Full text data of ACTR2
ACTR2
(ARP2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Actin-related protein 2 (Actin-like protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Actin-related protein 2 (Actin-like protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00005159
IPI00005159 Actin-like protein 2 Part of a complex implicated in the control of actin polymerization in cells soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00005159 Actin-like protein 2 Part of a complex implicated in the control of actin polymerization in cells soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P61160
ID ARP2_HUMAN Reviewed; 394 AA.
AC P61160; B2RCP5; D6W5F4; E9PF41; O15142; Q96C82;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 10-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Actin-related protein 2;
DE AltName: Full=Actin-like protein 2;
GN Name=ACTR2; Synonyms=ARP2;
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).
RX PubMed=9230079; DOI=10.1083/jcb.138.2.375;
RA Welch M.D., Depace A.H., Verma S., Iwamatsu A., Mitchison T.J.;
RT "The human Arp2/3 complex is composed of evolutionarily conserved
RT subunits and is localized to cellular regions of dynamic actin
RT filament assembly.";
RL J. Cell Biol. 138:375-384(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
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 2).
RC TISSUE=Liver;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [7]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION OF THE ARP2/3 COMPLEX,
RP IDENTIFICATION IN THE ARP2/3 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=9000076; DOI=10.1038/385265a0;
RA Welch M.D., Iwamatsu A., Mitchison T.J.;
RT "Actin polymerization is induced by Arp2/3 protein complex at the
RT surface of Listeria monocytogenes.";
RL Nature 385:265-269(1997).
RN [8]
RP RECONSTITUTION OF THE ARP2/3 COMPLEX.
RX PubMed=11741539; DOI=10.1016/S1097-2765(01)00393-8;
RA Gournier H., Goley E.D., Niederstrasser H., Trinh T., Welch M.D.;
RT "Reconstitution of human Arp2/3 complex reveals critical roles of
RT individual subunits in complex structure and activity.";
RL Mol. Cell 8:1041-1052(2001).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-299 AND LYS-322, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
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).
CC -!- FUNCTION: Functions as ATP-binding component of the Arp2/3 complex
CC which is involved in regulation of actin polymerization and
CC together with an activating nucleation-promoting factor (NPF)
CC mediates the formation of branched actin networks. Seems to
CC contact the pointed end of the daughter actin filament.
CC -!- SUBUNIT: Component of the Arp2/3 complex composed of ARP2, ARP3,
CC ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and
CC ARPC5/p16-ARC.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell projection.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61160-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61160-2; Sequence=VSP_046178;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the actin family. ARP2 subfamily.
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DR EMBL; AF006082; AAB64187.1; -; mRNA.
DR EMBL; AK315205; BAG37642.1; -; mRNA.
DR EMBL; BX649080; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC007318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99908.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99910.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99912.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99913.1; -; Genomic_DNA.
DR EMBL; BC014546; AAH14546.1; -; mRNA.
DR RefSeq; NP_001005386.1; NM_001005386.2.
DR RefSeq; NP_005713.1; NM_005722.3.
DR UniGene; Hs.643727; -.
DR UniGene; Hs.744913; -.
DR ProteinModelPortal; P61160; -.
DR SMR; P61160; 9-362.
DR DIP; DIP-33165N; -.
DR IntAct; P61160; 8.
DR MINT; MINT-5000145; -.
DR STRING; 9606.ENSP00000367220; -.
DR ChEMBL; CHEMBL6090; -.
DR PhosphoSite; P61160; -.
DR DMDM; 47117648; -.
DR SWISS-2DPAGE; P61160; -.
DR PaxDb; P61160; -.
DR PRIDE; P61160; -.
DR DNASU; 10097; -.
DR Ensembl; ENST00000260641; ENSP00000260641; ENSG00000138071.
DR Ensembl; ENST00000377982; ENSP00000367220; ENSG00000138071.
DR GeneID; 10097; -.
DR KEGG; hsa:10097; -.
DR UCSC; uc002sdp.3; human.
DR CTD; 10097; -.
DR GeneCards; GC02P065454; -.
DR HGNC; HGNC:169; ACTR2.
DR HPA; CAB005083; -.
DR HPA; HPA015050; -.
DR MIM; 604221; gene.
DR neXtProt; NX_P61160; -.
DR PharmGKB; PA24488; -.
DR eggNOG; COG5277; -.
DR HOGENOM; HOG000233340; -.
DR HOVERGEN; HBG003771; -.
DR KO; K17260; -.
DR OMA; ETMFEKY; -.
DR OrthoDB; EOG78D7K6; -.
DR PhylomeDB; P61160; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P61160; -.
DR ChiTaRS; ACTR2; human.
DR GeneWiki; ACTR2; -.
DR GenomeRNAi; 10097; -.
DR NextBio; 38189; -.
DR PRO; PR:P61160; -.
DR ArrayExpress; P61160; -.
DR Bgee; P61160; -.
DR CleanEx; HS_ACTR2; -.
DR Genevestigator; P61160; -.
DR GO; GO:0030478; C:actin cap; IEA:Ensembl.
