ACTN4_MOUSE
ID ACTN4_MOUSE Reviewed; 912 AA.
AC P57780;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Alpha-actinin-4 {ECO:0000305};
DE AltName: Full=Non-muscle alpha-actinin 4 {ECO:0000305};
GN Name=Actn4 {ECO:0000312|MGI:MGI:1890773};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129;
RX PubMed=10964513; DOI=10.1006/geno.2000.6289;
RA Dear T.N., Meier N.T., Hunn M., Boehm T.;
RT "Gene structure, chromosomal localization and expression pattern of Capn12,
RT a new member of the calpain large subunit gene family.";
RL Genomics 68:152-160(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP PROTEIN SEQUENCE OF 85-96 AND 311-319, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP FUNCTION IN TIGHT JUNCTION ASSEMBLY, INTERACTION WITH MICALL2, SUBCELLULAR
RP LOCATION, AND REGION.
RX PubMed=18332111; DOI=10.1128/mcb.00144-08;
RA Nakatsuji H., Nishimura N., Yamamura R., Kanayama H.O., Sasaki T.;
RT "Involvement of actinin-4 in the recruitment of JRAB/MICAL-L2 to cell-cell
RT junctions and the formation of functional tight junctions.";
RL Mol. Cell. Biol. 28:3324-3335(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-780 AND LYS-860, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP INTERACTION WITH SEPTIN14, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=33228246; DOI=10.3390/biomedicines8110518;
RA Lin Y.H., Huang C.Y., Ke C.C., Wang Y.Y., Lai T.H., Liu H.C., Ku W.C.,
RA Chan C.C., Lin Y.H.;
RT "ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects.";
RL Biomedicines 8:0-0(2020).
CC -!- FUNCTION: F-actin cross-linking protein which is thought to anchor
CC actin to a variety of intracellular structures. This is a bundling
CC protein. Probably involved in vesicular trafficking via its association
CC with the CART complex. The CART complex is necessary for efficient
CC transferrin receptor recycling but not for EGFR degradation (By
CC similarity). Involved in tight junction assembly in epithelial cells
CC probably through interaction with MICALL2. Links MICALL2 to the actin
CC cytoskeleton and recruits it to the tight junctions (PubMed:18332111).
CC May also function as a transcriptional coactivator, stimulating
CC transcription mediated by the nuclear hormone receptors PPARG and RARA
CC (By similarity). {ECO:0000250|UniProtKB:O43707,
CC ECO:0000269|PubMed:18332111}.
CC -!- SUBUNIT: Homodimer; antiparallel. Interacts with MAGI1 (By similarity).
CC Interacts with PDLIM2 (By similarity). Identified in a complex with
CC CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity).
CC Identified in a IGF2BP1-dependent mRNP granule complex containing
CC untranslated mRNAs (By similarity). Component of the CART complex, at
CC least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity).
CC Binds TRIM3 at the N-terminus (By similarity). Interacts with MICALL2
CC (preferentially in opened conformation); stimulated by RAB13 activation
CC (PubMed:18332111). Interacts with PPARG and RARA (By similarity). Binds
CC to VCL; this interaction triggers VCL conformational changes (By
CC similarity). Interacts with SEPTIN14 (PubMed:33228246).
CC {ECO:0000250|UniProtKB:O43707, ECO:0000250|UniProtKB:Q9QXQ0,
CC ECO:0000269|PubMed:18332111, ECO:0000269|PubMed:33228246}.
CC -!- INTERACTION:
CC P57780; Q8K4E0: Alms1; NbExp=4; IntAct=EBI-445071, EBI-6272972;
CC P57780; Q3TN34: Micall2; NbExp=9; IntAct=EBI-445071, EBI-1779852;
CC P57780; P39447: Tjp1; NbExp=6; IntAct=EBI-445071, EBI-79508;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O43707}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43707}. Cell junction
CC {ECO:0000269|PubMed:18332111}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000250|UniProtKB:O43707}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:33228246}. Note=Localized in cytoplasmic mRNP
CC granules containing untranslated mRNAs. Expressed in the perinuclear
CC rim and manchette structure in early elongating spermatids during
CC spermiogenesis (PubMed:33228246). {ECO:0000250|UniProtKB:O43707,
CC ECO:0000269|PubMed:33228246}.
CC -!- DEVELOPMENTAL STAGE: Expressed in early elongating spermatids during
CC spermiogenesis. {ECO:0000269|PubMed:33228246}.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates
CC interaction with nuclear receptors. {ECO:0000250|UniProtKB:O43707}.
CC -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
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DR EMBL; AJ289242; CAC10069.1; -; mRNA.
DR EMBL; BC013616; AAH13616.1; -; mRNA.
DR EMBL; BC087554; AAH87554.1; -; mRNA.
DR CCDS; CCDS21061.1; -.
DR RefSeq; NP_068695.1; NM_021895.2.
DR AlphaFoldDB; P57780; -.
DR BMRB; P57780; -.
DR SMR; P57780; -.
DR BioGRID; 208624; 53.
DR CORUM; P57780; -.
DR IntAct; P57780; 20.
DR MINT; P57780; -.
DR STRING; 10090.ENSMUSP00000066068; -.
DR iPTMnet; P57780; -.
DR PhosphoSitePlus; P57780; -.
DR SwissPalm; P57780; -.
DR EPD; P57780; -.
DR jPOST; P57780; -.
DR PaxDb; P57780; -.
DR PeptideAtlas; P57780; -.
DR PRIDE; P57780; -.
DR ProteomicsDB; 285753; -.
DR Antibodypedia; 974; 431 antibodies from 42 providers.
DR DNASU; 60595; -.
