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Protein

Alpha-actinin-4

Gene

ACTN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).By similarity1 Publication2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi778 – 789121PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi819 – 830122PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • actin filament binding Source: UniProtKB
  • calcium ion binding Source: InterPro
  • integrin binding Source: UniProtKB
  • ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  • nuclear hormone receptor binding Source: UniProtKB
  • nucleoside binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • retinoic acid receptor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Actin-binding, Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_23832. Nephrin interactions.
REACT_318. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-actinin-4Curated
Alternative name(s):
Non-muscle alpha-actinin 41 Publication
Gene namesi
Name:ACTN4Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:166. ACTN4.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • cortical cytoskeleton Source: Ensembl
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • neuron projection Source: Ensembl
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • platelet alpha granule lumen Source: Reactome
  • protein complex Source: UniProtKB
  • pseudopodium Source: UniProtKB
  • ribonucleoprotein complex Source: UniProtKB
  • stress fiber Source: Ensembl
  • Z disc Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Focal segmental glomerulosclerosis 1 (FSGS1)3 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.

See also OMIM:603278
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti255 – 2551K → E in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939374 [ dbSNP | Ensembl ].
VAR_010378
Natural varianti259 – 2591T → I in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939375 [ dbSNP | Ensembl ].
VAR_010379
Natural varianti262 – 2621S → F in FSGS1. 1 Publication
VAR_072115
Natural varianti262 – 2621S → P in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939376 [ dbSNP | Ensembl ].
VAR_010380
Natural varianti427 – 4271A → T in FSGS1. 1 Publication
VAR_072116
Natural varianti748 – 7481N → D in FSGS1. 1 Publication
VAR_072117

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi87 – 882LL → AA: Reduced interaction with RARA. Loss of the transcriptional coativator activity toward RARA. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi603278. phenotype.
Orphaneti93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBiPA23.

Polymorphism and mutation databases

BioMutaiACTN4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 911911Alpha-actinin-4PRO_0000073440Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei31 – 311PhosphotyrosineBy similarity
Modified residuei114 – 1141N6-acetyllysine1 Publication
Modified residuei214 – 2141N6-acetyllysineBy similarity
Modified residuei249 – 2491Phosphothreonine1 Publication
Cross-linki378 – 378Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei592 – 5921N6-acetyllysine1 Publication
Modified residuei625 – 6251N6-acetyllysine1 Publication
Modified residuei696 – 6961PhosphoserineBy similarity
Modified residuei779 – 7791N6-acetyllysineBy similarity
Modified residuei859 – 8591N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO43707.
PaxDbiO43707.
PeptideAtlasiO43707.
PRIDEiO43707.

2D gel databases

REPRODUCTION-2DPAGEO43707.

PTM databases

PhosphoSiteiO43707.

Miscellaneous databases

PMAP-CutDBO43707.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiO43707.
CleanExiHS_ACTN4.
ExpressionAtlasiO43707. baseline and differential.
GenevisibleiO43707. HS.

Organism-specific databases

HPAiHPA001873.
HPA006035.

Interactioni

Subunit structurei

Homodimer; antiparallel (By similarity). Binds TRIM3 at the N-terminus (By similarity). Interacts with MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation (By similarity). Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with BAIAP1 and PDLIM2. Interacts with PPARG and RARA.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
B2R8Y43EBI-351526,EBI-10175581
BMP7A8K5713EBI-351526,EBI-10174327
CTNNB1P352227EBI-351526,EBI-491549
IQGAP1P469403EBI-351526,EBI-297509
MYOZ2Q9NPC67EBI-351526,EBI-746712
NPP034662EBI-351526,EBI-2547640From a different organism.
NPQ5L4H45EBI-351526,EBI-9512099From a different organism.
TJP1Q071574EBI-351526,EBI-79553

Protein-protein interaction databases

BioGridi106596. 72 interactions.
DIPiDIP-33179N.
IntActiO43707. 45 interactions.
MINTiMINT-4998602.
STRINGi9606.ENSP00000252699.