DR GO; GO:0005885; C:Arp2/3 protein complex; TAS:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IEA:InterPro.
DR GO; GO:0008356; P:asymmetric cell division; IEA:Ensembl.
DR GO; GO:0006928; P:cellular component movement; TAS:UniProtKB.
DR GO; GO:0016482; P:cytoplasmic transport; IEA:Ensembl.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IEA:Ensembl.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0033206; P:meiotic cytokinesis; IEA:Ensembl.
DR GO; GO:0051653; P:spindle localization; IEA:Ensembl.
DR InterPro; IPR004000; Actin-related.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR027306; Arp2.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR PANTHER; PTHR11937:SF37; PTHR11937:SF37; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; ATP-binding;
KW Cell projection; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Nucleotide-binding; Reference proteome.
FT CHAIN 1 394 Actin-related protein 2.
FT /FTId=PRO_0000089067.
FT NP_BIND 160 162 ATP (By similarity).
FT NP_BIND 214 218 ATP (By similarity).
FT NP_BIND 305 310 ATP (By similarity).
FT MOD_RES 299 299 N6-acetyllysine.
FT MOD_RES 322 322 N6-acetyllysine.
FT VAR_SEQ 53 53 K -> KNNKKM (in isoform 2).
FT /FTId=VSP_046178.
FT CONFLICT 67 67 M -> T (in Ref. 6; AAH14546).
FT CONFLICT 172 172 G -> S (in Ref. 6; AAH14546).
SQ SEQUENCE 394 AA; 44761 MW; 1BFA6B442ED1A797 CRC64;
MDSQGRKVVV CDNGTGFVKC GYAGSNFPEH IFPALVGRPI IRSTTKVGNI EIKDLMVGDE
ASELRSMLEV NYPMENGIVR NWDDMKHLWD YTFGPEKLNI DTRNCKILLT EPPMNPTKNR
EKIVEVMFET YQFSGVYVAI QAVLTLYAQG LLTGVVVDSG DGVTHICPVY EGFSLPHLTR
RLDIAGRDIT RYLIKLLLLR GYAFNHSADF ETVRMIKEKL CYVGYNIEQE QKLALETTVL
VESYTLPDGR IIKVGGERFE APEALFQPHL INVEGVGVAE LLFNTIQAAD IDTRSEFYKH
IVLSGGSTMY PGLPSRLERE LKQLYLERVL KGDVEKLSKF KIRIEDPPRR KHMVFLGGAV
LADIMKDKDN FWMTRQEYQE KGVRVLEKLG VTVR
//
ID ARP2_HUMAN Reviewed; 394 AA.
AC P61160; B2RCP5; D6W5F4; E9PF41; O15142; Q96C82;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 10-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=Actin-related protein 2;
DE AltName: Full=Actin-like protein 2;
GN Name=ACTR2; Synonyms=ARP2;
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).
RX PubMed=9230079; DOI=10.1083/jcb.138.2.375;
RA Welch M.D., Depace A.H., Verma S., Iwamatsu A., Mitchison T.J.;
RT "The human Arp2/3 complex is composed of evolutionarily conserved
RT subunits and is localized to cellular regions of dynamic actin
RT filament assembly.";
RL J. Cell Biol. 138:375-384(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
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 2).
RC TISSUE=Liver;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [7]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION OF THE ARP2/3 COMPLEX,
RP IDENTIFICATION IN THE ARP2/3 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=9000076; DOI=10.1038/385265a0;
RA Welch M.D., Iwamatsu A., Mitchison T.J.;
RT "Actin polymerization is induced by Arp2/3 protein complex at the
RT surface of Listeria monocytogenes.";
RL Nature 385:265-269(1997).
RN [8]
RP RECONSTITUTION OF THE ARP2/3 COMPLEX.
RX PubMed=11741539; DOI=10.1016/S1097-2765(01)00393-8;
RA Gournier H., Goley E.D., Niederstrasser H., Trinh T., Welch M.D.;
RT "Reconstitution of human Arp2/3 complex reveals critical roles of
RT individual subunits in complex structure and activity.";
RL Mol. Cell 8:1041-1052(2001).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-299 AND LYS-322, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
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).
CC -!- FUNCTION: Functions as ATP-binding component of the Arp2/3 complex
CC which is involved in regulation of actin polymerization and
CC together with an activating nucleation-promoting factor (NPF)
CC mediates the formation of branched actin networks. Seems to
CC contact the pointed end of the daughter actin filament.
CC -!- SUBUNIT: Component of the Arp2/3 complex composed of ARP2, ARP3,
CC ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and
CC ARPC5/p16-ARC.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell projection.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P61160-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61160-2; Sequence=VSP_046178;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Belongs to the actin family. ARP2 subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF006082; AAB64187.1; -; mRNA.
DR EMBL; AK315205; BAG37642.1; -; mRNA.
DR EMBL; BX649080; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC007318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAW99908.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99910.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99912.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99913.1; -; Genomic_DNA.
DR EMBL; BC014546; AAH14546.1; -; mRNA.
DR RefSeq; NP_001005386.1; NM_001005386.2.
DR RefSeq; NP_005713.1; NM_005722.3.
