ID PACS1_HUMAN Reviewed; 963 AA. AC Q6VY07; Q6PJY6; Q6PKB6; Q7Z590; Q7Z5W4; Q8N8K6; Q96MW0; Q9NW92; AC Q9ULP5; DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot. DT 13-SEP-2004, sequence version 2. DT 05-OCT-2010, entry version 67. DE RecName: Full=Phosphofurin acidic cluster sorting protein 1; DE Short=PACS-1; GN Name=PACS1; Synonyms=KIAA1175; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Wan L., Xiang Y., Simmen T., Thomas G.; RT "Human PACS-1, a endosome-TGN sorting connector."; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Embryo, and Fetal brain; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Kidney, and Uterus; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-963 (ISOFORM 1). RC TISSUE=Brain; RX MEDLINE=20039618; PubMed=10574461; DOI=10.1093/dnares/6.5.329; RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.; RT "Characterization of cDNA clones selected by the GeneMark analysis RT from size-fractionated cDNA libraries from human brain."; RL DNA Res. 6:329-336(1999). RN [5] RP FUNCTION. RX MEDLINE=21231166; PubMed=11331585; DOI=10.1093/emboj/20.9.2191; RA Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., RA Thomas G.; RT "PACS-1 binding to adaptors is required for acidic cluster motif- RT mediated protein traffic."; RL EMBO J. 20:2191-2201(2001). RN [6] RP INTERACTION WITH HIV-1 NEF. RX MEDLINE=20173876; PubMed=10707087; DOI=10.1038/35004038; RA Piguet V., Wan L., Borel C., Mangasarian A., Demaurex N., Thomas G., RA Trono D.; RT "HIV-1 Nef protein binds to the cellular protein PACS-1 to RT downregulate class I major histocompatibility complexes."; RL Nat. Cell Biol. 2:163-167(2000). RN [7] RP INTERACTION WITH HIV-1 NEF. RX MEDLINE=22414808; PubMed=12526811; DOI=10.1016/S0092-8674(02)01162-5; RA Blagoveshchenskaya A.D., Thomas L., Feliciangeli S.F., Hung C.-H., RA Thomas G.; RT "HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 RT endocytic pathway."; RL Cell 111:853-866(2002). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [9] RP INTERACTION WITH NPHP1. RX PubMed=16308564; DOI=10.1038/sj.emboj.7600885; RA Schermer B., Hoepker K., Omran H., Ghenoiu C., Fliegauf M., Fekete A., RA Horvath J., Koettgen M., Hackl M., Zschiedrich S., Huber T.B., RA Kramer-Zucker A., Zentgraf H., Blaukat A., Walz G., Benzing T.; RT "Phosphorylation by casein kinase 2 induces PACS-1 binding of RT nephrocystin and targeting to cilia."; RL EMBO J. 24:4415-4424(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-251, AND MASS RP SPECTROMETRY. RC TISSUE=Lung carcinoma; RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-407 AND SER-410, AND RP MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [12] RP INTERACTION WITH HIV-1 NEF. 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 RT triggers major histocompatibility complex class I (MHC-I) down- RT regulation: analysis using short interfering RNA and knock-out mice."; RL J. Biol. Chem. 283:11772-11784(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-379; SER-381; SER-430; RP SER-495; THR-504; SER-528; SER-529 AND SER-534, AND MASS SPECTROMETRY. 