ID TRI16_HUMAN Reviewed; 564 AA. AC O95361; Q6IAL8; Q7Z6I2; Q96BE8; Q96J43; DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 3. DT 10-JUN-2026, entry version 209. DE RecName: Full=Tripartite motif-containing protein 16; DE EC=2.3.2.27 {ECO:0000269|PubMed:22629402}; DE AltName: Full=E3 ubiquitin-protein ligase TRIM16; DE AltName: Full=Estrogen-responsive B box protein; GN Name=TRIM16; Synonyms=EBBP; 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] (ISOFORM 1), AND VARIANT VAL-561. RC TISSUE=Mammary gland; RX PubMed=9817599; DOI=10.1210/mend.12.11.0193; RA Liu H.-L.C., Golder-Novoselsky E., Seto M.H., Webster L., McClary J., RA Zajchowski D.A.; RT "The novel estrogen-responsive B box protein (EBBP) gene is tamoxifen RT regulated in cells expressing an estrogen receptor DNA-binding domain RT mutant."; RL Mol. Endocrinol. 12:1733-1748(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-561. RX PubMed=11919186; DOI=10.1074/jbc.m111233200; RA Beer H.-D., Munding C., Dubois N., Mamie C., Hohl D., Werner S.; RT "The estrogen-responsive B box protein: a novel regulator of keratinocyte RT differentiation."; RL J. Biol. Chem. 277:20740-20749(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-561. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP VAL-561. RC TISSUE=Placenta, and Skin; 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 FUNCTION, SUBUNIT, INTERACTION WITH TRIM24; PML AND MID1, AND REGION. RX PubMed=22629402; DOI=10.1371/journal.pone.0037470; RA Bell J.L., Malyukova A., Holien J.K., Koach J., Parker M.W., Kavallaris M., RA Marshall G.M., Cheung B.B.; RT "TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other RT TRIM family members."; RL PLoS ONE 7:E37470-E37470(2012). RN [6] RP FUNCTION, INTERACTION WITH LGALS3 AND BECN1, PHOSPHORYLATION AT SER-116 AND RP SER-203, MUTAGENESIS OF SER-116 AND SER-203, AND SUBCELLULAR LOCATION. RX PubMed=27693506; DOI=10.1016/j.devcel.2016.08.003; RA Chauhan S., Kumar S., Jain A., Ponpuak M., Mudd M.H., Kimura T., Choi S.W., RA Peters R., Mandell M., Bruun J.A., Johansen T., Deretic V.; RT "TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct RT Autophagy in Endomembrane Damage Homeostasis."; RL Dev. Cell 39:13-27(2016). RN [7] RP FUNCTION, AND INTERACTION WITH SQSTM; ATG16L1 AND MAP1LC3B. RX PubMed=30143514; DOI=10.15252/embj.201798358; RA Jena K.K., Kolapalli S.P., Mehto S., Nath P., Das B., Sahoo P.K., Ahad A., RA Syed G.H., Raghav S.K., Senapati S., Chauhan S., Chauhan S.; RT "TRIM16 controls assembly and degradation of protein aggregates by RT modulating the p62-NRF2 axis and autophagy."; RL EMBO J. 37:0-0(2018). CC -!- FUNCTION: E3 ubiquitin ligase that plays an essential role in the CC organization of autophagic response and ubiquitination upon lysosomal CC and phagosomal damages. Plays a role in the stress-induced biogenesis CC and degradation of protein aggresomes by regulating the p62-KEAP1-NRF2 CC signaling and particularly by modulating the ubiquitination levels and CC thus stability of NRF2. Acts as a scaffold protein and facilitates CC autophagic degradation of protein aggregates by interacting with CC p62/SQSTM, ATG16L1 and LC3B/MAP1LC3B. In turn, protects the cell CC against oxidative stress-induced cell death as a consequence of CC endomembrane damage. {ECO:0000269|PubMed:22629402, CC ECO:0000269|PubMed:27693506, ECO:0000269|PubMed:30143514}. 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:22629402}; CC -!- SUBUNIT: Homodimerizes via its coiled-coil domain. Heterodimerizes with CC MID1, TRIM24 and PML. Interacts with Galectin-3/LGALS3 in a ULK1- CC dependent manner; this interaction mediates autophagy of damage CC endomembranes. Interacts with BECN1. Interacts with ATG16L1. Interacts CC with p62/SQSTM and LC3B/MAP1LC3B. {ECO:0000269|PubMed:22629402, CC ECO:0000269|PubMed:27693506, ECO:0000269|PubMed:30143514}. CC -!