DR UniGene; Hs.643727; -.
DR UniGene; Hs.744913; -.
DR ProteinModelPortal; P61160; -.
DR SMR; P61160; 9-362.
DR DIP; DIP-33165N; -.
DR IntAct; P61160; 8.
DR MINT; MINT-5000145; -.
DR STRING; 9606.ENSP00000367220; -.
DR ChEMBL; CHEMBL6090; -.
DR PhosphoSite; P61160; -.
DR DMDM; 47117648; -.
DR SWISS-2DPAGE; P61160; -.
DR PaxDb; P61160; -.
DR PRIDE; P61160; -.
DR DNASU; 10097; -.
DR Ensembl; ENST00000260641; ENSP00000260641; ENSG00000138071.
DR Ensembl; ENST00000377982; ENSP00000367220; ENSG00000138071.
DR GeneID; 10097; -.
DR KEGG; hsa:10097; -.
DR UCSC; uc002sdp.3; human.
DR CTD; 10097; -.
DR GeneCards; GC02P065454; -.
DR HGNC; HGNC:169; ACTR2.
DR HPA; CAB005083; -.
DR HPA; HPA015050; -.
DR MIM; 604221; gene.
DR neXtProt; NX_P61160; -.
DR PharmGKB; PA24488; -.
DR eggNOG; COG5277; -.
DR HOGENOM; HOG000233340; -.
DR HOVERGEN; HBG003771; -.
DR KO; K17260; -.
DR OMA; ETMFEKY; -.
DR OrthoDB; EOG78D7K6; -.
DR PhylomeDB; P61160; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P61160; -.
DR ChiTaRS; ACTR2; human.
DR GeneWiki; ACTR2; -.
DR GenomeRNAi; 10097; -.
DR NextBio; 38189; -.
DR PRO; PR:P61160; -.
DR ArrayExpress; P61160; -.
DR Bgee; P61160; -.
DR CleanEx; HS_ACTR2; -.
DR Genevestigator; P61160; -.
DR GO; GO:0030478; C:actin cap; IEA:Ensembl.
DR GO; GO:0005885; C:Arp2/3 protein complex; TAS:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IEA:InterPro.
DR GO; GO:0008356; P:asymmetric cell division; IEA:Ensembl.
DR GO; GO:0006928; P:cellular component movement; TAS:UniProtKB.
DR GO; GO:0016482; P:cytoplasmic transport; IEA:Ensembl.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IEA:Ensembl.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0033206; P:meiotic cytokinesis; IEA:Ensembl.
DR GO; GO:0051653; P:spindle localization; IEA:Ensembl.
DR InterPro; IPR004000; Actin-related.
DR InterPro; IPR020902; Actin/actin-like_CS.
DR InterPro; IPR027306; Arp2.
DR PANTHER; PTHR11937; PTHR11937; 1.
DR PANTHER; PTHR11937:SF37; PTHR11937:SF37; 1.
DR Pfam; PF00022; Actin; 1.
DR PRINTS; PR00190; ACTIN.
DR SMART; SM00268; ACTIN; 1.
DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Alternative splicing; ATP-binding;
KW Cell projection; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Nucleotide-binding; Reference proteome.
FT CHAIN 1 394 Actin-related protein 2.
FT /FTId=PRO_0000089067.
FT NP_BIND 160 162 ATP (By similarity).
FT NP_BIND 214 218 ATP (By similarity).
FT NP_BIND 305 310 ATP (By similarity).
FT MOD_RES 299 299 N6-acetyllysine.
FT MOD_RES 322 322 N6-acetyllysine.
FT VAR_SEQ 53 53 K -> KNNKKM (in isoform 2).
FT /FTId=VSP_046178.
FT CONFLICT 67 67 M -> T (in Ref. 6; AAH14546).
FT CONFLICT 172 172 G -> S (in Ref. 6; AAH14546).
