PACN3_MOUSE
ID PACN3_MOUSE Reviewed; 424 AA.
AC Q99JB8; Q9EQP9;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Protein kinase C and casein kinase II substrate protein 3;
GN Name=Pacsin3;
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 [MRNA], FUNCTION, INTERACTION WITH DNM1; SYNJ1 AND
RP WASL, HOMOOLIGOMERIZATION, HETEROOLIGOMERIZATION WITH PACSIN1 AND PACSIN2,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF PRO-415.
RC STRAIN=C57BL/6J;
RX PubMed=11082044; DOI=10.1242/jcs.113.24.4511;
RA Modregger J., Ritter B., Witter B., Paulsson M., Plomann M.;
RT "All three PACSIN isoforms bind to endocytic proteins and inhibit
RT endocytosis.";
RL J. Cell Sci. 113:4511-4521(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11179684; DOI=10.1016/s0378-1119(00)00531-x;
RA Sumoy L., Pluvinet R., Andreu N., Estivill X., Escarceller M.;
RT "PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of the pacsin-
RT syndapin-FAP52 gene family.";
RL Gene 262:199-205(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuron;
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 [4]
RP FUNCTION, AND INTERACTION WITH TRPV4.
RX PubMed=16627472; DOI=10.1074/jbc.m602452200;
RA Cuajungco M.P., Grimm C., Oshima K., D'hoedt D., Nilius B.,
RA Mensenkamp A.R., Bindels R.J., Plomann M., Heller S.;
RT "PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the
RT subcellular localization of TRPV4.";
RL J. Biol. Chem. 281:18753-18762(2006).
RN [5]
RP FUNCTION.
RX PubMed=17320047; DOI=10.1016/j.bbrc.2007.02.025;
RA Roach W., Plomann M.;
RT "PACSIN3 overexpression increases adipocyte glucose transport through
RT GLUT1.";
RL Biochem. Biophys. Res. Commun. 355:745-750(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP FUNCTION, AND INTERACTION WITH TRPV4.
RX PubMed=18174177; DOI=10.1074/jbc.m706386200;
RA D'hoedt D., Owsianik G., Prenen J., Cuajungco M.P., Grimm C., Heller S.,
RA Voets T., Nilius B.;
RT "Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3.";
RL J. Biol. Chem. 283:6272-6280(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-354, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-319; SER-354 AND
RP SER-383, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC and Testis;
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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-320, COILED COIL, SUBUNIT,
RP LIPID-BINDING, AND DOMAIN.
RX PubMed=22573331; DOI=10.1074/jbc.m112.358960;
RA Bai X., Meng G., Luo M., Zheng X.;
RT "Rigidity of wedge loop in PACSIN 3 protein is a key factor in dictating
RT diameters of tubules.";
RL J. Biol. Chem. 287:22387-22396(2012).
CC -!- FUNCTION: Plays a role in endocytosis and regulates internalization of
CC plasma membrane proteins. Overexpression impairs internalization of
CC SLC2A1/GLUT1 and TRPV4 and increases the levels of SLC2A1/GLUT1 and
CC TRPV4 at the cell membrane. Inhibits the TRPV4 calcium channel
CC activity. {ECO:0000269|PubMed:11082044, ECO:0000269|PubMed:16627472,
CC ECO:0000269|PubMed:17320047, ECO:0000269|PubMed:18174177}.
CC -!- SUBUNIT: Homodimer. May form heterooligomers with other PACSINs.
CC Interacts (via SH3 domain) with DNM1, SYNJ1 and WASL. Interacts with
CC TRPV4. {ECO:0000269|PubMed:11082044, ECO:0000269|PubMed:16627472,
CC ECO:0000269|PubMed:18174177, ECO:0000269|PubMed:22573331}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11082044}. Cell
CC membrane {ECO:0000269|PubMed:11082044}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11082044}; Cytoplasmic side
CC {ECO:0000269|PubMed:11082044}. Note=Detected at the inner aspect of the
CC plasma membrane in myotubes.
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, heart and
CC lung; also detected in brain, kidney and uterus (at protein level).
CC {ECO:0000269|PubMed:11082044}.
CC -!- DOMAIN: The F-BAR domain forms a coiled coil and mediates membrane-
CC binding and membrane tubulation. {ECO:0000269|PubMed:22573331}.
CC -!- PTM: Phosphorylated by casein kinase 2 (CK2) and protein kinase C
CC (PKC).
CC -!- SIMILARITY: Belongs to the PACSIN family. {ECO:0000305}.
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DR EMBL; AF149824; AAG31022.1; -; mRNA.
DR EMBL; AF242531; AAK29208.1; -; mRNA.
DR EMBL; BC003884; AAH03884.1; -; mRNA.
DR CCDS; CCDS16429.1; -.
DR RefSeq; NP_001276606.1; NM_001289677.1.
DR RefSeq; NP_001276607.1; NM_001289678.1.
DR RefSeq; NP_083009.1; NM_028733.4.
DR RefSeq; NP_112019.2; NM_030880.3.
DR RefSeq; XP_006500487.1; XM_006500424.3.
DR RefSeq; XP_006500488.1; XM_006500425.1.
DR RefSeq; XP_006500490.1; XM_006500427.3.
DR RefSeq; XP_006500491.1; XM_006500428.3.
