ACTN4_RAT
ID ACTN4_RAT Reviewed; 911 AA.
AC Q9QXQ0; Q6P786;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Alpha-actinin-4 {ECO:0000305};
DE AltName: Full=Non-muscle alpha-actinin 4 {ECO:0000305};
GN Name=Actn4 {ECO:0000312|RGD:61816};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10673389; DOI=10.1006/bbrc.1999.2045;
RA El-Husseini A.E.-D., Kwasnicka D., Yamada T., Hirohashi S., Vincent S.R.;
RT "BERP, a novel ring finger protein, binds to alpha-actinin-4.";
RL Biochem. Biophys. Res. Commun. 267:906-911(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [3]
RP INTERACTION WITH PDLIM2.
RX PubMed=15505042; DOI=10.1167/iovs.04-0721;
RA Torrado M., Senatorov V.V., Trivedi R., Fariss R.N., Tomarev S.I.;
RT "Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and
RT filamin A.";
RL Invest. Ophthalmol. Vis. Sci. 45:3955-3963(2004).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH CASK; IQGAP1; MAGI2; NPHS1; SPTAN1 AND
RP SPTBN1, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
RX PubMed=15994232; DOI=10.1073/pnas.0504166102;
RA Lehtonen S., Ryan J.J., Kudlicka K., Iino N., Zhou H., Farquhar M.G.;
RT "Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and
RT alpha-actinin are components of the nephrin multiprotein complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9814-9819(2005).
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. Involved
CC in tight junction assembly in epithelial cells probably through
CC interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and
CC recruits it to the tight junctions. May also function as a
CC transcriptional coactivator, stimulating transcription mediated by the
CC nuclear hormone receptors PPARG and RARA.
CC {ECO:0000250|UniProtKB:O43707}.
CC -!- SUBUNIT: Homodimer; antiparallel. Interacts with MAGI1 (By similarity).
CC Interacts with MICALL2 (preferentially in opened conformation);
CC stimulated by RAB13 activation (By similarity). Identified in a
CC IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs
CC (By similarity). Component of the CART complex, at least composed of
CC ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity). Binds TRIM3 at the N-
CC terminus (By similarity). Interacts with PDLIM2 (PubMed:15505042).
CC Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and
CC SPTBN1 (PubMed:15994232). Interacts with PPARG and RARA (By
CC similarity). Binds to VCL; this interaction triggers VCL conformational
CC changes (By similarity). Interacts with SEPTIN14 (By similarity).
CC {ECO:0000250|UniProtKB:O43707, ECO:0000250|UniProtKB:P57780,
CC ECO:0000269|PubMed:15505042, ECO:0000269|PubMed:15994232}.
CC -!- INTERACTION:
CC Q9QXQ0; P19357: Slc2a4; NbExp=3; IntAct=EBI-919056, EBI-915426;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O43707}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43707}. Cell junction
CC {ECO:0000250|UniProtKB:P57780}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000250|UniProtKB:O43707}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P57780}. 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 (By similarity). {ECO:0000250|UniProtKB:O43707,
CC ECO:0000250|UniProtKB:P57780}.
CC -!- TISSUE SPECIFICITY: Expressed in the foot process layer of podocytes in
CC the kidney glomerulus but not in tubules (at protein level).
CC {ECO:0000269|PubMed:15994232}.
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; AF190909; AAF20064.1; -; mRNA.
DR EMBL; BC061788; AAH61788.1; -; mRNA.
DR PIR; JC7186; JC7186.
DR RefSeq; NP_113863.2; NM_031675.2.
DR AlphaFoldDB; Q9QXQ0; -.
DR BMRB; Q9QXQ0; -.
DR SMR; Q9QXQ0; -.
DR BioGRID; 248895; 7.
DR CORUM; Q9QXQ0; -.
DR IntAct; Q9QXQ0; 4.
DR MINT; Q9QXQ0; -.
DR STRING; 10116.ENSRNOP00000027773; -.
DR iPTMnet; Q9QXQ0; -.
DR PhosphoSitePlus; Q9QXQ0; -.
DR jPOST; Q9QXQ0; -.
DR PaxDb; Q9QXQ0; -.
DR PRIDE; Q9QXQ0; -.
DR GeneID; 63836; -.
DR KEGG; rno:63836; -.
DR UCSC; RGD:61816; rat.
DR CTD; 81; -.
DR RGD; 61816; Actn4.
DR VEuPathDB; HostDB:ENSRNOG00000020433; -.
DR eggNOG; KOG0035; Eukaryota.
DR InParanoid; Q9QXQ0; -.
DR OMA; INTAWHT; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; Q9QXQ0; -.
DR TreeFam; TF352676; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR PRO; PR:Q9QXQ0; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020433; Expressed in jejunum and 19 other tissues.
DR ExpressionAtlas; Q9QXQ0; baseline and differential.
DR Genevisible; Q9QXQ0; RN.