SQ SEQUENCE 394 AA; 44761 MW; 1BFA6B442ED1A797 CRC64;
MDSQGRKVVV CDNGTGFVKC GYAGSNFPEH IFPALVGRPI IRSTTKVGNI EIKDLMVGDE
ASELRSMLEV NYPMENGIVR NWDDMKHLWD YTFGPEKLNI DTRNCKILLT EPPMNPTKNR
EKIVEVMFET YQFSGVYVAI QAVLTLYAQG LLTGVVVDSG DGVTHICPVY EGFSLPHLTR
RLDIAGRDIT RYLIKLLLLR GYAFNHSADF ETVRMIKEKL CYVGYNIEQE QKLALETTVL
VESYTLPDGR IIKVGGERFE APEALFQPHL INVEGVGVAE LLFNTIQAAD IDTRSEFYKH
IVLSGGSTMY PGLPSRLERE LKQLYLERVL KGDVEKLSKF KIRIEDPPRR KHMVFLGGAV
LADIMKDKDN FWMTRQEYQE KGVRVLEKLG VTVR
//
MIM
604221
*RECORD*
*FIELD* NO
604221
*FIELD* TI
*604221 ACTIN-RELATED PROTEIN 2; ACTR2
;;ARP2
ARP2/3 COMPLEX, INCLUDED
*FIELD* TX
read moreCLONING
The protrusion of the cell membrane is fundamental to cell shape change
and locomotion. Actin polymerization (see 102560) plays a critical role
in this process. The leading edge of motile cells is dominated by thin
actin-rich structures called lamellipodia, which exhibit highly dynamic
behavior characterized by rapid extension and retraction. Many aspects
of the mechanism of lamellipodial protrusion are echoed in the
intracellular motility of certain bacterial and viral pathogens, such as
the bacterium Listeria monocytogenes. Welch et al. (1997) purified an
approximately 220-kD multiprotein complex from human platelets that
induces actin polymerization at the L. monocytogenes cell surface and
mediates bacterial motility. This complex contains actin-related
proteins (Arps) in the Arp2 and Arp3 families and therefore was named
the Arp2/3 complex. In addition to 43-kD ARP2 and 50-kD ARP3 (ACTR3;
604222), the human complex consists of 41/40- (ARPC1B; 604223), 34-
(ARPC2; 604224), 21- (ARPC3; 604225), 20- (ARPC4; 604226), and 16-kD
(ARPC5; 604227) subunits, all present in approximately equal
stoichiometry. By searching an EST database with peptide sequences from
the 7 subunits of the human ARP2/3 complex, Welch et al. (1997)
identified full-length human cDNAs encoding each subunit. The ARP2 cDNA
encodes a deduced 394-amino acid protein that is 99% identical to
chicken Arp2 and 67% identical to S. cerevisiae Arp2. Welch et al.
(1997) localized several subunits of the ARP2/3 complex to the
lamellipodia of stationary and locomoting fibroblasts, as well as to the
actin tails assembled by L. monocytogenes. They suggested that the
ARP2/3 complex promotes actin assembly in lamellipodia and may
participate in lamellipodial protrusion.
Machesky et al. (1997) purified the ARP2/3 complex from human
neutrophils and sequenced peptides from each of the subunits.
GENE FUNCTION
Leisel et al. (1999) used pure components of the actin cytoskeleton to
reconstitute sustained movement in Listeria and Shigella in vitro.
Actin-based propulsion was driven by the free energy released by ATP
hydrolysis linked to actin polymerization and did not require myosin
(see 601478). In addition to actin and activated Arp2/3 complex, actin
depolymerizing factor and capping protein (see 601571) were also
required for motility as they maintained a high steady-state level of
G-actin (see 102610), which controls the rate of unidirectional growth
of actin filaments at the surface of the bacterium. The movement was
more effective when profilin (see 176610), alpha-actinin (see 102575),
and, in the case of Listeria, VASP (601703) were also included.
The protein N-WASP (WASL; 605056) regulates actin polymerization by
stimulating the actin-nucleating activity of the Arp2/3 complex. N-WASP
is tightly regulated by multiple signals; only costimulation by CDC42
(116952) and phosphatidylinositol (4,5)-bisphosphate (PIP2) yields
potent polymerization. Prehoda et al. (2000) found that regulation
requires N-WASP's constitutively active output domain
(verprolin/cofilin/acidic (VCA) domain) and 2 regulatory domains, a
CDC42-binding domain and a PIP2-binding domain. In the absence of
stimuli, the regulatory modules together hold the VCA-Arp2/3 complex in
an inactive 'closed' conformation. In this state, both the CDC42- and
PIP2-binding sites are masked. Binding of either input destabilizes the
closed state and enhances binding of the other input. This cooperative
activation mechanism shows how combinations of simple binding domains
can be used to integrate and amplify coincident signals.
Using fluorescence anisotropy analysis, Marchand et al. (2001) showed
that efficient actin nucleation requires both recruitment of an actin
monomer to the ARP2/3 complex and a subsequent activation step. The
initial steps in this pathway involve binding by the WA domain of
WASP/SCAR (605035) proteins, which consists of a WH2 motif (W) that
binds to the actin monomers and an acidic tail (A) that binds to the
ARP2/3 complex. Actin filaments seem to stimulate nucleation by
enhancing binding of WA to the ARP2/3 complex and favoring the formation
of a productive nucleus.
Weisswange et al. (2009) analyzed the dynamics of N-WASP,
WASP-interacting protein (WIP; 602357), GRB2 (108355), and NCK (600508),
which are required to stimulate ARP2/3 complex-dependent actin-based
motility of vaccinia virus, using fluorescence recovery after
photobleaching. Weisswange et al. (2009) showed that all 4 proteins are
rapidly exchanging, albeit at different rates, and that the turnover of
N-WASP depends on its ability to stimulate ARP2/3 complex-mediated actin
polymerization. Conversely, disruption of the interaction of N-WASP with
GRB2 and/or the barbed ends of actin filaments increases its exchange
rate and results in a faster rate of virus movement. Weisswange et al.
(2009) suggested that the exchange rate of N-WASP controls the rate of
ARP2/3 complex-dependent actin-based motility by regulating the extent
of actin polymerization by antagonizing filament capping.
