ID   TRI66_HUMAN             Reviewed;        1351 AA.
AC   O15016; A0A2R8YEA1; Q9BQQ4;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2022, sequence version 5.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Tripartite motif-containing protein 66;
GN   Name=TRIM66; Synonyms=C11orf29, KIAA0298;
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 [GENOMIC DNA] (ISOFORM 2).
RX   PubMed=11528127; DOI=10.1159/000056999;
RA   Amid C., Bahr A., Mujica A., Sampson N., Bikar S.E., Winterpacht A.,
RA   Zabel B., Hankeln T., Schmidt E.R.;
RT   "Comparative genomic sequencing reveals a strikingly similar architecture
RT   of a conserved syntenic region on human chromosome 11p15.3 (including gene
RT   ST5) and mouse chromosome 7.";
RL   Cytogenet. Cell Genet. 93:284-290(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Brain;
RX   PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA   Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VII. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 4:141-150(1997).
RN   [3]
RP   SEQUENCE REVISION.
RA   Nagase T., Ishikawa K., Seki N., Nakajima D., Ohira M., Miyajima N.,
RA   Kotani H., Nomura N., Ohara O.;
RL   Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   SUBCELLULAR LOCATION.
RX   PubMed=25593309; DOI=10.1101/gad.252189.114;
RA   Gong F., Chiu L.Y., Cox B., Aymard F., Clouaire T., Leung J.W.,
RA   Cammarata M., Perez M., Agarwal P., Brodbelt J.S., Legube G., Miller K.M.;
RT   "Screen identifies bromodomain protein ZMYND8 in chromatin recognition of
RT   transcription-associated DNA damage that promotes homologous
RT   recombination.";
RL   Genes Dev. 29:197-211(2015).
CC   -!- FUNCTION: May function as transcription repressor; The repressive
CC       effects are mediated, at least in part, by recruitment of deacetylase
CC       activity. May play a role as negative regulator of postmeiotic genes
CC       acting through CBX3 complex formation and centromere association (By
CC       similarity). {ECO:0000250|UniProtKB:Q924W6}.
CC   -!- SUBUNIT: Can form homodimers and heterodimers. Interacts with CBX5,
CC       CBX1 and CBX3 via PxVxL motif (By similarity).
CC       {ECO:0000250|UniProtKB:Q924W6}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25593309}. Note=Forms
CC       discrete foci within the centromeric chromocenter and surrounding
CC       nucleoplasm. {ECO:0000250|UniProtKB:Q924W6}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O15016-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O15016-2; Sequence=VSP_061677, VSP_061678, VSP_061680;
CC       Name=3;
CC         IsoId=O15016-3; Sequence=VSP_061677, VSP_061679, VSP_061681;
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA20758.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AJ400879; CAC35389.1; -; Genomic_DNA.
DR   EMBL; AB002296; BAA20758.2; ALT_INIT; mRNA.
DR   EMBL; AC091053; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC104360; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_055633.1; NM_014818.1.
DR   PDB; 6IET; X-ray; 2.10 A; A=1103-1295.
DR   PDB; 6IEU; X-ray; 1.79 A; A=1103-1295.
DR   PDBsum; 6IET; -.
DR   PDBsum; 6IEU; -.
DR   AlphaFoldDB; O15016; -.
DR   SMR; O15016; -.
DR   BioGRID; 115199; 200.
DR   IntAct; O15016; 3.
DR   STRING; 9606.ENSP00000495413; -.
DR   ChEMBL; CHEMBL4296267; -.
DR   GlyGen; O15016; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O15016; -.
DR   PhosphoSitePlus; O15016; -.
DR   BioMuta; TRIM66; -.
DR   EPD; O15016; -.
DR   jPOST; O15016; -.
DR   MassIVE; O15016; -.
DR   PaxDb; 9606-ENSP00000384876; -.
DR   PeptideAtlas; O15016; -.
DR   ProteomicsDB; 48372; -. [O15016-1]
DR   ProteomicsDB; 48373; -. [O15016-2]
DR   Antibodypedia; 5888; 40 antibodies from 12 providers.
DR   DNASU; 9866; -.
DR   GeneID; 9866; -.
DR   KEGG; hsa:9866; -.
DR   UCSC; uc010rbo.2; human. [O15016-1]
DR   AGR; HGNC:29005; -.
DR   CTD; 9866; -.
DR   DisGeNET; 9866; -.
DR   GeneCards; TRIM66; -.
