PACS2_HUMAN
ID PACS2_HUMAN Reviewed; 889 AA.
AC Q86VP3; A2VDJ9; G8JLK3; O60342; Q6P191; Q96FL7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Phosphofurin acidic cluster sorting protein 2 {ECO:0000305};
DE Short=PACS-2;
DE AltName: Full=PACS1-like protein;
GN Name=PACS2 {ECO:0000312|HGNC:HGNC:23794}; Synonyms=KIAA0602, PACS1L;
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 [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BID,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=15692567; DOI=10.1038/sj.emboj.7600559;
RA Simmen T., Aslan J.E., Blagoveshchenskaya A.D., Thomas L., Wan L.,
RA Xiang Y., Feliciangeli S.F., Hung C.-H., Crump C.M., Thomas G.;
RT "PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-
RT mediated apoptosis.";
RL EMBO J. 24:717-729(2005).
RN [2]
RP SEQUENCE REVISION TO 479; 508; 540 AND 714.
RA Xiang Y., Wan L., Simmen T., Thomas G.;
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Eye, and Hippocampus;
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 [6]
RP FUNCTION, AND INTERACTION WITH PKD2.
RX PubMed=15692563; DOI=10.1038/sj.emboj.7600566;
RA Koettgen M., Benzing T., Simmen T., Tauber R., Buchholz B.,
RA Feliciangeli S., Huber T.B., Schermer B., Kramer-Zucker A., Hoepker K.,
RA Simmen K.C., Tschucke C.C., Sandford R., Kim E., Thomas G., Walz G.;
RT "Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion
RT channel regulation.";
RL EMBO J. 24:705-716(2005).
RN [7]
RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=18296443; DOI=10.1074/jbc.m707572200;
RA Atkins K.M., Thomas L., Youker R.T., Harriff M.J., Pissani F., You H.,
RA Thomas G.;
RT "HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers
RT major histocompatibility complex class I (MHC-I) down-regulation: analysis
RT using short interfering RNA and knock-out mice.";
RL J. Biol. Chem. 283:11772-11784(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416 AND SER-453, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP INTERACTION WITH SIRT1; HDAC1 AND TRPV1, INVOLVEMENT IN DEE66, VARIANT
RP DEE66 LYS-209, AND CHARACTERIZATION OF VARIANT DEE66 LYS-209.
RX PubMed=29656858; DOI=10.1016/j.ajhg.2018.03.005;
RG DDD Study;
RG C4RCD Research Group;
RA Olson H.E., Jean-Marcais N., Yang E., Heron D., Tatton-Brown K.,
RA van der Zwaag P.A., Bijlsma E.K., Krock B.L., Backer E., Kamsteeg E.J.,
RA Sinnema M., Reijnders M.R.F., Bearden D., Begtrup A., Telegrafi A.,
RA Lunsing R.J., Burglen L., Lesca G., Cho M.T., Smith L.A., Sheidley B.R.,
RA Moufawad El Achkar C., Pearl P.L., Poduri A., Skraban C.M., Tarpinian J.,
RA Nesbitt A.I., Fransen van de Putte D.E., Ruivenkamp C.A.L., Rump P.,
RA Chatron N., Sabatier I., De Bellescize J., Guibaud L., Sweetser D.A.,
RA Waxler J.L., Wierenga K.J., Donadieu J., Narayanan V., Ramsey K.M.,
RA Nava C., Riviere J.B., Vitobello A., Tran Mau-Them F., Philippe C.,
RA Bruel A.L., Duffourd Y., Thomas L., Lelieveld S.H., Schuurs-Hoeijmakers J.,
RA Brunner H.G., Keren B., Thevenon J., Faivre L., Thomas G.,
RA Thauvin-Robinet C.;
RT "A recurrent de novo PACS2 heterozygous missense variant causes neonatal-
RT onset developmental epileptic encephalopathy, facial dysmorphism, and
RT cerebellar dysgenesis.";
RL Am. J. Hum. Genet. 102:995-1007(2018).
CC -!- FUNCTION: Multifunctional sorting protein that controls the endoplasmic
CC reticulum (ER)-mitochondria communication, including the apposition of
CC mitochondria with the ER and ER homeostasis. In addition, in response
CC to apoptotic inducer, translocates BIB to mitochondria, which initiates
CC a sequence of events including the formation of mitochondrial truncated
CC BID, the release of cytochrome c, the activation of caspase-3 thereby
CC causing cell death. May also be involved in ion channel trafficking,
CC directing acidic cluster-containing ion channels to distinct
CC subcellular compartments. {ECO:0000269|PubMed:15692563,
CC ECO:0000269|PubMed:15692567}.
CC -!- SUBUNIT: Interacts with BID and PKD2 (PubMed:15692567,
CC PubMed:15692563). Interacts with SIRT1 (PubMed:29656858). Interacts
CC with HDAC1 (PubMed:29656858). Interacts with TRPV1 (PubMed:29656858).