- INTERACTION: CC O95361; Q01094: E2F1; NbExp=2; IntAct=EBI-727384, EBI-448924; CC O95361; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-727384, EBI-717399; CC O95361; Q309B1: TRIM16L; NbExp=4; IntAct=EBI-727384, EBI-21372540; CC O95361; P08670: VIM; NbExp=3; IntAct=EBI-727384, EBI-353844; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27693506}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Alpha; CC IsoId=O95361-1; Sequence=Displayed; CC Name=2; Synonyms=Beta; CC IsoId=O95361-2; Sequence=VSP_009098; CC -!- TISSUE SPECIFICITY: Highest levels found in testis, ovary, small CC intestine, colon, placenta, heart, skeletal muscle and mammary gland. CC More highly expressed in the fetus than in the corresponding adult CC tissues. Expressed in basal keratinocytes. CC -!- PTM: Phosphorylated by ULK1. {ECO:0000269|PubMed:27693506}. CC -!- PTM: Auto-ubiquitinates via its B-Boxes. {ECO:0000269|PubMed:22629402}. CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}. 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; AF096870; AAC79080.1; -; mRNA. DR EMBL; CR457136; CAG33417.1; -; mRNA. DR EMBL; BC001564; AAH01564.1; -; mRNA. DR EMBL; BC053514; AAH53514.1; -; mRNA. DR EMBL; BC067096; AAH67096.1; -; mRNA. DR CCDS; CCDS11171.1; -. [O95361-1] DR CCDS; CCDS86578.1; -. [O95361-2] DR RefSeq; NP_001335048.1; NM_001348119.1. [O95361-1] DR RefSeq; NP_001335049.1; NM_001348120.1. [O95361-1] DR RefSeq; NP_001335053.1; NM_001348124.1. [O95361-2] DR RefSeq; NP_001335054.1; NM_001348125.1. [O95361-2] DR RefSeq; NP_006461.3; NM_006470.4. [O95361-1] DR PDB; 7QS3; X-ray; 1.75 A; A=352-558. DR PDBsum; 7QS3; -. DR AlphaFoldDB; O95361; -. DR SMR; O95361; -. DR BioGRID; 115870; 70. DR FunCoup; O95361; 596. DR IntAct; O95361; 23. DR MINT; O95361; -. DR STRING; 9606.ENSP00000497185; -. DR GlyGen; O95361; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O95361; -. DR PhosphoSitePlus; O95361; -. DR BioMuta; TRIM16; -. DR jPOST; O95361; -. DR MassIVE; O95361; -. DR PaxDb; 9606-ENSP00000497185; -. DR PeptideAtlas; O95361; -. DR ProteomicsDB; 50822; -. [O95361-1] DR ProteomicsDB; 50823; -. [O95361-2] DR Pumba; O95361; -. DR Antibodypedia; 21540; 247 antibodies from 28 providers. DR DNASU; 10626; -. DR Ensembl; ENST00000336708.11; ENSP00000338989.7; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000577886.5; ENSP00000462903.1; ENSG00000221926.14. [O95361-2] DR Ensembl; ENST00000578237.5; ENSP00000463188.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000649191.2; ENSP00000497185.2; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000852769.1; ENSP00000522828.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000932631.1; ENSP00000602690.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000932632.1; ENSP00000602691.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000932633.1; ENSP00000602692.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000932634.1; ENSP00000602693.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967546.1; ENSP00000637605.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967547.1; ENSP00000637606.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967548.1; ENSP00000637607.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967549.1; ENSP00000637608.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967550.1; ENSP00000637609.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967551.1; ENSP00000637610.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967552.1; ENSP00000637611.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967553.1; ENSP00000637612.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967554.1; ENSP00000637613.