Full text data of PACSIN2
PACSIN2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein kinase C and casein kinase substrate in neurons protein 2 (Syndapin-2; Syndapin-II)
Protein kinase C and casein kinase substrate in neurons protein 2 (Syndapin-2; Syndapin-II)
UniProt
Q9UNF0
ID PACN2_HUMAN Reviewed; 486 AA.
AC Q9UNF0; O95921; Q96HV9; Q9H0D3; Q9NPN1; Q9Y4V2;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-AUG-2002, sequence version 2.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=Protein kinase C and casein kinase substrate in neurons protein 2;
DE AltName: Full=Syndapin-2;
DE AltName: Full=Syndapin-II;
GN Name=PACSIN2;
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).
RC TISSUE=Brain, and Retina;
RX PubMed=10431838; DOI=10.1016/S0014-5793(99)00830-3;
RA Ritter B., Modregger J., Paulsson M., Plomann M.;
RT "PACSIN 2, a novel member of the PACSIN family of cytoplasmic adapter
RT proteins.";
RL FEBS Lett. 454:356-362(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 335-486 (ISOFORM 2).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11082044;
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 [8]
RP 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
RT pacsin-syndapin-FAP52 gene family.";
RL Gene 262:199-205(2001).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=21610094; DOI=10.1242/jcs.086264;
RA Senju Y., Itoh Y., Takano K., Hamada S., Suetsugu S.;
RT "Essential role of PACSIN2/syndapin-II in caveolae membrane
RT sculpting.";
RL J. Cell Sci. 124:2032-2040(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAC1.
RX PubMed=21693584; DOI=10.1242/jcs.080630;
RA de Kreuk B.J., Nethe M., Fernandez-Borja M., Anthony E.C.,
RA Hensbergen P.J., Deelder A.M., Plomann M., Hordijk P.L.;
RT "The F-BAR domain protein PACSIN2 associates with Rac1 and regulates
RT cell spreading and migration.";
RL J. Cell Sci. 124:2375-2388(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23129763; DOI=10.1074/jbc.M112.391078;
RA de Kreuk B.J., Anthony E.C., Geerts D., Hordijk P.L.;
RT "The F-BAR protein PACSIN2 regulates epidermal growth factor receptor
RT internalization.";
RL J. Biol. Chem. 287:43438-43453(2012).
RN [16]
RP FUNCTION, 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 [17]
RP FUNCTION IN MEMBRANE TUBULATION, LIPID-BINDING, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH EHD1; EHD3 AND MICALL1.
RX PubMed=23596323; DOI=10.1091/mbc.E13-01-0026;
RA Giridharan S.S., Cai B., Vitale N., Naslavsky N., Caplan S.;
RT "Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular
RT recycling endosome biogenesis.";
RL Mol. Biol. Cell 24:1776-1790(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.78 ANGSTROMS), AND 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
RT by the F-BAR protein Pacsin/Syndapin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12700-12705(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-305, AND DOMAIN.
RX PubMed=20188097; DOI=10.1016/j.febslet.2010.02.058;
RA Shimada A., Takano K., Shirouzu M., Hanawa-Suetsugu K., Terada T.,
RA Toyooka K., Umehara T., Yamamoto M., Yokoyama S., Suetsugu S.;
RT "Mapping of the basic amino-acid residues responsible for tubulation
RT and cellular protrusion by the EFC/F-BAR domain of pacsin2/Syndapin
RT II.";
RL FEBS Lett. 584:1111-1118(2010).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 16-304.
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
RT dictating diameters of tubules.";
RL J. Biol. Chem. 287:22387-22396(2012).
CC -!- FUNCTION: Lipid-binding protein that is able to promote the
CC tubulation of the phosphatidic acid-containing membranes it
CC preferentially binds. Plays a role in intracellular vesicle-
CC mediated transport. Involved in the endocytosis of cell-surface
CC receptors like the EGF receptor, contributing to its
CC internalization in the absence of EGF stimulus. May also play a
CC role in the formation of caveolae at the cell membrane. Recruits
CC DNM2 to caveolae, and thereby plays a role in caveola-mediated
CC endocytosis.
CC -!- SUBUNIT: Homodimer. May form heterooligomers with other PACSINs.
CC Interacts (via NPF motifs) with EHD1 (via EH domain). Interacts
CC with EHD3. Interacts (via the SH3 domain) with MICALL1. Interacts
CC with RAC1. Interacts (via SH3 domain) with DNM1, SYN1, SYNJ1 and
CC WASL. Interacts with CAV1. Interacts with TRPV4.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-742503, EBI-742503;
CC P50570:DNM2; NbExp=4; IntAct=EBI-742503, EBI-346547;
CC P48023:FASLG; NbExp=4; IntAct=EBI-742503, EBI-495538;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm,
CC cytoskeleton (By similarity). Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Early endosome.