DR Ensembl; ENSMUST00000068045; ENSMUSP00000066068; ENSMUSG00000054808.
DR GeneID; 60595; -.
DR KEGG; mmu:60595; -.
DR UCSC; uc009gah.1; mouse.
DR CTD; 81; -.
DR MGI; MGI:1890773; Actn4.
DR VEuPathDB; HostDB:ENSMUSG00000054808; -.
DR eggNOG; KOG0035; Eukaryota.
DR GeneTree; ENSGT00940000159343; -.
DR HOGENOM; CLU_005217_1_1_1; -.
DR InParanoid; P57780; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; P57780; -.
DR TreeFam; TF352676; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 60595; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Actn4; mouse.
DR PRO; PR:P57780; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P57780; protein.
DR Bgee; ENSMUSG00000054808; Expressed in substantia propria of cornea and 260 other tissues.
DR ExpressionAtlas; P57780; baseline and differential.
DR Genevisible; P57780; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031143; C:pseudopodium; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0001725; C:stress fiber; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0051015; F:actin filament binding; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISS:UniProtKB.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISO:MGI.
DR GO; GO:0001882; F:nucleoside binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051017; P:actin filament bundle assembly; IDA:UniProtKB.
DR GO; GO:0070830; P:bicellular tight junction assembly; IMP:UniProtKB.
DR GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; ISO:MGI.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0048549; P:positive regulation of pinocytosis; IMP:UniProtKB.
DR GO; GO:1902396; P:protein localization to bicellular tight junction; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903506; P:regulation of nucleic acid-templated transcription; ISO:MGI.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0030050; P:vesicle transport along actin filament; ISO:MGI.
DR CDD; cd00014; CH; 2.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00176; SPEC; 3.
DR Gene3D; 1.10.418.10; -; 2.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR014837; EF-hand_Ca_insen.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF08726; EFhand_Ca_insen; 1.
DR Pfam; PF00435; Spectrin; 4.
DR SMART; SM00033; CH; 2.
DR SMART; SM00054; EFh; 2.
DR SMART; SM00150; SPEC; 4.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW Acetylation; Actin-binding; Calcium; Cell junction; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Metal-binding; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport.
FT CHAIN 1..912
FT /note="Alpha-actinin-4"
FT /id="PRO_0000073441"
FT DOMAIN 51..155
FT /note="Calponin-homology (CH) 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 164..270
FT /note="Calponin-homology (CH) 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REPEAT 294..404
FT /note="Spectrin 1"
FT /evidence="ECO:0000255"
FT REPEAT 414..519
FT /note="Spectrin 2"
FT /evidence="ECO:0000255"
FT REPEAT 529..640
FT /note="Spectrin 3"
FT /evidence="ECO:0000255"
FT REPEAT 650..753
FT /note="Spectrin 4"
FT /evidence="ECO:0000255"
FT DOMAIN 766..801
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 807..842
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..267
FT /note="Actin-binding"
FT REGION 12..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 12..27
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 41..62
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 109..127
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 178..193
FT /note="Polyphosphoinositide (PIP2)-binding"
FT /evidence="ECO:0000255"
FT REGION 737..912
FT /note="Mediates interaction with MICALL2"
FT /evidence="ECO:0000269|PubMed:18332111"
FT MOTIF 85..89
FT /note="LXXLL motif"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT BINDING 779
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 781
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 790
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 32
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 115
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 593
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 626
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 780
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 860
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 910
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1P2"
SQ SEQUENCE 912 AA; 104977 MW; 07AA9C92AC228B5A CRC64;
MVDYHAANQA YQYGPNSGGG NGAGGGGSMG DYMAQEDDWD RDLLLDPAWE KQQRKTFTAW
CNSHLRKAGT QIENIDEDFR DGLKLMLLLE VISGERLPKP ERGKMRVHKI NNVNKALDFI
ASKGVKLVSI GAEEIVDGNA KMTLGMIWTI ILRFAIQDIS VEETSAKEGL LLWCQRKTAP
YKNVNVQNFH ISWKDGLAFN ALIHRHRPEL IEYDKLRKDD PVTNLNNAFE VAEKYLDIPK
MLDAEDIVNT ARPDEKAIMT YVSSFYHAFS GAQKAETAAN RICKVLAVNQ ENEHLMEDYE
RLASDLLEWI RRTIPWLEDR VPQKTIQEMQ QKLEDFRDYR RVHKPPKVQE KCQLEINFNT
LQTKLRLSNR PAFMPSEGRM VSDINNGWQH LEQAEKGYEE WLLNEIRRLE RLDHLAEKFR
QKASIHEAWT DGKEAMLKQR DYETATLSDI KALIRKHEAF ESDLAAHQDR VEQIAAIAQE
LNELDYYDSH NVNTRCQKIC DQWDNLGSLT HSRREALEKT EKQLETIDQL HLEYAKRAAP
FNNWMESAME DLQDMFIVHT IEEIEGLISA HDQFKSTLPD ADREREAILA IHKEAQRIAE
SNHIKLSGSN PYTTVTPQII NSKWEKVQQL VPKRDHALLE EQSKQQSNEH LRRQFASQAN
MVGPWIQTKM EEIGRISIEM NGTLEDQLSH LKQYERSIVD YKPSLDLLEQ QHQLIQEALI
FDNKHTNYTM EHIRVGWEQL LTTIARTINE VENQILTRDA KGISQEQMQE FRASFNHFDK
DHGGALGPEE FKACLISLGY DVENDRQGDA EFNRIMSVVD PNHSGLVTFQ AFIDFMSRET
TDTDTADQVI ASFKVLAGDK NFITAEELRR ELPPDQAEYC IARMAPYQGP DAAPGALDYK
SFSTALYGES DL
