ID   ANKR1_HUMAN             Reviewed;         319 AA.
AC   Q15327; Q96LE7;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 173.
DE   RecName: Full=Ankyrin repeat domain-containing protein 1;
DE   AltName: Full=Cardiac ankyrin repeat protein;
DE   AltName: Full=Cytokine-inducible gene C-193 protein;
DE   AltName: Full=Cytokine-inducible nuclear protein;
GN   Name=ANKRD1; Synonyms=C193, CARP, HA1A2;
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], INDUCTION BY TNF AND IL1A, TISSUE SPECIFICITY,
RP   SUBCELLULAR LOCATION, AND FUNCTION.
RC   TISSUE=Skin;
RX   PubMed=7730328; DOI=10.1074/jbc.270.17.10236;
RA   Chu W., Burns D.K., Swerlick R.A., Presky D.H.;
RT   "Identification and characterization of a novel cytokine-inducible nuclear
RT   protein from human endothelial cells.";
RL   J. Biol. Chem. 270:10236-10245(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY PARTHELONIDE, FUNCTION, TISSUE
RP   SPECIFICITY, AND SUBCELLULAR LOCATION.
RX   PubMed=15805281; DOI=10.1158/0008-5472.can-04-2221;
RA   Park J.-H., Liu L., Kim I.-H., Kim J.-H., You K.-R., Kim D.-G.;
RT   "Identification of the genes involved in enhanced fenretinide-induced
RT   apoptosis by parthenolide in human hepatoma cells.";
RL   Cancer Res. 65:2804-2814(2005).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
RP   INTERACTION WITH TTN.
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   [6]
RP   VARIANT MET-116.
RX   PubMed=18273862; DOI=10.1002/humu.20711;
RA   Cinquetti R., Badi I., Campione M., Bortoletto E., Chiesa G., Parolini C.,
RA   Camesasca C., Russo A., Taramelli R., Acquati F.;
RT   "Transcriptional deregulation and a missense mutation define ANKRD1 as a
RT   candidate gene for total anomalous pulmonary venous return.";
RL   Hum. Mutat. 29:468-474(2008).
CC   -!- FUNCTION: May play an important role in endothelial cell activation.
CC       May act as a nuclear transcription factor that negatively regulates the
CC       expression of cardiac genes. Induction seems to be correlated with
CC       apoptotic cell death in hepatoma cells. {ECO:0000269|PubMed:15805281,
CC       ECO:0000269|PubMed:7730328}.
CC   -!- SUBUNIT: Interacts with YBX1 (By similarity). Interacts with TTN/titin.
CC       {ECO:0000250, ECO:0000269|PubMed:14583192}.
CC   -!- INTERACTION:
CC       Q15327; Q96GN5: CDCA7L; NbExp=3; IntAct=EBI-5653378, EBI-5278764;
CC       Q15327; Q9UPY8: MAPRE3; NbExp=5; IntAct=EBI-5653378, EBI-726739;
CC       Q15327; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-5653378, EBI-16439278;
CC       Q15327; Q9UJ70-2: NAGK; NbExp=3; IntAct=EBI-5653378, EBI-11526455;
CC       Q15327; Q5MJ10: SPANXN2; NbExp=3; IntAct=EBI-5653378, EBI-12023934;
CC       Q15327; Q9NWS9-2: ZNF446; NbExp=6; IntAct=EBI-5653378, EBI-740232;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15805281,
CC       ECO:0000269|PubMed:7730328}.
CC   -!- TISSUE SPECIFICITY: Mainly expressed in activated vascular endothelial
CC       cells. To a lower extent, also expressed in hepatoma cells.
CC       {ECO:0000269|PubMed:15805281, ECO:0000269|PubMed:7730328}.
CC   -!- INDUCTION: By TNF, IL1A/interleukin-1 alpha and parthenolide.
CC       {ECO:0000269|PubMed:15805281, ECO:0000269|PubMed:7730328}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X83703; CAA58676.1; -; mRNA.
DR   EMBL; AY903446; AAX23581.1; -; mRNA.
DR   EMBL; AL590622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC018667; AAH18667.1; -; mRNA.
DR   CCDS; CCDS7412.1; -.
DR   PIR; A57291; A57291.
DR   RefSeq; NP_055206.2; NM_014391.2.
DR   AlphaFoldDB; Q15327; -.
DR   SMR; Q15327; -.
DR   BioGRID; 117975; 27.
DR   IntAct; Q15327; 20.
DR   STRING; 9606.ENSP00000360762; -.
DR   iPTMnet; Q15327; -.
DR   PhosphoSitePlus; Q15327; -.
DR   BioMuta; ANKRD1; -.
DR   DMDM; 109940213; -.
DR   EPD; Q15327; -.
DR   MassIVE; Q15327; -.
DR   MaxQB; Q15327; -.
DR   PaxDb; 9606-ENSP00000360762; -.
DR   PeptideAtlas; Q15327; -.
DR   ProteomicsDB; 60530; -.
DR   Pumba; Q15327; -.
DR   Antibodypedia; 30337; 282 antibodies from 28 providers.
DR   DNASU; 27063; -.
DR   Ensembl; ENST00000371697.4; ENSP00000360762.3; ENSG00000148677.7.
DR   GeneID; 27063; -.
DR   KEGG; hsa:27063; -.