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 [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT THR-46, AND MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). CC -!- FUNCTION: Coat protein that is involved in the localization of CC trans-Golgi network (TGN) membrane proteins that contain acidic CC cluster sorting motifs. Controls the endosome-to-Golgi trafficking CC of furin and mannose-6-phosphate receptor by connecting the CC acidic-cluster-containing cytoplasmic domain of these molecules CC with the adapter-protein complex-1 (AP-1) of endosomal clathrin- CC coated membrane pits. Involved in HIV-1 nef-mediated removal of CC MHC-I from the cell surface to the TGN. CC -!- SUBUNIT: Interacts with HIV-1 Nef. Associates with AP-1 and AP-3 CC but not with AP-2 complexes. Interacts with NPHP1; the interaction CC is dependent of NPHP1 phosphorylation by CK2. CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network (By CC similarity). Note=Localizes in the perinuclear region, probably CC the TGN (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6VY07-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6VY07-2; Sequence=VSP_011557; CC Note=No experimental confirmation available; CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- SIMILARITY: Belongs to the PACS family. CC -!- SEQUENCE CAUTION: CC Sequence=AAH09936.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; CC Sequence=BAB71164.1; Type=Erroneous initiation; Note=Translation N-terminally extended; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AY320283; AAQ67682.1; -; mRNA. DR EMBL; AK001071; BAA91491.1; -; mRNA. DR EMBL; AK056361; BAB71164.1; ALT_INIT; mRNA. DR EMBL; AK096644; BAC04831.1; -; mRNA. DR EMBL; BC003173; AAH03173.1; -; mRNA. DR EMBL; BC010096; AAH10096.1; -; mRNA. DR EMBL; BC009936; AAH09936.1; ALT_INIT; mRNA. DR EMBL; BC052577; AAH52577.1; -; mRNA. DR EMBL; BC055288; AAH55288.1; -; mRNA. DR EMBL; AB033001; BAA86489.1; -; mRNA. DR IPI; IPI00376229; -. DR IPI; IPI00456262; -. DR RefSeq; NP_060496.2; -. DR UniGene; Hs.644326; -. DR ProteinModelPortal; Q6VY07; -. DR MINT; MINT-3372090; -. DR STRING; Q6VY07; -. DR PhosphoSite; Q6VY07; -. DR PRIDE; Q6VY07; -. DR Ensembl; ENST00000320580; ENSP00000316454; ENSG00000175115. DR GeneID; 55690; -. DR KEGG; hsa:55690; -. DR UCSC; uc001oha.1; human. DR CTD; 55690; -. DR GeneCards; GC11P065837; -. DR H-InvDB; HIX0009824; -. DR HGNC; HGNC:30032; PACS1. DR MIM; 607492; gene. DR PharmGKB; PA134989529; -. DR eggNOG; prNOG16580; -. DR HOVERGEN; HBG053488; -. DR InParanoid; Q6VY07; -. DR OMA; KSTWIKN; -. DR OrthoDB; EOG9GJ284; -. DR PhylomeDB; Q6VY07; -. DR Reactome; REACT_6185; HIV Infection. DR NextBio; 60497; -. DR ArrayExpress; Q6VY07; -. DR Bgee; Q6VY07; -. DR