RN125_HUMAN
ID RN125_HUMAN Reviewed; 232 AA.
AC Q96EQ8; Q9NX39;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 4.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=E3 ubiquitin-protein ligase RNF125 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:15843525, ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:17643463, ECO:0000269|PubMed:25591766, ECO:0000269|PubMed:26027934, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:27411375};
DE AltName: Full=RING finger protein 125 {ECO:0000312|HGNC:HGNC:21150};
DE AltName: Full=T-cell RING activation protein 1 {ECO:0000303|PubMed:12974981};
DE Short=TRAC-1 {ECO:0000303|PubMed:12974981};
GN Name=RNF125 {ECO:0000312|HGNC:HGNC:21150};
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=Carcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [3]
RP IDENTIFICATION, AND TISSUE SPECIFICITY.
RX PubMed=12974981; DOI=10.1186/1475-4924-2-21;
RA Chu P., Pardo J., Zhao H., Li C.C., Pali E., Shen M.M., Qu K., Yu S.X.,
RA Huang B.C.B., Yu P., Masuda E.S., Molineaux S.M., Kolbinger F., Aversa G.,
RA de Vries J., Payan D.G., Liao X.C.;
RT "Systematic identification of regulatory proteins critical for T-cell
RT activation.";
RL J. Biol. 2:21.1-21.16(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLY-2;
RP CYS-37; CYS-40; HIS-54; CYS-57; CYS-72 AND CYS-75.
RX PubMed=15843525; DOI=10.4049/jimmunol.174.9.5288;
RA Zhao H., Li C.C., Pardo J., Chu P.C., Liao C.X., Huang J., Dong J.G.,
RA Zhou X., Huang Q., Huang B.C.B., Bennett M.K., Molineaux S.M., Lu H.,
RA Daniel-Issakani S., Payan D.G., Masuda E.S.;
RT "A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell
RT activation.";
RL J. Immunol. 174:5288-5297(2005).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-72 AND CYS-75.
RX PubMed=17460044; DOI=10.1073/pnas.0611551104;
RA Arimoto K., Takahashi H., Hishiki T., Konishi H., Fujita T., Shimotohno K.;
RT "Negative regulation of the RIG-I signaling by the ubiquitin ligase
RT RNF125.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7500-7505(2007).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF CYS-37 AND CYS-40.
RX PubMed=17643463; DOI=10.1016/j.virol.2007.06.028;
RA Shoji-Kawata S., Zhong Q., Kameoka M., Iwabu Y., Sapsutthipas S.,
RA Luftig R.B., Ikuta K.;
RT "The RING finger ubiquitin ligase RNF125/TRAC-1 down-modulates HIV-1
RT replication in primary human peripheral blood mononuclear cells.";
RL Virology 368:191-204(2007).
RN [7]
RP SUBCELLULAR LOCATION, AUTOUBIQUITINATION, MYRISTOYLATION AT GLY-2, AND
RP MUTAGENESIS OF GLY-2; CYS-37; CYS-40; VAL-217 AND SER-221.
RX PubMed=17990982; DOI=10.1042/bj20070995;
RA Giannini A.L., Gao Y., Bijlmakers M.J.;
RT "T-cell regulator RNF125/TRAC-1 belongs to a novel family of ubiquitin
RT ligases with zinc fingers and a ubiquitin-binding domain.";
RL Biochem. J. 410:101-111(2008).
RN [8]
RP INVOLVEMENT IN TNORS, AND VARIANTS TNORS ILE-112; LEU-163 AND CYS-174.