CC Recycling endosome membrane. Cell projection, ruffle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell projection (By
CC similarity). Membrane, caveola. Note=Detected at the neck of
CC flask-shaped caveolae. Localization to tubular recycling endosomes
CC probably requires interaction with MICALL1 and EHD1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UNF0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNF0-2; Sequence=VSP_004517;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The F-BAR domain forms a coiled coil and mediates
CC membrane-binding and membrane tubulation. In the autoinhibited
CC conformation, interaction with the SH3 domain inhibits membrane
CC tubulation mediated by the F-BAR domain.
CC -!- PTM: Phosphorylated by casein kinase 2 (CK2) and protein kinase C
CC (PKC) (By similarity).
CC -!- SIMILARITY: Belongs to the PACSIN family.
CC -!- SIMILARITY: Contains 1 FCH domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; AF128536; AAD41781.1; -; mRNA.
DR EMBL; AL136845; CAB66779.1; -; mRNA.
DR EMBL; CR456536; CAG30422.1; -; mRNA.
DR EMBL; AL022476; CAI20163.1; -; Genomic_DNA.
DR EMBL; AL049758; CAI20163.1; JOINED; Genomic_DNA.
DR EMBL; AL049758; CAI20948.1; -; Genomic_DNA.
DR EMBL; AL022476; CAI20948.1; JOINED; Genomic_DNA.
DR EMBL; BC008037; AAH08037.1; -; mRNA.
DR EMBL; AL389984; CAB97538.1; -; mRNA.
DR RefSeq; NP_001171899.1; NM_001184970.1.
DR RefSeq; NP_001171900.1; NM_001184971.1.
DR RefSeq; NP_009160.2; NM_007229.3.
DR RefSeq; XP_005261376.1; XM_005261319.1.
DR UniGene; Hs.162877; -.
DR PDB; 3ABH; X-ray; 2.00 A; A/B=1-305.
DR PDB; 3ACO; X-ray; 2.70 A; A/B=1-343.
DR PDB; 3HAJ; X-ray; 2.78 A; A/B=1-486.
DR PDB; 3Q0K; X-ray; 2.60 A; A/B/C/D=16-304.
DR PDBsum; 3ABH; -.
DR PDBsum; 3ACO; -.
DR PDBsum; 3HAJ; -.
DR PDBsum; 3Q0K; -.
DR ProteinModelPortal; Q9UNF0; -.
DR SMR; Q9UNF0; 16-303, 429-484.
DR IntAct; Q9UNF0; 8.
DR MINT; MINT-5005738; -.
DR STRING; 9606.ENSP00000263246; -.
DR PhosphoSite; Q9UNF0; -.
DR DMDM; 22256968; -.
DR PaxDb; Q9UNF0; -.
DR PRIDE; Q9UNF0; -.
DR DNASU; 11252; -.
DR Ensembl; ENST00000263246; ENSP00000263246; ENSG00000100266.
DR Ensembl; ENST00000337959; ENSP00000338379; ENSG00000100266.
DR Ensembl; ENST00000402229; ENSP00000385040; ENSG00000100266.
DR Ensembl; ENST00000403744; ENSP00000385372; ENSG00000100266.
DR Ensembl; ENST00000407585; ENSP00000385952; ENSG00000100266.
DR GeneID; 11252; -.
DR KEGG; hsa:11252; -.
DR UCSC; uc003bdg.4; human.
DR CTD; 11252; -.
DR GeneCards; GC22M043243; -.
DR HGNC; HGNC:8571; PACSIN2.
DR HPA; CAB009929; -.
DR HPA; HPA028852; -.
DR HPA; HPA049854; -.
DR MIM; 604960; gene.
DR neXtProt; NX_Q9UNF0; -.
DR PharmGKB; PA32897; -.
DR eggNOG; NOG283356; -.
DR HOGENOM; HOG000007245; -.
DR HOVERGEN; HBG053486; -.
DR InParanoid; Q9UNF0; -.
DR OMA; CKQDVLK; -.
DR PhylomeDB; Q9UNF0; -.
DR ChiTaRS; PACSIN2; human.
DR EvolutionaryTrace; Q9UNF0; -.
DR GeneWiki; PACSIN2; -.
DR GenomeRNAi; 11252; -.
DR NextBio; 42818; -.
DR PRO; PR:Q9UNF0; -.
DR ArrayExpress; Q9UNF0; -.
DR Bgee; Q9UNF0; -.
DR Genevestigator; Q9UNF0; -.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0070836; P:caveola assembly; IMP:UniProtKB.
DR GO; GO:0072584; P:caveolin-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:0048858; P:cell projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0097320; P:membrane tubulation; IDA:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0036010; P:protein localization to endosome; IMP:UniProtKB.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028521; PACSIN2.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10959:SF2; PTHR10959:SF2; 1.
DR Pfam; PF00611; FCH; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50133; FCH; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Coiled coil; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Endocytosis; Endosome; Lipid-binding; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; SH3 domain.
FT CHAIN 1 486 Protein kinase C and casein kinase
FT substrate in neurons protein 2.
FT /FTId=PRO_0000161795.
FT DOMAIN 11 75 FCH.
FT DOMAIN 426 486 SH3.
FT REGION 1 306 F-BAR domain.
