ACTN4_HUMAN
ID ACTN4_HUMAN Reviewed; 911 AA.
AC O43707; A4K467; D6PXK4; O76048;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Alpha-actinin-4 {ECO:0000305};
DE AltName: Full=Non-muscle alpha-actinin 4 {ECO:0000303|PubMed:10656685};
GN Name=ACTN4 {ECO:0000312|HGNC:HGNC:166};
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).
RC TISSUE=Neuroblastoma;
RX PubMed=10656685; DOI=10.1038/sj.onc.1203310;
RA Nikolopoulos S.N., Spengler B.A., Kisselbach K., Evans A.E., Biedler J.L.,
RA Ross R.A.;
RT "The human non-muscle alpha-actinin protein encoded by the ACTN4 gene
RT suppresses tumorigenicity of human neuroblastoma cells.";
RL Oncogene 19:380-386(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ACTN4ISO), SUBCELLULAR LOCATION, AND
RP ALTERNATIVE SPLICING.
RX PubMed=22567897;
RA Aksenova V.I.U., Khotin M.G., Turoverova L.V., Iudintseva N.M.,
RA Magnusson K.E., Pinaev G.P., Tentler D.G.;
RT "Novel splicing isoform of actin-binding protein alpha-actinin 4 in
RT epidermoid carcinoma cells A431.";
RL Tsitologiia 54:25-32(2012).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Chakraborty S., Cheng X., Lam M., Reineke E.L., Li X., Liu Y., Gao C.,
RA Khurana S., Kao H.-Y.;
RT "Actinin alpha4, an actin binding protein, is a transcriptional coactivator
RT that antagonizes class II HDAC activity.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-170 (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224 (ISOFORM 1).
RX PubMed=16344560; DOI=10.1101/gr.4039406;
RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA Sugano S.;
RT "Diversification of transcriptional modulation: large-scale identification
RT and characterization of putative alternative promoters of human genes.";
RL Genome Res. 16:55-65(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-911 (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9508771; DOI=10.1083/jcb.140.6.1383;
RA Honda K., Yamada T., Endo R., Ino Y., Gotoh M., Tsuda H., Yamada Y.,
RA Chiba H., Hirohashi S.;
RT "Actinin-4, a novel actin-bundling protein associated with cell motility
RT and cancer invasion.";
RL J. Cell Biol. 140:1383-1393(1998).
RN [9]
RP ERRATUM OF PUBMED:9508771.
RA Honda K., Yamada T., Endo R., Ino Y., Gotoh M., Tsuda H., Yamada Y.,
RA Chiba H., Hirohashi S.;
RL J. Cell Biol. 143:276-276(1998).
RN [10]
RP INTERACTION WITH MAGI1.
RX PubMed=12042308; DOI=10.1074/jbc.m203072200;
RA Patrie K.M., Drescher A.J., Welihinda A., Mundel P., Margolis B.;
RT "Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-
RT 4, with the tight junction protein MAGI-1.";
RL J. Biol. Chem. 277:30183-30190(2002).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN THE CART COMPLEX.
RX PubMed=15772161; DOI=10.1091/mbc.e04-11-1014;
RA Yan Q., Sun W., Kujala P., Lotfi Y., Vida T.A., Bean A.J.;
RT "CART: an Hrs/actinin-4/BERP/myosin V protein complex required for
RT efficient receptor recycling.";
RL Mol. Biol. Cell 16:2470-2482(2005).
RN [12]
RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.m600346-mcp200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114; LYS-592 AND LYS-625, 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 [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-249, AND IDENTIFICATION BY
RP 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 [16]
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 [17]
RP INTERACTION WITH SEPTIN14.
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).
RN [18]
RP STRUCTURE BY NMR OF 519-645.
RA Kowalski K., Merkel A.L., Booker G.W.;
RT "Solution structure of the third spectrin repeat of alpha-actinin-4.";
RL Submitted (JUN-2004) to the PDB data bank.
