ARPC2_HUMAN
ID ARPC2_HUMAN Reviewed; 300 AA.
AC O15144; Q92801; Q9P1D4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Actin-related protein 2/3 complex subunit 2;
DE AltName: Full=Arp2/3 complex 34 kDa subunit;
DE Short=p34-ARC;
GN Name=ARPC2; Synonyms=ARC34; ORFNames=PRO2446;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION IN THE ARP2/2 COMPLEX, AND
RP SUBCELLULAR LOCATION.
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 subunits
RT and is localized to cellular regions of dynamic actin filament assembly.";
RL J. Cell Biol. 138:375-384(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8812419; DOI=10.1006/geno.1996.0428;
RA Couch F.J., Rommens J.M., Neuhausen S.L., Belanger C., Dumont M.,
RA Kenneth A., Bell R., Berry S., Bogden R., Cannon-Albright L., Farid L.,
RA Frye C., Hattier T., Janecki T., Jiang P., Kehrer R., Leblanc J.F.,
RA McArthur-Morrison J., McSweeney D., Miki Y., Peng Y., Samson C.,
RA Schroeder M., Snyder S.C., Stringfellow M., Stroup C., Swedlund B.,
RA Swensen J., Teng D., Thakur S., Tran T., Tranchant M., Welver-Feldhaus J.,
RA Wong A.K.C., Shizuya H., Labrie F., Skolnick M.H., Goldgar D.E., Kamb A.,
RA Weber B.L., Tavtigian S.V., Simard J.;
RT "Generation of an integrated transcription map of the BRCA2 region on
RT chromosome 13q12-q13.";
RL Genomics 36:86-99(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-9.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 25-290.
RC TISSUE=Fetal liver;
RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J.,
RA Liu M., He F.;
RT "Functional prediction of the coding sequences of 121 new genes deduced by
RT analysis of cDNA clones from human fetal liver.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 191-203, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP ACTIN-BINDING, AND 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-275 AND LYS-295, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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., Buerckstuemmer T.,
RA 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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29925947; DOI=10.1038/s41586-018-0237-5;
RA Schrank B.R., Aparicio T., Li Y., Chang W., Chait B.T., Gundersen G.G.,
RA Gottesman M.E., Gautier J.;
RT "Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.";
RL Nature 559:61-66(2018).
RN [15]
RP INTERACTION WITH DNAI3.
RX PubMed=32128961; DOI=10.15252/embr.201949269;
RA Zhao K., Wang D., Zhao X., Wang C., Gao Y., Liu K., Wang F., Wu X.,
RA Wang X., Sun L., Zang J., Mei Y.;
RT "WDR63 inhibits Arp2/3-dependent actin polymerization and mediates the
RT function of p53 in suppressing metastasis.";
RL EMBO Rep. 21:e49269-e49269(2020).
CC -!- FUNCTION: Actin-binding component of the Arp2/3 complex, a multiprotein
CC complex that mediates actin polymerization upon stimulation by
CC nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex
CC mediates the formation of branched actin networks in the cytoplasm,
CC providing the force for cell motility (PubMed:9230079). Seems to
CC contact the mother actin filament (PubMed:9230079). In addition to its
CC role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes
CC actin polymerization in the nucleus, thereby regulating gene
CC transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3
CC complex promotes homologous recombination (HR) repair in response to
CC DNA damage by promoting nuclear actin polymerization, leading to drive
CC motility of double-strand breaks (DSBs) (PubMed:29925947).
CC {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}.
CC -!- SUBUNIT: Component of the Arp2/3 complex composed of ACTR2/ARP2,
CC ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC
CC and ARPC5/p16-ARC (PubMed:9230079, PubMed:11741539). Interacts with
CC SHANK3; the interaction probably mediates the association of SHANK3
CC with the Arp2/3 complex (By similarity). Interacts with DNAI3; this
CC interaction reduces binding of the Arp2/3 complex to the VCA domain of
CC nucleation promoting factors (PubMed:32128961).
CC {ECO:0000250|UniProtKB:Q9CVB6, ECO:0000269|PubMed:11741539,
CC ECO:0000269|PubMed:32128961, ECO:0000269|PubMed:9230079}.
CC -!- INTERACTION:
CC O15144; Q7Z6K5-1: ARPIN; NbExp=2; IntAct=EBI-352356, EBI-16079078;
CC O15144; Q9BR76: CORO1B; NbExp=2; IntAct=EBI-352356, EBI-351152;
CC O15144; Q16236: NFE2L2; NbExp=5; IntAct=EBI-352356, EBI-2007911;
CC O15144; P18206: VCL; NbExp=2; IntAct=EBI-352356, EBI-716775;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9230079}. Cell projection
CC {ECO:0000269|PubMed:9230079}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q9CVB6}. Nucleus {ECO:0000269|PubMed:29925947}.
CC -!- SIMILARITY: Belongs to the ARPC2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50874.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF71122.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF006085; AAB64190.1; -; mRNA.
DR EMBL; U50523; AAC50874.1; ALT_FRAME; mRNA.
DR EMBL; BT006898; AAP35544.1; -; mRNA.
DR EMBL; BC000590; AAH00590.1; -; mRNA.
DR EMBL; AF116702; AAF71122.1; ALT_INIT; mRNA.
DR CCDS; CCDS2410.1; -.
DR RefSeq; NP_005722.1; NM_005731.3.
DR RefSeq; NP_690601.1; NM_152862.2.
DR PDB; 6UHC; EM; 3.90 A; D=1-300.
DR PDB; 6YW6; EM; 4.20 A; D=1-300.
