TRI16_HUMAN
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 03-AUG-2022, entry version 192.
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; 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}.
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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 AlphaFoldDB; O95361; -.
DR SMR; O95361; -.
DR BioGRID; 115870; 44.
DR IntAct; O95361; 13.
DR STRING; 9606.ENSP00000463188; -.
DR GlyGen; O95361; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95361; -.
DR PhosphoSitePlus; O95361; -.
DR BioMuta; TRIM16; -.
DR EPD; O95361; -.
DR jPOST; O95361; -.
DR MassIVE; O95361; -.
DR MaxQB; O95361; -.
DR PaxDb; O95361; -.
DR PeptideAtlas; O95361; -.
DR PRIDE; O95361; -.
DR ProteomicsDB; 50822; -. [O95361-1]
DR ProteomicsDB; 50823; -. [O95361-2]
DR Antibodypedia; 21540; 253 antibodies from 27 providers.
DR DNASU; 10626; -.
DR Ensembl; ENST00000336708.11; ENSP00000338989.7; ENSG00000221926.13. [O95361-1]
DR Ensembl; ENST00000577886.5; ENSP00000462903.1; ENSG00000221926.13. [O95361-2]
DR Ensembl; ENST00000578237.5; ENSP00000463188.1; ENSG00000221926.13. [O95361-1]
DR Ensembl; ENST00000649191.2; ENSP00000497185.2; ENSG00000221926.13. [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 CTD; 10626; -.
DR DisGeNET; 10626; -.
DR GeneCards; TRIM16; -.
DR HGNC; HGNC:17241; TRIM16.
DR HPA; ENSG00000221926; Tissue enhanced (esophagus).
DR MIM; 609505; gene.
DR neXtProt; NX_O95361; -.
DR OpenTargets; ENSG00000221926; -.
DR PharmGKB; PA38215; -.
DR VEuPathDB; HostDB:ENSG00000221926; -.
DR eggNOG; ENOG502QRVY; Eukaryota.
DR GeneTree; ENSGT00940000161116; -.
DR HOGENOM; CLU_013137_0_2_1; -.
DR InParanoid; O95361; -.
DR OMA; CRALKSC; -.
DR OrthoDB; 273204at2759; -.
DR PhylomeDB; O95361; -.
DR TreeFam; TF351086; -.
DR PathwayCommons; O95361; -.
DR SignaLink; O95361; -.
DR BioGRID-ORCS; 10626; 12 hits in 1111 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 98 other tissues.
DR ExpressionAtlas; O95361; baseline and differential.
DR Genevisible; O95361; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; 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:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB.
DR GO; GO:0043967; P:histone H4 acetylation; 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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0060416; P:response to growth hormone; IDA:UniProtKB.
DR GO; GO:0046683; P:response to organophosphorus; IEP:UniProtKB.
DR GO; GO:0032526; P:response to retinoic acid; IEP:UniProtKB.
DR Gene3D; 2.60.120.920; -; 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; IPR006574; PRY.
DR InterPro; IPR003877; SPRY_dom.
DR InterPro; IPR000315; Znf_B-box.
DR Pfam; PF13765; PRY; 1.
DR Pfam; PF00622; SPRY; 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; SSF49899; SSF49899; 1.
DR PROSITE; PS50188; B302_SPRY; 1.
DR PROSITE; PS50119; ZF_BBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW 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 13..27
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..59
FT /note="Basic and acidic residues"
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"
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