Structurei

Secondary structure

1
911
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi47 – 6418Combined sources
Helixi65 – 673Combined sources
Turni74 – 807Combined sources
Helixi82 – 9211Combined sources
Helixi105 – 12016Combined sources
Turni121 – 1233Combined sources
Helixi131 – 1355Combined sources
Helixi139 – 15315Combined sources
Turni154 – 1574Combined sources
Helixi165 – 17713Combined sources
Beta strandi187 – 1893Combined sources
Helixi190 – 1923Combined sources
Helixi196 – 20510Combined sources
Helixi207 – 2093Combined sources
Helixi212 – 2143Combined sources
Helixi220 – 23415Combined sources
Helixi243 – 2486Combined sources
Beta strandi249 – 2513Combined sources
Helixi254 – 26714Combined sources
Helixi519 – 55234Combined sources
Helixi560 – 60041Combined sources
Beta strandi606 – 6083Combined sources
Helixi616 – 64126Combined sources
Helixi736 – 75621Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WLXNMR-A519-645[»]
1YDIX-ray1.80B734-757[»]
2R0OX-ray2.20A/B47-271[»]
ProteinModelPortaliO43707.
SMRiO43707. Positions 46-909.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43707.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 269269Actin-bindingAdd
BLAST
Domaini50 – 154105CH 1PROSITE-ProRule annotationAdd
BLAST
Domaini163 – 269107CH 2PROSITE-ProRule annotationAdd
BLAST
Repeati293 – 403111Spectrin 1Add
BLAST
Repeati413 – 518106Spectrin 2Add
BLAST
Repeati528 – 639112Spectrin 3Add
BLAST
Repeati649 – 752104Spectrin 4Add
BLAST
Domaini765 – 80036EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini806 – 84136EF-hand 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni177 – 19216Polyphosphoinositide (PIP2)-bindingSequence AnalysisAdd
BLAST
Regioni736 – 911176Mediates interaction with MICALL2By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi84 – 885LXXLL motif1 Publication

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi19 – 268Poly-Gly

Domaini

Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.1 Publication

Sequence similaritiesi

Belongs to the alpha-actinin family.Curated
Contains 1 actin-binding domain.Curated
Contains 2 CH (calponin-homology) domains.PROSITE-ProRule annotation
Contains 2 EF-hand domains.PROSITE-ProRule annotation
Contains 4 spectrin repeats.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG5069.
GeneTreeiENSGT00760000118813.
HOGENOMiHOG000263418.
HOVERGENiHBG050453.
InParanoidiO43707.
KOiK05699.
OMAiIVGPWIQ.
OrthoDBiEOG72C4ZJ.
PhylomeDBiO43707.
TreeFamiTF352676.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
1.10.418.10. 2 hits.
InterProiIPR001589. Actinin_actin-bd_CS.
IPR029637. ACTN4.
IPR001715. CH-domain.
IPR011992. EF-hand-dom_pair.
IPR014837. EF-hand_Ca_insen.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR018159. Spectrin/alpha-actinin.
IPR002017. Spectrin_repeat.
[Graphical view]
PANTHERiPTHR11915:SF271. PTHR11915:SF271. 1 hit.
PfamiPF00307. CH. 2 hits.
PF13405. EF-hand_6. 1 hit.
PF08726. EFhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]
SMARTiSM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 4 hits.
[Graphical view]
SUPFAMiSSF47576. SSF47576. 1 hit.
PROSITEiPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43707-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVDYHAANQS YQYGPSSAGN GAGGGGSMGD YMAQEDDWDR DLLLDPAWEK
60 70 80 90 100
QQRKTFTAWC NSHLRKAGTQ IENIDEDFRD GLKLMLLLEV ISGERLPKPE
110 120 130 140 150
RGKMRVHKIN NVNKALDFIA SKGVKLVSIG AEEIVDGNAK MTLGMIWTII
160 170 180 190 200
LRFAIQDISV EETSAKEGLL LWCQRKTAPY KNVNVQNFHI SWKDGLAFNA
210 220 230 240 250
LIHRHRPELI EYDKLRKDDP VTNLNNAFEV AEKYLDIPKM LDAEDIVNTA
260 270 280 290 300
RPDEKAIMTY VSSFYHAFSG AQKAETAANR ICKVLAVNQE NEHLMEDYEK
310 320 330 340 350
LASDLLEWIR RTIPWLEDRV PQKTIQEMQQ KLEDFRDYRR VHKPPKVQEK
360 370 380 390 400
CQLEINFNTL QTKLRLSNRP AFMPSEGKMV SDINNGWQHL EQAEKGYEEW
410 420 430 440 450
LLNEIRRLER LDHLAEKFRQ KASIHEAWTD GKEAMLKHRD YETATLSDIK
460 470 480 490 500
ALIRKHEAFE SDLAAHQDRV EQIAAIAQEL NELDYYDSHN VNTRCQKICD
510 520 530 540 550
QWDALGSLTH SRREALEKTE KQLEAIDQLH LEYAKRAAPF NNWMESAMED
560 570 580 590 600
LQDMFIVHTI EEIEGLISAH DQFKSTLPDA DREREAILAI HKEAQRIAES
610 620 630 640 650
NHIKLSGSNP YTTVTPQIIN SKWEKVQQLV PKRDHALLEE QSKQQSNEHL
660 670 680 690 700
RRQFASQANV VGPWIQTKME EIGRISIEMN GTLEDQLSHL KQYERSIVDY
710 720 730 740 750
KPNLDLLEQQ HQLIQEALIF DNKHTNYTME HIRVGWEQLL TTIARTINEV
760 770 780 790 800
ENQILTRDAK GISQEQMQEF RASFNHFDKD HGGALGPEEF KACLISLGYD
810 820 830 840 850
VENDRQGEAE FNRIMSLVDP NHSGLVTFQA FIDFMSRETT DTDTADQVIA
860 870 880 890 900
SFKVLAGDKN FITAEELRRE LPPDQAEYCI ARMAPYQGPD AVPGALDYKS
910
FSTALYGESD L
Length:911
Mass (Da):104,854
Last modified:February 21, 2001 - v2
Checksum:i461580C3F22937D1
GO
Isoform ACTN4ISO (identifier: O43707-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     54-272: Missing.