FT COILED 25 274
FT MOTIF 362 364 NPF1.
FT MOTIF 405 407 NPF2.
FT MOTIF 417 419 NPF3.
FT VAR_SEQ 344 384 Missing (in isoform 2).
FT /FTId=VSP_004517.
FT VARIANT 175 175 N -> S (in dbSNP:rs35383004).
FT /FTId=VAR_053555.
FT VARIANT 294 294 M -> I (in dbSNP:rs2746984).
FT /FTId=VAR_013711.
FT VARIANT 324 324 V -> F (in dbSNP:rs1062913).
FT /FTId=VAR_013712.
FT CONFLICT 182 182 L -> F (in Ref. 1; AAD41781).
FT CONFLICT 256 256 D -> N (in Ref. 1; AAD41781).
FT CONFLICT 309 309 N -> I (in Ref. 1; AAD41781).
FT CONFLICT 336 336 S -> F (in Ref. 1; AAD41781).
FT CONFLICT 378 380 DDT -> EDI (in Ref. 1; AAD41781).
FT TURN 21 24
FT HELIX 25 72
FT HELIX 77 106
FT HELIX 108 119
FT STRAND 126 128
FT HELIX 129 169
FT HELIX 172 177
FT HELIX 185 188
FT HELIX 189 191
FT TURN 192 195
FT HELIX 197 255
FT HELIX 257 259
FT HELIX 263 275
FT HELIX 279 290
SQ SEQUENCE 486 AA; 55739 MW; 821DBEF65DAD1AA8 CRC64;
MSVTYDDSVG VEVSSDSFWE VGNYKRTVKR IDDGHRLCSD LMNCLHERAR IEKAYAQQLT
EWARRWRQLV EKGPQYGTVE KAWMAFMSEA ERVSELHLEV KASLMNDDFE KIKNWQKEAF
HKQMMGGFKE TKEAEDGFRK AQKPWAKKLK EVEAAKKAHH AACKEEKLAI SREANSKADP
SLNPEQLKKL QDKIEKCKQD VLKTKEKYEK SLKELDQGTP QYMENMEQVF EQCQQFEEKR
LRFFREVLLE VQKHLDLSNV AGYKAIYHDL EQSIRAADAV EDLRWFRANH GPGMAMNWPQ
FEEWSADLNR TLSRREKKKA TDGVTLTGIN QTGDQSLPSK PSSTLNVPSN PAQSAQSQSS
YNPFEDEDDT GSTVSEKDDT KAKNVSSYEK TQSYPTDWSD DESNNPFSST DANGDSNPFD
DDATSGTEVR VRALYDYEGQ EHDELSFKAG DELTKMEDED EQGWCKGRLD NGQVGLYPAN
YVEAIQ
//
ID PACN2_HUMAN Reviewed; 486 AA.
AC Q9UNF0; O95921; Q96HV9; Q9H0D3; Q9NPN1; Q9Y4V2;
DT 13-AUG-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-AUG-2002, sequence version 2.
DT 22-JAN-2014, entry version 119.
DE RecName: Full=Protein kinase C and casein kinase substrate in neurons protein 2;
DE AltName: Full=Syndapin-2;
DE AltName: Full=Syndapin-II;
GN Name=PACSIN2;
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).
RC TISSUE=Brain, and Retina;
RX PubMed=10431838; DOI=10.1016/S0014-5793(99)00830-3;
RA Ritter B., Modregger J., Paulsson M., Plomann M.;
RT "PACSIN 2, a novel member of the PACSIN family of cytoplasmic adapter
RT proteins.";
RL FEBS Lett. 454:356-362(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 335-486 (ISOFORM 2).
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11082044;
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 [8]
RP 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
RT pacsin-syndapin-FAP52 gene family.";
RL Gene 262:199-205(2001).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, DOMAIN, AND SUBCELLULAR LOCATION.
RX PubMed=21610094; DOI=10.1242/jcs.086264;
RA Senju Y., Itoh Y., Takano K., Hamada S., Suetsugu S.;
RT "Essential role of PACSIN2/syndapin-II in caveolae membrane
RT sculpting.";
RL J. Cell Sci. 124:2032-2040(2011).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAC1.
RX PubMed=21693584; DOI=10.1242/jcs.080630;
RA de Kreuk B.J., Nethe M., Fernandez-Borja M., Anthony E.C.,
RA Hensbergen P.J., Deelder A.M., Plomann M., Hordijk P.L.;
RT "The F-BAR domain protein PACSIN2 associates with Rac1 and regulates
RT cell spreading and migration.";
RL J. Cell Sci. 124:2375-2388(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23129763; DOI=10.1074/jbc.M112.391078;
RA de Kreuk B.J., Anthony E.C., Geerts D., Hordijk P.L.;
RT "The F-BAR protein PACSIN2 regulates epidermal growth factor receptor
RT internalization.";
RL J. Biol. Chem. 287:43438-43453(2012).
RN [16]
RP FUNCTION, 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 [17]
RP FUNCTION IN MEMBRANE TUBULATION, LIPID-BINDING, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH EHD1; EHD3 AND MICALL1.
