ANKR2_HUMAN
ID ANKR2_HUMAN Reviewed; 360 AA.
AC Q9GZV1; Q3B778; Q5T456; Q70EZ9; Q8WUD7; Q96MG0; Q9NQC9;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Ankyrin repeat domain-containing protein 2;
DE AltName: Full=Skeletal muscle ankyrin repeat protein;
DE Short=hArpp;
GN Name=ANKRD2; Synonyms=ARPP;
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 [GENOMIC DNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA]
RP OF 25-360 (ISOFORM 1), VARIANT THR-62, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=11444853; DOI=10.1006/bbrc.2001.5131;
RA Pallavicini A., Kojic S., Bean C., Vainzof M., Salamon M., Ievolella C.,
RA Bortoletto G., Pacchioni B., Zatz M., Lanfranchi G., Faulkner G., Valle G.;
RT "Characterization of human skeletal muscle Ankrd2.";
RL Biochem. Biophys. Res. Commun. 285:378-386(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH TTN, AND VARIANT THR-62.
RC TISSUE=Heart;
RX PubMed=14583192; DOI=10.1016/j.jmb.2003.09.012;
RA Miller M.K., Bang M.-L., Witt C.C., Labeit D., Trombitas C., Watanabe K.,
RA Granzier H., McElhinny A.S., Gregorio C.C., Labeit S.;
RT "The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family
RT of titin filament-based stress response molecules.";
RL J. Mol. Biol. 333:951-964(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-62.
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 25-360 (ISOFORM 2).
RC TISSUE=Skeletal muscle;
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 [MRNA] OF 25-360 (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT THR-62.
RX PubMed=11453652; DOI=10.1006/bbrc.2001.5216;
RA Moriyama M., Tsukamoto Y., Fujiwara M., Kondo G., Nakada C., Baba T.,
RA Ishiguro N., Miyazaki A., Nakamura K., Hori N., Sato K., Shomori K.,
RA Takeuchi K., Satoh H., Mori S., Ito H.;
RT "Identification of a novel human ankyrin-repeated protein homologous to
RT CARP.";
RL Biochem. Biophys. Res. Commun. 285:715-723(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 49-150.
RC TISSUE=Skeletal muscle;
RX PubMed=10873377; DOI=10.1006/geno.2000.6213;
RA Kemp T.J., Sadusky T.J., Saltisi F., Carey N., Moss J., Yang S.Y.,
RA Sassoon D.A., Goldspink G., Coulton G.R.;
RT "Identification of Ankrd2, a novel skeletal muscle gene coding for a
RT stretch-responsive ankyrin-repeat protein.";
RL Genomics 66:229-241(2000).
RN [8]
RP INTERACTION WITH PML; TCAP; TP53/P53 AND YBX1, AND SUBCELLULAR LOCATION.
RX PubMed=15136035; DOI=10.1016/j.jmb.2004.03.071;
RA Kojic S., Medeot E., Guccione E., Krmac H., Zara I., Martinelli V.,
RA Valle G., Faulkner G.;
RT "The Ankrd2 protein, a link between the sarcomere and the nucleus in
RT skeletal muscle.";
RL J. Mol. Biol. 339:313-325(2004).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-99 BY PKB/AKT2, MUTAGENESIS OF SER-99,
RP INTERACTION WITH AKT2, AND SUBCELLULAR LOCATION.
RX PubMed=21737686; DOI=10.1091/mbc.e10-11-0928;
RA Cenni V., Bavelloni A., Beretti F., Tagliavini F., Manzoli L., Lattanzi G.,
RA Maraldi N.M., Cocco L., Marmiroli S.;
RT "Ankrd2/ARPP is a novel Akt2 specific substrate and regulates myogenic
RT differentiation upon cellular exposure to H(2)O(2).";
RL Mol. Biol. Cell 22:2946-2956(2011).
RN [10]
RP FUNCTION, AND INTERACTION WITH TJP1.
RX PubMed=22016770; DOI=10.1371/journal.pone.0025519;
RA Belgrano A., Rakicevic L., Mittempergher L., Campanaro S., Martinelli V.C.,
RA Mouly V., Valle G., Kojic S., Faulkner G.;
RT "Multi-tasking role of the mechanosensing protein Ankrd2 in the signaling
RT network of striated muscle.";
RL PLoS ONE 6:E25519-E25519(2011).
