ANKL1_HUMAN
ID ANKL1_HUMAN Reviewed; 615 AA.
AC Q8NAG6; A8VU82; Q8N8J8;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Ankyrin repeat and LEM domain-containing protein 1;
DE EC=3.1.-.- {ECO:0000269|PubMed:22399800};
DE AltName: Full=Ankyrin repeat domain-containing protein 41;
DE AltName: Full=LEM-domain containing protein 3;
GN Name=ANKLE1; Synonyms=ANKRD41, LEM3;
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], AND VARIANTS THR-31; VAL-71; GLN-94; TRP-184;
RP PRO-311 AND ARG-435.
RA Brachner A., Foisner R., Gotzmann J.;
RT "LEM3 is a novel LEM-domain containing protein.";
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 253-615 (ISOFORM 1), AND VARIANTS VAL-71; PRO-311 AND
RP ARG-435.
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 [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BANF1, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN, AND MUTAGENESIS OF
RP TYR-453; GLY-488 AND GLU-551.
RX PubMed=22399800; DOI=10.1242/jcs.098392;
RA Brachner A., Braun J., Ghodgaonkar M., Castor D., Zlopasa L., Ehrlich V.,
RA Jiricny J., Gotzmann J., Knasmueller S., Foisner R.;
RT "The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA
RT cleavage in vivo.";
RL J. Cell Sci. 125:1048-1057(2012).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL, NUCLEAR LOCALIZATION
RP SIGNAL, AND MUTAGENESIS OF 110-LEU--LEU-117; 271-LEU--LEU-280 AND
RP 486-TYR--GLY-488.
RX PubMed=27245214; DOI=10.1186/s12860-016-0102-z;
RA Zlopasa L., Brachner A., Foisner R.;
RT "Nucleo-cytoplasmic shuttling of the endonuclease ankyrin repeats and LEM
RT domain-containing protein 1 (Ankle1) is mediated by canonical nuclear
RT export- and nuclear import signals.";
RL BMC Cell Biol. 17:23-23(2016).
CC -!- FUNCTION: Endonuclease that probably plays a role in the DNA damage
CC response and DNA repair. {ECO:0000269|PubMed:22399800,
CC ECO:0000269|PubMed:27245214}.
CC -!- SUBUNIT: Interacts (via LEM domain) with BANF1; the interaction may
CC favor BANF1 dimerization. {ECO:0000269|PubMed:22399800}.
CC -!- INTERACTION:
CC Q8NAG6-2; O75531: BANF1; NbExp=2; IntAct=EBI-27052251, EBI-1055977;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22399800,
CC ECO:0000269|PubMed:27245214}. Nucleus {ECO:0000269|PubMed:22399800,
CC ECO:0000269|PubMed:27245214}. Note=At the steady state, localizes
CC predominantly in the cytoplasm. {ECO:0000269|PubMed:22399800,
CC ECO:0000269|PubMed:27245214}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NAG6-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NAG6-1; Sequence=VSP_039879, VSP_039880;
CC -!- TISSUE SPECIFICITY: Expression is predominant in adult bone marrow.
CC {ECO:0000269|PubMed:22399800}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal spleen, liver and thymus.
CC {ECO:0000269|PubMed:22399800}.
CC -!- DOMAIN: The LEM domain is required for GIY-YIG domain-mediated DNA
CC cleavage and induction of DNA damage response.
CC {ECO:0000269|PubMed:22399800}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC04840.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EU184013; ABW73565.1; -; mRNA.
DR EMBL; AK092706; BAC03953.1; -; mRNA.
DR EMBL; AK096688; BAC04840.1; ALT_INIT; mRNA.
DR EMBL; AC010463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS12354.3; -. [Q8NAG6-2]
DR RefSeq; NP_001265372.1; NM_001278443.1.
DR RefSeq; NP_001265374.1; NM_001278445.1. [Q8NAG6-1]
DR RefSeq; NP_689576.5; NM_152363.5. [Q8NAG6-2]
DR AlphaFoldDB; Q8NAG6; -.