RX PubMed=23596323; DOI=10.1091/mbc.E13-01-0026;
RA Giridharan S.S., Cai B., Vitale N., Naslavsky N., Caplan S.;
RT "Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular
RT recycling endosome biogenesis.";
RL Mol. Biol. Cell 24:1776-1790(2013).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.78 ANGSTROMS), AND 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
RT by the F-BAR protein Pacsin/Syndapin.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:12700-12705(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-305, AND DOMAIN.
RX PubMed=20188097; DOI=10.1016/j.febslet.2010.02.058;
RA Shimada A., Takano K., Shirouzu M., Hanawa-Suetsugu K., Terada T.,
RA Toyooka K., Umehara T., Yamamoto M., Yokoyama S., Suetsugu S.;
RT "Mapping of the basic amino-acid residues responsible for tubulation
RT and cellular protrusion by the EFC/F-BAR domain of pacsin2/Syndapin
RT II.";
RL FEBS Lett. 584:1111-1118(2010).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 16-304.
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
RT dictating diameters of tubules.";
RL J. Biol. Chem. 287:22387-22396(2012).
CC -!- FUNCTION: Lipid-binding protein that is able to promote the
CC tubulation of the phosphatidic acid-containing membranes it
CC preferentially binds. Plays a role in intracellular vesicle-
CC mediated transport. Involved in the endocytosis of cell-surface
CC receptors like the EGF receptor, contributing to its
CC internalization in the absence of EGF stimulus. May also play a
CC role in the formation of caveolae at the cell membrane. Recruits
CC DNM2 to caveolae, and thereby plays a role in caveola-mediated
CC endocytosis.
CC -!- SUBUNIT: Homodimer. May form heterooligomers with other PACSINs.
CC Interacts (via NPF motifs) with EHD1 (via EH domain). Interacts
CC with EHD3. Interacts (via the SH3 domain) with MICALL1. Interacts
CC with RAC1. Interacts (via SH3 domain) with DNM1, SYN1, SYNJ1 and
CC WASL. Interacts with CAV1. Interacts with TRPV4.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-742503, EBI-742503;
CC P50570:DNM2; NbExp=4; IntAct=EBI-742503, EBI-346547;
CC P48023:FASLG; NbExp=4; IntAct=EBI-742503, EBI-495538;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm,
CC cytoskeleton (By similarity). Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Early endosome.
CC Recycling endosome membrane. Cell projection, ruffle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell projection (By
CC similarity). Membrane, caveola. Note=Detected at the neck of
CC flask-shaped caveolae. Localization to tubular recycling endosomes
CC probably requires interaction with MICALL1 and EHD1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UNF0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNF0-2; Sequence=VSP_004517;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The F-BAR domain forms a coiled coil and mediates
CC membrane-binding and membrane tubulation. In the autoinhibited
CC conformation, interaction with the SH3 domain inhibits membrane
CC tubulation mediated by the F-BAR domain.
CC -!- PTM: Phosphorylated by casein kinase 2 (CK2) and protein kinase C
CC (PKC) (By similarity).
CC -!- SIMILARITY: Belongs to the PACSIN family.
CC -!- SIMILARITY: Contains 1 FCH domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; AF128536; AAD41781.1; -; mRNA.
DR EMBL; AL136845; CAB66779.1; -; mRNA.
DR EMBL; CR456536; CAG30422.1; -; mRNA.
DR EMBL; AL022476; CAI20163.1; -; Genomic_DNA.
DR EMBL; AL049758; CAI20163.1; JOINED; Genomic_DNA.
DR EMBL; AL049758; CAI20948.1; -; Genomic_DNA.
DR EMBL; AL022476; CAI20948.1; JOINED; Genomic_DNA.
DR EMBL; BC008037; AAH08037.1; -; mRNA.
DR EMBL; AL389984; CAB97538.1; -; mRNA.
DR RefSeq; NP_001171899.1; NM_001184970.1.
DR RefSeq; NP_001171900.1; NM_001184971.1.
DR RefSeq; NP_009160.2; NM_007229.3.
DR RefSeq; XP_005261376.1; XM_005261319.1.
DR UniGene; Hs.162877; -.
DR PDB; 3ABH; X-ray; 2.00 A; A/B=1-305.
DR PDB; 3ACO; X-ray; 2.70 A; A/B=1-343.
DR PDB; 3HAJ; X-ray; 2.78 A; A/B=1-486.
DR PDB; 3Q0K; X-ray; 2.60 A; A/B/C/D=16-304.
DR PDBsum; 3ABH; -.
DR PDBsum; 3ACO; -.
DR PDBsum; 3HAJ; -.
DR PDBsum; 3Q0K; -.
DR ProteinModelPortal; Q9UNF0; -.
DR SMR; Q9UNF0; 16-303, 429-484.
DR IntAct; Q9UNF0; 8.
DR MINT; MINT-5005738; -.
DR STRING; 9606.ENSP00000263246; -.