Nolen et al. (2009) described 2 classes of small molecules that bind to
different sites on the Arp2/3 complex and inhibit its ability to
nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where
it appears to block movement of Arp2 and Arp3 into their active
conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and
alters its conformation. Both classes of compounds inhibit formation of
actin filament comet tails by Listeria and podosomes by monocytes.
Using immunofluorescence microscopy, Western blot analysis, and
knockdown strategies with human lung fibroblasts, Hanisch et al. (2011)
showed that Salmonella entered nonphagocytic cells by manipulating 2
machineries of actin-based motility in the host: actin polymerization
through the ARP2/3 complex, and actomyosin-mediated contractility in a
myosin IIA (MYH9; 160775)- and myosin IIB (MYH10; 160776)-dependent
manner. Hanisch et al. (2011) concluded that Salmonella entry can be
effected independently of membrane ruffling.
Li et al. (2012) showed that interactions between diverse synthetic,
multivalent macromolecules (including multidomain proteins and RNA)
produce sharp liquid-liquid-demixing phase separations, generating
micrometer-sized liquid droplets in aqueous solution. This macroscopic
transition corresponds to a molecular transition between small complexes
and large, dynamic supramolecular polymers. The concentrations needed
for phase transition are directly related to the valency of the
interacting species. In the case of the actin-regulatory protein N-WASP
(605056) interacting with its established biologic partners NCK (600508)
and phosphorylated nephrin (602716), the phase transition corresponds to
a sharp increase in activity towards an actin nucleation factor, the
ARP2/3 complex. The transition is governed by the degree of
phosphorylation of nephrin, explaining how this property of the system
can be controlled to regulatory effect by kinases. Li et al. (2012)
concluded that the widespread occurrence of multivalent systems suggests
that phase transitions may be used to spatially organize and
biochemically regulate information throughout biology.
BIOCHEMICAL FEATURES
Volkmann et al. (2001) performed electron cryomicroscopy and
3-dimensional reconstruction of Acanthamoeba castellanii and S.
cerevisiae Arp2/3 complexes bound to the WASP (301000) carboxy-terminal
domain. Asymmetric, oblate ellipsoids were revealed. Image analysis of
actin branches indicated that the complex binds the side of the mother
filament, and ARP2 and ARP3 are the first 2 subunits of the daughter
filament. Comparison to the actin-free WASP-activated complexes suggests
that branch initiation involves large-scale structural rearrangements
within ARP2/3.
Robinson et al. (2001) determined the crystal structure of bovine ARP2/3
complex at 2.0-angstrom resolution. ARP2 and ARP3 are folded like actin,
with distinctive surface features. Subunits ARPC2 and ARPC4 in the core
of the complex associate through long carboxy-terminal alpha helices and
have similarly folded amino-terminal alpha/beta domains. ARPC1 is a
7-blade beta propeller with an insertion that may associate with the
side of an actin filament. ARPC3 and ARPC5 are globular alpha-helical
subunits. Robinson et al. (2001) predicted that WASP/SCAR proteins
activate ARP2/3 complex by bringing ARP2 into proximity with ARP3 for
nucleation of a branch on the side of a preexisting actin filament.
*FIELD* RF
1. Hanisch, J.; Kolm, R.; Wozniczka, M.; Bumann, D.; Rottner, K.;
Stradal, T. E. B.: Activation of a RhoA/myosin II-dependent but Arp2/3
complex-independent pathway facilitates Salmonella invasion. Cell
Host Microbe 9: 273-285, 2011.
2. Leisel, T. P.; Boujemaa, R.; Pantaloni, D.; Carlier, M.-F.: Reconstitution
of actin-based motility of Listeria and Shigella using pure proteins. Nature 401:
613-616, 1999.
3. Li, P.; Banjade, S.; Cheng, H.-C.; Kim, S.; Chen, B.; Guo, L.;
Llaguno, M.; Hollingsworth, J. V.; King, D. S.; Banani, S. F.; Russo,
P. S.; Jiang, Q.-X.; Nixon, B. T.; Rosen, M. K.: Phase transitions
in the assembly of multivalent signalling proteins. Nature 483:
336-340, 2012.
4. Machesky, L. M.; Reeves, E.; Wientjes, F.; Mattheyse, F. J.; Grogan,
A.; Totty, N. F.; Burlingame, A. L.; Hsuan, J. J.; Segal, A. W.:
Mammalian actin-related protein 2/3 complex localizes to regions of
lamellipodial protrusion and is composed of evolutionarily conserved
proteins. Biochem. J. 328: 105-112, 1997.
5. Marchand, J.-B.; Kaiser, D. A.; Pollard, T. D.; Higgs, H. N.:
Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3
complex. Nature Cell Biol. 3: 76-82, 2001.
6. Nolen, B. J.; Tomasevic, N.; Russell, A.; Pierce, D. W.; Jia, Z.;
McCormick, C. D.; Hartman, J.; Sakowicz, R.; Pollard, T. D.: Characterization
of two classes of small molecule inhibitors of Arp2/3 complex. Nature 460:
1031-1034, 2009.
7. Prehoda, K. E.; Scott, J. A.; Mullins, R. D.; Lim, W. A.: Integration
of multiple signals through cooperative regulation of the N-WASP-Arp2/3
complex. Science 290: 801-806, 2000.