Note: Does not colocalize with actin cytoskeleton structures.1 Publication
Show »
Length:692
Mass (Da):79,913
Checksum:i34C43B1217B8AA25
GO
Isoform 3 (identifier: O43707-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     89-478: Missing.

Show »
Length:521
Mass (Da):59,579
Checksum:i66A7C97A6AF6C87D
GO

Sequence cautioni

The sequence AAC17470.1 differs from that shown. Reason: Frameshift at positions 19, 26, 124, 130, 589, 594, 787 and 806. Curated
The sequence BAA24447.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 601C → S in AAC17470 (PubMed:10656685).Curated
Sequence conflicti164 – 1641S → L in AL047603 (PubMed:17974005).Curated
Sequence conflicti221 – 2211V → F in AU118403 (PubMed:16344560).Curated
Sequence conflicti276 – 2761T → TET in AAC17470 (PubMed:10656685).Curated
Sequence conflicti292 – 2943EHL → CSTS in AAC17470 (PubMed:10656685).Curated
Sequence conflicti359 – 3602TL → SV in AAC17470 (PubMed:10656685).Curated
Sequence conflicti476 – 4761I → S in AAC17470 (PubMed:10656685).Curated
Sequence conflicti526 – 5261I → II in AAC17470 (PubMed:10656685).Curated
Sequence conflicti536 – 5361R → P in AAC17470 (PubMed:10656685).Curated
Sequence conflicti645 – 6451Q → QQ in AAC17470 (PubMed:10656685).Curated
Sequence conflicti673 – 6742GR → A in AAC17470 (PubMed:10656685).Curated
Sequence conflicti850 – 8501A → T in AAC17470 (PubMed:10656685).Curated
Sequence conflicti891 – 8933AVP → GVR in AAC17470 (PubMed:10656685).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti255 – 2551K → E in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939374 [ dbSNP | Ensembl ].
VAR_010378
Natural varianti259 – 2591T → I in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939375 [ dbSNP | Ensembl ].
VAR_010379
Natural varianti262 – 2621S → F in FSGS1. 1 Publication
VAR_072115
Natural varianti262 – 2621S → P in FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coativator activity; dominant negative effect on nuclear receptors-mediated transcription. 2 Publications
Corresponds to variant rs28939376 [ dbSNP | Ensembl ].
VAR_010380
Natural varianti427 – 4271A → T in FSGS1. 1 Publication
VAR_072116
Natural varianti748 – 7481N → D in FSGS1. 1 Publication
VAR_072117
Natural varianti784 – 7841A → V Rare variant found in patients with IgA nephropathy; unknown pathological significance. 1 Publication
VAR_072118
Natural varianti786 – 7861G → R.1 Publication
VAR_072119
Natural varianti787 – 7871P → L.1 Publication
VAR_072120
Natural varianti787 – 7871P → S.1 Publication
VAR_072121
Natural varianti793 – 7931C → Y Rare variant found in patients with IgA nephropathy; unknown pathological significance. 1 Publication
VAR_072122
Natural varianti798 – 7981G → D Rare variant found in patients with IgA nephropathy; unknown pathological significance. 1 Publication
VAR_072123
Natural varianti801 – 8011V → M.1 Publication
VAR_072124