RX PubMed=25196541; DOI=10.1002/humu.22689;
RG SOGRI Consortium;
RA Tenorio J., Mansilla A., Valencia M., Martinez-Glez V., Romanelli V.,
RA Arias P., Castrejon N., Poletta F., Guillen-Navarro E., Gordo G.,
RA Mansilla E., Garcia-Santiago F., Gonzalez-Casado I., Vallespin E.,
RA Palomares M., Mori M.A., Santos-Simarro F., Garcia-Minaur S., Fernandez L.,
RA Mena R., Benito-Sanz S., del Pozo A., Silla J.C., Ibanez K.,
RA Lopez-Granados E., Martin-Trujillo A., Montaner D., Heath K.E.,
RA Campos-Barros A., Dopazo J., Nevado J., Monk D., Ruiz-Perez V.L.,
RA Lapunzina P.;
RT "A new overgrowth syndrome is due to mutations in RNF125.";
RL Hum. Mutat. 35:1436-1441(2014).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-72 AND CYS-75.
RX PubMed=25591766; DOI=10.1159/000369691;
RA Yang L., Zhou B., Li X., Lu Z., Li W., Huo X., Miao Z.;
RT "RNF125 is a ubiquitin-protein ligase that promotes p53 degradation.";
RL Cell. Physiol. Biochem. 35:237-245(2015).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=26027934; DOI=10.1016/j.celrep.2015.04.049;
RA Kim H., Frederick D.T., Levesque M.P., Cooper Z.A., Feng Y., Krepler C.,
RA Brill L., Samuels Y., Hayward N.K., Perlina A., Piris A., Zhang T.,
RA Halaban R., Herlyn M.M., Brown K.M., Wargo J.A., Dummer R., Flaherty K.T.,
RA Ronai Z.A.;
RT "Downregulation of the ubiquitin ligase RNF125 underlies resistance of
RT melanoma cells to BRAF inhibitors via JAK1 deregulation.";
RL Cell Rep. 11:1458-1473(2015).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH VCP.
RX PubMed=26471729; DOI=10.15252/embj.201591888;
RA Hao Q., Jiao S., Shi Z., Li C., Meng X., Zhang Z., Wang Y., Song X.,
RA Wang W., Zhang R., Zhao Y., Wong C.C., Zhou Z.;
RT "A non-canonical role of the p97 complex in RIG-I antiviral signaling.";
RL EMBO J. 34:2903-2920(2015).
RN [12]
RP INDUCTION.
RX PubMed=26202983; DOI=10.4049/jimmunol.1500370;
RA Zhu B., Ye J., Nie Y., Ashraf U., Zohaib A., Duan X., Fu Z.F., Song Y.,
RA Chen H., Cao S.;
RT "MicroRNA-15b Modulates Japanese Encephalitis Virus-Mediated Inflammation
RT via Targeting RNF125.";
RL J. Immunol. 195:2251-2262(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) IN COMPLEX WITH ZINC, FUNCTION,
RP CATALYTIC ACTIVITY, INTERACTION WITH UBE2D1, DOMAIN, AND MUTAGENESIS OF
RP 100-CYS--CYS-103 AND 109-LEU--ARG-113.
RX PubMed=27411375; DOI=10.1038/srep29232;
RA Bijlmakers M.J., Teixeira J.M., Boer R., Mayzel M., Puig-Sarries P.,
RA Karlsson G., Coll M., Pons M., Crosas B.;
RT "A C2HC zinc finger is essential for the RING-E2 interaction of the
RT ubiquitin ligase RNF125.";
RL Sci. Rep. 6:29232-29232(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins, such as
CC DDX58/RIG-I, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525,
CC PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729,
CC PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type
CC I interferon production by mediating ubiquitination of DDX58/RIG-I at
CC 'Lys-181', leading to DDX58/RIG-I degradation (PubMed:17460044,
CC PubMed:26471729). Mediates ubiquitination and subsequent degradation of
CC p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent
CC degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of
CC T-cell activation (PubMed:15843525). {ECO:0000269|PubMed:15843525,
CC ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:17643463,
CC ECO:0000269|PubMed:25591766, ECO:0000269|PubMed:26027934,
CC ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:27411375}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:15843525,
CC ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:17643463,
CC ECO:0000269|PubMed:25591766, ECO:0000269|PubMed:26027934,
CC ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:27411375};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:15843525, ECO:0000269|PubMed:17460044,
CC ECO:0000269|PubMed:17643463, ECO:0000269|PubMed:25591766,
CC ECO:0000269|PubMed:26027934, ECO:0000269|PubMed:26471729,
CC ECO:0000269|PubMed:27411375}.
