ANKR9_HUMAN
ID ANKR9_HUMAN Reviewed; 317 AA.
AC Q96BM1; A8K753;
DT 09-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Ankyrin repeat domain-containing protein 9;
GN Name=ANKRD9;
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 [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Duodenum;
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 FUNCTION.
RX PubMed=24522796; DOI=10.1038/ncomms4301;
RA Malinouski M., Hasan N.M., Zhang Y., Seravalli J., Lin J., Avanesov A.,
RA Lutsenko S., Gladyshev V.N.;
RT "Genome-wide RNAi ionomics screen reveals new genes and regulation of human
RT trace element metabolism.";
RL Nat. Commun. 5:3301-3301(2014).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH IMPDH2.
RX PubMed=30293565; DOI=10.1016/j.bbadis.2018.07.001;
RA Lee Y., Lim B., Lee S.W., Lee W.R., Kim Y.I., Kim M., Ju H., Kim M.Y.,
RA Kang S.J., Song J.J., Lee J.E., Kang C.;
RT "ANKRD9 is associated with tumor suppression as a substrate receptor
RT subunit of ubiquitin ligase.";
RL Biochim. Biophys. Acta 1864:3145-3153(2018).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-109; CYS-110 AND
RP ARG-125.
RX PubMed=31337707; DOI=10.1074/jbc.ra119.008231;
RA Hayward D., Kouznetsova V.L., Pierson H.E., Hasan N.M., Guzman E.R.,
RA Tsigelny I.F., Lutsenko S.;
RT "ANKRD9 is a metabolically-controlled regulator of IMPDH2 abundance and
RT macro-assembly.";
RL J. Biol. Chem. 294:14454-14466(2019).
CC -!- FUNCTION: Substrate receptor subunit of a cullin-RING superfamily E3
CC ligase complex (CUL5-based E3 ubiquitin ligase complex) which mediates
CC the ubiquitination and subsequent proteasomal degradation of target
CC proteins (PubMed:30293565). Depending of the metabolic state of the
CC cell, promotes the proteasomal degradation of IMPDH2, the rate-limiting
CC enzyme in GTP biosynthesis or protects IMPDH2 by stabilizing IMPDH2
CC filaments assembly (PubMed:30293565, PubMed:31337707). Implicated in
CC different cellular processes, like copper homeostasis and cell
CC proliferation (PubMed:24522796, PubMed:30293565).
CC {ECO:0000269|PubMed:24522796, ECO:0000269|PubMed:30293565,
CC ECO:0000269|PubMed:31337707}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000305|PubMed:30293565}.
CC -!- SUBUNIT: Part of an E3 ubiquitin-protein ligase complex with Elongin BC
CC (ELOB and ELOC), CUL5 and ANKRD9 (PubMed:30293565). Interacts with
CC IMPDH2; leading to ubiquitination of IMPDH2 and its subsequent
CC proteasomal degradation (PubMed:31337707).
CC {ECO:0000269|PubMed:30293565, ECO:0000269|PubMed:31337707}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000269|PubMed:31337707}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:30293565, ECO:0000269|PubMed:31337707}.
CC Note=Detected in long filamentous cytosolic structures where it
CC colocalizes with IMPDH2 (PubMed:31337707). Under basal conditions
CC ANKRD9 is mainly in vesicle-like structures, upon nutrient limitation
CC (guanine nucleotides deficiency) ANKRD9 loses its vesicular pattern and
CC assembles with IMPDH2 into rodlike filaments (PubMed:31337707).
CC {ECO:0000269|PubMed:31337707}.
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DR EMBL; BX161460; CAD61921.1; -; mRNA.
DR EMBL; AK291868; BAF84557.1; -; mRNA.
DR EMBL; AL136293; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81792.1; -; Genomic_DNA.
DR EMBL; BC015422; AAH15422.1; -; mRNA.
DR EMBL; BC027479; AAH27479.1; -; mRNA.
DR CCDS; CCDS9973.1; -.
DR RefSeq; NP_001335580.1; NM_001348651.1.
DR RefSeq; NP_001335581.1; NM_001348652.1.
DR RefSeq; NP_689539.1; NM_152326.3.
DR RefSeq; XP_005267367.1; XM_005267310.2.
DR AlphaFoldDB; Q96BM1; -.
DR SMR; Q96BM1; -.
DR BioGRID; 125768; 26.
DR IntAct; Q96BM1; 2.
DR STRING; 9606.ENSP00000286918; -.
DR iPTMnet; Q96BM1; -.
DR PhosphoSitePlus; Q96BM1; -.
DR BioMuta; ANKRD9; -.
DR DMDM; 34582329; -.
DR EPD; Q96BM1; -.
DR MassIVE; Q96BM1; -.