DR PDB; 3M3W; X-ray; 2.60 A; A/B=1-320.
DR PDB; 3QE6; X-ray; 2.60 A; A/B=1-304.
DR PDB; 3SYV; X-ray; 3.10 A; A/B/C/D/E/F/G/H=1-341.
DR PDBsum; 3M3W; -.
DR PDBsum; 3QE6; -.
DR PDBsum; 3SYV; -.
DR AlphaFoldDB; Q99JB8; -.
DR SMR; Q99JB8; -.
DR BioGRID; 219797; 8.
DR IntAct; Q99JB8; 4.
DR MINT; Q99JB8; -.
DR STRING; 10090.ENSMUSP00000106981; -.
DR iPTMnet; Q99JB8; -.
DR PhosphoSitePlus; Q99JB8; -.
DR SwissPalm; Q99JB8; -.
DR jPOST; Q99JB8; -.
DR MaxQB; Q99JB8; -.
DR PaxDb; Q99JB8; -.
DR PRIDE; Q99JB8; -.
DR ProteomicsDB; 294147; -.
DR Antibodypedia; 26590; 500 antibodies from 33 providers.
DR DNASU; 80708; -.
DR Ensembl; ENSMUST00000028694; ENSMUSP00000028694; ENSMUSG00000027257.
DR Ensembl; ENSMUST00000059566; ENSMUSP00000054391; ENSMUSG00000027257.
DR Ensembl; ENSMUST00000111349; ENSMUSP00000106981; ENSMUSG00000027257.
DR Ensembl; ENSMUST00000168916; ENSMUSP00000129175; ENSMUSG00000027257.
DR GeneID; 80708; -.
DR KEGG; mmu:80708; -.
DR UCSC; uc008kvm.2; mouse.
DR CTD; 29763; -.
DR MGI; MGI:1891410; Pacsin3.
DR VEuPathDB; HostDB:ENSMUSG00000027257; -.
DR eggNOG; KOG2856; Eukaryota.
DR GeneTree; ENSGT00950000182973; -.
DR HOGENOM; CLU_030752_2_0_1; -.
DR InParanoid; Q99JB8; -.
DR OMA; HAKADST; -.
DR OrthoDB; 727724at2759; -.
DR PhylomeDB; Q99JB8; -.
DR TreeFam; TF313677; -.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 80708; 7 hits in 72 CRISPR screens.
DR ChiTaRS; Pacsin3; mouse.
DR PRO; PR:Q99JB8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q99JB8; protein.
DR Bgee; ENSMUSG00000027257; Expressed in hindlimb stylopod muscle and 201 other tissues.
DR ExpressionAtlas; Q99JB8; baseline and differential.
DR Genevisible; Q99JB8; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0019855; F:calcium channel inhibitor activity; IMP:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IMP:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; IDA:MGI.
DR GO; GO:0097320; P:plasma membrane tubulation; IDA:UniProtKB.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028523; PACSIN3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR23065:SF18; PTHR23065:SF18; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Coiled coil; Cytoplasm; Endocytosis;
KW Lipid-binding; Membrane; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..424
FT /note="Protein kinase C and casein kinase II substrate
FT protein 3"
FT /id="PRO_0000161801"
FT DOMAIN 10..280
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 363..424
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 154..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 312..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 23..272
FT /evidence="ECO:0000269|PubMed:22573331"
FT COMPBIAS 154..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKS6"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 324
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKS6"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKS6"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 415
FT /note="P->L: Loss of DNM1-, SYNJ1- and WASL-binding. Loss
FT of effect on transferrin endocytosis."
FT /evidence="ECO:0000269|PubMed:11082044"
FT CONFLICT 360
FT /note="R -> G (in Ref. 1; AAG31022)"
FT /evidence="ECO:0000305"
FT TURN 19..22
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 23..70
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 75..103
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 105..117
FT /evidence="ECO:0007829|PDB:3M3W"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:3SYV"
FT HELIX 127..170
FT /evidence="ECO:0007829|PDB:3M3W"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:3M3W"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 194..253
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 259..274
FT /evidence="ECO:0007829|PDB:3M3W"
FT HELIX 277..288
FT /evidence="ECO:0007829|PDB:3M3W"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:3QE6"
SQ SEQUENCE 424 AA; 48585 MW; 00475BC0321485B7 CRC64;
MAPEEDAGGE VLGGSFWEAG NYRRTVQRVE DGHRLCGDLV SCFQERARIE KAYAQQLADW
ARKWRGAVEK GPQYGTLEKA WHAFFTAAER LSELHLEVRE KLHGPDSERV RTWQRGAFHR
PVLGGFRESR AAEDGFRKAQ KPWLKRLKEV EASKKSYHTA RKDEKTAQTR ESHAKADSSM
SQEQLRKLQE RVGRCTKEAE KMKTQYEQTL AELNRYTPRY MEDMEQAFES CQAAERQRLL
FFKDVLLTLH QHLDLSSSDK FHELHRDLQQ SIEAASDEED LRWWRSTHGP GMAMNWPQFE
EWSLDTQRAI SRKEKGGRSP DEVTLTSIVP TRDGTAPPPQ SPSSPGSGQD EDWSDEESPR
KVATGVRVRA LYDYAGQEAD ELSFRAGEEL LKMSEEDEQG WCQGQLQSGR IGLYPANYVE
CVGA