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 734-757 IN COMPLEX WITH VCL, AND
RP INTERACTION WITH VCL.
RX PubMed=15988023; DOI=10.1128/mcb.25.14.6112-6122.2005;
RA Bois P.R.J., Borgon R.A., Vonrhein C., Izard T.;
RT "Structural dynamics of alpha-actinin-vinculin interactions.";
RL Mol. Cell. Biol. 25:6112-6122(2005).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 47-271, AND CHARACTERIZATION OF
RP VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262.
RX PubMed=18164029; DOI=10.1016/j.jmb.2007.11.084;
RA Lee S.H., Weins A., Hayes D.B., Pollak M.R., Dominguez R.;
RT "Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu
RT mutant implicated in focal segmental glomerulosclerosis.";
RL J. Mol. Biol. 376:317-324(2008).
RN [21]
RP CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262, FUNCTION,
RP INTERACTION WITH PPARG AND RARA, MUTAGENESIS OF 87-LEU-LEU-88, DOMAIN, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22351778; DOI=10.1074/jbc.m112.345421;
RA Khurana S., Chakraborty S., Lam M., Liu Y., Su Y.T., Zhao X., Saleem M.A.,
RA Mathieson P.W., Bruggeman L.A., Kao H.Y.;
RT "Familial focal segmental glomerulosclerosis (FSGS)-linked alpha-actinin 4
RT (ACTN4) protein mutants lose ability to activate transcription by nuclear
RT hormone receptors.";
RL J. Biol. Chem. 287:12027-12035(2012).
RN [22]
RP VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262.
RC TISSUE=Lymphocyte;
RX PubMed=10700177; DOI=10.1038/73456;
RA Kaplan J.M., Kim S.H., North K.N., Rennke H., Correia L.A., Tong H.-Q.,
RA Mathis B.J., Rodriguez-Perez J.-C., Allen P.G., Beggs A.H., Pollak M.R.;
RT "Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal
RT segmental glomerulosclerosis.";
RL Nat. Genet. 24:251-256(2000).
RN [23]
RP VARIANT FSGS1 PHE-262.
RX PubMed=18436095; DOI=10.1053/j.ajkd.2008.01.018;
RA Choi H.J., Lee B.H., Cho H.Y., Moon K.C., Ha I.S., Nagata M., Choi Y.,
RA Cheong H.I.;
RT "Familial focal segmental glomerulosclerosis associated with an ACTN4
RT mutation and paternal germline mosaicism.";
RL Am. J. Kidney Dis. 51:834-838(2008).
RN [24]
RP VARIANT FSGS1 GLN-310.
RX PubMed=22732337; DOI=10.5414/cn107320;
RA Buescher A.K., Konrad M., Nagel M., Witzke O., Kribben A., Hoyer P.F.,
RA Weber S.;
RT "Mutations in podocyte genes are a rare cause of primary FSGS associated
RT with ESRD in adult patients.";
RL Clin. Nephrol. 78:47-53(2012).
RN [25]
RP VARIANTS FSGS1 THR-427 AND ASP-748, AND VARIANTS VAL-784; ARG-786; LEU-787;
RP SER-787; TYR-793; ASP-798 AND MET-801.
RX PubMed=23890478;
RA Safarikova M., Reiterova J., Safrankova H., Stekrova J., Zidkova A.,
RA Obeidova L., Kohoutova M., Tesar V.;
RT "Mutational analysis of ACTN4, encoding alpha-actinin 4, in patients with
RT focal segmental glomerulosclerosis using HRM method.";
RL Folia Biol. (Praha) 59:110-115(2013).
RN [26]
RP VARIANTS FSGS1 ARG-59; GLN-72; LEU-153; GLU-255; ILE-259 AND PRO-262.
RX PubMed=23014460; DOI=10.1038/ki.2012.349;
RA Barua M., Brown E.J., Charoonratana V.T., Genovese G., Sun H., Pollak M.R.;
RT "Mutations in the INF2 gene account for a significant proportion of
RT familial but not sporadic focal and segmental glomerulosclerosis.";
RL Kidney Int. 83:316-322(2013).