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei54 – 272219Missing in isoform ACTN4ISO. 1 PublicationVSP_047733Add
BLAST
Alternative sequencei89 – 478390Missing in isoform 3. 1 PublicationVSP_053401Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48734 mRNA. Translation: AAC17470.1. Frameshift.
GU987085 mRNA. Translation: ADG03678.1.
DQ431186 mRNA. Translation: ABD96103.1.
AC008649 Genomic DNA. No translation available.
AC022144 Genomic DNA. No translation available.
BC005033 mRNA. Translation: AAH05033.1.
AL047603 mRNA. No translation available.
AU118403 mRNA. No translation available.
D89980 mRNA. Translation: BAA24447.1. Different initiation.
CCDSiCCDS12518.1. [O43707-1]
RefSeqiNP_004915.2. NM_004924.4. [O43707-1]
UniGeneiHs.270291.

Genome annotation databases

EnsembliENST00000252699; ENSP00000252699; ENSG00000130402. [O43707-1]
ENST00000390009; ENSP00000439497; ENSG00000130402. [O43707-2]
GeneIDi81.
KEGGihsa:81.
UCSCiuc002oja.2. human. [O43707-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U48734 mRNA. Translation: AAC17470.1. Frameshift.
GU987085 mRNA. Translation: ADG03678.1.
DQ431186 mRNA. Translation: ABD96103.1.
AC008649 Genomic DNA. No translation available.
AC022144 Genomic DNA. No translation available.
BC005033 mRNA. Translation: AAH05033.1.
AL047603 mRNA. No translation available.
AU118403 mRNA. No translation available.
D89980 mRNA. Translation: BAA24447.1. Different initiation.
CCDSiCCDS12518.1. [O43707-1]
RefSeqiNP_004915.2. NM_004924.4. [O43707-1]
UniGeneiHs.270291.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WLXNMR-A519-645[»]
1YDIX-ray1.80B734-757[»]
2R0OX-ray2.20A/B47-271[»]
ProteinModelPortaliO43707.
SMRiO43707. Positions 46-909.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106596. 72 interactions.
DIPiDIP-33179N.
IntActiO43707. 45 interactions.
MINTiMINT-4998602.
STRINGi9606.ENSP00000252699.

PTM databases

PhosphoSiteiO43707.

Polymorphism and mutation databases

BioMutaiACTN4.

2D gel databases

REPRODUCTION-2DPAGEO43707.

Proteomic databases

MaxQBiO43707.
PaxDbiO43707.
PeptideAtlasiO43707.
PRIDEiO43707.

Protocols and materials databases

DNASUi81.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252699; ENSP00000252699; ENSG00000130402. [O43707-1]
ENST00000390009; ENSP00000439497; ENSG00000130402. [O43707-2]
GeneIDi81.
KEGGihsa:81.
UCSCiuc002oja.2. human. [O43707-1]

Organism-specific databases

CTDi81.
GeneCardsiGC19P039138.
HGNCiHGNC:166. ACTN4.
HPAiHPA001873.
HPA006035.
MIMi603278. phenotype.
604638. gene.
neXtProtiNX_O43707.
Orphaneti93213. Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis.
PharmGKBiPA23.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5069.
GeneTreeiENSGT00760000118813.
HOGENOMiHOG000263418.
HOVERGENiHBG050453.
InParanoidiO43707.
KOiK05699.
OMAiIVGPWIQ.
OrthoDBiEOG72C4ZJ.
PhylomeDBiO43707.
TreeFamiTF352676.

Enzyme and pathway databases

ReactomeiREACT_23832. Nephrin interactions.
REACT_318. Platelet degranulation.

Miscellaneous databases

ChiTaRSiACTN4. human.
EvolutionaryTraceiO43707.
GeneWikiiActinin_alpha_4.
GenomeRNAii81.
NextBioi303.
PMAP-CutDBO43707.
PROiO43707.
SOURCEiSearch...

Gene expression databases

BgeeiO43707.
CleanExiHS_ACTN4.
ExpressionAtlasiO43707. baseline and differential.
GenevisibleiO43707. HS.

