ARPC4_HUMAN
ID ARPC4_HUMAN Reviewed; 168 AA.
AC P59998; C9JWM7; E7ETI0; F6TTL5; O15509; Q6P0W5; Q96QJ3;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Actin-related protein 2/3 complex subunit 4;
DE AltName: Full=Arp2/3 complex 20 kDa subunit;
DE Short=p20-ARC;
GN Name=ARPC4; Synonyms=ARC20;
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] (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN THE ARP2/2 COMPLEX.
RX PubMed=9359840; DOI=10.1042/bj3280105;
RA Machesky L.M., Reeves E., Wientjes F., Mattheyse F.J., Grogan A.,
RA Totty N.F., Burlingame A.L., Hsuan J.J., Segal A.W.;
RT "Mammalian actin-related protein 2/3 complex localizes to regions of
RT lamellipodial protrusion and is composed of evolutionarily conserved
RT proteins.";
RL Biochem. J. 328:105-112(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND IDENTIFICATION IN THE ARP2/2
RP COMPLEX.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2-168 (ISOFORM 1).
RC TISSUE=Choriocarcinoma, and Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 2-13, AND ACETYLATION AT THR-2.
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 [7]
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 [8]
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).
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). In addition to
CC its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also
CC promotes 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. {ECO:0000269|PubMed:11741539,
CC ECO:0000269|PubMed:9230079, ECO:0000269|PubMed:9359840}.
CC -!- INTERACTION:
CC P59998; O15145: ARPC3; NbExp=4; IntAct=EBI-351872, EBI-351829;
CC P59998; Q9BPX5: ARPC5L; NbExp=7; IntAct=EBI-351872, EBI-711189;
CC P59998; Q8WXB1: METTL21A; NbExp=3; IntAct=EBI-351872, EBI-8652459;
CC P59998; Q96PV4: PNMA5; NbExp=7; IntAct=EBI-351872, EBI-10171633;
CC P59998; O00401: WASL; NbExp=3; IntAct=EBI-351872, EBI-957615;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9359840}. Cell projection
CC {ECO:0000269|PubMed:9359840}. Nucleus {ECO:0000269|PubMed:29925947}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P59998-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P59998-2; Sequence=VSP_046151;
CC Name=3;
CC IsoId=P59998-3; Sequence=VSP_046150;
CC Name=4;
CC IsoId=P59998-4; Sequence=VSP_046753;
CC -!- SIMILARITY: Belongs to the ARPC4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH12596.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF019888; AAB71548.1; -; mRNA.
DR EMBL; AF006087; AAB64192.1; -; mRNA.
DR EMBL; BX419672; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC022382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012596; AAH12596.3; ALT_INIT; mRNA.
DR EMBL; BC025289; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS43047.1; -. [P59998-1]
DR CCDS; CCDS46743.1; -. [P59998-4]
DR CCDS; CCDS56238.1; -. [P59998-3]
DR RefSeq; NP_001020130.1; NM_001024959.2. [P59998-4]
DR RefSeq; NP_001020131.1; NM_001024960.2. [P59998-4]
DR RefSeq; NP_001185709.1; NM_001198780.1. [P59998-3]
DR RefSeq; NP_005709.1; NM_005718.4. [P59998-1]
DR PDB; 6UHC; EM; 3.90 A; F=1-168.
DR PDB; 6YW6; EM; 4.20 A; F=1-168.
DR PDB; 6YW7; EM; 4.50 A; F=1-168.
DR PDBsum; 6UHC; -.
DR PDBsum; 6YW6; -.
DR PDBsum; 6YW7; -.
DR AlphaFoldDB; P59998; -.
DR SMR; P59998; -.
DR BioGRID; 115400; 131.
DR BioGRID; 1529294; 21.
DR CORUM; P59998; -.
DR DIP; DIP-33188N; -.
DR IntAct; P59998; 65.
DR MINT; P59998; -.
DR STRING; 9606.ENSP00000388169; -.
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; P59998; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P59998; -.
DR MetOSite; P59998; -.
DR PhosphoSitePlus; P59998; -.
DR SwissPalm; P59998; -.
DR BioMuta; ARPC4; -.
DR DMDM; 38372625; -.
DR EPD; P59998; -.
DR jPOST; P59998; -.
DR MassIVE; P59998; -.
DR MaxQB; P59998; -.
DR PaxDb; P59998; -.
DR PeptideAtlas; P59998; -.
DR PRIDE; P59998; -.
DR ProteomicsDB; 12011; -.
DR ProteomicsDB; 18209; -.
DR ProteomicsDB; 27989; -.
DR ProteomicsDB; 57176; -. [P59998-1]
DR TopDownProteomics; P59998-1; -. [P59998-1]
DR Antibodypedia; 34895; 218 antibodies from 30 providers.
DR DNASU; 10093; -.
DR Ensembl; ENST00000397261.8; ENSP00000380431.2; ENSG00000241553.13. [P59998-1]
DR Ensembl; ENST00000433034.1; ENSP00000388169.1; ENSG00000241553.13. [P59998-3]
DR Ensembl; ENST00000498623.6; ENSP00000432235.1; ENSG00000241553.13. [P59998-4]
DR GeneID; 10093; -.
