TRIM5

Summary

TRIM5 (tripartite motif containing 5, HGNC:16276) is a protein-coding gene on chromosome 11p15.4, encoding Tripartite motif-containing protein 5 (Q9C035). Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses.

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 85363 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 122 total
• MANE Select transcript: NM_033034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16276
Approved symbol	TRIM5
Name	tripartite motif containing 5
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	RNF88, TRIM5alpha
Ensembl gene	ENSG00000132256
Ensembl biotype	protein_coding
OMIM	608487
Entrez	85363

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000380027, ENST00000380034, ENST00000396847, ENST00000412903, ENST00000419850, ENST00000433961, ENST00000438025, ENST00000465634, ENST00000483835, ENST00000487241, ENST00000492086, ENST00000682968, ENST00000684417, ENST00000684655, ENST00000957480, ENST00000957481

RefSeq mRNA: 4 — MANE Select: NM_033034 NM_001410958, NM_033034, NM_033092, NM_033093

CCDS: CCDS31392, CCDS31393, CCDS31394, CCDS91425

Canonical transcript exons

ENST00000380034 — 8 exons

Exon	Start	End
ENSE00000903262	5679761	5680238
ENSE00001342726	5684868	5685074
ENSE00001811417	5663195	5665395
ENSE00003496416	5678204	5678434
ENSE00003499028	5667689	5667711
ENSE00003595528	5665656	5665682
ENSE00003613146	5665981	5666081
ENSE00003643691	5679074	5679169

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 92.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6154 / max 390.4914, expressed in 1764 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118383	13.0694	1759
118381	1.1310	472
118382	0.3267	118
118387	0.0884	32

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.15	gold quality
germinal epithelium of ovary	UBERON:0001304	91.11	gold quality
palpebral conjunctiva	UBERON:0001812	89.31	gold quality
stromal cell of endometrium	CL:0002255	88.69	gold quality
body of pancreas	UBERON:0001150	88.52	gold quality
endometrium	UBERON:0001295	87.58	gold quality
seminal vesicle	UBERON:0000998	87.51	gold quality
monocyte	CL:0000576	86.93	gold quality
descending thoracic aorta	UBERON:0002345	86.74	gold quality
mononuclear cell	CL:0000842	86.59	gold quality
visceral pleura	UBERON:0002401	86.57	silver quality
blood vessel layer	UBERON:0004797	86.55	gold quality
leukocyte	CL:0000738	86.48	gold quality
blood	UBERON:0000178	86.16	gold quality
pancreas	UBERON:0001264	86.16	gold quality
thoracic aorta	UBERON:0001515	86.05	gold quality
ascending aorta	UBERON:0001496	86.02	gold quality
right adrenal gland cortex	UBERON:0035827	85.91	gold quality
colonic epithelium	UBERON:0000397	85.68	gold quality
right lobe of liver	UBERON:0001114	85.51	gold quality
right adrenal gland	UBERON:0001233	85.30	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.28	silver quality
ectocervix	UBERON:0012249	85.13	gold quality
parietal pleura	UBERON:0002400	85.06	silver quality
left adrenal gland	UBERON:0001234	85.03	gold quality
pleura	UBERON:0000977	85.02	silver quality
right lobe of thyroid gland	UBERON:0001119	84.63	gold quality
left adrenal gland cortex	UBERON:0035825	84.61	gold quality
left ovary	UBERON:0002119	84.60	gold quality
upper lobe of left lung	UBERON:0008952	84.53	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.39
E-ENAD-27	yes	6.19
E-GEOD-100618	no	199.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

Upstream regulators (CollecTRI, top): HR, NR2C2

miRNA regulators (miRDB)

96 targeting TRIM5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-6124	99.87	69.78	3551

Literature-anchored findings (GeneRIF, showing 40)