DR PaxDb; Q96BM1; -.
DR PeptideAtlas; Q96BM1; -.
DR PRIDE; Q96BM1; -.
DR ProteomicsDB; 76089; -.
DR Antibodypedia; 27869; 75 antibodies from 17 providers.
DR DNASU; 122416; -.
DR Ensembl; ENST00000286918.9; ENSP00000286918.4; ENSG00000156381.9.
DR Ensembl; ENST00000559651.1; ENSP00000454100.1; ENSG00000156381.9.
DR Ensembl; ENST00000560748.5; ENSP00000453650.1; ENSG00000156381.9.
DR GeneID; 122416; -.
DR KEGG; hsa:122416; -.
DR MANE-Select; ENST00000286918.9; ENSP00000286918.4; NM_152326.4; NP_689539.1.
DR UCSC; uc001ylx.2; human.
DR CTD; 122416; -.
DR DisGeNET; 122416; -.
DR GeneCards; ANKRD9; -.
DR HGNC; HGNC:20096; ANKRD9.
DR HPA; ENSG00000156381; Tissue enhanced (heart muscle, skeletal muscle).
DR MIM; 618605; gene.
DR neXtProt; NX_Q96BM1; -.
DR OpenTargets; ENSG00000156381; -.
DR PharmGKB; PA134971966; -.
DR VEuPathDB; HostDB:ENSG00000156381; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00390000018116; -.
DR HOGENOM; CLU_066027_0_0_1; -.
DR InParanoid; Q96BM1; -.
DR OMA; MPWSVRW; -.
DR OrthoDB; 1244686at2759; -.
DR PhylomeDB; Q96BM1; -.
DR TreeFam; TF331214; -.
DR PathwayCommons; Q96BM1; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q96BM1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 122416; 7 hits in 1070 CRISPR screens.
DR GenomeRNAi; 122416; -.
DR Pharos; Q96BM1; Tdark.
DR PRO; PR:Q96BM1; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96BM1; protein.
DR Bgee; ENSG00000156381; Expressed in pancreatic ductal cell and 184 other tissues.
DR ExpressionAtlas; Q96BM1; baseline and differential.
DR Genevisible; Q96BM1; HS.
DR GO; GO:0031466; C:Cul5-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IMP:UniProtKB.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Cytoplasm; Cytoplasmic vesicle; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..317
FT /note="Ankyrin repeat domain-containing protein 9"
FT /id="PRO_0000066903"
FT REPEAT 71..100
FT /note="ANK 1"
FT REPEAT 112..141
FT /note="ANK 2"
FT REPEAT 158..187
FT /note="ANK 3"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..110
FT /note="Important role in both nutrient sensing and
FT binding/regulation of IMPDH2"
FT /evidence="ECO:0000269|PubMed:31337707"
FT MUTAGEN 109
FT /note="C->S: Inhibits the vesicle-to-rods transition under
FT nutrient-limiting conditions. Inhibits the vesicle-to-rods
FT transition under nutrient-limiting conditions; when
FT associated with C-110. Prevents the colocalization of
FT ANKRD9 with IMPDH2 filaments. Increases the abundance of
FT IMPDH2. Increases the abundance of IMPDH2; when associated
FT with C-110."
FT /evidence="ECO:0000269|PubMed:31337707"
FT MUTAGEN 110
FT /note="C->S: Inhibits the vesicle-to-rods transition under
FT nutrient-limiting conditions. Inhibits the vesicle-to-rods
FT transition under nutrient-limiting conditions; when
FT associated with C-109. Does not affect the abundance of
FT IMPDH2."
FT /evidence="ECO:0000269|PubMed:31337707"
FT MUTAGEN 125
FT /note="R->A: Loss the vesicle-like pattern and becomes
FT diffuse in the cytosol."
FT /evidence="ECO:0000269|PubMed:31337707"
SQ SEQUENCE 317 AA; 34295 MW; 9667F8A9437BC790 CRC64;
MPWDARRPGG GADGGPEASG AARSRAQKQC RKSSFAFYQA VRDLLPVWLL EDMRASEAFH
WDERGRAAAY SPSEALLYAL VHDHQAYAHY LLATFPRRAL APPSAGFRCC AAPGPHVALA
VRYNRVGILR RILRTLRDFP AEERARVLDR RGCSRVEGGG TSLHVACELA RPECLFLLLG
HGASPGLRDG GGLTPLELLL RQLGRDAGAT PSAAGAPASA PGEPRQRRLL LLDLLALYTP
VGAAGSARQE LLGDRPRWQR LLGEDKFQWL AGLAPPSLFA RAMQVLVTAI SPGRFPEALD
ELPLPPFLQP LDLTGKG
