ANRA2_HUMAN
ID ANRA2_HUMAN Reviewed; 313 AA.
AC Q9H9E1;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Ankyrin repeat family A protein 2;
DE AltName: Full=RFXANK-like protein 2;
GN Name=ANKRA2; Synonyms=ANKRA;
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].
RX PubMed=11095640; DOI=10.1681/asn.v11122167;
RA Rader K., Orlando R.A., Lou X., Farquhar M.G.;
RT "Characterization of ANKRA, a novel ankyrin repeat protein that interacts
RT with the cytoplasmic domain of megalin.";
RL J. Am. Soc. Nephrol. 11:2167-2178(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [MRNA].
RA Mao Y., Xie Y., Zhou Z., Zhao W., Zhao S., Wang W., Huang Y., Wang S.,
RA Tang R., Chen X., Wu C.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J.,
RA Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for its
RT short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 148-313 IN COMPLEX WITH HDAC4 AND
RP LRP2 PEPTIDES, DOMAIN ANK REPEATS, INTERACTION WITH LRP2; HDAC4 AND HDAC5,
RP AND MUTAGENESIS OF TRP-188 AND TYR-254.
RX PubMed=22649097; DOI=10.1126/scisignal.2002979;
RA Xu C., Jin J., Bian C., Lam R., Tian R., Weist R., You L., Nie J.,
RA Bochkarev A., Tempel W., Tan C.S., Wasney G.A., Vedadi M., Gish G.D.,
RA Arrowsmith C.H., Pawson T., Yang X.J., Min J.;
RT "Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat
RT tumbler lock.";
RL Sci. Signal. 5:RA39-RA39(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 142-313 IN COMPLEX WITH CCDC8,
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 142-313 IN COMPLEX WITH RFX7,
RP FUNCTION, INTERACTION WITH RFX7 AND THE 3M COMPLEX, DOMAIN, AND MUTAGENESIS
RP OF LYS-31 AND TRP-188.
RX PubMed=25752541; DOI=10.1016/j.str.2015.02.001;
RA Nie J., Xu C., Jin J., Aka J.A., Tempel W., Nguyen V., You L., Weist R.,
RA Min J., Pawson T., Yang X.J.;
RT "Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome
RT protein CCDC8.";
RL Structure 23:700-712(2015).
CC -!- FUNCTION: May regulate the interaction between the 3M complex and the
CC histone deacetylases HDAC4 and HDAC5 (PubMed:25752541). May also
CC regulate LRP2/megalin (By similarity). {ECO:0000250|UniProtKB:A2ARV4,
CC ECO:0000269|PubMed:25752541}.
CC -!- SUBUNIT: Interacts (via ANK repeats) with CCDC8 (via PxLPxI/L motif);
CC mediates the interaction with the 3M complex which is composed of
CC CCDC8, CUL7 and OBSL1 (PubMed:25752541). Interacts (via ANK repeats)
CC with HDAC4 (via PxLPxI/L motif) (PubMed:22649097). Interacts (via ANK
CC repeats) with HDAC5 (via PxLPxI/L motif) (PubMed:22649097). Interacts
CC (via ANK repeats) with LRP2/megalin (via PxLPxI/L motif)
CC (PubMed:22649097). Interacts (via ANK repeats) with RFX7 (via PxLPxI/L
CC motif) (PubMed:25752541). Interacts with AHRR (By similarity).
CC Interacts with NEK6 (PubMed:20873783). {ECO:0000250|UniProtKB:Q99PE2,
CC ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:22649097,
CC ECO:0000269|PubMed:25752541}.
CC -!- INTERACTION:
CC Q9H9E1; Q9H0W5: CCDC8; NbExp=4; IntAct=EBI-10215533, EBI-5236005;
CC Q9H9E1; P56524: HDAC4; NbExp=4; IntAct=EBI-10215533, EBI-308629;
CC Q9H9E1; Q9UQL6: HDAC5; NbExp=2; IntAct=EBI-10215533, EBI-715576;
CC Q9H9E1; Q2KHR2: RFX7; NbExp=2; IntAct=EBI-10215533, EBI-1222187;
CC Q9H9E1; Q9UPU9-3: SAMD4A; NbExp=3; IntAct=EBI-10215533, EBI-11986417;
CC Q9H9E1; Q63HK5: TSHZ3; NbExp=4; IntAct=EBI-10215533, EBI-9053916;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q99PE2}. Membrane
CC {ECO:0000250|UniProtKB:Q99PE2}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q99PE2}.
CC -!- DOMAIN: The ankyrin repeats, mainly ANK 2, ANK 3 and ANK 4, mediate
CC interaction with a wide array of PxLPxI/L motif-containing proteins
CC including HDAC4 and LRP2. The PxLPxI/L motif of interactors can contain
CC a Ser or a Thr residue in position 2, which phosphorylation prevents
CC the interaction with ANKRA2. {ECO:0000269|PubMed:22649097,
CC ECO:0000269|PubMed:25752541}.
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DR EMBL; AF314032; AAK01621.1; -; mRNA.
DR EMBL; AK022876; BAB14288.1; -; mRNA.
DR EMBL; AF251051; AAK34941.1; -; mRNA.
DR EMBL; BC012917; AAH12917.1; -; mRNA.
DR CCDS; CCDS4020.1; -.
DR RefSeq; NP_075526.1; NM_023039.4.
DR PDB; 3SO8; X-ray; 1.90 A; A=149-310.
DR PDB; 3V2O; X-ray; 1.89 A; A=148-313.
DR PDB; 3V2X; X-ray; 1.85 A; A=148-313.