• TRIM5delta colocalized with BTBD1/2 and appeared to serve as a scaffold for the assembly of endogenous BTBD1/2 proteins (PMID:12878161)
• HIV-1 infection is restricted more efficiently by rhesus monkey TRIM5alpha than by human TRIM5alpha (PMID:14985764)
• Human TRIM5alpha interacts with HIV-1 p2 capsid protein to partially block HIV infection. Rhesus macaque TRIM5alpha AAS48505.1 provides stronger block to HIV-1. (PMID:14985764)
• Data show that lentivirus susceptibility factor 1 and Ref1 are species-specific variants of tripartite interaction motif 5alpha (TRIM5alpha), a cytoplasmic body component that can block infection by widely divergent retroviruses. (PMID:15249685)
• Data show that the human and African green monkey (AGM) TRIM5alpha genes encode Ref1 and Lv1 antiretroviral activities, respectively. (PMID:15249687)
• human, rhesus, and African green monkey Trim5alpha can restrict N-tropic murine leukemia virus (PMID:15249690)
• TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells; B-MLV was resistant to TRIM5alpha-mediated restriction; species-specific variation in TRIM5alpha governs its ability to block infection by diverse retroviruses (PMID:15280539)
• The Trim5alpha SPRY domain was found to be responsible for targeting HIV-1 restriction. (PMID:15649369)
• the major determinant of anti-HIV-1 potency is the B30.2(SPRY) domain (PMID:15709033)
• TRIM5alpha, potently restricted infection by N-tropic murine leukemia virus (N-MLV) and moderately restricted human immunodeficiency virus type 1 (HIV-1) infection (PMID:15767395)
• heterologous expression of TRIM5alpha(rh) or TRIMCyp interferes with the anti-N-MLV activity of endogenous TRIM5alpha; data show TRIM5 orthologues form heteromultimers & C-terminal extensions alter virus recognition by multimers of these proteins (PMID:15919943)
• The SPRY domain of TRIM5alpha, showed higher nonsynonymous/synonymous substitution ratios than the non-SPRY domain, indicating that the adaptive evolution of TRIM5alpha in primates might be an innate strategy developed in defending retrovirus infection (PMID:16226405)
• results indicate that the transcription and protein synthesis of TRIM5alpha could be modulated by IFN, suggesting that TRIM5alpha may play a role in an IFN-induced antiviral state against retrovirus infection (PMID:16289103)
• An SNP at the human TRIM5 locus was found to have a functional consequence on in vitro retroviral infection of B cells. (PMID:16401428)
• TRIM5alpha levels are maintained by continuous synthesis and rapid proteasome-mediated degradation, imbalances in which result in the formation of pre-aggresomal cytoplasmic bodies; turnover of TRIM5alpha is not required for its antiretroviral activity (PMID:16472833)
• concluded that Fv1 and TRIM5 can both recognize retroviral particles early after cell entry and before reverse transcription (PMID:16474118)
• observed no effect of individual TRIM5alpha nonsynonymous mutations on the in vitro HIV-1 susceptibility of CD4(+) T cells (PMID:16474153)
• promotes HIV-1 infectivity completely independent of cyclophilin A (PMID:16501094)
• Mechanism of HIV-1 restriction by TRIM5 alpha involves engagement of the viral capsid by the restriction factor prior to completion of uncoating. (PMID:16624363)
• the positive effects of Cyp A-CA binding on HIV-1 infectivity do not depend on human TRIM5alpha (PMID:16643975)
• polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection (PMID:16887163)
• This study revealed the importance of all three variable regions of TIRM5alpha B30.2 domain for determining retrovirus restriction specificity. (PMID:16912305)
• diverse TRIM5 proteins inhibit retroviral infection in multiple ways (PMID:16973579)
• TRIM5alpha-mediated HIV-1 restriction is related to selective degradation of cytosolic capsid normally associated with productive viral entry (PMID:17028189)
• results show that even a moderate over expression of wild-type TRIM5alpha in human cells (2 fold as determined by quantitative RT-PCR) confers substantial restriction to infection for HIV-1 but only a weaker restriction to infection for HIV-2 (PMID:17087820)
• The expression of TRIM5alpha, but not Fv-1, specifically promoted the premature conversion of particulate N-MLV capsids within infected cells to soluble capsid proteins. (PMID:17135314)
• investigation of properties & antiviral activities of six TRIM family members, including those closely related to TRIM5alpha; only TRIM5alpha exhibited potent antiretroviral activity; also TRIM5alpha was unique in other biochemical & genetic properties (PMID:17156811)
• Data suggest that TRIM5 alpha cytoplasmic bodies are dynamic structures more consistent with a role in function or regulation rather than protein aggregates or inclusion bodies that represent dead-end static structures. (PMID:17392513)
• H43Y has a very minor effect on anti-HIV-1 activity of TRIM5alpha, suggesting that this allele is immaterial, at least in HIV-1-infected Europeans and Asians. (PMID:17406861)
• Some alterations in the TRIM5alpha B-box 2 domain apparently affect the orientation or conformation of the B30.2(SPRY) domain, influencing capsid recognition. (PMID:17543365)
• TRIM5 alpha may have protected early humans from invasion by Pan troglodytes endogenous retrovirus (PMID:17588933)
• TRIM5alpha plays an essential role in controlling both the initial retroviral exposure and the subsequent viral dissemination in vivo. (PMID:17609277)
• TRIM5alpha-mediated retroviral restriction results from the direct binding of the antiviral PRYSPRY domain to the viral capsid in murine leukemia virus infection (PMID:18166079)
• Polymorphisms in the Trim5 gene may influence the clinical course of HIV-1 infection underscoring the antiviral effect of Trim5alpha on HIV-1 in vivo. (PMID:18248091)
• TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with E2 ubiquitin-conjugating enzyme UbcH5B. (PMID:18312418)
• Engagement of a restriction-sensitive retrovirus core results in TRIM5alpha degradation by a proteasome-dependent mechanism. (PMID:18497858)
• TRIM5alpha variants lacking the SPRY domain are useful for silencing TRIM5alpha activity. (PMID:18524394)
• Thus, the range of retroviruses restricted by human TRIM5alpha can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid. (PMID:18586294)
• TRIM5 alpha is implicated in IFN-induced anti-retroviral response in primate cells. (PMID:18613956)
• The TRIM5alpha B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association. (PMID:18799578)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim30a	ENSMUSG00000030921
mus_musculus	Trim30b	ENSMUSG00000052749
mus_musculus	Trim12c	ENSMUSG00000057143
mus_musculus	Trim30d	ENSMUSG00000057596
mus_musculus	Trim5	ENSMUSG00000060441
mus_musculus	Trim12a	ENSMUSG00000066258
mus_musculus	Trim30c	ENSMUSG00000078616
rattus_norvegicus	Trim5	ENSRNOG00000017191
rattus_norvegicus	Trim30c	ENSRNOG00000031202
rattus_norvegicus		ENSRNOG00000071278

