PDZD8_HUMAN
ID PDZD8_HUMAN Reviewed; 1154 AA.
AC Q8NEN9; Q86WE0; Q86WE5; Q9UFF1;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=PDZ domain-containing protein 8 {ECO:0000305};
DE AltName: Full=Sarcoma antigen NY-SAR-84/NY-SAR-104 {ECO:0000303|PubMed:12601173};
GN Name=PDZD8 {ECO:0000312|HGNC:HGNC:26974}; Synonyms=PDZK8;
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 232-491 AND 1007-1154.
RX PubMed=12601173; DOI=10.1073/pnas.0437972100;
RA Lee S.-Y., Obata Y., Yoshida M., Stockert E., Williamson B.,
RA Jungbluth A.A., Chen Y.-T., Old L.J., Scanlan M.J.;
RT "Immunomic analysis of human sarcoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2651-2656(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 642-1154.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496 AND SER-538, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP CAUTION, AND INTERACTION WITH HIV-1 GAG (MICROBIAL INFECTION).
RX PubMed=20573829; DOI=10.1128/jvi.00843-10;
RA Henning M.S., Morham S.G., Goff S.P., Naghavi M.H.;
RT "PDZD8 is a novel Gag-interacting factor that promotes retroviral
RT infection.";
RL J. Virol. 84:8990-8995(2010).
RN [8]
RP FUNCTION.
RX PubMed=21834987; DOI=10.1186/1741-7007-9-54;
RA Bai S.W., Herrera-Abreu M.T., Rohn J.L., Racine V., Tajadura V.,
RA Suryavanshi N., Bechtel S., Wiemann S., Baum B., Ridley A.J.;
RT "Identification and characterization of a set of conserved and new
RT regulators of cytoskeletal organisation, cell morphology and migration.";
RL BMC Biol. 9:54-54(2011).
RN [9]
RP FUNCTION, AND INTERACTION WITH MSN.
RX PubMed=21549406; DOI=10.1016/j.virol.2011.04.006;
RA Henning M.S., Stiedl P., Barry D.S., McMahon R., Morham S.G., Walsh D.,
RA Naghavi M.H.;
RT "PDZD8 is a novel moesin-interacting cytoskeletal regulatory protein that
RT suppresses infection by herpes simplex virus type 1.";
RL Virology 415:114-121(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-496; SER-521; SER-538 AND
RP SER-967, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP CAUTION.
RX PubMed=24554657; DOI=10.1128/jvi.02945-13;
RA Guth C.A., Sodroski J.;
RT "Contribution of PDZD8 to stabilization of the human immunodeficiency virus
RT type 1 capsid.";
RL J. Virol. 88:4612-4623(2014).
RN [12]
RP CAUTION.
RX PubMed=25771112; DOI=10.1016/j.virol.2015.01.034;
RA Zhang S., Sodroski J.;
RT "Efficient human immunodeficiency virus (HIV-1) infection of cells lacking
RT PDZD8.";
RL Virology 481:73-78(2015).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29097544; DOI=10.1126/science.aan6009;
RA Hirabayashi Y., Kwon S.K., Paek H., Pernice W.M., Paul M.A., Lee J.,
RA Erfani P., Raczkowski A., Petrey D.S., Pon L.A., Polleux F.;
RT "ER-mitochondria tethering by PDZD8 regulates Ca(2+) dynamics in mammalian
RT neurons.";
RL Science 358:623-630(2017).
CC -!- FUNCTION: Molecular tethering protein that connects endoplasmic
CC reticulum and mitochondria membranes (PubMed:29097544). PDZD8-dependent
CC endoplasmic reticulum-mitochondria membrane tethering is essential for
CC endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544).
CC In neurons, involved in the regulation of dendritic Ca(2+) dynamics by
CC regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544).
CC Plays an indirect role in the regulation of cell morphology and
CC cytoskeletal organization (PubMed:21834987). May inhibit herpes simplex
CC virus 1 infection at an early stage (PubMed:21549406).
CC {ECO:0000269|PubMed:21549406, ECO:0000269|PubMed:21834987,
CC ECO:0000269|PubMed:29097544}.
CC -!- SUBUNIT: Interacts with MSN. {ECO:0000269|PubMed:21549406}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Gag polyprotein
CC p55. {ECO:0000269|PubMed:20573829}.
