ZFAN5_MOUSE
ID ZFAN5_MOUSE Reviewed; 213 AA.
AC O88878; Q3B7K8;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=AN1-type zinc finger protein 5;
DE AltName: Full=Zinc finger A20 domain-containing protein 2;
DE AltName: Full=Zinc finger protein 216;
GN Name=Zfand5; Synonyms=Za20d2, Zfp216, Znf216;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9758550; DOI=10.1016/s0378-1119(98)00316-3;
RA Scott D.A., Greinwald J.H. Jr., Marietta J.R., Drury S., Swiderski R.E.,
RA Vinas A., DeAngelis M.M., Carmi R., Ramesh A., Kraft M.L., Elbedour K.,
RA Skworak A.B., Friedman R.A., Srikumari Srisailapathy C.R., Verhoeven K.,
RA Van Camp G., Lovett M., Deininger P.L., Batzer M.A., Morton C.C.,
RA Keats B.J., Smith R.J.H., Sheffield V.C.;
RT "Identification and mutation analysis of a cochlear-expressed, zinc finger
RT protein gene at the DFNB7/11 and dn hearing-loss loci on human chromosome
RT 9q and mouse chromosome 19.";
RL Gene 215:461-469(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129; TISSUE=Mammary gland;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=14754897; DOI=10.1074/jbc.m309491200;
RA Huang J., Teng L., Li L., Liu T., Li L., Chen D., Xu L.-G., Zhai Z.,
RA Shu H.-B.;
RT "ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor of
RT NFkappaB activation.";
RL J. Biol. Chem. 279:16847-16853(2004).
RN [5]
RP INDUCTION, AND FUNCTION.
RX PubMed=16194934; DOI=10.1080/10799890500240781;
RA Hishiya A., Ikeda K., Watanabe K.;
RT "A RANKL-inducible gene Znf216 in osteoclast differentiation.";
RL J. Recept. Signal Transduct. 25:199-216(2005).
RN [6]
RP DISRUPTION PHENOTYPE, UBIQUITIN-BINDING, DOMAIN A20-TYPE ZINC-FINGER, AND
RP FUNCTION.
RX PubMed=16424905; DOI=10.1038/sj.emboj.7600945;
RA Hishiya A., Iemura S., Natsume T., Takayama S., Ikeda K., Watanabe K.;
RT "A novel ubiquitin-binding protein ZNF216 functioning in muscle atrophy.";
RL EMBO J. 25:554-564(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48 AND SER-58, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-209, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [9]
RP STRUCTURE BY NMR OF 132-194.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ZF-AN1 domain from mouse zinc finger protein
RT 216.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Involved in protein degradation via the ubiquitin-proteasome
CC system. May act by anchoring ubiquitinated proteins to the proteasome.
CC Plays a role in ubiquitin-mediated protein degradation during muscle
CC atrophy. Plays a role in the regulation of NF-kappa-B activation and
CC apoptosis. Inhibits NF-kappa-B activation triggered by overexpression
CC of RIPK1 and TRAF6 but not of RELA. Inhibits also tumor necrosis factor
CC (TNF), IL-1 and TLR4-induced NF-kappa-B activation in a dose-dependent
CC manner. Overexpression sensitizes cells to TNF-induced apoptosis. Is a
CC potent inhibitory factor for osteoclast differentiation.
CC {ECO:0000269|PubMed:16194934, ECO:0000269|PubMed:16424905}.
CC -!- SUBUNIT: Homooligomer and/or heterooligomer. Interacts (via A20-type
CC domain) with IKBKG and RIPK1 and with TRAF6 (via AN1-type domain) (By
CC similarity). Interacts with ubiquitin and polyubiquitinated proteins.
CC Identified in a heterotrimeric complex with ubiquitin and SQSTM1, where
CC ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, muscle, eye, and heart, lower
CC expression in lung, kidney, and spleen, and very low expression in
CC liver. Expressed in myoblast C2C12 cells (at protein level).
CC {ECO:0000269|PubMed:14754897, ECO:0000269|PubMed:9758550}.
CC -!- INDUCTION: Up-regulated after TNFSF11 stimulation. Expression also
CC induced by other cytokines such as TNF and IL1B. No significant
CC inhibitory effect on the NF-kappa-B pathway is observed. Expression is
CC increased in both denervation- and fasting-induced muscle atrophy.
CC {ECO:0000269|PubMed:16194934}.
CC -!- DOMAIN: The A20-type zinc finger directly binds polyubiquitin chains
CC and associates with the 26S proteasome. The zinc-finger A20-type domain
CC is essential for inhibition of NF-kappa-B activation.
CC {ECO:0000269|PubMed:16424905}.