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 (Probable). Probably involved in vesicular trafficking via its
CC association with the CART complex. The CART complex is necessary for
CC efficient transferrin receptor recycling but not for EGFR degradation
CC (PubMed:15772161). Involved in tight junction assembly in epithelial
CC cells probably through interaction with MICALL2. Links MICALL2 to the
CC actin cytoskeleton and recruits it to the tight junctions (By
CC similarity). May also function as a transcriptional coactivator,
CC stimulating transcription mediated by the nuclear hormone receptors
CC PPARG and RARA (PubMed:22351778). {ECO:0000250|UniProtKB:P57780,
CC ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778,
CC ECO:0000305|PubMed:9508771}.
CC -!- SUBUNIT: Homodimer; antiparallel. Binds TRIM3 at the N-terminus
CC (PubMed:15772161). Interacts with MICALL2 (preferentially in opened
CC conformation); stimulated by RAB13 activation (By similarity).
CC Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and
CC SPTBN1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule
CC complex containing untranslated mRNAs (PubMed:17289661). Component of
CC the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3
CC (PubMed:15772161). Interacts with MAGI1 (PubMed:12042308). Interacts
CC with PDLIM2 (By similarity). Interacts with PPARG and RARA
CC (PubMed:22351778). Binds to VCL; this interaction triggers VCL
CC conformational changes (PubMed:15988023). Interacts with SEPTIN14
CC (PubMed:33228246). {ECO:0000250|UniProtKB:P57780,
CC ECO:0000250|UniProtKB:Q9QXQ0, ECO:0000269|PubMed:12042308,
CC ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:15988023,
CC ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:22351778,
CC ECO:0000269|PubMed:33228246}.
CC -!- INTERACTION:
CC O43707; Q08043: ACTN3; NbExp=3; IntAct=EBI-351526, EBI-2880652;
CC O43707; A8K571: BMP7; NbExp=3; IntAct=EBI-351526, EBI-10174327;
CC O43707; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-351526, EBI-725606;
CC O43707; P35222: CTNNB1; NbExp=7; IntAct=EBI-351526, EBI-491549;
CC O43707; P46940: IQGAP1; NbExp=4; IntAct=EBI-351526, EBI-297509;
CC O43707; O60294: LCMT2; NbExp=3; IntAct=EBI-351526, EBI-11023122;
CC O43707; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-351526, EBI-739832;
CC O43707; P50222: MEOX2; NbExp=3; IntAct=EBI-351526, EBI-748397;
CC O43707; Q8IY33: MICALL2; NbExp=3; IntAct=EBI-351526, EBI-2555563;
CC O43707; Q9NPC6: MYOZ2; NbExp=16; IntAct=EBI-351526, EBI-746712;
CC O43707; O00151: PDLIM1; NbExp=3; IntAct=EBI-351526, EBI-724897;
CC O43707; O94875-10: SORBS2; NbExp=4; IntAct=EBI-351526, EBI-12037893;
CC O43707; Q07157: TJP1; NbExp=4; IntAct=EBI-351526, EBI-79553;
CC O43707; B2R8Y4; NbExp=3; IntAct=EBI-351526, EBI-10175581;
CC O43707; P03466: NP; Xeno; NbExp=2; IntAct=EBI-351526, EBI-2547640;
CC O43707; Q5L4H4: NP; Xeno; NbExp=5; IntAct=EBI-351526, EBI-9512099;
CC O43707-1; P10276: RARA; NbExp=2; IntAct=EBI-15971664, EBI-413374;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22351778,
CC ECO:0000269|PubMed:9508771}. Cytoplasm {ECO:0000269|PubMed:22351778,
CC ECO:0000269|PubMed:9508771}. Cell junction
CC {ECO:0000250|UniProtKB:P57780}. Cytoplasm, cytoskeleton, stress fiber
CC {ECO:0000269|PubMed:9508771}. 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). Nuclear translocation can be induced by
CC the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively
CC localized in the nucleus in a limited number of cell lines (breast
CC cancer cell line MCF-7, oral floor cancer IMC-2, and bladder cancer KU-
CC 7). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:17289661,
CC ECO:0000269|PubMed:9508771}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O43707-1; Sequence=Displayed;
CC Name=ACTN4ISO;
CC IsoId=O43707-2; Sequence=VSP_047733;
CC Name=3;
CC IsoId=O43707-3; Sequence=VSP_053401;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9508771}.