CC -!- FUNCTION: Functions as a negative regulator of myocyte differentiation.
CC May interact with both sarcoplasmic structural proteins and nuclear
CC proteins to regulate gene expression during muscle development and in
CC response to muscle stress. {ECO:0000269|PubMed:21737686,
CC ECO:0000269|PubMed:22016770}.
CC -!- SUBUNIT: Interacts with ID3; both proteins cooperate in myoblast
CC differentiation (By similarity). Interacts with TTN/titin. Interacts
CC (via ANK repeats) with TCAP; the interaction is direct. Interacts with
CC TJP1 (via PDZ domains). Interacts with PML; the interaction is direct.
CC Interacts with p53/TP53. Interacts with YBX1. Interacts with AKT2.
CC {ECO:0000250, ECO:0000269|PubMed:14583192, ECO:0000269|PubMed:15136035,
CC ECO:0000269|PubMed:21737686, ECO:0000269|PubMed:22016770}.
CC -!- INTERACTION:
CC Q9GZV1; Q16659: MAPK6; NbExp=7; IntAct=EBI-12111292, EBI-1384105;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, I band
CC {ECO:0000250}. Cytoplasm, cytosol. Nucleus. Nucleus, PML body. Note=In
CC the sarcoplasm of differentiated striated muscle cells, where it is
CC cytosolic and enriched in the I band. In nucleus and PML bodies of
CC proliferating and undifferentiated myoblasts. Associates with the
CC euchromatin in the nucleus of myocytes upon muscle stress.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GZV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZV1-2; Sequence=VSP_000269;
CC -!- TISSUE SPECIFICITY: Mostly expressed in skeletal and cardiac muscles.
CC Found in slow fibers. Also expressed in kidney, but to a lower extent
CC (at protein level). {ECO:0000269|PubMed:11444853,
CC ECO:0000269|PubMed:11453652}.
CC -!- PTM: Phosphorylation at Ser-99 by PKB/AKT2 in response to oxidative
CC stress induces translocation to the nucleus and negatively regulates
CC myoblast differentiation. {ECO:0000269|PubMed:21737686}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK056990; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB60958.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC19411.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAC19412.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAE47432.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ304804; CAC19411.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ304805; CAC19412.1; ALT_INIT; mRNA.
DR EMBL; AJ583444; CAE47432.1; ALT_INIT; mRNA.
DR EMBL; AK056990; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL355315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020817; AAH20817.2; -; mRNA.
DR EMBL; BC107759; AAI07760.1; -; mRNA.
DR EMBL; AB058599; BAB60958.1; ALT_INIT; mRNA.
DR EMBL; AJ249975; CAB99416.1; -; mRNA.
DR CCDS; CCDS44468.1; -. [Q9GZV1-2]
DR CCDS; CCDS7466.1; -. [Q9GZV1-1]
DR PIR; JC7713; JC7713.
DR RefSeq; NP_001123453.1; NM_001129981.2. [Q9GZV1-2]
DR RefSeq; NP_001278147.1; NM_001291218.1.
DR RefSeq; NP_001278148.2; NM_001291219.2.
DR RefSeq; NP_001333726.1; NM_001346797.1.
DR RefSeq; NP_065082.2; NM_020349.3. [Q9GZV1-1]
DR AlphaFoldDB; Q9GZV1; -.
DR SMR; Q9GZV1; -.
DR BioGRID; 117669; 16.
DR IntAct; Q9GZV1; 4.
DR STRING; 9606.ENSP00000306163; -.
DR iPTMnet; Q9GZV1; -.
DR PhosphoSitePlus; Q9GZV1; -.
DR BioMuta; ANKRD2; -.
DR DMDM; 182676433; -.
DR EPD; Q9GZV1; -.
DR jPOST; Q9GZV1; -.
DR MassIVE; Q9GZV1; -.
DR MaxQB; Q9GZV1; -.
DR PaxDb; Q9GZV1; -.
DR PeptideAtlas; Q9GZV1; -.
DR PRIDE; Q9GZV1; -.
DR ProteomicsDB; 80153; -. [Q9GZV1-1]
DR ProteomicsDB; 80154; -. [Q9GZV1-2]
DR Antibodypedia; 30973; 91 antibodies from 22 providers.
DR DNASU; 26287; -.