CC -!- DISRUPTION PHENOTYPE: Resistance to muscle atrophy accompanied by
CC abnormal accumulation of polyubiquitinated proteins in skeletal muscle.
CC {ECO:0000269|PubMed:16424905}.
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; AF062071; AAC42600.1; -; mRNA.
DR EMBL; AK076397; BAC36321.1; -; mRNA.
DR EMBL; BC107566; AAI07567.1; -; mRNA.
DR EMBL; BC119124; AAI19125.1; -; mRNA.
DR EMBL; BC119126; AAI19127.1; -; mRNA.
DR CCDS; CCDS29697.1; -.
DR RefSeq; NP_033577.1; NM_009551.5.
DR RefSeq; XP_006527121.1; XM_006527058.3.
DR PDB; 1WFL; NMR; -; A=134-194.
DR PDBsum; 1WFL; -.
DR AlphaFoldDB; O88878; -.
DR BMRB; O88878; -.
DR SMR; O88878; -.
DR BioGRID; 204649; 6.
DR STRING; 10090.ENSMUSP00000025659; -.
DR iPTMnet; O88878; -.
DR PhosphoSitePlus; O88878; -.
DR EPD; O88878; -.
DR MaxQB; O88878; -.
DR PaxDb; O88878; -.
DR PeptideAtlas; O88878; -.
DR PRIDE; O88878; -.
DR ProteomicsDB; 274981; -.
DR Antibodypedia; 12564; 232 antibodies from 17 providers.
DR Ensembl; ENSMUST00000025659; ENSMUSP00000025659; ENSMUSG00000024750.
DR Ensembl; ENSMUST00000237651; ENSMUSP00000158187; ENSMUSG00000024750.
DR GeneID; 22682; -.
DR KEGG; mmu:22682; -.
DR UCSC; uc008gyw.2; mouse.
DR CTD; 7763; -.
DR MGI; MGI:1278334; Zfand5.
DR VEuPathDB; HostDB:ENSMUSG00000024750; -.
DR eggNOG; KOG3173; Eukaryota.
DR GeneTree; ENSGT00940000156165; -.
DR HOGENOM; CLU_057016_1_0_1; -.
DR InParanoid; O88878; -.
DR OMA; AHGCSFD; -.
DR OrthoDB; 1551371at2759; -.
DR PhylomeDB; O88878; -.
DR TreeFam; TF313612; -.
DR BioGRID-ORCS; 22682; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Zfand5; mouse.
DR EvolutionaryTrace; O88878; -.
DR PRO; PR:O88878; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; O88878; protein.
DR Bgee; ENSMUSG00000024750; Expressed in habenula and 270 other tissues.
DR ExpressionAtlas; O88878; baseline and differential.
DR Genevisible; O88878; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0060324; P:face development; IMP:MGI.
DR GO; GO:0010761; P:fibroblast migration; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0003016; P:respiratory system process; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0048745; P:smooth muscle tissue development; IMP:MGI.
DR GO; GO:0001944; P:vasculature development; IMP:MGI.
DR Gene3D; 4.10.1110.10; -; 1.
DR InterPro; IPR035896; AN1-like_Znf.
DR InterPro; IPR002653; Znf_A20.
DR InterPro; IPR000058; Znf_AN1.
DR Pfam; PF01754; zf-A20; 1.
DR Pfam; PF01428; zf-AN1; 1.
DR SMART; SM00259; ZnF_A20; 1.
DR SMART; SM00154; ZnF_AN1; 1.
DR SUPFAM; SSF118310; SSF118310; 1.
DR PROSITE; PS51036; ZF_A20; 1.
DR PROSITE; PS51039; ZF_AN1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Metal-binding; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..213
FT /note="AN1-type zinc finger protein 5"
FT /id="PRO_0000066558"
FT ZN_FING 8..42
FT /note="A20-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 148..194
FT /note="AN1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT REGION 39..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 14
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 18
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 33
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00449"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 209
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:1WFL"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:1WFL"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:1WFL"
FT TURN 181..185
FT /evidence="ECO:0007829|PDB:1WFL"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:1WFL"
SQ SEQUENCE 213 AA; 23058 MW; 65B3B001DA6B8F59 CRC64;
MAQETNQTPG PMLCSTGCGF YGNPRTNGMC SVCYKEHLQR QQNSGRMSPM GTASGSNSPT
SDSASVQRAD AGLNNCEGAA GSTSEKSRNV PVAALPVTQQ MTEMSISRED KITTPKTEVS
EPVVTQPSPS VSQPSSSQSE EKAPELPKPK KNRCFMCRKK VGLTGFDCRC GNLFCGLHRY
SDKHNCPYDY KAEAAAKIRK ENPVVVAEKI QRI