8. Robinson, R. C.; Turbedsky, K.; Kaiser, D. A.; Marchand, J.-B.;
Higgs, H. N.; Choe, S.; Pollard, T. D.: Crystal structure of Arp2/3
complex. Science 294: 1679-1684, 2001.
9. Volkmann, N.; Amann, K. J.; Stoilova-McPhie, S.; Egile, C.; Winter,
D. C.; Hazelwood, L.; Heuser, J. E.; Li, R.; Pollard, T. D.; Hanein,
D.: Structure of Arp2/3 complex in its activated state and in actin
filament branch junctions. Science 293: 2456-2459, 2001.
10. Weisswange, I.; Newsome, T. P.; Schleich, S.; Way, M.: The rate
of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based
motility. Nature 458: 87-91, 2009.
11. Welch, M. D.; DePace, A. H.; Verma, S.; Iwamatsu, A.; Mitchison,
T. J.: The human Arp2/3 complex is composed of evolutionarily conserved
subunits and is localized to cellular regions of dynamic actin filament
assembly. J. Cell Biol. 138: 375-384, 1997.
12. Welch, M. D.; Iwamatsu, A.; Mitchison, T. J.: Actin polymerization
is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 385:
265-269, 1997.
*FIELD* CN
Ada Hamosh - updated: 4/16/2012
Paul J. Converse - updated: 3/1/2012
Ada Hamosh - updated: 9/15/2009
Ada Hamosh - updated: 4/2/2009
Paul J. Converse - updated: 2/21/2002
Ada Hamosh - updated: 1/10/2002
Ada Hamosh - updated: 10/11/2001
Ada Hamosh - updated: 11/7/2000
Patti M. Sherman - updated: 10/29/1999
Ada Hamosh - updated: 10/12/1999
*FIELD* CD
Patti M. Sherman: 10/8/1999
*FIELD* ED
alopez: 04/17/2012
terry: 4/16/2012
mgross: 3/2/2012
terry: 3/1/2012
alopez: 9/15/2009
terry: 9/15/2009
alopez: 4/3/2009
terry: 4/2/2009
mgross: 2/21/2002
alopez: 1/10/2002
alopez: 10/11/2001
mgross: 11/7/2000
mgross: 11/1/1999
psherman: 10/29/1999
mgross: 10/15/1999
psherman: 10/13/1999
alopez: 10/12/1999
psherman: 10/11/1999
*RECORD*
*FIELD* NO
604221
*FIELD* TI
*604221 ACTIN-RELATED PROTEIN 2; ACTR2
;;ARP2
ARP2/3 COMPLEX, INCLUDED
*FIELD* TX
read moreCLONING
The protrusion of the cell membrane is fundamental to cell shape change
and locomotion. Actin polymerization (see 102560) plays a critical role
in this process. The leading edge of motile cells is dominated by thin
actin-rich structures called lamellipodia, which exhibit highly dynamic
behavior characterized by rapid extension and retraction. Many aspects
of the mechanism of lamellipodial protrusion are echoed in the
intracellular motility of certain bacterial and viral pathogens, such as
the bacterium Listeria monocytogenes. Welch et al. (1997) purified an
approximately 220-kD multiprotein complex from human platelets that
induces actin polymerization at the L. monocytogenes cell surface and
mediates bacterial motility. This complex contains actin-related
proteins (Arps) in the Arp2 and Arp3 families and therefore was named
the Arp2/3 complex. In addition to 43-kD ARP2 and 50-kD ARP3 (ACTR3;
604222), the human complex consists of 41/40- (ARPC1B; 604223), 34-
(ARPC2; 604224), 21- (ARPC3; 604225), 20- (ARPC4; 604226), and 16-kD
(ARPC5; 604227) subunits, all present in approximately equal
stoichiometry. By searching an EST database with peptide sequences from
the 7 subunits of the human ARP2/3 complex, Welch et al. (1997)
identified full-length human cDNAs encoding each subunit. The ARP2 cDNA
encodes a deduced 394-amino acid protein that is 99% identical to
chicken Arp2 and 67% identical to S. cerevisiae Arp2. Welch et al.
(1997) localized several subunits of the ARP2/3 complex to the
lamellipodia of stationary and locomoting fibroblasts, as well as to the
actin tails assembled by L. monocytogenes. They suggested that the
ARP2/3 complex promotes actin assembly in lamellipodia and may
participate in lamellipodial protrusion.
Machesky et al. (1997) purified the ARP2/3 complex from human
neutrophils and sequenced peptides from each of the subunits.
GENE FUNCTION
Leisel et al. (1999) used pure components of the actin cytoskeleton to
reconstitute sustained movement in Listeria and Shigella in vitro.
Actin-based propulsion was driven by the free energy released by ATP
hydrolysis linked to actin polymerization and did not require myosin
(see 601478). In addition to actin and activated Arp2/3 complex, actin
depolymerizing factor and capping protein (see 601571) were also
required for motility as they maintained a high steady-state level of
G-actin (see 102610), which controls the rate of unidirectional growth
of actin filaments at the surface of the bacterium. The movement was
more effective when profilin (see 176610), alpha-actinin (see 102575),
and, in the case of Listeria, VASP (601703) were also included.
