ID   PACN1_HUMAN             Reviewed;         444 AA.
AC   Q9BY11; Q9P2G8;
DT   13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Protein kinase C and casein kinase substrate in neurons protein 1;
DE   AltName: Full=Syndapin-1;
GN   Name=PACSIN1; Synonyms=KIAA1379;
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], AND TISSUE SPECIFICITY.
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA   Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XVI. The
RT   complete sequences of 150 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:65-73(2000).
RN   [3]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Amygdala;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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, INTERACTION WITH DNM1, SUBCELLULAR LOCATION, AND DOMAIN.
RX   PubMed=23236520; DOI=10.1371/journal.pone.0051628;
RA   Goh S.L., Wang Q., Byrnes L.J., Sondermann H.;
RT   "Versatile membrane deformation potential of activated pacsin.";
RL   PLoS ONE 7:E51628-E51628(2012).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 1-325, FUNCTION, LIPID-BINDING,
RP   SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-125 AND MET-126, AND
RP   DOMAIN.
RX   PubMed=19549836; DOI=10.1073/pnas.0902974106;
RA   Wang Q., Navarro M.V., Peng G., Molinelli E., Goh S.L., Judson B.L.,
RA   Rajashankar K.R., Sondermann H.;
RT   "Molecular mechanism of membrane constriction and tubulation mediated by
RT   the F-BAR protein Pacsin/Syndapin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:12700-12705(2009).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 14-308, FUNCTION, 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 the reorganization of the microtubule
CC       cytoskeleton via its interaction with MAPT; this decreases microtubule
CC       stability and inhibits MAPT-induced microtubule polymerization. Plays a
CC       role in cellular transport processes by recruiting DNM1, DNM2 and DNM3
CC       to membranes. Plays a role in the reorganization of the actin
CC       cytoskeleton and in neuron morphogenesis via its interaction with COBL
CC       and WASL, and by recruiting COBL to the cell cortex. Plays a role in
CC       the regulation of neurite formation, neurite branching and the
CC       regulation of neurite length. Required for normal synaptic vesicle
CC       endocytosis; this process retrieves previously released
CC       neurotransmitters to accommodate multiple cycles of neurotransmission.
CC       Required for normal excitatory and inhibitory synaptic transmission (By
CC       similarity). Binds to membranes via its F-BAR domain and mediates
CC       membrane tubulation. {ECO:0000250, ECO:0000269|PubMed:19549836,
CC       ECO:0000269|PubMed:22573331, ECO:0000269|PubMed:23236520}.
CC   -!- SUBUNIT: May form heterooligomers with other PACSINs. Interacts with
CC       MAPT. Interacts with TRPV4 (By similarity). Interacts (via SH3 domain)
CC       with SYNJ1 and WASL. Interacts with DNM2 and DNM3. Interacts with both
CC       COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and
CC       WASL. Interacts with EHD1 and EHD3 (By similarity). Homodimer.
CC       Interacts (via SH3 domain) with DNM1; the interaction is reduced by
CC       DNM1 phosphorylation. {ECO:0000250, ECO:0000269|PubMed:19549836,
CC       ECO:0000269|PubMed:23236520}.
CC   -!- INTERACTION:
CC       Q9BY11; O14672: ADAM10; NbExp=2; IntAct=EBI-721769, EBI-1536151;
CC       Q9BY11; A0A024R9H7: CCDC26; NbExp=3; IntAct=EBI-721769, EBI-10271580;
CC       Q9BY11; O75128: COBL; NbExp=3; IntAct=EBI-721769, EBI-3446582;
CC       Q9BY11; P48023: FASLG; NbExp=4; IntAct=EBI-721769, EBI-495538;
CC       Q9BY11; P42858: HTT; NbExp=3; IntAct=EBI-721769, EBI-466029;
CC       Q9BY11; O00746: NME4; NbExp=3; IntAct=EBI-721769, EBI-744871;
CC       Q9BY11; Q9UNF0: PACSIN2; NbExp=10; IntAct=EBI-721769, EBI-742503;
CC       Q9BY11; Q9UKS6: PACSIN3; NbExp=8; IntAct=EBI-721769, EBI-77926;
CC       Q9BY11; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-721769, EBI-742388;
CC       Q9BY11; Q9NUX5: POT1; NbExp=2; IntAct=EBI-721769, EBI-752420;
CC       Q9BY11; Q8IYM2: SLFN12; NbExp=3; IntAct=EBI-721769, EBI-2822550;
CC       Q9BY11; Q9UMY4: SNX12; NbExp=3; IntAct=EBI-721769, EBI-1752602;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection
CC       {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Cell projection,
CC       ruffle membrane {ECO:0000250}. Membrane; Peripheral membrane protein.
CC       Cytoplasmic vesicle membrane {ECO:0000250}; Peripheral membrane protein
CC       {ECO:0000250}. Synapse {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}.