DR SMR; Q8NAG6; -.
DR IntAct; Q8NAG6; 1.
DR STRING; 9606.ENSP00000377971; -.
DR iPTMnet; Q8NAG6; -.
DR PhosphoSitePlus; Q8NAG6; -.
DR BioMuta; ANKLE1; -.
DR DMDM; 308153409; -.
DR MassIVE; Q8NAG6; -.
DR PaxDb; Q8NAG6; -.
DR PeptideAtlas; Q8NAG6; -.
DR PRIDE; Q8NAG6; -.
DR ProteomicsDB; 72677; -. [Q8NAG6-2]
DR ProteomicsDB; 72678; -. [Q8NAG6-1]
DR Antibodypedia; 27599; 41 antibodies from 22 providers.
DR DNASU; 126549; -.
DR Ensembl; ENST00000404085.7; ENSP00000384008.3; ENSG00000160117.16. [Q8NAG6-2]
DR GeneID; 126549; -.
DR KEGG; hsa:126549; -.
DR MANE-Select; ENST00000404085.7; ENSP00000384008.3; NM_152363.6; NP_689576.6.
DR UCSC; uc002nga.3; human. [Q8NAG6-2]
DR CTD; 126549; -.
DR DisGeNET; 126549; -.
DR GeneCards; ANKLE1; -.
DR HGNC; HGNC:26812; ANKLE1.
DR HPA; ENSG00000160117; Group enriched (bone marrow, brain).
DR MIM; 619348; gene.
DR neXtProt; NX_Q8NAG6; -.
DR OpenTargets; ENSG00000160117; -.
DR PharmGKB; PA162376509; -.
DR VEuPathDB; HostDB:ENSG00000160117; -.
DR eggNOG; KOG4177; Eukaryota.
DR GeneTree; ENSGT00510000049316; -.
DR InParanoid; Q8NAG6; -.
DR OrthoDB; 1451150at2759; -.
DR PhylomeDB; Q8NAG6; -.
DR TreeFam; TF319333; -.
DR PathwayCommons; Q8NAG6; -.
DR BioGRID-ORCS; 126549; 17 hits in 975 CRISPR screens.
DR ChiTaRS; ANKLE1; human.
DR GenomeRNAi; 126549; -.
DR Pharos; Q8NAG6; Tbio.
DR PRO; PR:Q8NAG6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8NAG6; protein.
DR Bgee; ENSG00000160117; Expressed in bone marrow and 96 other tissues.
DR ExpressionAtlas; Q8NAG6; baseline and differential.
DR Genevisible; Q8NAG6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0045950; P:negative regulation of mitotic recombination; IEA:Ensembl.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IC:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
DR GO; GO:1905456; P:regulation of lymphoid progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:1905453; P:regulation of myeloid progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR Gene3D; 1.10.720.40; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR034998; ANKLE1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR000305; GIY-YIG_endonuc.
DR InterPro; IPR011015; LEM/LEM-like_dom_sf.
DR InterPro; IPR003887; LEM_dom.
DR PANTHER; PTHR46427; PTHR46427; 1.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF03020; LEM; 1.
DR SMART; SM00248; ANK; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF63451; SSF63451; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50164; GIY_YIG; 1.
DR PROSITE; PS50954; LEM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; Cytoplasm; DNA damage; DNA repair;
KW Endonuclease; Hydrolase; Nuclease; Nucleus; Reference proteome; Repeat.
