PACER_MOUSE
ID PACER_MOUSE Reviewed; 648 AA.
AC Q3TD16;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Protein associated with UVRAG as autophagy enhancer {ECO:0000303|PubMed:30704899};
DE Short=Pacer {ECO:0000303|PubMed:30704899};
DE AltName: Full=Protein Rubicon-like {ECO:0000305};
GN Name=Rubcnl {ECO:0000312|MGI:MGI:2685590};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND ACETYLATION.
RX PubMed=30704899; DOI=10.1016/j.molcel.2018.12.017;
RA Cheng X., Ma X., Zhu Q., Song D., Ding X., Li L., Jiang X., Wang X.,
RA Tian R., Su H., Shen Z., Chen S., Liu T., Gong W., Liu W., Sun Q.;
RT "Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of
RT autophagosome maturation and lipid metabolism.";
RL Mol. Cell 73:1-15(2019).
CC -!- FUNCTION: Regulator of autophagy that promotes autophagosome maturation
CC by facilitating the biogenesis of phosphatidylinositol 3-phosphate
CC (PtdIns(3)P) in late steps of autophagy. Acts by antagonizing RUBCN,
CC thereby stimulating phosphatidylinositol 3-kinase activity of the
CC PI3K/PI3KC3 complex (By similarity). Following anchorage to the
CC autophagosomal SNARE STX17, promotes the recruitment of PI3K/PI3KC3 and
CC HOPS complexes to the autophagosome to regulate the fusion specificity
CC of autophagosomes with late endosomes/lysosomes (By similarity). Binds
CC phosphoinositides phosphatidylinositol 3-phosphate (PtdIns(3)P), 4-
CC phosphate (PtdIns(4)P) and 5-phosphate (PtdIns(5)P) (By similarity). In
CC addition to its role in autophagy, acts as a regulator of lipid and
CC glycogen homeostasis (PubMed:30704899). May act as a tumor suppressor
CC (By similarity). {ECO:0000250|UniProtKB:Q9H714,
CC ECO:0000269|PubMed:30704899}.
CC -!- SUBUNIT: Interacts with UVRAG; the interaction is direct and promotes
CC association with the PI3K/PI3KC3 and HOPS complexes. Interacts with
CC STX17. {ECO:0000250|UniProtKB:Q9H714}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000250|UniProtKB:Q9H714}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9H714}. Note=Associates with late autophagic
CC structure. Recruitment to autophagosome membrane is promoted by
CC autophagic stimuli. {ECO:0000250|UniProtKB:Q9H714}.
CC -!- PTM: Phosphorylated by MTOR at Ser-144 under nutrient-rich conditions.
CC Phosphorylation prevents acetylation by KAT5/TIP60 and impairs
CC RUBCNL/PACER function and autophagosome maturation. Under autophagy
CC induction, Phosphorylation by MTOR is repressed, enabling acetylation
CC by KAT5/TIP60. {ECO:0000250|UniProtKB:Q9H714}.
CC -!- PTM: Acetylated by KAT5/TIP60 under autophagy induction, promoting
CC autophagosome maturation and lipid metabolism (PubMed:30704899).
CC Acetylation is prevented by phosphorylation by MTOR (By similarity).
CC Lys-469 and Lys-559 constitute the key sites for tuning function in
CC autophagy (By similarity). {ECO:0000250|UniProtKB:Q9H714,
CC ECO:0000269|PubMed:30704899}.
CC -!- DISRUPTION PHENOTYPE: Mice display an increase in the ratio of liver to
CC body weight and significantly lower total ketone bodies in the serum
CC and liver after 24 hours of fasting (PubMed:30704899). Conditional
CC deletion in the liver results in impaired autophagy flux, glycogen and
CC lipid accumulation and liver fibrosis (PubMed:30704899).
CC {ECO:0000269|PubMed:30704899}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE41789.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK170426; BAE41789.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q3TD16; -.
DR SMR; Q3TD16; -.
DR STRING; 10090.ENSMUSP00000045566; -.
DR iPTMnet; Q3TD16; -.
DR PhosphoSitePlus; Q3TD16; -.
DR MaxQB; Q3TD16; -.
DR PaxDb; Q3TD16; -.
DR PRIDE; Q3TD16; -.
DR ProteomicsDB; 256642; -.
DR MGI; MGI:2685590; Rubcnl.
DR eggNOG; KOG1829; Eukaryota.
DR InParanoid; Q3TD16; -.
DR PhylomeDB; Q3TD16; -.
DR PRO; PR:Q3TD16; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q3TD16; protein.
DR GO; GO:0000421; C:autophagosome membrane; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IBA:GO_Central.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISS:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISS:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IMP:UniProtKB.
DR GO; GO:0061910; P:autophagosome-endosome fusion; ISO:MGI.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0070873; P:regulation of glycogen metabolic process; IMP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR InterPro; IPR025258; Zf-RING_9.
DR Pfam; PF13901; zf-RING_9; 1.
DR SMART; SM01175; DUF4206; 1.
PE 1: Evidence at protein level;
KW Acetylation; Autophagy; Cytoplasmic vesicle; Lipid metabolism;
KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome.
FT CHAIN 1..648
FT /note="Protein associated with UVRAG as autophagy enhancer"
FT /id="PRO_0000350567"
FT REGION 131..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..222
FT /note="Interaction with UVRAG"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 509
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 519
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 559
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
FT MOD_RES 619
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H714"
SQ SEQUENCE 648 AA; 72279 MW; 7CA89F03BEABFD5B CRC64;
MVSQSIGWGD SPVDLCEGSN RAFQDTDQPA CQLDVRLLRH KASWINPLCV QQPLQELCPQ
RPTVQSSENH VVLDTPSPLR LSILSYRDSL AEMPLSENTA DVICSNSAHC SGGKEGDFFL
ATEEQEVHLQ QESLLKNPKT VATSPSPKEG SARSESPHLT ASTDDGDARS SSRSHAWNFF
PLETFMLPAD VEKENLHFYA ADIIISVIEN MKCNLPNQQQ PERWDTEDAS RLRGTGAEMT
FYTHIKQEPG SSASSHTGCE GCAALQVSPV AETLSYCPVA GEACKHDLNK LVMLELGKYN
DITKGCRCSY NSSKSATCES NLSPAGCLAR ELFRGFCKCW MLSEVNCQLP GSPTTASSGV
GDEEYAEEDF DSSVDAAREV MLKSRVPGTE DWVLPRCQII LTVHPPIKRD IAVVAQNFFC
AGCGTPIQPK FVKRLRYCEY LGKYFCASCH SSAESCIPAR ILTMWDFRKY QVSDFSKWLL
DSVWHQPVFK LLGGHHSLYA KAKELDRVKD LQEQLFHIKK LLKTCRFADS VLKEFEQVPS
HLTDECHIFS MDDFLRTKKG LLAPLLKDIL RASLAHVDSC ELCQGKGFIC EFCQSTTVIF
PFQTTTCRRC AACRACFHKQ CFQSSRCPRC ARIIARRQHL ESLPTAAT