Family and domain databases

Gene3Di1.10.238.10. 2 hits.
1.10.418.10. 2 hits.
InterProiIPR001589. Actinin_actin-bd_CS.
IPR029637. ACTN4.
IPR001715. CH-domain.
IPR011992. EF-hand-dom_pair.
IPR014837. EF-hand_Ca_insen.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR018159. Spectrin/alpha-actinin.
IPR002017. Spectrin_repeat.
[Graphical view]
PANTHERiPTHR11915:SF271. PTHR11915:SF271. 1 hit.
PfamiPF00307. CH. 2 hits.
PF13405. EF-hand_6. 1 hit.
PF08726. EFhand_Ca_insen. 1 hit.
PF00435. Spectrin. 4 hits.
[Graphical view]
SMARTiSM00033. CH. 2 hits.
SM00054. EFh. 2 hits.
SM00150. SPEC. 4 hits.
[Graphical view]
SUPFAMiSSF47576. SSF47576. 1 hit.
PROSITEiPS00019. ACTININ_1. 1 hit.
PS00020. ACTININ_2. 1 hit.
PS50021. CH. 2 hits.
PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 2 hits.
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Publicationsi

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  1. "The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells."
    Nikolopoulos S.N., Spengler B.A., Kisselbach K., Evans A.E., Biedler J.L., Ross R.A.
    Oncogene 19:380-386(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Neuroblastoma.
  2. "Novel splicing isoform of actin-binding protein alpha-actinin 4 in epidermoid carcinoma cells A431."
    Aksenova V.I.U., Khotin M.G., Turoverova L.V., Iudintseva N.M., Magnusson K.E., Pinaev G.P., Tentler D.G.
    Tsitologiia 54:25-32(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ACTN4ISO), SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
  3. "Actinin alpha4, an actin binding protein, is a transcriptional coactivator that antagonizes class II HDAC activity."
    Chakraborty S., Cheng X., Lam M., Reineke E.L., Li X., Liu Y., Gao C., Khurana S., Kao H.-Y.
    Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  4. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Placenta.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-170 (ISOFORM 1).
    Tissue: Uterus.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224 (ISOFORM 1).
  8. "Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion."
    Honda K., Yamada T., Endo R., Ino Y., Gotoh M., Tsuda H., Yamada Y., Chiba H., Hirohashi S.
    J. Cell Biol. 140:1383-1393(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-911 (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. Erratum
    Honda K., Yamada T., Endo R., Ino Y., Gotoh M., Tsuda H., Yamada Y., Chiba H., Hirohashi S.
    J. Cell Biol. 143:276-276(1998)
  10. "Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1."
    Patrie K.M., Drescher A.J., Welihinda A., Mundel P., Margolis B.
    J. Biol. Chem. 277:30183-30190(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BAIAP1.
  11. "CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling."
    Yan Q., Sun W., Kujala P., Lotfi Y., Vida T.A., Bean A.J.
    Mol. Biol. Cell 16:2470-2482(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN THE CART COMPLEX.
  12. Cited for: IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
  13. "Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
    Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
    Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-378.
    Tissue: Mammary cancer.
  14. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114; LYS-592 AND LYS-625, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  16. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-249, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  17. "Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors."
    Khurana S., Chakraborty S., Lam M., Liu Y., Su Y.T., Zhao X., Saleem M.A., Mathieson P.W., Bruggeman L.A., Kao H.Y.
    J. Biol. Chem. 287:12027-12035(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262, FUNCTION, INTERACTION WITH PPARG AND RARA, MUTAGENESIS OF 87-LEU-LEU-88, DOMAIN, SUBCELLULAR LOCATION.
  18. "Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis."
    Kaplan J.M., Kim S.H., North K.N., Rennke H., Correia L.A., Tong H.-Q., Mathis B.J., Rodriguez-Perez J.-C., Allen P.G., Beggs A.H., Pollak M.R.
    Nat. Genet. 24:251-256(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262.
    Tissue: Lymphocyte.
  19. "Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism."
    Choi H.J., Lee B.H., Cho H.Y., Moon K.C., Ha I.S., Nagata M., Choi Y., Cheong H.I.
    Am. J. Kidney Dis. 51:834-838(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT FSGS1 PHE-262.
  20. "Mutational analysis of ACTN4, encoding alpha-actinin 4, in patients with focal segmental glomerulosclerosis using HRM method."
    Safarikova M., Reiterova J., Safrankova H., Stekrova J., Zidkova A., Obeidova L., Kohoutova M., Tesar V.
    Folia Biol. (Praha) 59:110-115(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS FSGS1 THR-427 AND ASP-748, VARIANTS VAL-784; ARG-786; LEU-787; SER-787; TYR-793; ASP-798 AND MET-801.

Entry informationi

Entry nameiACTN4_HUMAN
AccessioniPrimary (citable) accession number: O43707
Secondary accession number(s): A4K467, D6PXK4, O76048
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: June 24, 2015
This is version 182 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.