FT CHAIN 1..615
FT /note="Ankyrin repeat and LEM domain-containing protein 1"
FT /id="PRO_0000244370"
FT REPEAT 39..71
FT /note="ANK 1"
FT REPEAT 75..104
FT /note="ANK 2"
FT REPEAT 108..137
FT /note="ANK 3"
FT DOMAIN 355..399
FT /note="LEM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00313"
FT DOMAIN 448..566
FT /note="GIY-YIG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00977"
FT REGION 138..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 271..280
FT /note="Nuclear export signal"
FT /evidence="ECO:0000269|PubMed:27245214"
FT MOTIF 579..586
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:27245214"
FT COMPBIAS 283..298
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..22
FT /note="MCSEARLARRLRDALREEEPWA -> MRCGRRSR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039879"
FT VAR_SEQ 374..399
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039880"
FT VARIANT 31
FT /note="A -> T (in dbSNP:rs8100241)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_063681"
FT VARIANT 71
FT /note="A -> V (in dbSNP:rs1864116)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1"
FT /id="VAR_063682"
FT VARIANT 94
FT /note="L -> Q (in dbSNP:rs8108174)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_033507"
FT VARIANT 160
FT /note="P -> S (in dbSNP:rs59119993)"
FT /id="VAR_061015"
FT VARIANT 184
FT /note="L -> W (in dbSNP:rs2363956)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_033508"
FT VARIANT 311
FT /note="T -> P (in dbSNP:rs891017)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1"
FT /id="VAR_033509"
FT VARIANT 435
FT /note="Q -> R (in dbSNP:rs11086065)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1"
FT /id="VAR_033510"
FT VARIANT 447
FT /note="V -> M (in dbSNP:rs34112069)"
FT /id="VAR_033511"
FT MUTAGEN 110..117
FT /note="LRPLDLAL->ARPADAAA: Slight increase in nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:27245214"
FT MUTAGEN 271..280
FT /note="LNARLQALTL->ANARAQAATA: Increased nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:27245214"
FT MUTAGEN 453
FT /note="Y->A: Loss of endonucleolytic activity."
FT /evidence="ECO:0000269|PubMed:22399800"
FT MUTAGEN 486..488
FT /note="YVG->AAA: Probable loss of endonucleolytic activity.
FT Fails to induce DNA damage response upon leptomycin-
FT mediated nuclear localization. No nuclear translocation
FT upon treatment with DNA damaging agents. Steady state
FT cytoplasmic localization is not affected."
FT /evidence="ECO:0000269|PubMed:27245214"
FT MUTAGEN 488
FT /note="G->A: Loss of endonucleolytic activity."
FT /evidence="ECO:0000269|PubMed:22399800"
FT MUTAGEN 551
FT /note="E->A: Loss of endonucleolytic activity."
FT /evidence="ECO:0000269|PubMed:22399800"
FT CONFLICT 444
FT /note="E -> G (in Ref. 2; BAC03953)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 615 AA; 66890 MW; 5889866143933668 CRC64;
MCSEARLARR LRDALREEEP WAVEELLRCG ADPNLVLEDG AAAVHLAAGA RHPRGLRCLG
ALLRQGGDPN ARSVEALTPL HVAAAWGCRR GLELLLSQGA DPALRDQDGL RPLDLALQQG
HLECARVLQD LDTRTRTRTR IGAETQEPEP APGTPGLSGP TDETLDSIAL QKQPCRGDNR
DIGLEADPGP PSLPVPLETV DKHGSSASPP GHWDYSSDAS FVTAVEVSGA EDPASDTPPW
AGSLPPTRQG LLHVVHANQR VPRSQGTEAE LNARLQALTL TPPNAAGFQS SPSSMPLLDR
SPAHSPPRTP TPGASDCHCL WEHQTSIDSD MATLWLTEDE ASSTGGREPV GPCRHLPVST
VSDLELLKGL RALGENPHPI TPFTRQLYHQ QLEEAQIAPG PEFSGHSLEL AAALRTGCIP
DVQADEDALA QQFEQPDPAR RWREGVVKSS FTYLLLDPRE TQDLPARAFS LTPAERLQTF
IRAIFYVGKG TRARPYVHLW EALGHHGRSR KQPHQACPKV RQILDIWASG CGVVSLHCFQ
HVVAVEAYTR EACIVEALGI QTLTNQKQGH CYGVVAGWPP ARRRRLGVHL LHRALLVFLA
EGERQLHPQD IQARG