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; ISO:RGD.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0030863; C:cortical cytoskeleton; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0031143; C:pseudopodium; ISO:RGD.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0001725; C:stress fiber; ISO:RGD.
DR GO; GO:0030018; C:Z disc; ISO:RGD.
DR GO; GO:0051015; F:actin filament binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISS:UniProtKB.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISO:RGD.
DR GO; GO:0001882; F:nucleoside binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0051017; P:actin filament bundle assembly; ISO:RGD.
DR GO; GO:0070830; P:bicellular tight junction assembly; ISO:RGD.
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:RGD.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0048549; P:positive regulation of pinocytosis; ISO:RGD.
DR GO; GO:1902396; P:protein localization to bicellular tight junction; ISO:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:RGD.
DR GO; GO:1903506; P:regulation of nucleic acid-templated transcription; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030050; P:vesicle transport along actin filament; ISO:RGD.
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; Metal-binding; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport.
FT CHAIN 1..911
FT /note="Alpha-actinin-4"
FT /id="PRO_0000073443"
FT DOMAIN 50..154
FT /note="Calponin-homology (CH) 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT DOMAIN 163..269
FT /note="Calponin-homology (CH) 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REPEAT 293..403
FT /note="Spectrin 1"
FT /evidence="ECO:0000255"
FT REPEAT 413..518
FT /note="Spectrin 2"
FT /evidence="ECO:0000255"
FT REPEAT 528..639
FT /note="Spectrin 3"
FT /evidence="ECO:0000255"
FT REPEAT 649..752
FT /note="Spectrin 4"
FT /evidence="ECO:0000255"
FT DOMAIN 765..800
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 806..841
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..269
FT /note="Actin-binding"
FT REGION 12..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 12..26
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 40..61
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 108..126
FT /note="Interaction with VCL"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT REGION 177..192
FT /note="Polyphosphoinositide (PIP2)-binding"
FT /evidence="ECO:0000255"
FT REGION 736..911
FT /note="Mediates interaction with MICALL2"
FT /evidence="ECO:0000250|UniProtKB:P57780"
FT MOTIF 84..88
FT /note="LXXLL motif"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT BINDING 778
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 780
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 789
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 31
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 114
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 592
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 625
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O43707"
FT MOD_RES 696
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 779
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P57780"
FT MOD_RES 859
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P57780"
FT MOD_RES 909
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1P2"
FT CONFLICT 250
FT /note="A -> G (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="R -> P (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 792
FT /note="A -> G (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 837
FT /note="R -> K (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 850
FT /note="A -> G (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 864
FT /note="A -> V (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
FT CONFLICT 869
FT /note="R -> K (in Ref. 1; AAF20064)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 911 AA; 104915 MW; 0C5FC2E43B5D8FD2 CRC64;
MVDYHAANQA YQYGPSSGGN GTGGGGGMGD YMAQEDDWDR DLLLDPAWEK QQRKTFTAWC
NSHLRKAGTQ IENIDEDFRD GLKLMLLLEV ISGERLPKPE RGKMRVHKIN NVNKALDFIA
SKGVKLVSIG AEEIVDGNAK MTLGMIWTII LRFAIQDISV EETSAKEGLL LWCQRKTAPY
KNVNVQNFHI SWKDGLAFNA LIHRHRPELI EYDKLRKDDP VTNLNNAFEV AEKYLDIPKM
LDAEDIVNTA RPDEKAIMTY VSSFYHAFSG AQKAETAANR ICKVLAVNQE NEHLMEDYER
LASDLLEWIR RTIPWLEDRV PQKTIQEMQQ KLEDFRDYRR VHKPPKVQEK CQLEINFNTL
QTKLRLSNRP AFMPSEGRMV SDINNGWQHL EQAEKGYEEW LLNEIRRLER LDHLAEKFRQ
KASIHEAWTD GKEAMLKHRD YETATLSDIK ALIRKHEAFE SDLAAHQDRV EQIAAIAQEL
NELDYYDSHN VNTRCQKICD QWDNLGSLTH SRREALEKTE KQLETIDQLH LEYAKRAAPF
NNWMESAMED LQDMFIVHTI EEIEGLISAH DQFKSTLPDA DREREAILAI HKEAQRIAES
NHIKLSGSNP YTSVTPQIIN SKWEKVQQLV PKRDHALLEE QSKQQSNEHL RRQFASQANM
VGPWIQTKME EIGRISIEMN GTLEDQLSHL KQYERSIVDY KPNLDLLEQQ HQLIQEALIF
DNKHTNYTME HLRVGWEQLL TTIARTINEV ENQILTRDAK GISQEQMQEF RASFNHFDKD
HGGALGPEEF KACLISLGYD VENDRQGDAE FNRIMSVVDP NHSGLVTFQA FIDFMSRETT
DTDTADQVIA SFKVLAGDKN FITAEELRRE LPPDQAEYCI ARMAPYQGPD AAPGALDYKS
FSTALYGESD L