CC       Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250};
CC       Cytoplasmic side {ECO:0000250}. Note=Colocalizes with MAPT in axons. In
CC       primary neuronal cultures, present at a high level in presynaptic nerve
CC       terminals and in the cell body. Colocalizes with DNM1 at vesicular
CC       structures in the cell body and neurites (By similarity). Associates
CC       with membranes via its F-BAR domain. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in brain and, at much lower
CC       levels, in heart and pancreas. {ECO:0000269|PubMed:11179684}.
CC   -!- DOMAIN: The F-BAR domain forms a coiled coil and mediates membrane-
CC       binding and membrane tubulation. In the autoinhibited conformation,
CC       interaction with the SH3 domain inhibits membrane tubulation mediated
CC       by the F-BAR domain. DNM1 binding abolishes autoinhibition (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated by casein kinase 2 (CK2) and protein kinase C
CC       (PKC). {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the PACSIN family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA92617.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF242529; AAK29206.1; -; mRNA.
DR   EMBL; AB037800; BAA92617.2; ALT_INIT; mRNA.
DR   EMBL; AL834211; CAD38895.1; -; mRNA.
DR   EMBL; BC040228; AAH40228.1; -; mRNA.
DR   CCDS; CCDS4793.1; -.
DR   RefSeq; NP_001186512.1; NM_001199583.2.
DR   RefSeq; NP_065855.1; NM_020804.4.
DR   RefSeq; XP_011512843.1; XM_011514541.1.
DR   PDB; 3HAH; X-ray; 2.77 A; A/B=1-325.
DR   PDB; 3HAI; X-ray; 2.88 A; A/B/C/D=1-308.
DR   PDB; 3Q84; X-ray; 2.80 A; A/B/G/H/M/N=14-308.
DR   PDB; 3QNI; X-ray; 2.80 A; A/B=1-307.
DR   PDBsum; 3HAH; -.
DR   PDBsum; 3HAI; -.
DR   PDBsum; 3Q84; -.
DR   PDBsum; 3QNI; -.
DR   AlphaFoldDB; Q9BY11; -.
DR   SMR; Q9BY11; -.
DR   BioGRID; 119018; 55.
DR   IntAct; Q9BY11; 47.
DR   MINT; Q9BY11; -.
DR   STRING; 9606.ENSP00000484060; -.
DR   iPTMnet; Q9BY11; -.
DR   PhosphoSitePlus; Q9BY11; -.
DR   SwissPalm; Q9BY11; -.
DR   BioMuta; PACSIN1; -.
DR   DMDM; 22256962; -.
DR   EPD; Q9BY11; -.
DR   jPOST; Q9BY11; -.
DR   MassIVE; Q9BY11; -.
DR   MaxQB; Q9BY11; -.
DR   PaxDb; 9606-ENSP00000484060; -.
DR   PeptideAtlas; Q9BY11; -.
DR   ProteomicsDB; 79560; -.
DR   Pumba; Q9BY11; -.
DR   ABCD; Q9BY11; 1 sequenced antibody.
DR   Antibodypedia; 4091; 279 antibodies from 34 providers.
DR   DNASU; 29993; -.
DR   Ensembl; ENST00000244458.7; ENSP00000244458.2; ENSG00000124507.11.
DR   Ensembl; ENST00000538621.2; ENSP00000439639.1; ENSG00000124507.11.
DR   Ensembl; ENST00000620693.4; ENSP00000484060.1; ENSG00000124507.11.
DR   GeneID; 29993; -.
DR   KEGG; hsa:29993; -.
DR   MANE-Select; ENST00000244458.7; ENSP00000244458.2; NM_020804.5; NP_065855.1.
DR   UCSC; uc003ojo.5; human.
DR   AGR; HGNC:8570; -.
DR   CTD; 29993; -.
DR   DisGeNET; 29993; -.
DR   GeneCards; PACSIN1; -.
DR   HGNC; HGNC:8570; PACSIN1.
DR   HPA; ENSG00000124507; Group enriched (brain, retina).
DR   MIM; 606512; gene.
DR   neXtProt; NX_Q9BY11; -.
DR   OpenTargets; ENSG00000124507; -.
DR   PharmGKB; PA32896; -.
DR   VEuPathDB; HostDB:ENSG00000124507; -.
DR   eggNOG; KOG2856; Eukaryota.
DR   GeneTree; ENSGT00950000182973; -.
DR   HOGENOM; CLU_030752_0_0_1; -.
DR   InParanoid; Q9BY11; -.
DR   OMA; EGGNTYN; -.
DR   OrthoDB; 9421at2759; -.
DR   PhylomeDB; Q9BY11; -.
DR   TreeFam; TF313677; -.
DR   PathwayCommons; Q9BY11; -.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   SignaLink; Q9BY11; -.
DR   SIGNOR; Q9BY11; -.
DR   BioGRID-ORCS; 29993; 12 hits in 1146 CRISPR screens.
DR   ChiTaRS; PACSIN1; human.
DR   EvolutionaryTrace; Q9BY11; -.
DR   GeneWiki; PACSIN1; -.
DR   GenomeRNAi; 29993; -.
DR   Pharos; Q9BY11; Tbio.
DR   PRO; PR:Q9BY11; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q9BY11; Protein.
DR   Bgee; ENSG00000124507; Expressed in right frontal lobe and 179 other cell types or tissues.