DR PhosphoSite; Q9UNF0; -.
DR DMDM; 22256968; -.
DR PaxDb; Q9UNF0; -.
DR PRIDE; Q9UNF0; -.
DR DNASU; 11252; -.
DR Ensembl; ENST00000263246; ENSP00000263246; ENSG00000100266.
DR Ensembl; ENST00000337959; ENSP00000338379; ENSG00000100266.
DR Ensembl; ENST00000402229; ENSP00000385040; ENSG00000100266.
DR Ensembl; ENST00000403744; ENSP00000385372; ENSG00000100266.
DR Ensembl; ENST00000407585; ENSP00000385952; ENSG00000100266.
DR GeneID; 11252; -.
DR KEGG; hsa:11252; -.
DR UCSC; uc003bdg.4; human.
DR CTD; 11252; -.
DR GeneCards; GC22M043243; -.
DR HGNC; HGNC:8571; PACSIN2.
DR HPA; CAB009929; -.
DR HPA; HPA028852; -.
DR HPA; HPA049854; -.
DR MIM; 604960; gene.
DR neXtProt; NX_Q9UNF0; -.
DR PharmGKB; PA32897; -.
DR eggNOG; NOG283356; -.
DR HOGENOM; HOG000007245; -.
DR HOVERGEN; HBG053486; -.
DR InParanoid; Q9UNF0; -.
DR OMA; CKQDVLK; -.
DR PhylomeDB; Q9UNF0; -.
DR ChiTaRS; PACSIN2; human.
DR EvolutionaryTrace; Q9UNF0; -.
DR GeneWiki; PACSIN2; -.
DR GenomeRNAi; 11252; -.
DR NextBio; 42818; -.
DR PRO; PR:Q9UNF0; -.
DR ArrayExpress; Q9UNF0; -.
DR Bgee; Q9UNF0; -.
DR Genevestigator; Q9UNF0; -.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0019898; C:extrinsic to membrane; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070300; F:phosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0005215; F:transporter activity; TAS:ProtInc.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0070836; P:caveola assembly; IMP:UniProtKB.
DR GO; GO:0072584; P:caveolin-mediated endocytosis; IMP:UniProtKB.
DR GO; GO:0048858; P:cell projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0097320; P:membrane tubulation; IDA:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0036010; P:protein localization to endosome; IMP:UniProtKB.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR028521; PACSIN2.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10959:SF2; PTHR10959:SF2; 1.
DR Pfam; PF00611; FCH; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50133; FCH; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Coiled coil; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Endocytosis; Endosome; Lipid-binding; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; SH3 domain.
FT CHAIN 1 486 Protein kinase C and casein kinase
FT substrate in neurons protein 2.
FT /FTId=PRO_0000161795.
FT DOMAIN 11 75 FCH.
FT DOMAIN 426 486 SH3.
FT REGION 1 306 F-BAR domain.
FT COILED 25 274
FT MOTIF 362 364 NPF1.
FT MOTIF 405 407 NPF2.
FT MOTIF 417 419 NPF3.
FT VAR_SEQ 344 384 Missing (in isoform 2).
FT /FTId=VSP_004517.
FT VARIANT 175 175 N -> S (in dbSNP:rs35383004).
FT /FTId=VAR_053555.
FT VARIANT 294 294 M -> I (in dbSNP:rs2746984).
FT /FTId=VAR_013711.
FT VARIANT 324 324 V -> F (in dbSNP:rs1062913).
FT /FTId=VAR_013712.
FT CONFLICT 182 182 L -> F (in Ref. 1; AAD41781).
FT CONFLICT 256 256 D -> N (in Ref. 1; AAD41781).
FT CONFLICT 309 309 N -> I (in Ref. 1; AAD41781).
FT CONFLICT 336 336 S -> F (in Ref. 1; AAD41781).
FT CONFLICT 378 380 DDT -> EDI (in Ref. 1; AAD41781).
FT TURN 21 24
FT HELIX 25 72
FT HELIX 77 106
FT HELIX 108 119
FT STRAND 126 128
FT HELIX 129 169
FT HELIX 172 177
FT HELIX 185 188
FT HELIX 189 191
FT TURN 192 195
FT HELIX 197 255
FT HELIX 257 259
FT HELIX 263 275
FT HELIX 279 290
SQ SEQUENCE 486 AA; 55739 MW; 821DBEF65DAD1AA8 CRC64;
MSVTYDDSVG VEVSSDSFWE VGNYKRTVKR IDDGHRLCSD LMNCLHERAR IEKAYAQQLT
EWARRWRQLV EKGPQYGTVE KAWMAFMSEA ERVSELHLEV KASLMNDDFE KIKNWQKEAF
HKQMMGGFKE TKEAEDGFRK AQKPWAKKLK EVEAAKKAHH AACKEEKLAI SREANSKADP
SLNPEQLKKL QDKIEKCKQD VLKTKEKYEK SLKELDQGTP QYMENMEQVF EQCQQFEEKR
LRFFREVLLE VQKHLDLSNV AGYKAIYHDL EQSIRAADAV EDLRWFRANH GPGMAMNWPQ
FEEWSADLNR TLSRREKKKA TDGVTLTGIN QTGDQSLPSK PSSTLNVPSN PAQSAQSQSS
YNPFEDEDDT GSTVSEKDDT KAKNVSSYEK TQSYPTDWSD DESNNPFSST DANGDSNPFD
DDATSGTEVR VRALYDYEGQ EHDELSFKAG DELTKMEDED EQGWCKGRLD NGQVGLYPAN
YVEAIQ
//
MIM
604960
*RECORD*
*FIELD* NO
604960
*FIELD* TI
*604960 PROTEIN KINASE C AND CASEIN KINASE SUBSTRATE IN NEURONS 2; PACSIN2
*FIELD* TX
read more
DESCRIPTION
Proteins containing a BIN (see 601248)/amphiphysin (AMPH; 600418)/Rvs167
(BAR) domain, such as PACSIN2, regulate membrane curvature. The
positively charged surface of the BAR domain binds to the negatively
charged inner surface of the plasma membrane, thereby bending the
membrane according to the protein structure (Senju et al., 2011).