CC -!- INTERACTION:
CC Q8NEN9; A0A0F6AZQ1: pipB; Xeno; NbExp=8; IntAct=EBI-4289868, EBI-27033737;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29097544}; Single-pass membrane protein
CC {ECO:0000255}. Note=Localizes at mitochondria-endoplasmic reticulum
CC contact sites. {ECO:0000269|PubMed:29097544}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that binds
CC phospholipids. {ECO:0000250|UniProtKB:A0FGR8}.
CC -!- CAUTION: (Microbial infection) Was initially reported to enhance
CC infectivity of retroviruses, such as HIV-1, by stabilizing the capsid
CC of retroviruses (PubMed:20573829, PubMed:24554657). However, it was
CC later shown that PDZD8 is not absolutely required for HIV-1 infection,
CC suggesting that its role in retroviral infection is probably indirect
CC (PubMed:25771112). {ECO:0000269|PubMed:20573829,
CC ECO:0000269|PubMed:24554657, ECO:0000269|PubMed:25771112}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO65182.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AL391988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028375; AAH28375.1; -; mRNA.
DR EMBL; AY211924; AAO65177.1; -; mRNA.
DR EMBL; AY211929; AAO65182.1; ALT_FRAME; mRNA.
DR EMBL; AL122051; CAB59184.1; -; mRNA.
DR CCDS; CCDS7600.1; -.
DR PIR; T34546; T34546.
DR RefSeq; NP_776152.1; NM_173791.4.
DR PDB; 7F6J; X-ray; 2.10 A; C=994-1123.
DR PDBsum; 7F6J; -.
DR AlphaFoldDB; Q8NEN9; -.
DR SMR; Q8NEN9; -.
DR BioGRID; 125631; 200.
DR IntAct; Q8NEN9; 40.
DR MINT; Q8NEN9; -.
DR STRING; 9606.ENSP00000334642; -.
DR TCDB; 1.R.1.1.1; the membrane contact site (mcs) family.
DR iPTMnet; Q8NEN9; -.
DR PhosphoSitePlus; Q8NEN9; -.
DR BioMuta; PDZD8; -.
DR DMDM; 73621383; -.
DR EPD; Q8NEN9; -.
DR jPOST; Q8NEN9; -.
DR MassIVE; Q8NEN9; -.
DR MaxQB; Q8NEN9; -.
DR PaxDb; Q8NEN9; -.
DR PeptideAtlas; Q8NEN9; -.
DR PRIDE; Q8NEN9; -.
DR ProteomicsDB; 73189; -.
DR Antibodypedia; 2575; 79 antibodies from 17 providers.
DR DNASU; 118987; -.
DR Ensembl; ENST00000334464.7; ENSP00000334642.5; ENSG00000165650.12.
DR GeneID; 118987; -.
DR KEGG; hsa:118987; -.
DR MANE-Select; ENST00000334464.7; ENSP00000334642.5; NM_173791.5; NP_776152.1.
DR UCSC; uc001lde.2; human.
DR CTD; 118987; -.
DR DisGeNET; 118987; -.
DR GeneCards; PDZD8; -.
DR HGNC; HGNC:26974; PDZD8.
DR HPA; ENSG00000165650; Tissue enhanced (bone).
DR MIM; 614235; gene.
DR neXtProt; NX_Q8NEN9; -.
DR OpenTargets; ENSG00000165650; -.
DR PharmGKB; PA134916380; -.
DR VEuPathDB; HostDB:ENSG00000165650; -.
DR eggNOG; KOG3532; Eukaryota.
DR GeneTree; ENSGT00390000017746; -.
DR HOGENOM; CLU_008594_0_0_1; -.
DR InParanoid; Q8NEN9; -.
DR OMA; TLIECTR; -.
DR OrthoDB; 1195477at2759; -.
DR PhylomeDB; Q8NEN9; -.
DR TreeFam; TF324166; -.
DR PathwayCommons; Q8NEN9; -.
DR SignaLink; Q8NEN9; -.
DR SIGNOR; Q8NEN9; -.
DR BioGRID-ORCS; 118987; 7 hits in 1073 CRISPR screens.
DR ChiTaRS; PDZD8; human.
DR GenomeRNAi; 118987; -.
DR Pharos; Q8NEN9; Tbio.
DR PRO; PR:Q8NEN9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q8NEN9; protein.
DR Bgee; ENSG00000165650; Expressed in sperm and 202 other tissues.
DR Genevisible; Q8NEN9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0044233; C:mitochondria-associated endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IDA:UniProtKB.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IDA:UniProtKB.
DR GO; GO:0022604; P:regulation of cell morphogenesis; IMP:UniProtKB.