CC -!- SUBUNIT: Interacts with UBE2D1 (PubMed:27411375). Interacts with
CC VCP/p97; leading to recruit RNF125 to DDX58/RIG-I and promote
CC ubiquitination of DDX58/RIG-I (PubMed:26471729).
CC {ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:27411375}.
CC -!- INTERACTION:
CC Q96EQ8; O95786-1: DDX58; NbExp=5; IntAct=EBI-2339208, EBI-15577823;
CC Q96EQ8; Q9BYX4: IFIH1; NbExp=2; IntAct=EBI-2339208, EBI-6115771;
CC Q96EQ8; Q7Z434-1: MAVS; NbExp=2; IntAct=EBI-2339208, EBI-15577799;
CC Q96EQ8; Q96LR5: UBE2E2; NbExp=5; IntAct=EBI-2339208, EBI-2129763;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:17990982}; Lipid-anchor
CC {ECO:0000269|PubMed:17990982}. Note=Shows a reticular staining pattern
CC within the cell and is probably expressed at other intracellular
CC membranes in addition to the Golgi membrane. Not detected at the plasma
CC membrane. {ECO:0000269|PubMed:17990982}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lymphoid tissues,
CC including bone marrow, spleen and thymus. Also weakly expressed in
CC other tissues. Predominant in the CD4(+) and CD8(+) T-cells, suggesting
CC that it is preferentially confined to T-cells.
CC {ECO:0000269|PubMed:12974981, ECO:0000269|PubMed:15843525}.
CC -!- INDUCTION: Down-regulated by miR-15b (PubMed:26202983). Down-regulated
CC in BRAFi resistant melanomas, leading to increased levels of JAK1 and
CC possibly promoting BRAFi resistance. {ECO:0000269|PubMed:26027934,
CC ECO:0000269|PubMed:26202983}.
CC -!- DOMAIN: The C2HC RNF-type zinc finger and the linker region stabilize
CC the RING-type zinc finger, leading to promote binding of the RING-type
CC zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin)
CC (PubMed:27411375). {ECO:0000269|PubMed:27411375}.
CC -!- PTM: Autoubiquitinated, leading to its subsequent proteasomal
CC degradation. {ECO:0000269|PubMed:17990982}.
CC -!- DISEASE: Tenorio syndrome (TNORS) [MIM:616260]: A disease characterized
CC by overgrowth, macrocephaly, and intellectual disability. Some patients
CC may have mild hydrocephaly, hypoglycemia, and inflammatory diseases
CC resembling Sjogren syndrome. {ECO:0000269|PubMed:25196541}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; AK000463; BAA91182.1; -; mRNA.
DR EMBL; BC012021; AAH12021.1; -; mRNA.
DR CCDS; CCDS11902.1; -.
DR RefSeq; NP_060301.2; NM_017831.3.
DR PDB; 5DKA; X-ray; 1.55 A; A/B=1-232.
DR PDBsum; 5DKA; -.
DR AlphaFoldDB; Q96EQ8; -.
DR SMR; Q96EQ8; -.
DR BioGRID; 120281; 34.
DR DIP; DIP-52778N; -.
DR ELM; Q96EQ8; -.
DR IntAct; Q96EQ8; 22.
DR MINT; Q96EQ8; -.
DR STRING; 9606.ENSP00000217740; -.
DR iPTMnet; Q96EQ8; -.
DR PhosphoSitePlus; Q96EQ8; -.
DR BioMuta; RNF125; -.
DR DMDM; 143811449; -.
DR jPOST; Q96EQ8; -.
DR MassIVE; Q96EQ8; -.
DR PaxDb; Q96EQ8; -.
DR PeptideAtlas; Q96EQ8; -.
DR PRIDE; Q96EQ8; -.
DR ProteomicsDB; 76441; -.
DR Antibodypedia; 22188; 218 antibodies from 30 providers.