CLONING
PACSIN family members, such as mouse Pacsin1 and chicken FAP52, are
cytoplasmic adaptor proteins with a common arrangement of domains and
conserved regions, including a CDC15 N-terminal domain, which contains a
RAEYL motif and a coiled-coil region, and a C-terminal SH3 domain. By
searching an EST database for novel members of the PACSIN family, Ritter
et al. (1999) identified ESTs encoding human and mouse PACSIN2. The
complete human PACSIN2 coding sequence, obtained from 2 overlapping
retina ESTs, encodes a deduced 486-amino acid protein that shares 93.6%
sequence identity with mouse Pacsin2. The PACSIN2 proteins contain a
CDC15 N-terminal domain, a C-terminal SRC (190090) homology-3 (SH3)
domain, 3 conserved regions specific to the PACSIN family, and 3
asn-pro-phe (NPF) motifs, which potentially bind to EH domains. The
PACSIN2 proteins share high sequence similarity with chicken FAP52 and
mouse Pacsin1 (606512). However, compared to these proteins, PACSIN2
proteins have a 41-amino acid insertion, which contains 1 NPF motif. In
contrast to the restricted neural expression of mouse Pacsin1 (Plomann
et al., 1998), Northern blot analysis detected mouse Pacsin2 expression
in all tissues examined, with the highest levels in brain, heart,
skeletal muscle, and ovary. Immunofluorescence microscopy of recombinant
Pacsin2 expressed in fibroblasts showed a broad, vesicle-like
cytoplasmic distribution that appeared to partially overlap with the
distributions of both the actin filament and microtubule networks.
Unlike FAP52, Pacsin2 was not detected at focal contacts. Ritter et al.
(1999) suggested that PACSIN2 may participate in the organization of the
actin cytoskeleton and the regulation of vesicular traffic.
By Northern blot analysis, Sumoy et al. (2001) detected ubiquitous
distribution of a 3.4-kb PACSIN2 transcript, with marked expression in
heart, and a predominant 2.4-kb alternate transcript in pancreas.
Senju et al. (2011) reported that the PACSIN2 protein contains an
N-terminal extended FES (190030)-CIP4 (TRIP10; 604504) homology BAR
(F-BAR) domain, in addition to the C-terminal SH3 domain and NPF motifs.
Immunogold electron microscopy localized endogenous PACSIN2 to the neck
region of caveolae in HeLa cells. PACSIN2 also localized to the plasma
membrane and cytosol.
De Kruek et al. (2012) stated that PACSIN2 localized to RAB5 (see
179512)-positive endosomes.
GENE FUNCTION
Senju et al. (2011) found that overexpression of the PACSIN2 F-BAR
domain in HeLa cells altered the localization of caveolin-1 (CAV1;
601047) and caused mesh-like plasma membrane invaginations. The isolated
F-BAR domain of PACSIN2 bound the N terminus of CAV1 more strongly than
full-length PACSIN2. Senju et al. (2011) determined that an
intramolecular interaction between the SH3 and F-BAR domains of PACSIN2
was autoinhibitory and that CAV1 interrupted this interaction. In
addition to binding CAV1, the F-BAR domain of PACSIN2 simultaneously
bound the plasma membrane and induced membrane tubulation. Knockdown of
PACSIN2 in HeLa cells via small interfering RNA reduced the number of
CAV1-positive invaginations, increased the diameter of caveolae necks,
increased caveolae depth, and interfered with recruitment of dynamin-2
(DNM2; 602378) for caveolae fission. The presence of PACSIN2 at caveolae
necks appeared to correspond to membrane tubulating activity, since
PACSIN2-induced tubules were antagonized by dynamin-2. Senju et al.
(2011) concluded that PACSIN2 induces membrane tubulation for caveolae
sculpting and fission.