DR   MANE-Select; ENST00000371697.4; ENSP00000360762.3; NM_014391.3; NP_055206.2.
DR   UCSC; uc001khe.2; human.
DR   AGR; HGNC:15819; -.
DR   CTD; 27063; -.
DR   DisGeNET; 27063; -.
DR   GeneCards; ANKRD1; -.
DR   GeneReviews; ANKRD1; -.
DR   HGNC; HGNC:15819; ANKRD1.
DR   HPA; ENSG00000148677; Tissue enriched (heart).
DR   MalaCards; ANKRD1; -.
DR   MIM; 609599; gene.
DR   neXtProt; NX_Q15327; -.
DR   OpenTargets; ENSG00000148677; -.
DR   Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR   PharmGKB; PA134882768; -.
DR   VEuPathDB; HostDB:ENSG00000148677; -.
DR   eggNOG; KOG0504; Eukaryota.
DR   GeneTree; ENSGT00940000153956; -.
DR   HOGENOM; CLU_000134_11_1_1; -.
DR   InParanoid; Q15327; -.
DR   OMA; IKNCQGK; -.
DR   OrthoDB; 5318579at2759; -.
DR   PhylomeDB; Q15327; -.
DR   TreeFam; TF331650; -.
DR   PathwayCommons; Q15327; -.
DR   Reactome; R-HSA-1989781; PPARA activates gene expression.
DR   SignaLink; Q15327; -.
DR   SIGNOR; Q15327; -.
DR   BioGRID-ORCS; 27063; 16 hits in 1154 CRISPR screens.
DR   ChiTaRS; ANKRD1; human.
DR   GeneWiki; ANKRD1; -.
DR   GenomeRNAi; 27063; -.
DR   Pharos; Q15327; Tbio.
DR   PRO; PR:Q15327; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q15327; Protein.
DR   Bgee; ENSG00000148677; Expressed in apex of heart and 97 other cell types or tissues.
DR   ExpressionAtlas; Q15327; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0031674; C:I band; ISS:BHF-UCL.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR   GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR   GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
DR   GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR   GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR   GO; GO:0070412; F:R-SMAD binding; IPI:BHF-UCL.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0031432; F:titin binding; IPI:BHF-UCL.
DR   GO; GO:0003713; F:transcription coactivator activity; IDA:BHF-UCL.
DR   GO; GO:0003714; F:transcription corepressor activity; TAS:BHF-UCL.
DR   GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IDA:BHF-UCL.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:BHF-UCL.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:UniProtKB.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:BHF-UCL.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IMP:BHF-UCL.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL.
DR   GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR   GO; GO:0050714; P:positive regulation of protein secretion; IMP:UniProtKB.
DR   GO; GO:0070528; P:protein kinase C signaling; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL.
DR   GO; GO:0045214; P:sarcomere organization; NAS:BHF-UCL.
DR   GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR   Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 2.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   PANTHER; PTHR24171; ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 39-RELATED; 1.
DR   PANTHER; PTHR24171:SF9; L-ASPARAGINASE; 1.
DR   Pfam; PF12796; Ank_2; 2.
DR   PRINTS; PR01415; ANKYRIN.
DR   SMART; SM00248; ANK; 4.
DR   SUPFAM; SSF48403; Ankyrin repeat; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 4.
DR   Genevisible; Q15327; HS.
PE   1: Evidence at protein level;
KW   ANK repeat; Coiled coil; Disease variant; Nucleus; Reference proteome;
KW   Repeat.
FT   CHAIN           1..319
FT                   /note="Ankyrin repeat domain-containing protein 1"
FT                   /id="PRO_0000240479"
FT   REPEAT          152..181
FT                   /note="ANK 1"
FT   REPEAT          185..214
FT                   /note="ANK 2"
FT   REPEAT          218..247
FT                   /note="ANK 3"
FT   REPEAT          251..280
FT                   /note="ANK 4"
FT   REPEAT          284..315
FT                   /note="ANK 5"
FT   COILED          61..89
FT                   /evidence="ECO:0000255"
FT   VARIANT         116
FT                   /note="T -> M (found in a sporadic case of total anomalous
FT                   pulmonary venous return; uncertain significance;
FT                   dbSNP:rs142354133)"
FT                   /evidence="ECO:0000269|PubMed:18273862"
FT                   /id="VAR_047112"
FT   CONFLICT        71
FT                   /note="K -> P (in Ref. 1; CAA58676)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   319 AA;  36252 MW;  9AD91D2B1344A235 CRC64;
     MMVLKVEELV TGKKNGNGEA GEFLPEDFRD GEYEAAVTLE KQEDLKTLLA HPVTLGEQQW
     KSEKQREAEL KKKKLEQRSK LENLEDLEII IQLKKRKKYR KTKVPVVKEP EPEIITEPVD
     VPTFLKAALE NKLPVVEKFL SDKNNPDVCD EYKRTALHRA CLEGHLAIVE KLMEAGAQIE
     FRDMLESTAI HWASRGGNLD VLKLLLNKGA KISARDKLLS TALHVAVRTG HYECAEHLIA
     CEADLNAKDR EGDTPLHDAV RLNRYKMIRL LIMYGADLNI KNCAGKTPMD LVLHWQNGTK
     AIFDSLRENS YKTSRIATF
//