DR   ExpressionAtlas; Q9BY11; baseline and differential.
DR   GO; GO:0043679; C:axon terminus; ISS:UniProtKB.
DR   GO; GO:0030137; C:COPI-coated vesicle; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR   GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR   GO; GO:0098684; C:photoreceptor ribbon synapse; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR   GO; GO:0098833; C:presynaptic endocytic zone; IEA:Ensembl.
DR   GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR   GO; GO:0045202; C:synapse; ISS:BHF-UCL.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR   GO; GO:0007015; P:actin filament organization; IEA:InterPro.
DR   GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0045806; P:negative regulation of endocytosis; IEA:Ensembl.
DR   GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR   GO; GO:0097320; P:plasma membrane tubulation; IDA:UniProtKB.
DR   GO; GO:1900006; P:positive regulation of dendrite development; ISS:BHF-UCL.
DR   GO; GO:0072657; P:protein localization to membrane; ISS:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; ISS:BHF-UCL.
DR   GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR   GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB.
DR   CDD; cd07680; F-BAR_PACSIN1; 1.
DR   CDD; cd11998; SH3_PACSIN1-2; 1.
DR   Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   InterPro; IPR027267; AH/BAR_dom_sf.
DR   InterPro; IPR031160; F_BAR.
DR   InterPro; IPR001060; FCH_dom.
DR   InterPro; IPR035743; PACSIN1/PACSIN2_SH3.
DR   InterPro; IPR037454; PACSIN1_F-BAR.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   PANTHER; PTHR23065; PROLINE-SERINE-THREONINE PHOSPHATASE INTERACTING PROTEIN 1; 1.
DR   PANTHER; PTHR23065:SF16; PROTEIN KINASE C AND CASEIN KINASE SUBSTRATE IN NEURONS PROTEIN 1; 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; BAR/IMD domain-like; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS51741; F_BAR; 1.
DR   PROSITE; PS50002; SH3; 1.
DR   Genevisible; Q9BY11; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW   Cytoplasmic vesicle; Endocytosis; Lipid-binding; Membrane; Phosphoprotein;
KW   Reference proteome; SH3 domain; Synapse; Synaptosome.
FT   CHAIN           1..444
FT                   /note="Protein kinase C and casein kinase substrate in
FT                   neurons protein 1"
FT                   /id="PRO_0000161792"
FT   DOMAIN          13..283
FT                   /note="F-BAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT   DOMAIN          385..444
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REGION          175..194
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          309..386
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          26..275
FT   COMPBIAS        309..323
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        331..355
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT   MOD_RES         79
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT   MOD_RES         184
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT   MOD_RES         346
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   MOD_RES         348
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   MOD_RES         349
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT   MOD_RES         361
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   MOD_RES         365
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Z0W5"
FT   MOD_RES         394
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   MOD_RES         405
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   MOD_RES         430
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q61644"
FT   VARIANT         334
FT                   /note="A -> V (in dbSNP:rs41312309)"
FT                   /id="VAR_053554"
FT   MUTAGEN         125
FT                   /note="I->E: Reduces membrane-binding. Abolishes membrane
FT                   tubulation."
FT                   /evidence="ECO:0000269|PubMed:19549836"
FT   MUTAGEN         126
FT                   /note="M->E: Reduces membrane-binding. Abolishes membrane
FT                   tubulation."
FT                   /evidence="ECO:0000269|PubMed:19549836"
FT   TURN            22..25
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           26..73
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           78..107
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           109..120
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   STRAND          127..129
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           130..170
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   TURN            176..179
FT                   /evidence="ECO:0007829|PDB:3HAI"
FT   HELIX           193..256
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           258..260
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   TURN            262..264
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           265..275
FT                   /evidence="ECO:0007829|PDB:3HAH"
FT   HELIX           280..291
FT                   /evidence="ECO:0007829|PDB:3HAH"
SQ   SEQUENCE   444 AA;  50966 MW;  6AAF801873770975 CRC64;
     MSSSYDEASL APEETTDSFW EVGNYKRTVK RIDDGHRLCN DLMNCVQERA KIEKAYGQQL
     TDWAKRWRQL IEKGPQYGSL ERAWGAIMTE ADKVSELHQE VKNNLLNEDL EKVKNWQKDA
     YHKQIMGGFK ETKEAEDGFR KAQKPWAKKM KELEAAKKAY HLACKEEKLA MTREMNSKTE
     QSVTPEQQKK LQDKVDKCKQ DVQKTQEKYE KVLEDVGKTT PQYMENMEQV FEQCQQFEEK
     RLVFLKEVLL DIKRHLNLAE NSSYIHVYRE LEQAIRGADA QEDLRWFRST SGPGMPMNWP
     QFEEWNPDLP HTTTKKEKQP KKAEGVALTN ATGAVESTSQ AGDRGSVSSY DRGQPYATEW
     SDDESGNPFG GSETNGGANP FEDDSKGVRV RALYDYDGQE QDELSFKAGD ELTKLGEEDE
     QGWCRGRLDS GQLGLYPANY VEAI
//