CC {ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:15692567,
CC ECO:0000269|PubMed:18296443, ECO:0000269|PubMed:29656858}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Nef.
CC {ECO:0000269|PubMed:18296443}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:15692567}. Mitochondrion
CC {ECO:0000269|PubMed:15692567}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q86VP3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86VP3-2; Sequence=VSP_021409, VSP_021410;
CC Name=4;
CC IsoId=Q86VP3-4; Sequence=VSP_053815, VSP_030294;
CC -!- TISSUE SPECIFICITY: Broadly expressed, with greatest levels in skeletal
CC muscle followed by heart, brain, pancreas and testis.
CC {ECO:0000269|PubMed:15692567}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 66 (DEE66)
CC [MIM:618067]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE66 is an autosomal dominant form characterized by
CC onset of seizures in first days or weeks of life.
CC {ECO:0000269|PubMed:29656858}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PACS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI31592.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA25528.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY320284; AAQ83882.2; -; mRNA.
DR EMBL; AB011174; BAA25528.1; ALT_INIT; mRNA.
DR EMBL; AL512355; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL928654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010663; AAH10663.1; -; mRNA.
DR EMBL; BC050351; AAH50351.2; -; mRNA.
DR EMBL; BC065220; AAH65220.2; -; mRNA.
DR EMBL; BC131591; AAI31592.1; ALT_INIT; mRNA.
DR CCDS; CCDS32168.1; -. [Q86VP3-1]
DR CCDS; CCDS45178.2; -. [Q86VP3-2]
DR CCDS; CCDS58339.1; -. [Q86VP3-4]
DR PIR; T00262; T00262.
DR RefSeq; NP_001094383.2; NM_001100913.2. [Q86VP3-2]
DR RefSeq; NP_001230056.1; NM_001243127.2. [Q86VP3-4]
DR RefSeq; NP_056012.2; NM_015197.3. [Q86VP3-1]
DR AlphaFoldDB; Q86VP3; -.
DR BioGRID; 116845; 21.
DR ELM; Q86VP3; -.
DR IntAct; Q86VP3; 16.
DR MINT; Q86VP3; -.
DR STRING; 9606.ENSP00000393559; -.
DR TCDB; 1.A.5.1.1; the polycystin cation channel (pcc) family.
DR GlyGen; Q86VP3; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q86VP3; -.
DR PhosphoSitePlus; Q86VP3; -.
DR BioMuta; PACS2; -.
DR DMDM; 117949768; -.
DR EPD; Q86VP3; -.
DR jPOST; Q86VP3; -.
DR MassIVE; Q86VP3; -.
DR MaxQB; Q86VP3; -.
DR PaxDb; Q86VP3; -.
DR PeptideAtlas; Q86VP3; -.
DR PRIDE; Q86VP3; -.
DR ProteomicsDB; 34256; -.
DR ProteomicsDB; 70048; -. [Q86VP3-1]
DR ProteomicsDB; 70049; -. [Q86VP3-2]
DR Antibodypedia; 93; 121 antibodies from 24 providers.
DR DNASU; 23241; -.
DR Ensembl; ENST00000325438.12; ENSP00000321834.8; ENSG00000179364.15. [Q86VP3-1]
DR Ensembl; ENST00000430725.6; ENSP00000393524.2; ENSG00000179364.15. [Q86VP3-4]
DR Ensembl; ENST00000447393.6; ENSP00000393559.2; ENSG00000179364.15. [Q86VP3-2]
DR GeneID; 23241; -.
DR KEGG; hsa:23241; -.
DR MANE-Select; ENST00000447393.6; ENSP00000393559.2; NM_001100913.3; NP_001094383.2. [Q86VP3-2]
DR UCSC; uc001yqs.4; human. [Q86VP3-1]
DR CTD; 23241; -.
DR DisGeNET; 23241; -.
DR GeneCards; PACS2; -.
DR HGNC; HGNC:23794; PACS2.
DR HPA; ENSG00000179364; Tissue enhanced (brain, skeletal muscle).
DR MalaCards; PACS2; -.
DR MIM; 610423; gene.
DR MIM; 618067; phenotype.
DR neXtProt; NX_Q86VP3; -.
DR OpenTargets; ENSG00000179364; -.
DR PharmGKB; PA134941470; -.
DR VEuPathDB; HostDB:ENSG00000179364; -.
DR eggNOG; KOG3709; Eukaryota.
DR GeneTree; ENSGT00950000183209; -.
DR HOGENOM; CLU_013074_0_0_1; -.
DR InParanoid; Q86VP3; -.
DR OMA; FANWETD; -.
DR OrthoDB; 291515at2759; -.
DR PhylomeDB; Q86VP3; -.
DR PathwayCommons; Q86VP3; -.