DR DNASU; 54941; -.
DR Ensembl; ENST00000217740.4; ENSP00000217740.3; ENSG00000101695.9.
DR GeneID; 54941; -.
DR KEGG; hsa:54941; -.
DR MANE-Select; ENST00000217740.4; ENSP00000217740.3; NM_017831.4; NP_060301.2.
DR UCSC; uc002kxf.2; human.
DR CTD; 54941; -.
DR DisGeNET; 54941; -.
DR GeneCards; RNF125; -.
DR HGNC; HGNC:21150; RNF125.
DR HPA; ENSG00000101695; Tissue enhanced (bone).
DR MalaCards; RNF125; -.
DR MIM; 610432; gene.
DR MIM; 616260; phenotype.
DR neXtProt; NX_Q96EQ8; -.
DR OpenTargets; ENSG00000101695; -.
DR PharmGKB; PA134950383; -.
DR VEuPathDB; HostDB:ENSG00000101695; -.
DR eggNOG; ENOG502RYGV; Eukaryota.
DR GeneTree; ENSGT00950000182909; -.
DR HOGENOM; CLU_092448_2_0_1; -.
DR InParanoid; Q96EQ8; -.
DR OMA; FKNCTEC; -.
DR OrthoDB; 1097558at2759; -.
DR PhylomeDB; Q96EQ8; -.
DR TreeFam; TF331012; -.
DR PathwayCommons; Q96EQ8; -.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR SignaLink; Q96EQ8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54941; 14 hits in 1113 CRISPR screens.
DR ChiTaRS; RNF125; human.
DR GeneWiki; RNF125; -.
DR GenomeRNAi; 54941; -.
DR Pharos; Q96EQ8; Tbio.
DR PRO; PR:Q96EQ8; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q96EQ8; protein.
DR Bgee; ENSG00000101695; Expressed in jejunal mucosa and 182 other tissues.
DR ExpressionAtlas; Q96EQ8; baseline and differential.
DR Genevisible; Q96EQ8; HS.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0039536; P:negative regulation of RIG-I signaling pathway; IDA:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR008598; Di19_Zn-bd.
DR InterPro; IPR034734; ZF_C2HC_RNF.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF05605; zf-Di19; 1.
DR Pfam; PF18574; zf_C2HC_14; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS51803; ZF_C2HC_RNF; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Disease variant; Golgi apparatus;
KW Immunity; Intellectual disability; Lipoprotein; Membrane; Metal-binding;
KW Myristate; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:17990982"
FT CHAIN 2..232
FT /note="E3 ubiquitin-protein ligase RNF125"
FT /id="PRO_0000056090"
FT ZN_FING 37..76
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 100..119
FT /note="C2HC RNF-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144,
FT ECO:0000303|PubMed:17990982"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 43..45
FT /note="Interaction with the C2HC RNF-type zinc finger"
FT /evidence="ECO:0000269|PubMed:27411375"
FT REGION 109..113
FT /note="Interaction with the RING-type zinc finger"
FT /evidence="ECO:0000269|PubMed:27411375"
FT REGION 120..128
FT /note="Linker region"
FT /evidence="ECO:0000269|PubMed:27411375"
FT REGION 210..224
FT /note="Required for interaction with ubiquitin and for
FT autoubiquitination"
FT /evidence="ECO:0000269|PubMed:17990982"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 40
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 52
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 54
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27411375,
FT ECO:0007744|PDB:5DKA"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144,
FT ECO:0000269|PubMed:27411375, ECO:0007744|PDB:5DKA"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144,
FT ECO:0000269|PubMed:27411375, ECO:0007744|PDB:5DKA"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144,
FT ECO:0000269|PubMed:27411375, ECO:0007744|PDB:5DKA"
FT BINDING 119
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01144,
FT ECO:0000269|PubMed:27411375, ECO:0007744|PDB:5DKA"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:17990982"
FT VARIANT 112
FT /note="M -> I (in TNORS; dbSNP:rs786201014)"
FT /evidence="ECO:0000269|PubMed:25196541"
FT /id="VAR_073353"
FT VARIANT 163
FT /note="S -> L (in TNORS; dbSNP:rs373764886)"
FT /evidence="ECO:0000269|PubMed:25196541"
FT /id="VAR_073354"
FT VARIANT 174
FT /note="R -> C (in TNORS; dbSNP:rs370242930)"
FT /evidence="ECO:0000269|PubMed:25196541"
FT /id="VAR_073355"
FT MUTAGEN 2
FT /note="G->A: Abolishes ability to regulate T-cell
FT activation but not E3 ligase activity in vitro. Also
FT abolishes myristoylation and membrane localization."
