Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

TRIM33

contributors: mct/npt/pgu - updated : 17-05-2019

HGNC name	tripartite motif-containing 33
HGNC id	16290

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	118.38 kb     20 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

motif

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D1S2756 - D1S2881 - TRIM33 - D1S250 - D1S2852 - cen
Authors	UCSC (2009)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015906 20 splicing 8339 122.4 1127 - 2004 15256250 NM_033020 19 splicing 8288 120.4 1110 ubiquitous 2004 15256250 lacking exon 15

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive salivary gland       highly Lymphoid/Immune lymph node       highly Reproductive male system testis     highly Respiratory respiratory tract larynx     predominantly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N-terminal RING zinc finger domain
	two zinc binding B-box (one type 1 and one type 2) domains
	an alpha-helical coiled-coil domain (RBCC) so called tripartite motif (TRIM)
	a PHD (plant homeodomain) motif, involved in ability to ubiquitinate its substrate SMAD4
	a C-terminal bromodomain

conjugated

PhosphoP

mono polymer

homomer , heteromer , trimer , oligo

HOMOLOGY

interspecies	ortholog to rattus Trim33 (97.1pc)
	ortholog to murine Trim33 (96.3pc)

intraspecies	paralog to TIF1
	paralog to TRIM28

Homologene

FAMILY	B-box family
	transcriptional coregulator-encoding genes family
	C-VI TRIM family

CATEGORY

enzyme , regulatory , transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	possible involvement of Tif1gamma in the control of embryonic development and spermatogenesis
	acting as a transcriptional repressor (inhibiting the transcriptional response to TGF-beta/BMP signaling cascade)
	acting as an E3 ubiquitin-protein ligase
	potentially critical for tumor suppression in the pancreas
	playing a role in the control of cell proliferation
	stimulating erythroid differentiation of hematopoietic stem/progenitor, by association with SMAD2 and SMAD3
	nuclear factor having a prominent role as SMAD4 monoubiquitin ligase
	acts on the TGFB pathway either as a monoubiquitin ligase for SMAD4 and/or as a cofactor for phosphorylated SMAD2/3
	TRIM33-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing
	direct role in TGFB-dependent gene expression
	TRIM33 is essential for the terminal differentiation of mammary alveolar epithelial cells and for lactation through SMAD4 inhibition
	contributes to the repression of TGFB1 activity during late pregnancy and prevents lactation by inhibiting SMAD4
	requires sumoylation to exert its repressive activity on TGFB1 signaling
	TRIM33 plays a role in PARP-dependent DNA damage response and regulates CHD1L activity by promoting its timely removal from sites of DNA damage
	is a tumour suppressor that can abolish tumour cell proliferation and tumorigenesis by degrading nuclear CTNNB1
	switches off IFNB1 gene transcription during the late phase of macrophage activation
	is an important transcriptional actor of monocyte/macrophage mediated inflammation
	essential for the navigation of macrophages and neutrophils towards developmental or inflammatory cues within vertebrate tissues
	TRIM33 is required for appropriate differentiation of precardiogenic mesoderm during late gastrulation

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

text	transcriptional corepressor

PATHWAY

metabolism

signaling

a component	heterooligomer with TRIM24 and TRIM28 family members
	found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta
	TRIM24 exists in a major complex with TRIM33 and a lesser abundant complex with TRIM33 and TRIM28

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	interacting with SMAD4 in unstimulated cells
	interacting with SMAD2 and SMAD3
	inhibiting SMAD4 responses and binds phospho-SMAD2
	with USPX act as antagonistic SMAD4 regulator during embryonic development
	acting as SMAD4 monoubiquitin ligase
	regulation of adult hematopoiesis through TRIM33-mediated transcriptional repression of TAL1 and SPI1 target genes
	cooperative action of TRIM24 and TRIM33 in tumor suppression
	molecular relationship between TRIM33 and SMAD4 in TGFB signalling and epithelial-to-mesenchymal transition
	contributes to the repression of TGFB1 activity during late pregnancy and prevents lactation by inhibiting SMAD4
	controls TGFBR1 turnover and promotes physiological aging of hematopoietic stem cells
	ubiquitination of DHX33 by TRIM33 is lysine 63 specific and is required for the formation of the DHX33-NLRP3 inflammasome complex
	TRIM33 inhibited TGFB1-induced EMT through competing with SMAD4 in in non-small-cell lung cancer (NSCLC) cells
	macrophage-specific regulation of IFNB1 transcription whereby TRIM33 is critical for IFNB1 gene transcription shutdown
	TRIM33 can be a positive target of osteoblast proliferation and differentiation through BMP pathway
	modulator of TGFB1 signaling that associates with SMAD2, and regulates the proinflammatory function of Th17 cell

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       chimeric protein 5' - RET - TRIM33 - 3' in thyroid nodules tumoral       loss of function leads to the expansion of a subset of myeloid cells characterizing the myelodysplastic/myeloproliferative neoplasm

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	in the mouse embryos a low level of ubiquitous expression at midgestation, and higher expression levels within the brain and spinal cord epithelium at later developmental stages
	Trim33-deficient mouse bone marrow-derived macrophages display a strongly reduced three-dimensional amoeboid mobility in fibrous collagen gels