CC -!- DOMAIN: Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates
CC interaction with nuclear receptors. {ECO:0000269|PubMed:22351778}.
CC -!- DISEASE: Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]: A
CC renal pathology defined by the presence of segmental sclerosis in
CC glomeruli and resulting in proteinuria, reduced glomerular filtration
CC rate and progressive decline in renal function. Renal insufficiency
CC often progresses to end-stage renal disease, a highly morbid state
CC requiring either dialysis therapy or kidney transplantation.
CC {ECO:0000269|PubMed:10700177, ECO:0000269|PubMed:18164029,
CC ECO:0000269|PubMed:18436095, ECO:0000269|PubMed:22351778,
CC ECO:0000269|PubMed:22732337, ECO:0000269|PubMed:23014460,
CC ECO:0000269|PubMed:23890478}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform ACTN4ISO]: Does not colocalize with actin
CC cytoskeleton structures. {ECO:0000269|PubMed:22567897}.
CC -!- SIMILARITY: Belongs to the alpha-actinin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC17470.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA24447.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U48734; AAC17470.1; ALT_FRAME; mRNA.
DR EMBL; GU987085; ADG03678.1; -; mRNA.
DR EMBL; DQ431186; ABD96103.1; -; mRNA.
DR EMBL; AC008649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005033; AAH05033.1; -; mRNA.
DR EMBL; AL047603; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AU118403; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; D89980; BAA24447.1; ALT_INIT; mRNA.
DR CCDS; CCDS12518.1; -. [O43707-1]
DR RefSeq; NP_004915.2; NM_004924.5. [O43707-1]
DR PDB; 1WLX; NMR; -; A=519-645.
DR PDB; 1YDI; X-ray; 1.80 A; B=734-757.
DR PDB; 2R0O; X-ray; 2.20 A; A/B=47-271.
DR PDB; 6O31; X-ray; 1.51 A; A=47-271.
DR PDB; 6OA6; X-ray; 1.37 A; A=47-271.
DR PDBsum; 1WLX; -.
DR PDBsum; 1YDI; -.
DR PDBsum; 2R0O; -.
DR PDBsum; 6O31; -.
DR PDBsum; 6OA6; -.
DR AlphaFoldDB; O43707; -.
DR BMRB; O43707; -.
DR SMR; O43707; -.
DR BioGRID; 106596; 261.
DR CORUM; O43707; -.
DR DIP; DIP-33179N; -.
DR IntAct; O43707; 115.
DR MINT; O43707; -.
DR STRING; 9606.ENSP00000252699; -.
DR CarbonylDB; O43707; -.
DR GlyGen; O43707; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43707; -.
DR MetOSite; O43707; -.
DR PhosphoSitePlus; O43707; -.
DR SwissPalm; O43707; -.
DR BioMuta; ACTN4; -.
DR REPRODUCTION-2DPAGE; O43707; -.
DR CPTAC; CPTAC-7; -.
DR CPTAC; CPTAC-8; -.
DR EPD; O43707; -.
DR jPOST; O43707; -.
DR MassIVE; O43707; -.
DR MaxQB; O43707; -.
DR PaxDb; O43707; -.
DR PeptideAtlas; O43707; -.
DR PRIDE; O43707; -.
DR ProteomicsDB; 12838; -.
DR ProteomicsDB; 49125; -. [O43707-1]
DR Antibodypedia; 974; 431 antibodies from 42 providers.