The protein N-WASP (WASL; 605056) regulates actin polymerization by
stimulating the actin-nucleating activity of the Arp2/3 complex. N-WASP
is tightly regulated by multiple signals; only costimulation by CDC42
(116952) and phosphatidylinositol (4,5)-bisphosphate (PIP2) yields
potent polymerization. Prehoda et al. (2000) found that regulation
requires N-WASP's constitutively active output domain
(verprolin/cofilin/acidic (VCA) domain) and 2 regulatory domains, a
CDC42-binding domain and a PIP2-binding domain. In the absence of
stimuli, the regulatory modules together hold the VCA-Arp2/3 complex in
an inactive 'closed' conformation. In this state, both the CDC42- and
PIP2-binding sites are masked. Binding of either input destabilizes the
closed state and enhances binding of the other input. This cooperative
activation mechanism shows how combinations of simple binding domains
can be used to integrate and amplify coincident signals.
Using fluorescence anisotropy analysis, Marchand et al. (2001) showed
that efficient actin nucleation requires both recruitment of an actin
monomer to the ARP2/3 complex and a subsequent activation step. The
initial steps in this pathway involve binding by the WA domain of
WASP/SCAR (605035) proteins, which consists of a WH2 motif (W) that
binds to the actin monomers and an acidic tail (A) that binds to the
ARP2/3 complex. Actin filaments seem to stimulate nucleation by
enhancing binding of WA to the ARP2/3 complex and favoring the formation
of a productive nucleus.
Weisswange et al. (2009) analyzed the dynamics of N-WASP,
WASP-interacting protein (WIP; 602357), GRB2 (108355), and NCK (600508),
which are required to stimulate ARP2/3 complex-dependent actin-based
motility of vaccinia virus, using fluorescence recovery after
photobleaching. Weisswange et al. (2009) showed that all 4 proteins are
rapidly exchanging, albeit at different rates, and that the turnover of
N-WASP depends on its ability to stimulate ARP2/3 complex-mediated actin
polymerization. Conversely, disruption of the interaction of N-WASP with
GRB2 and/or the barbed ends of actin filaments increases its exchange
rate and results in a faster rate of virus movement. Weisswange et al.
(2009) suggested that the exchange rate of N-WASP controls the rate of
ARP2/3 complex-dependent actin-based motility by regulating the extent
of actin polymerization by antagonizing filament capping.
Nolen et al. (2009) described 2 classes of small molecules that bind to
different sites on the Arp2/3 complex and inhibit its ability to
nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where
it appears to block movement of Arp2 and Arp3 into their active
conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and
alters its conformation. Both classes of compounds inhibit formation of
actin filament comet tails by Listeria and podosomes by monocytes.
Using immunofluorescence microscopy, Western blot analysis, and
knockdown strategies with human lung fibroblasts, Hanisch et al. (2011)
showed that Salmonella entered nonphagocytic cells by manipulating 2
machineries of actin-based motility in the host: actin polymerization
through the ARP2/3 complex, and actomyosin-mediated contractility in a
myosin IIA (MYH9; 160775)- and myosin IIB (MYH10; 160776)-dependent
manner. Hanisch et al. (2011) concluded that Salmonella entry can be
effected independently of membrane ruffling.
Li et al. (2012) showed that interactions between diverse synthetic,
multivalent macromolecules (including multidomain proteins and RNA)
produce sharp liquid-liquid-demixing phase separations, generating
micrometer-sized liquid droplets in aqueous solution. This macroscopic
transition corresponds to a molecular transition between small complexes
and large, dynamic supramolecular polymers. The concentrations needed
for phase transition are directly related to the valency of the
interacting species. In the case of the actin-regulatory protein N-WASP
(605056) interacting with its established biologic partners NCK (600508)
and phosphorylated nephrin (602716), the phase transition corresponds to
a sharp increase in activity towards an actin nucleation factor, the
ARP2/3 complex. The transition is governed by the degree of
phosphorylation of nephrin, explaining how this property of the system
can be controlled to regulatory effect by kinases. Li et al. (2012)
concluded that the widespread occurrence of multivalent systems suggests
that phase transitions may be used to spatially organize and
biochemically regulate information throughout biology.
BIOCHEMICAL FEATURES
Volkmann et al. (2001) performed electron cryomicroscopy and
3-dimensional reconstruction of Acanthamoeba castellanii and S.
cerevisiae Arp2/3 complexes bound to the WASP (301000) carboxy-terminal
domain. Asymmetric, oblate ellipsoids were revealed. Image analysis of
actin branches indicated that the complex binds the side of the mother
filament, and ARP2 and ARP3 are the first 2 subunits of the daughter
filament. Comparison to the actin-free WASP-activated complexes suggests
that branch initiation involves large-scale structural rearrangements
within ARP2/3.