DR PDB; 3V31; X-ray; 1.57 A; A=148-313.
DR PDB; 4LG6; X-ray; 1.80 A; A=142-313.
DR PDB; 4QQI; X-ray; 2.03 A; A=142-313.
DR PDBsum; 3SO8; -.
DR PDBsum; 3V2O; -.
DR PDBsum; 3V2X; -.
DR PDBsum; 3V31; -.
DR PDBsum; 4LG6; -.
DR PDBsum; 4QQI; -.
DR AlphaFoldDB; Q9H9E1; -.
DR SMR; Q9H9E1; -.
DR BioGRID; 121758; 34.
DR CORUM; Q9H9E1; -.
DR ELM; Q9H9E1; -.
DR IntAct; Q9H9E1; 50.
DR STRING; 9606.ENSP00000296785; -.
DR iPTMnet; Q9H9E1; -.
DR PhosphoSitePlus; Q9H9E1; -.
DR BioMuta; ANKRA2; -.
DR DMDM; 27734215; -.
DR EPD; Q9H9E1; -.
DR jPOST; Q9H9E1; -.
DR MassIVE; Q9H9E1; -.
DR MaxQB; Q9H9E1; -.
DR PaxDb; Q9H9E1; -.
DR PeptideAtlas; Q9H9E1; -.
DR PRIDE; Q9H9E1; -.
DR ProteomicsDB; 81315; -.
DR Antibodypedia; 24269; 189 antibodies from 23 providers.
DR DNASU; 57763; -.
DR Ensembl; ENST00000296785.8; ENSP00000296785.3; ENSG00000164331.10.
DR GeneID; 57763; -.
DR KEGG; hsa:57763; -.
DR MANE-Select; ENST00000296785.8; ENSP00000296785.3; NM_023039.5; NP_075526.1.
DR UCSC; uc003kcu.3; human.
DR CTD; 57763; -.
DR DisGeNET; 57763; -.
DR GeneCards; ANKRA2; -.
DR HGNC; HGNC:13208; ANKRA2.
DR HPA; ENSG00000164331; Low tissue specificity.
DR MIM; 605787; gene.
DR neXtProt; NX_Q9H9E1; -.
DR OpenTargets; ENSG00000164331; -.
DR PharmGKB; PA24803; -.
DR VEuPathDB; HostDB:ENSG00000164331; -.
DR eggNOG; KOG0502; Eukaryota.
DR GeneTree; ENSGT00940000157156; -.
DR HOGENOM; CLU_078123_0_0_1; -.
DR InParanoid; Q9H9E1; -.
DR OMA; LMWACAH; -.
DR OrthoDB; 1348558at2759; -.
DR PhylomeDB; Q9H9E1; -.
DR TreeFam; TF333112; -.
DR PathwayCommons; Q9H9E1; -.
DR SignaLink; Q9H9E1; -.
DR BioGRID-ORCS; 57763; 14 hits in 1078 CRISPR screens.
DR ChiTaRS; ANKRA2; human.
DR GenomeRNAi; 57763; -.
DR Pharos; Q9H9E1; Tbio.
DR PRO; PR:Q9H9E1; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9H9E1; protein.
DR Bgee; ENSG00000164331; Expressed in left ovary and 192 other tissues.
DR ExpressionAtlas; Q9H9E1; baseline and differential.
DR Genevisible; Q9H9E1; HS.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
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; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cytoplasm; Cytoskeleton; Membrane;
KW Reference proteome; Repeat.
FT CHAIN 1..313
FT /note="Ankyrin repeat family A protein 2"
FT /id="PRO_0000066895"
FT REPEAT 148..180
FT /note="ANK 1"
FT REPEAT 181..213
FT /note="ANK 2"
FT REPEAT 214..246
FT /note="ANK 3"
FT REPEAT 247..279
FT /note="ANK 4"
FT REPEAT 280..313
FT /note="ANK 5"
FT MUTAGEN 31
FT /note="K->R: No effect on interaction with CCDC8."
FT /evidence="ECO:0000269|PubMed:25752541"
FT MUTAGEN 188
FT /note="W->A: Loss of interaction with CCDC8. Decreased
FT affinity for HDAC4."
FT /evidence="ECO:0000269|PubMed:22649097,
FT ECO:0000269|PubMed:25752541"
FT MUTAGEN 254
FT /note="Y->A: Decreased affinity for HDAC4."
FT /evidence="ECO:0000269|PubMed:22649097"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:4QQI"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:3V2X"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 162..171
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 185..191
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 195..203
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 218..225
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 228..237
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 251..257
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 261..269
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 284..291
FT /evidence="ECO:0007829|PDB:3V31"
FT HELIX 294..307
FT /evidence="ECO:0007829|PDB:3V31"
SQ SEQUENCE 313 AA; 34272 MW; 31C653B10B4ED6E1 CRC64;
MDTSTNLDIG AQLIVEECPS TYSLTGMPDI KIEHPLDPNS EEGSAQGVAM GMKFILPNRF
DMNVCSRFVK SLNEEDSKNI QDQVNSDLEV ASVLFKAECN IHTSPSPGIQ VRHVYTPSTT
KHFSPIKQST TLTNKHRGNE VSTTPLLANS LSVHQLAAQG EMLYLATRIE QENVINHTDE
EGFTPLMWAA AHGQIAVVEF LLQNGADPQL LGKGRESALS LACSKGYTDI VKMLLDCGVD
VNEYDWNGGT PLLYAVHGNH VKCVKMLLES GADPTIETDS GYNSMDLAVA LGYRSVQQVI
ESHLLKLLQN IKE