DR SignaLink; Q86VP3; -.
DR BioGRID-ORCS; 23241; 20 hits in 1077 CRISPR screens.
DR ChiTaRS; PACS2; human.
DR GenomeRNAi; 23241; -.
DR Pharos; Q86VP3; Tbio.
DR PRO; PR:Q86VP3; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q86VP3; protein.
DR Bgee; ENSG00000179364; Expressed in C1 segment of cervical spinal cord and 191 other tissues.
DR ExpressionAtlas; Q86VP3; baseline and differential.
DR Genevisible; Q86VP3; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0044325; F:transmembrane transporter binding; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000045; P:autophagosome assembly; IDA:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IMP:CACAO.
DR GO; GO:1990456; P:mitochondrion-endoplasmic reticulum membrane tethering; IMP:CACAO.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IDA:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:BHF-UCL.
DR InterPro; IPR019381; Phosphofurin_acidic_CS-1.
DR PANTHER; PTHR13280; PTHR13280; 1.
DR Pfam; PF10254; Pacs-1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Disease variant; Endoplasmic reticulum;
KW Epilepsy; Host-virus interaction; Mitochondrion; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..889
FT /note="Phosphofurin acidic cluster sorting protein 2"
FT /id="PRO_0000259511"
FT REGION 180..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 687..740
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..194
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..457
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..715
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 722..737
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3Q7"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3Q7"
FT MOD_RES 694
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3V3Q7"
FT VAR_SEQ 1..67
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_053815"
FT VAR_SEQ 240..247
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030294"
FT VAR_SEQ 467
FT /note="Q -> QVQLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9628581"
FT /id="VSP_021409"
FT VAR_SEQ 662
FT /note="K -> KRKKHFHFDFTL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9628581"
FT /id="VSP_021410"
FT VARIANT 185
FT /note="T -> A (in dbSNP:rs8010888)"
FT /id="VAR_028947"
FT VARIANT 209
FT /note="E -> K (in DEE66; increased interaction with SIRT1;
FT increased interaction with HDAC1; increased interaction
FT with TRPV1; dbSNP:rs1555408401)"
FT /evidence="ECO:0000269|PubMed:29656858"
FT /id="VAR_081137"
FT VARIANT 493
FT /note="L -> S (in dbSNP:rs4076933)"
FT /id="VAR_053798"
FT CONFLICT 13
FT /note="P -> L (in Ref. 1; AAQ83882)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="E -> D (in Ref. 5; AAH50351)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="D -> G (in Ref. 5; AAH50351)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="P -> H (in Ref. 5; AAH50351)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 889 AA; 97702 MW; 0AAFC1515B13A58D CRC64;
MAERGRLGLP GAPGALNTPV PMNLFATWEV DGSSPSCVPR LCSLTLKKLV VFKELEKELI
SVVIAVKMQG SKRILRSHEI VLPPSGQVET DLALTFSLQY PHFLKREGNK LQIMLQRRKR
YKNRTILGYK TLAAGSISMA EVMQHPSEGG QVLSLCSSIK EAPVKAAEIW IASLSSQPID
HEDSTMQAGP KAKSTDNYSE EEYESFSSEQ EASDDAVQGQ DLDEDDFDVG KPKKQRRSIV
RTTSMTRQQN FKQKVVALLR RFKVSDEVLD SEQDPAEHIP EAEEDLDLLY DTLDMEHPSD
SGPDMEDDDS VLSTPKPKLR PYFEGLSHSS SQTEIGSIHS ARSHKEPPSP ADVPEKTRSL
GGRQPSDSVS DTVALGVPGP REHPGQPEDS PEAEASTLDV FTERLPPSGR ITKTESLVIP
STRSEGKQAG RRGRSTSLKE RQAARPQNER ANSLDNERCP DARSQLQIPR KTVYDQLNHI
LISDDQLPEN IILVNTSDWQ GQFLSDVLQR HTLPVVCTCS PADVQAAFST IVSRIQRYCN
CNSQPPTPVK IAVAGAQHYL SAILRLFVEQ LSHKTPDWLG YMRFLVIPLG SHPVARYLGS
VDYRYNNFFQ DLAWRDLFNK LEAQSAVQDT PDIVSRITQY IAGANCAHQL PIAEAMLTYK
QKSPDEESSQ KFIPFVGVVK VGIVEPSSAT SGDSDDAAPS GSGTLSSTPP SASPAAKEAS
PTPPSSPSVS GGLSSPSQGV GAELMGLQVD YWTAAQPADR KRDAEKKDLP VTKNTLKCTF
RSLQVSRLPS SGEAAATPTM SMTVVTKEKN KKVMFLPKKA KDKDVESKSQ CIEGISRLIC
TARQQQNMLR VLIDGVECSD VKFFQLAAQW SSHVKHFPIC IFGHSKATF