DR CDD; cd00029; C1; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR039275; PDZD8.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR031468; SMP_LBD.
DR PANTHER; PTHR21519; PTHR21519; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS51847; SMP; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Endoplasmic reticulum; Host-virus interaction;
KW Lipid transport; Lipid-binding; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Zinc;
KW Zinc-finger.
FT CHAIN 1..1154
FT /note="PDZ domain-containing protein 8"
FT /id="PRO_0000058299"
FT TRANSMEM 2..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 91..294
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194,
FT ECO:0000305|PubMed:29097544"
FT DOMAIN 366..449
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT ZN_FING 840..891
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 66..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 955..999
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1132..1154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1028..1063
FT /evidence="ECO:0000255"
FT COMPBIAS 586..600
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 967..996
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 980
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B9EJ80"
FT VARIANT 806
FT /note="V -> A (in dbSNP:rs35664484)"
FT /id="VAR_051265"
FT VARIANT 897
FT /note="R -> Q (in dbSNP:rs363294)"
FT /id="VAR_051266"
FT CONFLICT 232
FT /note="V -> G (in Ref. 3; AAO65182)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="A -> T (in Ref. 3; AAO65182)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="D -> N (in Ref. 3; AAO65182)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="S -> K (in Ref. 3; AAO65182)"
FT /evidence="ECO:0000305"
FT CONFLICT 666
FT /note="S -> F (in Ref. 4; CAB59184)"
FT /evidence="ECO:0000305"
FT CONFLICT 1007..1008
FT /note="GL -> RG (in Ref. 3; AAO65177)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1154 AA; 128563 MW; B09263C483645B13 CRC64;
MGLLLMILAS AVLGSFLTLL AQFFLLYRRQ PEPPADEAAR AGEGFRYIKP VPGLLLREYL
YGGGRDEEPS GAAPEGGATP TAAPETPAPP TRETCYFLNA TILFLFRELR DTALTRRWVT
KKIKVEFEEL LQTKTAGRLL EGLSLRDVFL GETVPFIKTI RLVRPVVPSA TGEPDGPEGE
ALPAACPEEL AFEAEVEYNG GFHLAIDVDL VFGKSAYLFV KLSRVVGRLR LVFTRVPFTH
WFFSFVEDPL IDFEVRSQFE GRPMPQLTSI IVNQLKKIIK RKHTLPNYKI RFKPFFPYQT
LQGFEEDEEH IHIQQWALTE GRLKVTLLEC SRLLIFGSYD REANVHCTLE LSSSVWEEKQ
RSSIKTVELI KGNLQSVGLT LRLVQSTDGY AGHVIIETVA PNSPAAIADL QRGDRLIAIG
GVKITSTLQV LKLIKQAGDR VLVYYERPVG QSNQGAVLQD NFGQLEENFL SSSCQSGYEE
EAAGLTVDTE SRELDSEFED LASDVRAQNE FKDEAQSLSH SPKRVPTTLS IKPLGAISPV
LNRKLAVGSH PLPPKIQSKD GNKPPPLKTS EITDPAQVSK PTQGSAFKPP VPPRPQAKVP
LPSADAPNQA EPDVLVEKPE KVVPPPLVDK SAEKQAKNVD AIDDAAAPKQ FLAKQEVAKD
VTSETSCPTK DSSDDRQTWE SSEILYRNKL GKWTRTRASC LFDIEACHRY LNIALWCRDP
FKLGGLICLG HVSLKLEDVA LGCLATSNTE YLSKLRLEAP SPKAIVTRTA LRNLSMQKGF
NDKFCYGDIT IHFKYLKEGE SDHHVVTNVE KEKEPHLVEE VSVLPKEEQF VGQMGLTENK
HSFQDTQFQN PTWCDYCKKK VWTKAASQCM FCAYVCHKKC QEKCLAETSV CGATDRRIDR
TLKNLRLEGQ ETLLGLPPRV DAEASKSVNK TTGLTRHIIN TSSRLLNLRQ VSKTRLSEPG
TDLVEPSPKH TPNTSDNEGS DTEVCGPNSP SKRGNSTGIK LVRKEGGLDD SVFIAVKEIG
RDLYRGLPTE ERIQKLEFML DKLQNEIDQE LEHNNSLVRE EKETTDTRKK SLLSAALAKS
GERLQALTLL MIHYRAGIED IETLESLSLD QHSKKISKYT DDTEEDLDNE ISQLIDSQPF
SSISDDLFGP SESV
