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FLASH GENE

Symbol

TRIM5

contributors: mct - updated : 19-03-2020

HGNC name	tripartite motif-containing 5
HGNC id	16276

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_033034 8 splicing 3363 NP_149023 56.2 493 - 2018 30282803 isoform alpha acts during the early postentry stages of the retroviral life cycle to block infection by a broad range of retroviruses, disrupting reverse transcription and integration NM_033092 7 splicing 3624 NP_149033 39.9 347 - 2018 30282803 isoform gamma NM_033093 8 splicing 1994 NP_149084 37.5 326 - 2018 30282803 isoform delta interacting with BTBD1 and BTBD2 exhibiting ubiquitylation in the presence of UBCH5B, dependent on the presence of zinc-coordinating cysteines in the RING domain

EXPRESSION

Type

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 Cardiovascular vessel       moderately Digestive mouth       moderately Endocrine thyroid       moderately Lymphoid/Immune thymus       predominantly Reproductive female system uterus     highly Urinary bladder       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal RING-type zinc finger
	a B box-type zinc finger (type 2)
	a C terminal B30.2/SPRY domain

HOMOLOGY

interspecies	ortholog to TRIM5, Pan troglodytes
	ortholog to Trim5, Mus musculus
	ortholog to Trim5, Rattus norvegicus

intraspecies

paralog to TRIM6, TRIM34

Homologene

FAMILY	TRIM/RBCC family
	B box family

CATEGORY

enzyme , immunity/defense

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	cytoplasmic bodies
	ability of TRIM5 to shuttle into and out of the nucleus

basic FUNCTION	may act as an E3 ubiquitin ligase
	potent inhibitor of infection by diverse retroviruses, modestly inhibits HIV1 strain carrying a mutation in the cyclophilin binding loop (Zhang 2006)
	is an intrinsic immunity factor against HIV-1 infection, and arginine at 437 aa in SPRY domain for the late restriction is species-specific
	a single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5
	promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice
	retrovirus restriction factor TRIM5 blocks post-entry infection of retroviruses in a species-specific manner
	novel function for TRIM5 as a pattern recognition receptor in innate immune recognition
	TRIM5 blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/PRYSPRY domain
	importance of TRIM5 recruitment to the Plasma membrane for TRIM5-mediated innate immune sensing and restriction of retroviral infection
	specific cytoskeleton structures involved in TRIM5 innate antiretroviral defenses
	TRIM5 acts as a selective autophagy receptor, and delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation
	is an antiviral factor that can greatly limit HIV-1 infection
	is an interferon-inducible retroviral restriction factor that prevents infection by inducing the abortive disassembly of capsid cores recognized by its C-terminal PRY/SPRY domain
	in the absence of a restriction-sensitive virus, TRIM5 is degraded by both proteasomal and autophagic degradation pathways
	link between TRIM5 and components of the autophagosome
	is a RING domain E3 ubiquitin ligase with potent antiretroviral function
	TRIM5 initiates innate immune signaling and orchestrates disassembly of the viral particle
	is an interferon inducible restriction factor which contributes to intrinsic defense against HIV infection by targeting the HIV capsid protein CA

CELLULAR PROCESS

protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein	unique function of TRIM5 is dependent on its association with the E2 ubiquitin-conjugating enzyme complex UBE2N-UBE2V1 and subsequent activation of the MAP3K7 complex and downstream genes involved in innate immune responses
	TRIM5 is a SUMO1 and SUMO2 substrate, and SUMO machinery is involved in TRIM5-mediated retroviral restriction
	MAP1LC3B binds to TRIM5 via the alpha-helical coiled-coil region

cell & other

REGULATION

induced by

interferons

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to risk of HIV-1 infection

Variant & Polymorphism SNP	polymorphism may influence susceptibility to HIV1 infection (Javanbakht 2006)
	TRIM5 H43Y polymorphism is associated with a decreased risk of HIV-1 infection in the homozygote comparison and recessive model

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology infectious   introduction of two aminoacid substitutions, R332G and R355G, in the TRIM5 domain responsible for retroviral capsid recognition leads to efficient HIV-1 restriction upon stable over-expression

ANIMAL & CELL MODELS