DR DNASU; 81; -.
DR Ensembl; ENST00000252699.7; ENSP00000252699.2; ENSG00000130402.13. [O43707-1]
DR Ensembl; ENST00000390009.7; ENSP00000439497.1; ENSG00000130402.13. [O43707-2]
DR Ensembl; ENST00000634692.1; ENSP00000488962.1; ENSG00000282844.2. [O43707-2]
DR Ensembl; ENST00000634960.2; ENSP00000489220.1; ENSG00000282844.2. [O43707-1]
DR GeneID; 81; -.
DR KEGG; hsa:81; -.
DR MANE-Select; ENST00000252699.7; ENSP00000252699.2; NM_004924.6; NP_004915.2.
DR UCSC; uc002oja.3; human. [O43707-1]
DR CTD; 81; -.
DR DisGeNET; 81; -.
DR GeneCards; ACTN4; -.
DR HGNC; HGNC:166; ACTN4.
DR HPA; ENSG00000130402; Low tissue specificity.
DR MalaCards; ACTN4; -.
DR MIM; 603278; phenotype.
DR MIM; 604638; gene.
DR neXtProt; NX_O43707; -.
DR OpenTargets; ENSG00000130402; -.
DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome.
DR PharmGKB; PA23; -.
DR VEuPathDB; HostDB:ENSG00000130402; -.
DR eggNOG; KOG0035; Eukaryota.
DR GeneTree; ENSGT00940000159343; -.
DR HOGENOM; CLU_005217_1_1_1; -.
DR InParanoid; O43707; -.
DR OMA; INTAWHT; -.
DR OrthoDB; 543832at2759; -.
DR PhylomeDB; O43707; -.
DR TreeFam; TF352676; -.
DR PathwayCommons; O43707; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR SignaLink; O43707; -.
DR SIGNOR; O43707; -.
DR BioGRID-ORCS; 81; 21 hits in 1087 CRISPR screens.
DR ChiTaRS; ACTN4; human.
DR EvolutionaryTrace; O43707; -.
DR GeneWiki; Actinin_alpha_4; -.
DR GenomeRNAi; 81; -.
DR Pharos; O43707; Tbio.
DR PRO; PR:O43707; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O43707; protein.
DR Bgee; ENSG00000130402; Expressed in popliteal artery and 99 other tissues.
DR ExpressionAtlas; O43707; baseline and differential.
DR Genevisible; O43707; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA: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:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0031143; C:pseudopodium; TAS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0001725; C:stress fiber; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; TAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; TAS:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IMP:UniProtKB.
DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IPI:UniProtKB.
DR GO; GO:0001882; F:nucleoside binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0055001; P:muscle cell development; IBA:GO_Central.
DR GO; GO:1900025; P:negative regulation of substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0035357; P:peroxisome proliferator activated receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0032417; P:positive regulation of sodium:proton antiporter activity; NAS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0042981; P:regulation of apoptotic process; NAS:UniProtKB.
DR GO; GO:1903506; P:regulation of nucleic acid-templated transcription; IMP:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0030050; P:vesicle transport along actin filament; IMP:UniProtKB.
DR CDD; cd00014; CH; 2.
DR CDD; cd00051; EFh; 1.
DR CDD; cd00176; SPEC; 3.
DR Gene3D; 1.10.418.10; -; 2.
DR IDEAL; IID00129; -.
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 3D-structure; Acetylation; Actin-binding; Alternative splicing; Calcium;
KW Cell junction; Cytoplasm; Cytoskeleton; Disease variant; Metal-binding;
KW Nucleus; Phosphoprotein; Protein transport; Reference proteome; Repeat;
KW Transport.