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Tripartite motif-containing protein 5 — Q9C035 (reviewed: Q9C035)

Alternative names: RING finger protein 88, RING-type E3 ubiquitin transferase TRIM5

All UniProt accessions (5): Q9C035, A0A804HHS7, C9JWN8, E7EQQ5, H7C134

UniProt curated annotations — full annotation on UniProt →

Function. Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates ‘Lys-63’-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by N-tropic murine leukemia virus (N-MLV), equine infectious anemia virus (EIAV), simian immunodeficiency virus of macaques (SIVmac), feline immunodeficiency virus (FIV), and bovine immunodeficiency virus (BIV). Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. Also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction.

Subunit / interactions. Can form homodimers and homotrimers. In addition to lower-order dimerization, also exhibits a higher-order multimerization and both low- and high-order multimerizations are essential for its restriction activity. Isoform Delta interacts with BTBD1 and BTBD2. Interacts with PSMC4, PSMC5, PSMD7 and HSPA8/HSC70. Interacts (via B30.2/SPRY domain) with HSPA1A/B. Interacts with PSMC2, MAP3K7/TAK1, TAB2 and TAB3. Interacts with SQSTM1. Interacts with TRIM6 and TRIM34. Interacts with ULK1 (phosphorylated form), GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3C and BECN1.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Degraded in a proteasome-independent fashion in the absence of viral infection but in a proteasome-dependent fashion following exposure to restriction sensitive virus. Autoubiquitinated in a RING finger- and UBE2D2-dependent manner. Monoubiquitinated by TRIM21. Deubiquitinated by Yersinia YopJ. Ubiquitination may not lead to proteasomal degradation.