FT /evidence="ECO:0000269|PubMed:15843525,
FT ECO:0000269|PubMed:17643463, ECO:0000269|PubMed:17990982"
FT MUTAGEN 37
FT /note="C->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-40."
FT /evidence="ECO:0000269|PubMed:15843525,
FT ECO:0000269|PubMed:17643463, ECO:0000269|PubMed:17990982"
FT MUTAGEN 40
FT /note="C->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-37."
FT /evidence="ECO:0000269|PubMed:15843525,
FT ECO:0000269|PubMed:17990982"
FT MUTAGEN 54
FT /note="H->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-57."
FT /evidence="ECO:0000269|PubMed:15843525"
FT MUTAGEN 57
FT /note="C->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-54."
FT /evidence="ECO:0000269|PubMed:15843525"
FT MUTAGEN 72
FT /note="C->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-75."
FT /evidence="ECO:0000269|PubMed:15843525,
FT ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:25591766"
FT MUTAGEN 75
FT /note="C->A: Abolishes ability to regulate T-cell
FT activation and E3 ligase activity in vitro; when associated
FT with A-72."
FT /evidence="ECO:0000269|PubMed:15843525,
FT ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:25591766"
FT MUTAGEN 100..103
FT /note="CAEC->AAEA: Abolished E3 ubiquitin-protein ligase
FT activity in vitro."
FT /evidence="ECO:0000269|PubMed:27411375"
FT MUTAGEN 109..113
FT /note="LSEMR->ASEAA: Abolished E3 ubiquitin-protein ligase
FT activity in vitro."
FT /evidence="ECO:0000269|PubMed:27411375"
FT MUTAGEN 217
FT /note="V->P: Reduced ubiquitination and reduced binding to
FT ubiquitinated proteins; when associated with Q-221."
FT /evidence="ECO:0000269|PubMed:17990982"
FT MUTAGEN 221
FT /note="S->Q: Reduced ubiquitination and reduced binding to
FT ubiquitinated proteins; when associated with P-217."
FT /evidence="ECO:0000269|PubMed:17990982"
FT CONFLICT 105..108
FT /note="TLVC -> IVLY (in Ref. 2; AAH12021)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="S -> N (in Ref. 1; BAA91182)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="T -> A (in Ref. 2; AAH12021)"
FT /evidence="ECO:0000305"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:5DKA"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:5DKA"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:5DKA"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:5DKA"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:5DKA"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:5DKA"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:5DKA"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:5DKA"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:5DKA"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:5DKA"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5DKA"
FT HELIX 112..118
FT /evidence="ECO:0007829|PDB:5DKA"
FT HELIX 120..126
FT /evidence="ECO:0007829|PDB:5DKA"
SQ SEQUENCE 232 AA; 26454 MW; E3D93D546AD99D81 CRC64;
MGSVLSTDSG KSAPASATAR ALERRRDPEL PVTSFDCAVC LEVLHQPVRT RCGHVFCRSC
IATSLKNNKW TCPYCRAYLP SEGVPATDVA KRMKSEYKNC AECDTLVCLS EMRAHIRTCQ
KYIDKYGPLQ ELEETAARCV CPFCQRELYE DSLLDHCITH HRSERRPVFC PLCRLIPDEN
PSSFSGSLIR HLQVSHTLFY DDFIDFNIIE EALIRRVLDR SLLEYVNHSN TT