FT CHAIN 1..911
FT /note="Alpha-actinin-4"
FT /id="PRO_0000073440"
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..26
FT /note="Interaction with VCL"
FT /evidence="ECO:0000269|PubMed:15988023,
FT ECO:0007744|PDB:1YDI"
FT REGION 40..61
FT /note="Interaction with VCL"
FT /evidence="ECO:0000269|PubMed:15988023,
FT ECO:0007744|PDB:1YDI"
FT REGION 108..126
FT /note="Interaction with VCL"
FT /evidence="ECO:0000269|PubMed:15988023,
FT ECO:0007744|PDB:1YDI"
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:0000269|PubMed:22351778"
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:0007744|PubMed:19608861"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P12814"
FT MOD_RES 249
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 592
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 625
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
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 VAR_SEQ 54..272
FT /note="Missing (in isoform ACTN4ISO)"
FT /evidence="ECO:0000303|PubMed:22567897"
FT /id="VSP_047733"
FT VAR_SEQ 89..478
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_053401"
FT VARIANT 59
FT /note="W -> R (in FSGS1)"
FT /evidence="ECO:0000269|PubMed:23014460"
FT /id="VAR_079797"
FT VARIANT 72
FT /note="E -> Q (in FSGS1)"
FT /evidence="ECO:0000269|PubMed:23014460"
FT /id="VAR_079798"
FT VARIANT 153
FT /note="F -> L (in FSGS1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23014460"
FT /id="VAR_079799"
FT VARIANT 255
FT /note="K -> E (in FSGS1; no effect on protein abundance; no
FT effect on homodimerization; loss of localization to the
FT nucleus; prevents nuclear localization of the wild-type
FT protein; decreased interaction with PPARG and RARA; loss of
FT transcriptional coactivator activity; dominant negative
FT effect on nuclear receptors-mediated transcription;
FT increased actin-binding affinity; dbSNP:rs121908415)"
FT /evidence="ECO:0000269|PubMed:10700177,
FT ECO:0000269|PubMed:18164029, ECO:0000269|PubMed:22351778,
FT ECO:0000269|PubMed:23014460"
FT /id="VAR_010378"
FT VARIANT 259
FT /note="T -> I (in FSGS1; no effect on protein abundance; no
FT effect on homodimerization; loss of localization to the
FT nucleus; prevents nuclear localization of the wild-type
FT protein; decreased interaction with PPARG and RARA; loss of
FT transcriptional coactivator activity; dominant negative
FT effect on nuclear receptors-mediated transcription;
FT increased actin-binding affinity; dbSNP:rs121908416)"
FT /evidence="ECO:0000269|PubMed:10700177,
FT ECO:0000269|PubMed:18164029, ECO:0000269|PubMed:22351778,
FT ECO:0000269|PubMed:23014460"
FT /id="VAR_010379"
FT VARIANT 262
FT /note="S -> F (in FSGS1)"
FT /evidence="ECO:0000269|PubMed:18436095"
FT /id="VAR_072115"
FT VARIANT 262
FT /note="S -> P (in FSGS1; no effect on protein abundance; no
FT effect on homodimerization; loss of localization to the
FT nucleus; prevents nuclear localization of the wild-type
FT protein; decreased interaction with PPARG and RARA; loss of
FT transcriptional coactivator activity; dominant negative
FT effect on nuclear receptors-mediated transcription;
FT increased actin-binding affinity; dbSNP:rs121908417)"
FT /evidence="ECO:0000269|PubMed:10700177,
FT ECO:0000269|PubMed:18164029, ECO:0000269|PubMed:22351778,
FT ECO:0000269|PubMed:23014460"
FT /id="VAR_010380"
FT VARIANT 310
FT /note="R -> Q (in FSGS1; unknown pathological significance;
FT dbSNP:rs112545413)"
FT /evidence="ECO:0000269|PubMed:22732337"
FT /id="VAR_079800"
FT VARIANT 427
FT /note="A -> T (in FSGS1; dbSNP:rs201128110)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072116"
FT VARIANT 748
FT /note="N -> D (in FSGS1)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072117"
FT VARIANT 784
FT /note="A -> V (rare variant found in patients with IgA
FT nephropathy; unknown pathological significance;
FT dbSNP:rs771421233)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072118"
FT VARIANT 786
FT /note="G -> R"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072119"
FT VARIANT 787
FT /note="P -> L"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072120"
FT VARIANT 787
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072121"
FT VARIANT 793
FT /note="C -> Y (rare variant found in patients with IgA
FT nephropathy; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072122"
FT VARIANT 798
FT /note="G -> D (rare variant found in patients with IgA
FT nephropathy; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072123"
FT VARIANT 801
FT /note="V -> M (in dbSNP:rs141727248)"
FT /evidence="ECO:0000269|PubMed:23890478"
FT /id="VAR_072124"
FT MUTAGEN 87..88
FT /note="LL->AA: Reduced interaction with RARA. Loss of the
FT transcriptional coac tivator activity toward RARA."