DR   HGNC; HGNC:29005; TRIM66.
DR   MIM; 612000; gene.
DR   neXtProt; NX_O15016; -.
DR   PharmGKB; PA134954583; -.
DR   VEuPathDB; HostDB:ENSG00000166436; -.
DR   eggNOG; KOG2177; Eukaryota.
DR   HOGENOM; CLU_005817_1_0_1; -.
DR   InParanoid; O15016; -.
DR   OrthoDB; 56754at2759; -.
DR   PhylomeDB; O15016; -.
DR   PathwayCommons; O15016; -.
DR   SignaLink; O15016; -.
DR   BioGRID-ORCS; 9866; 3 hits in 329 CRISPR screens.
DR   ChiTaRS; TRIM66; human.
DR   GenomeRNAi; 9866; -.
DR   Pharos; O15016; Tbio.
DR   PRO; PR:O15016; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; O15016; Protein.
DR   Bgee; ENSG00000166436; Expressed in sural nerve and 151 other cell types or tissues.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   CDD; cd19811; Bbox1_TRIM66; 1.
DR   CDD; cd19794; Bbox2_TRIM66-like; 1.
DR   CDD; cd05502; Bromo_tif1_like; 1.
DR   Gene3D; 1.20.920.10; Bromodomain-like; 1.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR003649; Bbox_C.
DR   InterPro; IPR001487; Bromodomain.
DR   InterPro; IPR036427; Bromodomain-like_sf.
DR   InterPro; IPR037372; TRIM66_Bbox1_Znf.
DR   InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR   InterPro; IPR000315; Znf_B-box.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR001965; Znf_PHD.
DR   InterPro; IPR019787; Znf_PHD-finger.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR45915; TRANSCRIPTION INTERMEDIARY FACTOR; 1.
DR   PANTHER; PTHR45915:SF7; TRIPARTITE MOTIF-CONTAINING PROTEIN 66; 1.
DR   Pfam; PF00439; Bromodomain; 1.
DR   Pfam; PF00628; PHD; 1.
DR   Pfam; PF00643; zf-B_box; 1.
DR   SMART; SM00502; BBC; 1.
DR   SMART; SM00336; BBOX; 2.
DR   SMART; SM00297; BROMO; 1.
DR   SMART; SM00249; PHD; 2.
DR   SUPFAM; SSF57845; B-box zinc-binding domain; 1.
DR   SUPFAM; SSF47370; Bromodomain; 1.
DR   SUPFAM; SSF57903; FYVE/PHD zinc finger; 1.
DR   PROSITE; PS50014; BROMODOMAIN_2; 1.
DR   PROSITE; PS50119; ZF_BBOX; 2.
DR   PROSITE; PS01359; ZF_PHD_1; 1.
DR   PROSITE; PS50016; ZF_PHD_2; 1.
DR   Genevisible; O15016; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Bromodomain; Coiled coil;
KW   Metal-binding; Nucleus; Reference proteome; Repeat; Zinc; Zinc-finger.
FT   CHAIN           1..1351
FT                   /note="Tripartite motif-containing protein 66"
FT                   /id="PRO_0000220375"
FT   DOMAIN          1191..1263
FT                   /note="Bromo"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT   ZN_FING         105..150
FT                   /note="B box-type 1; atypical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   ZN_FING         164..205
FT                   /note="B box-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   ZN_FING         1105..1152
FT                   /note="PHD-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT   REGION          542..608
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          663..730
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          857..895
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1067..1098
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1289..1351
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          234..304
FT                   /evidence="ECO:0000255"
FT   MOTIF           995..999
FT                   /note="PxVxL motif"
FT   COMPBIAS        542..557
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        558..589
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        663..682
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        711..730
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        857..884
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1323..1340
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         109
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         112
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         133
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         139