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967555.1; ENSP00000637614.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967556.1; ENSP00000637615.1; ENSG00000221926.14. [O95361-1] DR Ensembl; ENST00000967557.1; ENSP00000637616.1; ENSG00000221926.14. [O95361-1] DR GeneID; 10626; -. DR KEGG; hsa:10626; -. DR MANE-Select; ENST00000649191.2; ENSP00000497185.2; NM_001348119.1; NP_001335048.1. DR UCSC; uc002gow.4; human. [O95361-1] DR AGR; HGNC:17241; -. DR ClinPGx; PA38215; -. DR CTD; 10626; -. DR DisGeNET; 10626; -. DR GeneCards; TRIM16; -. DR HGNC; HGNC:17241; TRIM16. DR HPA; ENSG00000221926; Tissue enhanced (esophagus). DR MIM; 609505; gene. DR OpenTargets; ENSG00000221926; -. DR VEuPathDB; HostDB:ENSG00000221926; -. DR eggNOG; ENOG502QRVY; Eukaryota. DR GeneTree; ENSGT00940000161116; -. DR HOGENOM; CLU_013137_0_2_1; -. DR InParanoid; O95361; -. DR OMA; SAWHSGV; -. DR OrthoDB; 6270329at2759; -. DR PAN-GO; O95361; 0 GO annotations based on evolutionary models. DR PhylomeDB; O95361; -. DR PathwayCommons; O95361; -. DR SignaLink; O95361; -. DR Agora; ENSG00000221926; -. DR BioGRID-ORCS; 10626; 12 hits in 1188 CRISPR screens. DR ChiTaRS; TRIM16; human. DR GeneWiki; TRIM16; -. DR GenomeRNAi; 10626; -. DR Pharos; O95361; Tbio. DR PRO; PR:O95361; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O95361; protein. DR Bgee; ENSG00000221926; Expressed in lower esophagus mucosa and 100 other cell types or tissues. DR ExpressionAtlas; O95361; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0019966; F:interleukin-1 binding; IPI:UniProtKB. DR GO; GO:0032089; F:NACHT domain binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:UniProtKB-EC. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:UniProtKB. DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IDA:UniProtKB. DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0060416; P:response to growth hormone; IDA:UniProtKB. DR GO; GO:0032526; P:response to retinoic acid; IEP:UniProtKB. DR CDD; cd19839; Bbox1_TRIM16; 1. DR CDD; cd12890; SPRY_PRY_TRIM16; 1. DR FunFam; 4.10.830.40:FF:000002; probable E3 ubiquitin-protein ligase MID2; 1. DR FunFam; 2.60.120.920:FF:000046; tripartite motif-containing protein 16; 1. DR Gene3D; 2.60.120.920; -; 1. DR Gene3D; 4.10.830.40; -; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR InterPro; IPR001870; B30.2/SPRY. DR InterPro; IPR043136; B30.2/SPRY_sf. DR InterPro; IPR003879; Butyrophylin_SPRY. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR051051; E3_ubiq-ligase_TRIM/RNF. DR InterPro; IPR006574; PRY. DR InterPro; IPR003877; SPRY_dom. DR InterPro; IPR058030; TRIM8/14/16/25/29/45/65_CC. DR InterPro; IPR000315; Znf_B-box. DR PANTHER; PTHR25465; B-BOX DOMAIN CONTAINING; 1. DR PANTHER; PTHR25465:SF10; TRIPARTITE MOTIF-CONTAINING PROTEIN 16-RELATED; 1. DR Pfam; PF13765; PRY; 1. DR Pfam; PF00622; SPRY; 1. DR Pfam; PF25600; TRIM_CC; 1. DR Pfam; PF00643; zf-B_box; 1. DR PRINTS; PR01407; BUTYPHLNCDUF. DR SMART; SM00336; BBOX; 2. DR SMART; SM00589; PRY; 1. DR SMART; SM00449; SPRY; 1. DR SUPFAM; SSF57845; B-box zinc-binding domain; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR PROSITE; PS50188; B302_SPRY; 1. DR PROSITE; PS50119; ZF_BBOX; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Metal-binding; KW Phosphoprotein; Proteomics identification; Reference proteome; Repeat; KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..564 FT /note="Tripartite motif-containing protein 16" FT /id="PRO_0000056222" FT DOMAIN 355..553 FT /note="B30.2/SPRY" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548" FT ZN_FING 72..122 FT /note="B box-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024, FT ECO:0000269|PubMed:22629402" FT ZN_FING 126..165 FT /note="B