP:rs894037)"
FT /id="VAR_061751"
FT VARIANT 27
FT /note="E -> Q (in dbSNP:rs2841280)"
FT /id="VAR_031119"
FT VARIANT 135
FT /note="V -> M (in dbSNP:rs3803295)"
FT /id="VAR_031120"
SQ SEQUENCE 506 AA; 55626 MW; D7F820C83131FE26 CRC64;
MLKPLWKAAV APTWPCSMPP RRPWDREAGT LQVLGALAVL WLGSVALICL LWQVPRPPTW
GQVQPKDVPR SWEHGSSPAW EPLEAEARQQ RDSCQLVLVE SIPQDLPSAA GSPSAQPLGQ
AWLQLLDTAQ ESVHVASYYW SLTGPDIGVN DSSSQLGEAL LQKLQQLLGR NISLAVATSS
PTLARTSTDL QVLAARGAHV RQVPMGRLTR GVLHSKFWVV DGRHIYMGSA NMDWRSLTQV
KELGAVIYNC SHLAQDLEKT FQTYWVLGVP KAVLPKTWPQ NFSSHFNRFQ PFHGLFDGVP
TTAYFSASPP ALCPQGRTRD LEALLAVMGS AQEFIYASVM EYFPTTRFSH PPRYWPVLDN
ALRAAAFGKG VRVRLLVGCG LNTDPTMFPY LRSLQALSNP AANVSVDVKV FIVPVGNHSN
IPFSRVNHSK FMVTEKAAYI GTSNWSEDYF SSTAGVGLVV TQSPGAQPAG ATVQEQLRQL
FERDWSSRYA VGLDGQAPGQ DCVWQG