DR PDB; 6YW7; EM; 4.50 A; D=1-300.
DR PDBsum; 6UHC; -.
DR PDBsum; 6YW6; -.
DR PDBsum; 6YW7; -.
DR AlphaFoldDB; O15144; -.
DR SMR; O15144; -.
DR BioGRID; 115415; 140.
DR CORUM; O15144; -.
DR DIP; DIP-33197N; -.
DR IntAct; O15144; 62.
DR MINT; O15144; -.
DR STRING; 9606.ENSP00000295685; -.
DR ChEMBL; CHEMBL4295657; -.
DR DrugBank; DB08236; (2S)-2-(3-bromophenyl)-3-(5-chloro-2-hydroxyphenyl)-1,3-thiazolidin-4-one.
DR DrugBank; DB08235; N-[2-(2-methyl-1H-indol-3-yl)ethyl]thiophene-2-carboxamide.
DR GlyGen; O15144; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15144; -.
DR MetOSite; O15144; -.
DR PhosphoSitePlus; O15144; -.
DR SwissPalm; O15144; -.
DR BioMuta; ARPC2; -.
DR OGP; O15144; -.
DR CPTAC; CPTAC-1597; -.
DR CPTAC; CPTAC-167; -.
DR CPTAC; CPTAC-168; -.
DR EPD; O15144; -.
DR jPOST; O15144; -.
DR MassIVE; O15144; -.
DR MaxQB; O15144; -.
DR PaxDb; O15144; -.
DR PeptideAtlas; O15144; -.
DR PRIDE; O15144; -.
DR ProteomicsDB; 48469; -.
DR TopDownProteomics; O15144; -.
DR Antibodypedia; 1901; 373 antibodies from 37 providers.
DR DNASU; 10109; -.
DR Ensembl; ENST00000295685.14; ENSP00000295685.10; ENSG00000163466.16.
DR Ensembl; ENST00000315717.10; ENSP00000327137.5; ENSG00000163466.16.
DR GeneID; 10109; -.
DR KEGG; hsa:10109; -.
DR MANE-Select; ENST00000315717.10; ENSP00000327137.5; NM_152862.3; NP_690601.1.
DR CTD; 10109; -.
DR DisGeNET; 10109; -.
DR GeneCards; ARPC2; -.
DR HGNC; HGNC:705; ARPC2.
DR HPA; ENSG00000163466; Low tissue specificity.
DR MIM; 604224; gene.
DR neXtProt; NX_O15144; -.
DR OpenTargets; ENSG00000163466; -.
DR PharmGKB; PA24999; -.
DR VEuPathDB; HostDB:ENSG00000163466; -.
DR eggNOG; KOG2826; Eukaryota.
DR GeneTree; ENSGT00390000016794; -.
DR HOGENOM; CLU_059439_2_0_1; -.
DR InParanoid; O15144; -.
DR OMA; GPYIVSP; -.
DR OrthoDB; 1345377at2759; -.
DR PhylomeDB; O15144; -.
DR TreeFam; TF315006; -.
DR PathwayCommons; O15144; -.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; O15144; -.
DR SIGNOR; O15144; -.
DR BioGRID-ORCS; 10109; 342 hits in 1086 CRISPR screens.
DR ChiTaRS; ARPC2; human.
DR GeneWiki; ARPC2; -.
DR GenomeRNAi; 10109; -.
DR Pharos; O15144; Tbio.
DR PRO; PR:O15144; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O15144; protein.
DR Bgee; ENSG00000163466; Expressed in esophagus squamous epithelium and 206 other tissues.
DR ExpressionAtlas; O15144; baseline and differential.
DR Genevisible; O15144; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005885; C:Arp2/3 protein complex; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0036195; C:muscle cell projection membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IDA:FlyBase.
DR GO; GO:0030041; P:actin filament polymerization; IEA:InterPro.
DR GO; GO:0070358; P:actin polymerization-dependent cell motility; TAS:UniProtKB.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IDA:FlyBase.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR Gene3D; 3.30.1460.20; -; 2.
DR InterPro; IPR007188; ARPC2.
DR InterPro; IPR034666; ARPC2/4.
DR PANTHER; PTHR12058; PTHR12058; 1.
DR Pfam; PF04045; P34-Arc; 1.
DR SUPFAM; SSF69645; SSF69645; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Cell projection; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Nucleus; Reference proteome;
KW Synapse; Synaptosome.
FT CHAIN 1..300
FT /note="Actin-related protein 2/3 complex subunit 2"
FT /id="PRO_0000124033"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 295
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CONFLICT 72
FT /note="A -> C (in Ref. 2; AAC50874)"
FT /evidence="ECO:0000305"
FT CONFLICT 289..300
FT /note="MKTITGKTFSSR -> KI (in Ref. 6; AAF71122)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 300 AA; 34333 MW; 3BA57121BE9A05F2 CRC64;
MILLEVNNRI IEETLALKFE NAAAGNKPEA VEVTFADFDG VLYHISNPNG DKTKVMVSIS
LKFYKELQAH GADELLKRVY GSFLVNPESG YNVSLLYDLE NLPASKDSIV HQAGMLKRNC
FASVFEKYFQ FQEEGKEGEN RAVIHYRDDE TMYVESKKDR VTVVFSTVFK DDDDVVIGKV
FMQEFKEGRR ASHTAPQVLF SHREPPLELK DTDAAVGDNI GYITFVLFPR HTNASARDNT
INLIHTFRDY LHYHIKCSKA YIHTRMRAKT SDFLKVLNRA RPDAEKKEMK TITGKTFSSR