DR Ensembl; ENST00000298808.9; ENSP00000298808.5; ENSG00000165887.12. [Q9GZV1-2]
DR Ensembl; ENST00000307518.9; ENSP00000306163.5; ENSG00000165887.12. [Q9GZV1-1]
DR GeneID; 26287; -.
DR KEGG; hsa:26287; -.
DR UCSC; uc001knw.5; human. [Q9GZV1-1]
DR CTD; 26287; -.
DR DisGeNET; 26287; -.
DR GeneCards; ANKRD2; -.
DR HGNC; HGNC:495; ANKRD2.
DR HPA; ENSG00000165887; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MIM; 610734; gene.
DR neXtProt; NX_Q9GZV1; -.
DR OpenTargets; ENSG00000165887; -.
DR PharmGKB; PA24804; -.
DR VEuPathDB; HostDB:ENSG00000165887; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000153956; -.
DR InParanoid; Q9GZV1; -.
DR OrthoDB; 1514637at2759; -.
DR PhylomeDB; Q9GZV1; -.
DR TreeFam; TF331650; -.
DR PathwayCommons; Q9GZV1; -.
DR SignaLink; Q9GZV1; -.
DR SIGNOR; Q9GZV1; -.
DR BioGRID-ORCS; 26287; 5 hits in 1032 CRISPR screens.
DR GeneWiki; ANKRD2; -.
DR GenomeRNAi; 26287; -.
DR Pharos; Q9GZV1; Tbio.
DR PRO; PR:Q9GZV1; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9GZV1; protein.
DR Bgee; ENSG00000165887; Expressed in hindlimb stylopod muscle and 140 other tissues.
DR ExpressionAtlas; Q9GZV1; baseline and differential.
DR Genevisible; Q9GZV1; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0031674; C:I band; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:MGI.
DR GO; GO:0008307; F:structural constituent of muscle; NAS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; NAS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; NAS:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IDA:MGI.
DR Gene3D; 1.25.40.20; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR Pfam; PF12796; Ank_2; 2.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 5.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..360
FT /note="Ankyrin repeat domain-containing protein 2"
FT /id="PRO_0000066897"
FT REPEAT 147..176
FT /note="ANK 1"
FT REPEAT 180..209
FT /note="ANK 2"
FT REPEAT 213..242
FT /note="ANK 3"
FT REPEAT 246..275
FT /note="ANK 4"
FT REPEAT 279..308
FT /note="ANK 5"
FT REGION 5..120
FT /note="May mediate interaction with PML, p53/TP53 and YBX1"
FT /evidence="ECO:0000269|PubMed:15136035"
FT REGION 126..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 99
FT /note="Phosphoserine; by PKB/AKT2"
FT /evidence="ECO:0000269|PubMed:21737686"
FT VAR_SEQ 246..278
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000269"
FT VARIANT 62
FT /note="A -> T (in dbSNP:rs7094973)"
FT /evidence="ECO:0000269|PubMed:11444853,
FT ECO:0000269|PubMed:11453652, ECO:0000269|PubMed:14583192,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_042498"
FT MUTAGEN 99
FT /note="S->A: Loss of interaction and phosphorylation by
FT PKB/AKT2, loss of translocation to the nucleus and loss of
FT function in myocyte differentiation."
FT /evidence="ECO:0000269|PubMed:21737686"
FT CONFLICT 49
FT /note="L -> S (in Ref. 7; CAB99416)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 39859 MW; E88FC3FA242D0739 CRC64;
MAKAPSWAGV GALAYKAPEA LWPAEAVMDG TMEDSEAVQR ATALIEQRLA QEEENEKLRG
DARQKLPMDL LVLEDEKHHG AQSAALQKVK GQERVRKTSL DLRREIIDVG GIQNLIELRK
KRKQKKRDAL AASHEPPPEP EEITGPVDEE TFLKAAVEGK MKVIEKFLAD GGSADTCDQF
RRTALHRASL EGHMEILEKL LDNGATVDFQ DRLDCTAMHW ACRGGHLEVV KLLQSHGADT
NVRDKLLSTP LHVAVRTGQV EIVEHFLSLG LEINARDREG DTALHDAVRL NRYKIIKLLL
LHGADMMTKN LAGKTPTDLV QLWQADTRHA LEHPEPGAEH NGLEGPNDSG RETPQPVPAQ