box-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024, FT ECO:0000269|PubMed:22629402" FT REGION 1..69 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 165..203 FT /evidence="ECO:0000255" FT COILED 243..274 FT /evidence="ECO:0000255" FT COILED 320..340 FT /evidence="ECO:0000255" FT COMPBIAS 24..39 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 131 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 134 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 153 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 157 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT MOD_RES 116 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27693506" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:27693506" FT VAR_SEQ 1..216 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_009098" FT VARIANT 121 FT /note="E -> D (in dbSNP:rs2074890)" FT /id="VAR_017412" FT VARIANT 493 FT /note="R -> W (in dbSNP:rs3174720)" FT /id="VAR_052133" FT VARIANT 561 FT /note="G -> V (in dbSNP:rs1060903)" FT /evidence="ECO:0000269|PubMed:11919186, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9817599, FT ECO:0000269|Ref.3" FT /id="VAR_031668" FT MUTAGEN 116 FT /note="S->A: Loss of protection from cell death during FT oxidative stress; when associated with A-203." FT /evidence="ECO:0000269|PubMed:27693506" FT MUTAGEN 203 FT /note="S->A: Loss of protection from cell death during FT oxidative stress; when associated with A-116." FT /evidence="ECO:0000269|PubMed:27693506" FT CONFLICT 235 FT /note="L -> P (in Ref. 1; AAC79080 and 2)" FT /evidence="ECO:0000305" FT CONFLICT 246 FT /note="S -> N (in Ref. 1; AAC79080 and 2)" FT /evidence="ECO:0000305" FT CONFLICT 465 FT /note="F -> L (in Ref. 4; AAH01564)" FT /evidence="ECO:0000305" FT CONFLICT 521 FT /note="K -> N (in Ref. 1; AAC79080 and 2)" FT /evidence="ECO:0000305" FT CONFLICT 541 FT /note="N -> S (in Ref. 1; AAC79080 and 2)" FT /evidence="ECO:0000305" FT HELIX 365..368 FT /evidence="ECO:0007829|PDB:7QS3" FT HELIX 369..371 FT /evidence="ECO:0007829|PDB:7QS3" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 386..389 FT /evidence="ECO:0007829|PDB:7QS3" FT TURN 390..393 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 394..397 FT /evidence="ECO:0007829|PDB:7QS3" FT HELIX 405..407 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 417..424 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 426..437 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 440..446 FT /evidence="ECO:0007829|PDB:7QS3" FT HELIX 456..458 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 467..471 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 476..480 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 483..486 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 493..500 FT /evidence="ECO:0007829|PDB:7QS3" FT TURN 501..504 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 505..512 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 515..523 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 530..536 FT /evidence="ECO:0007829|PDB:7QS3" FT STRAND 542..545 FT /evidence="ECO:0007829|PDB:7QS3" SQ SEQUENCE 564 AA; 63955 MW; A6760717937D82F8 CRC64; MAELDLMAPG PLPRATAQPP APLSPDSGSP SPDSGSASPV EEEDVGSSEK LGRETEEQDS DSAEQGDPAG EGKEVLCDFC LDDTRRVKAV KSCLTCMVNY CEEHLQPHQV NIKLQSHLLT EPVKDHNWRY CPAHHSPLSA FCCPDQQCIC QDCCQEHSGH TIVSLDAARR DKEAELQCTQ LDLERKLKLN ENAISRLQAN QKSVLVSVSE VKAVAEMQFG ELLAAVRKAQ ANVMLFLEEK EQAALSQANG IKAHLEYRSA EMEKSKQELE RMAAISNTVQ FLEEYCKFKN TEDITFPSVY VGLKDKLSGI RKVITESTVH LIQLLENYKK KLQEFSKEEE YDIRTQVSAV VQRKYWTSKP EPSTREQFLQ YAYDITFDPD TAHKYLRLQE ENRKVTNTTP WEHPYPDLPS RFLHWRQVLS QQSLYLHRYY FEVEIFGAGT YVGLTCKGID RKGEERNSCI SGNNFSWSLQ WNGKEFTAWY SDMETPLKAG PFRRLGVYID FPGGILSFYG VEYDTMTLVH KFACKFSEPV YAAFWLSKKE NAIRIVDLGE EPEKPAPSLV GTAP //