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         192
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   BINDING         197
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT   VAR_SEQ         1..104
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11528127,
FT                   ECO:0000303|PubMed:9205841"
FT                   /id="VSP_061677"
FT   VAR_SEQ         201..202
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11528127"
FT                   /id="VSP_061678"
FT   VAR_SEQ         902..972
FT                   /note="MESEDSTRFTDLLGQGPIVPGLDAPKDLAIPSELEEPINLSVKKPPLAPVVS
FT                   TSTALQQYQNPKECENFEQ -> VSPGEMLSKLPLFIIGQKIGHWDPYSDLSLTVLRPL
FT                   MTTMSEFFDSCRHFTFERWKVRIPLASLTYWDKVP (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9205841"
FT                   /id="VSP_061679"
FT   VAR_SEQ         902..934
FT                   /note="MESEDSTRFTDLLGQGPIVPGLDAPKDLAIPSE -> VK (in isoform
FT                   2)"
FT                   /evidence="ECO:0000303|PubMed:11528127"
FT                   /id="VSP_061680"
FT   VAR_SEQ         973..1351
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:9205841"
FT                   /id="VSP_061681"
FT   TURN            1109..1111
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   STRAND          1115..1119
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   STRAND          1121..1124
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   TURN            1129..1131
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   STRAND          1132..1134
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1147..1149
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1179..1194
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1196..1201
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   STRAND          1209..1211
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1212..1215
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1222..1228
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1240..1257
FT                   /evidence="ECO:0007829|PDB:6IEU"
FT   HELIX           1263..1282
FT                   /evidence="ECO:0007829|PDB:6IEU"
SQ   SEQUENCE   1351 AA;  149469 MW;  EC3AC054A2720E04 CRC64;
     MSFMGLPLAG QKHCPKSGQM EAMVMTCSLC HQDLPGMGSH LLSCQHLLRK DCFQGLIQEL
     GQIAKAHETV ADELISCPGC ERVYLTRDVT EHFFLHCVPT EQPKMARNCS ECKEKRAAHI
     LCTYCNRWLC SSCTEEHRHS PVPGGPFFPR AQKGSPGVNG GPGDFTLYCP LHTQEVLKLF
     CETCDMLTCH SCLVVEHKEH RCRHVEEVLQ NQRMLLEGVT TQVAHKKSSL QTSAKQIEDR
     IFEVKHQHRK VENQIKMAKM VLMNELNKQA NGLIEELEGI TNERKRKLEQ QLQSIMVLNR
     QFEHVQNFIN WAVCSKTSVP FLFSKELIVF QMQRLLETSC NTDPGSPWSI RFTWEPNFWT
     KQLASLGCIT TEGGQMSRAD APAYGGLQGS SPFYQSHQSP VAQQEALSHP SHKFQSPAVC
     SSSVCCSHCS PVSPSLKGQV PPPSIHPAHS FRQPPEMVPQ QLGSLQCSAL LPREKELACS
     PHPPKLLQPW LETQPPVEQE STSQRLGQQL TSQPVCIVPP QDVQQGAHAQ PTLQTPSIQV
     QFGHHQKLKL SHFQQQPQQQ LPPPPPPLPH PPPPLPPPPQ QPHPPLPPSQ HLASSQHESP
     PGPACSQNMD IMHHKFELEE MQKDLELLLQ AQQPSLQLSQ TKSPQHLQQT IVGQINYIVR
     QPAPVQSQSQ EETLQATDEP PASQGSKPAL PLDKNTAAAL PQASGEETPL SVPPVDSTIQ
     HSSPNVVRKH STSLSIMGFS NTLEMELSST RLERPLEPQI QSVSNLTAGA PQAVPSLLSA
     PPKMVSSLTS VQNQAMPSLT TSHLQTVPSL VHSTFQSMPN LISDSPQAMA SLASDHPQAG
     PSLMSGHTQA VPSLATCPLQ SIPPVSDMQP ETGSSSSSGR TSGSLCPRDG ADPSLENALC
     KMESEDSTRF TDLLGQGPIV PGLDAPKDLA IPSELEEPIN LSVKKPPLAP VVSTSTALQQ
     YQNPKECENF EQGALELDAK ENQSIRAFNS EHKIPYVRLE RLKICAASSG EMPVFKLKPQ
     KNDQDGSFLL IIECGTESSS MSIKVSQDRL SEATQAPGLE GRKVTVTSLA GQRPPEVEGT
     SPEEHRLIPR TPGAKKGPPA PIENEDFCAV CLNGGELLCC DRCPKVFHLS CHVPALLSFP
     GGEWVCTLCR SLTQPEMEYD CENACYNQPG MRASPGLSMY DQKKCEKLVL SLCCNNLSLP
     FHEPVSPLAR HYYQIIKRPM DLSIIRRKLQ KKDPAHYTTP EEVVSDVRLM FWNCAKFNYP
     DSEVAEAGRC LEVFFEGWLK EIYPEKRFAQ PRQEDSDSEE VSSESGCSTP QGFPWPPYMQ
     EGIQPKRRRR HMENERAKRM SFRLANSISQ V
//