FT /evidence="ECO:0000269|PubMed:22351778"
FT CONFLICT 60
FT /note="C -> S (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="S -> L (in Ref. 6; AL047603)"
FT /evidence="ECO:0000305"
FT CONFLICT 221
FT /note="V -> F (in Ref. 7; AU118403)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="T -> TET (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 292..294
FT /note="EHL -> CSTS (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 359..360
FT /note="TL -> SV (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="I -> S (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="I -> II (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="R -> P (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 645
FT /note="Q -> QQ (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 673..674
FT /note="GR -> A (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 850
FT /note="A -> T (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT CONFLICT 891..893
FT /note="AVP -> GVR (in Ref. 1; AAC17470)"
FT /evidence="ECO:0000305"
FT HELIX 47..64
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:6OA6"
FT TURN 74..80
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 82..92
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 105..121
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 131..136
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 139..154
FT /evidence="ECO:0007829|PDB:6OA6"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:6OA6"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 196..205
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 220..234
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:6OA6"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:6O31"
FT HELIX 254..268
FT /evidence="ECO:0007829|PDB:6OA6"
FT HELIX 519..552
FT /evidence="ECO:0007829|PDB:1WLX"
FT HELIX 560..600
FT /evidence="ECO:0007829|PDB:1WLX"
FT STRAND 606..608
FT /evidence="ECO:0007829|PDB:1WLX"
FT HELIX 616..641
FT /evidence="ECO:0007829|PDB:1WLX"
FT HELIX 736..756
FT /evidence="ECO:0007829|PDB:1YDI"
SQ SEQUENCE 911 AA; 104854 MW; 461580C3F22937D1 CRC64;
MVDYHAANQS YQYGPSSAGN GAGGGGSMGD 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 NEHLMEDYEK
LASDLLEWIR RTIPWLEDRV PQKTIQEMQQ KLEDFRDYRR VHKPPKVQEK CQLEINFNTL
QTKLRLSNRP AFMPSEGKMV SDINNGWQHL EQAEKGYEEW LLNEIRRLER LDHLAEKFRQ
KASIHEAWTD GKEAMLKHRD YETATLSDIK ALIRKHEAFE SDLAAHQDRV EQIAAIAQEL
NELDYYDSHN VNTRCQKICD QWDALGSLTH SRREALEKTE KQLEAIDQLH LEYAKRAAPF
NNWMESAMED LQDMFIVHTI EEIEGLISAH DQFKSTLPDA DREREAILAI HKEAQRIAES
NHIKLSGSNP YTTVTPQIIN SKWEKVQQLV PKRDHALLEE QSKQQSNEHL RRQFASQANV
VGPWIQTKME EIGRISIEMN GTLEDQLSHL KQYERSIVDY KPNLDLLEQQ HQLIQEALIF
DNKHTNYTME HIRVGWEQLL TTIARTINEV ENQILTRDAK GISQEQMQEF RASFNHFDKD
HGGALGPEEF KACLISLGYD VENDRQGEAE FNRIMSLVDP NHSGLVTFQA FIDFMSRETT
DTDTADQVIA SFKVLAGDKN FITAEELRRE LPPDQAEYCI ARMAPYQGPD AVPGALDYKS
FSTALYGESD L