De Kruek et al. (2012) observed that EGF (131530) and EGF receptor
(EGFR; 131550) were internalized into PACSIN2-positive endosomes in HeLa
cells. Knockdown of PACSIN2 increased the surface level of EGFR and
enhanced EGF-stimulated EGFR phosphorylation and downstream signaling
via ERK (see 176948) and AKT (see 164730). Knockdown of PACSIN2 did not
inhibit EGFR internalization, but blocked its degradation. Expression of
PACSIN2 mutants with inactivating mutations in the SH3 domain or BAR
domain increased surface expression of EGFR in unstimulated cells.
Knockdown of PACSIN2 also elevated signaling initiated by HGF (142409)
in HeLa cells and by TNF-alpha (TNF; 191160) and VEGF (VEGFA; 192240) in
human endothelial cells. De Kruek et al. (2012) hypothesized that
PACSIN2 may be a general regulator of growth factor receptor surface
expression, possibly by regulating receptor sorting.
MAPPING
Sumoy et al. (2001) stated that the PACSIN2 gene maps to 22q13.
*FIELD* RF
1. de Kruek, B.-J.; Anthony, E. C.; Geerts, D.; Hordijk, P. L.: The
F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J.
Biol. Chem. 287: 43438-43453, 2012.
2. Plomann, M.; Lange, R.; Vopper, G.; Cremer, H.; Heinlein, U. A.
O.; Scheff, S.; Baldwin, S. A.; Leitges, M.; Cramer, M.; Paulsson,
M.; Barthels, D.: PACSIN, a brain protein that is upregulated upon
differentiation into neuronal cells. Europ. J. Biochem. 256: 201-211,
1998.
3. Ritter, B.; Modregger, J.; Paulsson, M.; Plomann, M.: PACSIN 2,
a novel member of the PACSIN family of cytoplasmic adapter proteins. FEBS
Lett. 454: 356-362, 1999.
4. Senju, Y.; Itoh, Y.; Takano, K.; Hamada, S.; Suetsugu, S.: Essential
role of PACSIN2/syndapin-II in caveolae membrane sculpting. J. Cell
Sci. 124: 2032-2040, 2011.
5. Sumoy, L.; Pluvinet, R.; Andreu, N.; Estivill, X.; Escarceller,
M.: PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of
the pacsin-syndapin-FAP52 gene family. Gene 262: 199-205, 2001.
*FIELD* CN
Patricia A. Hartz: 10/9/2013
Paul J. Converse - updated: 11/27/2001
*FIELD* CD
Patti M. Sherman: 5/11/2000
*FIELD* ED
mgross: 11/04/2013
mgross: 11/4/2013
tpirozzi: 10/9/2013
terry: 5/12/2005
mgross: 11/27/2001
mcapotos: 8/31/2000
psherman: 5/18/2000
mcapotos: 5/16/2000
psherman: 5/12/2000
*RECORD*
*FIELD* NO
604960
*FIELD* TI
*604960 PROTEIN KINASE C AND CASEIN KINASE SUBSTRATE IN NEURONS 2; PACSIN2
*FIELD* TX
read more
DESCRIPTION
Proteins containing a BIN (see 601248)/amphiphysin (AMPH; 600418)/Rvs167
(BAR) domain, such as PACSIN2, regulate membrane curvature. The
positively charged surface of the BAR domain binds to the negatively
charged inner surface of the plasma membrane, thereby bending the
membrane according to the protein structure (Senju et al., 2011).
CLONING
PACSIN family members, such as mouse Pacsin1 and chicken FAP52, are
cytoplasmic adaptor proteins with a common arrangement of domains and
conserved regions, including a CDC15 N-terminal domain, which contains a
RAEYL motif and a coiled-coil region, and a C-terminal SH3 domain. By
searching an EST database for novel members of the PACSIN family, Ritter
et al. (1999) identified ESTs encoding human and mouse PACSIN2. The
complete human PACSIN2 coding sequence, obtained from 2 overlapping
retina ESTs, encodes a deduced 486-amino acid protein that shares 93.6%
sequence identity with mouse Pacsin2. The PACSIN2 proteins contain a
CDC15 N-terminal domain, a C-terminal SRC (190090) homology-3 (SH3)
domain, 3 conserved regions specific to the PACSIN family, and 3
asn-pro-phe (NPF) motifs, which potentially bind to EH domains. The
PACSIN2 proteins share high sequence similarity with chicken FAP52 and
mouse Pacsin1 (606512). However, compared to these proteins, PACSIN2
proteins have a 41-amino acid insertion, which contains 1 NPF motif. In
contrast to the restricted neural expression of mouse Pacsin1 (Plomann
et al., 1998), Northern blot analysis detected mouse Pacsin2 expression
in all tissues examined, with the highest levels in brain, heart,
skeletal muscle, and ovary. Immunofluorescence microscopy of recombinant
Pacsin2 expressed in fibroblasts showed a broad, vesicle-like
cytoplasmic distribution that appeared to partially overlap with the
distributions of both the actin filament and microtubule networks.
Unlike FAP52, Pacsin2 was not detected at focal contacts. Ritter et al.