Genevestigator; Q6VY07; -. DR GermOnline; ENSG00000175115; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR InterPro; IPR019381; Phosphofurin_acidic_CSp-1. DR Pfam; PF10254; Pacs-1; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Coiled coil; Complete proteome; KW Golgi apparatus; Host-virus interaction; Phosphoprotein; Polymorphism. FT INIT_MET 1 1 Removed. FT CHAIN 2 963 Phosphofurin acidic cluster sorting FT protein 1. FT /FTId=PRO_0000058171. FT REGION 168 175 Involved in binding to AP-1. FT COILED 353 377 Potential. FT COMPBIAS 5 44 Gly-rich. FT COMPBIAS 35 40 Poly-Gln. FT COMPBIAS 55 84 Ser-rich. FT COMPBIAS 62 65 Poly-Ala. FT COMPBIAS 112 115 Poly-Ser. FT COMPBIAS 279 283 Poly-Glu. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 28 28 Phosphoserine (By similarity). FT MOD_RES 46 46 Phosphothreonine. FT MOD_RES 251 251 Phosphotyrosine. FT MOD_RES 379 379 Phosphoserine. FT MOD_RES 381 381 Phosphoserine. FT MOD_RES 407 407 Phosphoserine. FT MOD_RES 410 410 Phosphoserine. FT MOD_RES 429 429 Phosphothreonine (By similarity). FT MOD_RES 430 430 Phosphoserine. FT MOD_RES 495 495 Phosphoserine. FT MOD_RES 504 504 Phosphothreonine. FT MOD_RES 528 528 Phosphoserine. FT MOD_RES 529 529 Phosphoserine. FT MOD_RES 534 534 Phosphoserine. FT VAR_SEQ 917 963 AKQQQTMLRVSIDGVEWSDIKFFQLAAQWPTHVKHFPVGLF FT SGSKAT -> SPSLGPSLGPDPSSQPGFPPAGSFPPCHLPL FT TNPGSEPLIPDRPCSQEWLRTQGPSPALCTPQPGHLRPTAP FT LELFSCPLTPSQKFLHRTSF (in isoform 2). FT /FTId=VSP_011557. FT VARIANT 302 302 F -> L (in dbSNP:rs12798852). FT /FTId=VAR_053797. FT CONFLICT 171 220 Missing (in Ref. 2; BAC04831). FT CONFLICT 649 649 K -> M (in Ref. 2; BAA91491). FT CONFLICT 771 771 P -> S (in Ref. 2; BAC04831). FT CONFLICT 803 803 S -> N (in Ref. 1; AAQ67682). FT CONFLICT 882 882 K -> L (in Ref. 1; AAQ67682). SQ SEQUENCE 963 AA; 104898 MW; 0F6B2CA24F7CD567 CRC64; MAERGGAGGG PGGAGGGSGQ RGSGVAQSPQ QPPPQQQQQQ PPQQPTPPKL AQATSSSSST SAAAASSSSS STSTSMAVAV ASGSAPPGGP GPGRTPAPVQ MNLYATWEVD RSSSSCVPRL FSLTLKKLVM LKEMDKDLNS VVIAVKLQGS KRILRSNEIV LPASGLVETE LQLTFSLQYP HFLKRDANKL QIMLQRRKRY KNRTILGYKT LAVGLINMAE VMQHPNEGAL VLGLHSNVKD VSVPVAEIKI YSLSSQPIDH EGIKSKLSDR SPDIDNYSEE EEESFSSEQE GSDDPLHGQD LFYEDEDLRK VKKTRRKLTS TSAITRQPNI KQKFVALLKR FKVSDEVGFG LEHVSREQIR EVEEDLDELY DSLEMYNPSD SGPEMEETES ILSTPKPKLK PFFEGMSQSS SQTEIGSLNS KGSLGKDTTS PMELAALEKI KSTWIKNQDD SLTETDTLEI TDQDMFGDAS TSLVVPEKVK TPMKSSKTDL QGSASPSKVE GVHTPRQKRS TPLKERQLSK PLSERTNSSD SERSPDLGHS TQIPRKVVYD QLNQILVSDA ALPENVILVN TTDWQGQYVA ELLQDQRKPV VCTCSTVEVQ AVLSALLTRI QRYCNCNSSM PRPVKVAAVG GQSYLSSILR FFVKSLANKT SDWLGYMRFL IIPLGSHPVA KYLGSVDSKY SSSFLDSGWR DLFSRSEPPV SEQLDVAGRV MQYVNGAATT HQLPVAEAML TCRHKFPDED SYQKFIPFIG VVKVGLVEDS PSTAGDGDDS PVVSLTVPST SPPSSSGLSR DATATPPSSP SMSSALAIVG SPNSPYGDVI GLQVDYWLGH PGERRREGDK RDASSKNTLK SVFRSVQVSR LPHSGEAQLS GTMAMTVVTK EKNKKVPTIF LSKKPREKEV DSKSQVIEGI SRLICSAKQQ QTMLRVSIDG VEWSDIKFFQ LAAQWPTHVK HFPVGLFSGS KAT //