DR KEGG; hsa:10093; -.
DR MANE-Select; ENST00000397261.8; ENSP00000380431.2; NM_005718.5; NP_005709.1.
DR UCSC; uc003bsz.3; human. [P59998-1]
DR CTD; 10093; -.
DR DisGeNET; 10093; -.
DR GeneCards; ARPC4; -.
DR HGNC; HGNC:707; ARPC4.
DR HPA; ENSG00000241553; Low tissue specificity.
DR MIM; 604226; gene.
DR neXtProt; NX_P59998; -.
DR OpenTargets; ENSG00000241553; -.
DR PharmGKB; PA25002; -.
DR VEuPathDB; HostDB:ENSG00000241553; -.
DR eggNOG; KOG1876; Eukaryota.
DR GeneTree; ENSGT00390000016233; -.
DR GeneTree; ENSGT00940000154857; -.
DR HOGENOM; CLU_187809_0_0_1; -.
DR InParanoid; P59998; -.
DR OMA; EAYLGEF; -.
DR PhylomeDB; P59998; -.
DR TreeFam; TF105621; -.
DR TreeFam; TF313087; -.
DR PathwayCommons; P59998; -.
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; P59998; -.
DR SIGNOR; P59998; -.
DR BioGRID-ORCS; 10093; 607 hits in 1072 CRISPR screens.
DR GeneWiki; ARPC4; -.
DR GenomeRNAi; 10093; -.
DR Pharos; P59998; Tbio.
DR PRO; PR:P59998; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P59998; protein.
DR Bgee; ENSG00000241553; Expressed in monocyte and 199 other tissues.
DR ExpressionAtlas; P59998; baseline and differential.
DR Genevisible; P59998; HS.
DR GO; GO:0005885; C:Arp2/3 protein complex; IDA:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IDA:FlyBase.
DR GO; GO:0030041; P:actin filament polymerization; IEA:InterPro.
DR GO; GO:0045010; P:actin nucleation; NAS:UniProtKB.
DR GO; GO:0034314; P:Arp2/3 complex-mediated actin nucleation; IDA:FlyBase.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IEA:InterPro.
DR Gene3D; 3.30.1460.20; -; 1.
DR InterPro; IPR034666; ARPC2/4.
DR InterPro; IPR008384; ARPC4.
DR PANTHER; PTHR22629; PTHR22629; 1.
DR Pfam; PF05856; ARPC4; 1.
DR PIRSF; PIRSF039100; ARPC4; 1.
DR SUPFAM; SSF69645; SSF69645; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing;
KW Cell projection; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CHAIN 2..168
FT /note="Actin-related protein 2/3 complex subunit 4"
FT /id="PRO_0000124049"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|PubMed:12665801"
FT VAR_SEQ 1..90
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_046753"
FT VAR_SEQ 1
FT /note="M -> MVREPGPRPGTPGCSASGQW (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_046150"
FT VAR_SEQ 110..168
FT /note="EGYDISFLITNFHTEQMYKHKLVDFVIHFMEEIDKEISEMKLSVNARARIVA
FT EEFLKNF -> EQKKIFTIQGCYPVIRCLLRRRGWVEKKMVHRSGPTLLPPQKDLDSSA
FT MGDSDTTEDEDEDEDEEFQPSQLFDFDDLLKFDDLDGTHALMVGLCLNLRNLPWFDEVD
FT ANSFFPRCYCLGAEDDKKAFIGDKQPKKQEKNPVLVSPEFVDEALCACEEYLSNLAHMD
FT IDKDLEAPLYLTPEGWSLFLQRYYQVVHEGAELRHLDTQVQRCEDILQQLQAVVPQIDM
FT EGDRNIWIVKPGAKSRGRGIMCMDHLEEMLKLVNGNPVVMKDGKWVVQKYIERPLLIFG
FT TKFDLRQWFLVTDWNPLTVWFYRDSYIRFSTQPFSLKNLDNSVHLCNNSIQKHLENSCH
FT RHPLLPPDNMWSSQRFQAHLQEMGAPNAWSTIIVPGMKDAVIHALQTSQDTVQCRKASF
FT ELYGADFVFGEDFQPWLIEINASPTMAPSTAVTARLCAGVQADTLRVVIDRMLDRNCDT
FT GAFELIYKQPVTTSPASTPRPSCLLPMYSDTRARSSDDSTASWWALRPCRPQARP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046151"
FT CONFLICT 94
FT /note="M -> T (in Ref. 5; AAH12596)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 168 AA; 19667 MW; 273CCB230AC703DF CRC64;
MTATLRPYLS AVRATLQAAL CLENFSSQVV ERHNKPEVEV RSSKELLLQP VTISRNEKEK
VLIEGSINSV RVSIAVKQAD EIEKILCHKF MRFMMMRAEN FFILRRKPVE GYDISFLITN
FHTEQMYKHK LVDFVIHFME EIDKEISEMK LSVNARARIV AEEFLKNF