(1999) suggested that PACSIN2 may participate in the organization of the
actin cytoskeleton and the regulation of vesicular traffic.
By Northern blot analysis, Sumoy et al. (2001) detected ubiquitous
distribution of a 3.4-kb PACSIN2 transcript, with marked expression in
heart, and a predominant 2.4-kb alternate transcript in pancreas.
Senju et al. (2011) reported that the PACSIN2 protein contains an
N-terminal extended FES (190030)-CIP4 (TRIP10; 604504) homology BAR
(F-BAR) domain, in addition to the C-terminal SH3 domain and NPF motifs.
Immunogold electron microscopy localized endogenous PACSIN2 to the neck
region of caveolae in HeLa cells. PACSIN2 also localized to the plasma
membrane and cytosol.
De Kruek et al. (2012) stated that PACSIN2 localized to RAB5 (see
179512)-positive endosomes.
GENE FUNCTION
Senju et al. (2011) found that overexpression of the PACSIN2 F-BAR
domain in HeLa cells altered the localization of caveolin-1 (CAV1;
601047) and caused mesh-like plasma membrane invaginations. The isolated
F-BAR domain of PACSIN2 bound the N terminus of CAV1 more strongly than
full-length PACSIN2. Senju et al. (2011) determined that an
intramolecular interaction between the SH3 and F-BAR domains of PACSIN2
was autoinhibitory and that CAV1 interrupted this interaction. In
addition to binding CAV1, the F-BAR domain of PACSIN2 simultaneously
bound the plasma membrane and induced membrane tubulation. Knockdown of
PACSIN2 in HeLa cells via small interfering RNA reduced the number of
CAV1-positive invaginations, increased the diameter of caveolae necks,
increased caveolae depth, and interfered with recruitment of dynamin-2
(DNM2; 602378) for caveolae fission. The presence of PACSIN2 at caveolae
necks appeared to correspond to membrane tubulating activity, since
PACSIN2-induced tubules were antagonized by dynamin-2. Senju et al.
(2011) concluded that PACSIN2 induces membrane tubulation for caveolae
sculpting and fission.
De Kruek et al. (2012) observed that EGF (131530) and EGF receptor
(EGFR; 131550) were internalized into PACSIN2-positive endosomes in HeLa
cells. Knockdown of PACSIN2 increased the surface level of EGFR and
enhanced EGF-stimulated EGFR phosphorylation and downstream signaling
via ERK (see 176948) and AKT (see 164730). Knockdown of PACSIN2 did not
inhibit EGFR internalization, but blocked its degradation. Expression of
PACSIN2 mutants with inactivating mutations in the SH3 domain or BAR
domain increased surface expression of EGFR in unstimulated cells.
Knockdown of PACSIN2 also elevated signaling initiated by HGF (142409)
in HeLa cells and by TNF-alpha (TNF; 191160) and VEGF (VEGFA; 192240) in
human endothelial cells. De Kruek et al. (2012) hypothesized that
PACSIN2 may be a general regulator of growth factor receptor surface
expression, possibly by regulating receptor sorting.
MAPPING
Sumoy et al. (2001) stated that the PACSIN2 gene maps to 22q13.
*FIELD* RF
1. de Kruek, B.-J.; Anthony, E. C.; Geerts, D.; Hordijk, P. L.: The
F-BAR protein PACSIN2 regulates epidermal growth factor receptor internalization. J.
Biol. Chem. 287: 43438-43453, 2012.
2. Plomann, M.; Lange, R.; Vopper, G.; Cremer, H.; Heinlein, U. A.
O.; Scheff, S.; Baldwin, S. A.; Leitges, M.; Cramer, M.; Paulsson,
M.; Barthels, D.: PACSIN, a brain protein that is upregulated upon
differentiation into neuronal cells. Europ. J. Biochem. 256: 201-211,
1998.
3. Ritter, B.; Modregger, J.; Paulsson, M.; Plomann, M.: PACSIN 2,
a novel member of the PACSIN family of cytoplasmic adapter proteins. FEBS
Lett. 454: 356-362, 1999.
4. Senju, Y.; Itoh, Y.; Takano, K.; Hamada, S.; Suetsugu, S.: Essential
role of PACSIN2/syndapin-II in caveolae membrane sculpting. J. Cell
Sci. 124: 2032-2040, 2011.
5. Sumoy, L.; Pluvinet, R.; Andreu, N.; Estivill, X.; Escarceller,
M.: PACSIN 3 is a novel SH3 domain cytoplasmic adapter protein of
the pacsin-syndapin-FAP52 gene family. Gene 262: 199-205, 2001.
*FIELD* CN
Patricia A. Hartz: 10/9/2013
Paul J. Converse - updated: 11/27/2001
*FIELD* CD
Patti M. Sherman: 5/11/2000
*FIELD* ED
mgross: 11/04/2013
mgross: 11/4/2013
tpirozzi: 10/9/2013
terry: 5/12/2005
mgross: 11/27/2001
mcapotos: 8/31/2000
psherman: 5/18/2000
mcapotos: 5/16/2000
psherman: 5/12/2000