Robinson et al. (2001) determined the crystal structure of bovine ARP2/3
complex at 2.0-angstrom resolution. ARP2 and ARP3 are folded like actin,
with distinctive surface features. Subunits ARPC2 and ARPC4 in the core
of the complex associate through long carboxy-terminal alpha helices and
have similarly folded amino-terminal alpha/beta domains. ARPC1 is a
7-blade beta propeller with an insertion that may associate with the
side of an actin filament. ARPC3 and ARPC5 are globular alpha-helical
subunits. Robinson et al. (2001) predicted that WASP/SCAR proteins
activate ARP2/3 complex by bringing ARP2 into proximity with ARP3 for
nucleation of a branch on the side of a preexisting actin filament.
*FIELD* RF
1. Hanisch, J.; Kolm, R.; Wozniczka, M.; Bumann, D.; Rottner, K.;
Stradal, T. E. B.: Activation of a RhoA/myosin II-dependent but Arp2/3
complex-independent pathway facilitates Salmonella invasion. Cell
Host Microbe 9: 273-285, 2011.
2. Leisel, T. P.; Boujemaa, R.; Pantaloni, D.; Carlier, M.-F.: Reconstitution
of actin-based motility of Listeria and Shigella using pure proteins. Nature 401:
613-616, 1999.
3. Li, P.; Banjade, S.; Cheng, H.-C.; Kim, S.; Chen, B.; Guo, L.;
Llaguno, M.; Hollingsworth, J. V.; King, D. S.; Banani, S. F.; Russo,
P. S.; Jiang, Q.-X.; Nixon, B. T.; Rosen, M. K.: Phase transitions
in the assembly of multivalent signalling proteins. Nature 483:
336-340, 2012.
4. Machesky, L. M.; Reeves, E.; Wientjes, F.; Mattheyse, F. J.; Grogan,
A.; Totty, N. F.; Burlingame, A. L.; Hsuan, J. J.; Segal, A. W.:
Mammalian actin-related protein 2/3 complex localizes to regions of
lamellipodial protrusion and is composed of evolutionarily conserved
proteins. Biochem. J. 328: 105-112, 1997.
5. Marchand, J.-B.; Kaiser, D. A.; Pollard, T. D.; Higgs, H. N.:
Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3
complex. Nature Cell Biol. 3: 76-82, 2001.
6. Nolen, B. J.; Tomasevic, N.; Russell, A.; Pierce, D. W.; Jia, Z.;
McCormick, C. D.; Hartman, J.; Sakowicz, R.; Pollard, T. D.: Characterization
of two classes of small molecule inhibitors of Arp2/3 complex. Nature 460:
1031-1034, 2009.
7. Prehoda, K. E.; Scott, J. A.; Mullins, R. D.; Lim, W. A.: Integration
of multiple signals through cooperative regulation of the N-WASP-Arp2/3
complex. Science 290: 801-806, 2000.
8. Robinson, R. C.; Turbedsky, K.; Kaiser, D. A.; Marchand, J.-B.;
Higgs, H. N.; Choe, S.; Pollard, T. D.: Crystal structure of Arp2/3
complex. Science 294: 1679-1684, 2001.
9. Volkmann, N.; Amann, K. J.; Stoilova-McPhie, S.; Egile, C.; Winter,
D. C.; Hazelwood, L.; Heuser, J. E.; Li, R.; Pollard, T. D.; Hanein,
D.: Structure of Arp2/3 complex in its activated state and in actin
filament branch junctions. Science 293: 2456-2459, 2001.
10. Weisswange, I.; Newsome, T. P.; Schleich, S.; Way, M.: The rate
of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based
motility. Nature 458: 87-91, 2009.
11. Welch, M. D.; DePace, A. H.; Verma, S.; Iwamatsu, A.; Mitchison,
T. J.: The human Arp2/3 complex is composed of evolutionarily conserved
subunits and is localized to cellular regions of dynamic actin filament
assembly. J. Cell Biol. 138: 375-384, 1997.
12. Welch, M. D.; Iwamatsu, A.; Mitchison, T. J.: Actin polymerization
is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 385:
265-269, 1997.
*FIELD* CN
Ada Hamosh - updated: 4/16/2012
Paul J. Converse - updated: 3/1/2012
Ada Hamosh - updated: 9/15/2009
Ada Hamosh - updated: 4/2/2009
Paul J. Converse - updated: 2/21/2002
Ada Hamosh - updated: 1/10/2002
Ada Hamosh - updated: 10/11/2001
Ada Hamosh - updated: 11/7/2000
Patti M. Sherman - updated: 10/29/1999
Ada Hamosh - updated: 10/12/1999
*FIELD* CD
Patti M. Sherman: 10/8/1999
*FIELD* ED
alopez: 04/17/2012
terry: 4/16/2012
mgross: 3/2/2012
terry: 3/1/2012
alopez: 9/15/2009
terry: 9/15/2009
alopez: 4/3/2009
terry: 4/2/2009
mgross: 2/21/2002
alopez: 1/10/2002
alopez: 10/11/2001
mgross: 11/7/2000
mgross: 11/1/1999
psherman: 10/29/1999
mgross: 10/15/1999
psherman: 10/13/1999
alopez: 10/12/1999
psherman: 10/11/1999