Domain organisation. The B box-type zinc finger domain and the coiled-coil domain contribute to the higher and low order multimerization respectively which is essential for restriction activity. The coiled coil domain is important for higher order multimerization by promoting the initial dimerization. The B30.2/SPRY domain acts as a capsid recognition domain. Polymorphisms in this domain explain the observed species-specific differences among orthologs. The RING-type zinc finger domain confers E3 ubiquitin ligase activity and is essential for retrovirus restriction activity, autoubiquitination and higher-order multimerization.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Probable artifact. Has dominant-negative activity against TRIM5alpha. Does not inhibit HIV-1 replication.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9C035-1	Alpha	yes
Q9C035-2	Beta
Q9C035-3	Gamma
Q9C035-4	Delta
Q9C035-5	Epsilon, Kappa
Q9C035-6	Iota

RefSeq proteins (4): NP_001397887, NP_149023, NP_149083, NP_149084 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13445

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (53 total): splice variant 10, sequence variant 10, turn 6, strand 6, binding site 4, mutagenesis site 4, modified residue 2, zinc finger region 2, sequence conflict 2, helix 2, initiator methionine 1, chain 1, domain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2ECV	SOLUTION NMR
2YRG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C035-F1	86.18	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 123; 95; 98; 117

Post-translational modifications (2): 2, 86

Mutagenesis-validated functional residues (4):

Position	Phenotype
15	abolishes e3 ligase activity.
332	increases strongly cell restriction against hiv-1 and sivmac infection.
332	increases strongly cell restriction against hiv-1 infection.
332	no effect on hiv-1 and sivmac infection.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 283 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_BIOLOGICAL_PROCESS_INVOLVED_IN_SYMBIOTIC_INTERACTION

GO Biological Process (18): activation of innate immune response (GO:0002218), autophagy (GO:0006914), regulation of gene expression (GO:0010468), regulation of lipopolysaccharide-mediated signaling pathway (GO:0031664), regulation of protein localization (GO:0032880), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), regulation of viral entry into host cell (GO:0046596), host-mediated suppression of symbiont invasion (GO:0046597), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), defense response to virus (GO:0051607), protein K63-linked ubiquitination (GO:0070534), immune system process (GO:0002376), protein ubiquitination (GO:0016567), positive regulation of DNA-templated transcription (GO:0045893), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (12): transcription coactivator activity (GO:0003713), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), pattern recognition receptor activity (GO:0038187), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), omegasome (GO:1990462)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of intracellular signal transduction	2
protein binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
activation of immune response	1
positive regulation of innate immune response	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of response to biotic stimulus	1
regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of response to external stimulus	1
intracellular protein localization	1
regulation of localization	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
defense response to virus	1
immune response	1
defense response to symbiont	1
symbiont entry into host cell	1
modulation by symbiont of entry into host	1
regulation of viral life cycle	1
innate immune response	1
host-mediated perturbation of symbiont process	1
defense response	1
response to virus	1
protein polyubiquitination	1
biological_process	1
protein modification by small protein conjugation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of metabolic process	1
primary metabolic process	1
transcription coregulator activity	1

Protein interactions and networks

STRING

1261 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM5	TRAT1	Q6PIZ9	947
TRIM5	BTBD2	Q9BX70	942
TRIM5	APOBEC3G	Q9HC16	920
TRIM5	BTBD1	Q9H0C5	903
TRIM5	PPIA	P05092	899
TRIM5	SAMHD1	Q9Y3Z3	884
TRIM5	BBOX1	O75936	854
TRIM5	BST2	Q10589	842
TRIM5	ATG16L1	Q676U5	803
TRIM5	UBE2N	P61088	795
TRIM5	AMBRA1	Q9C0C7	773
TRIM5	TMLHE	Q9NVH6	772
TRIM5	TNPO3	Q9Y5L0	768
TRIM5	BECN1	Q14457	744
TRIM5	CCR5	P51681	734

IntAct

42 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
TRIM5	TRIM5	psi-mi:“MI:0915”(physical association)	0.630
CFTR	TRIM5	psi-mi:“MI:0915”(physical association)	0.550
TRIM5	TRIM34	psi-mi:“MI:0915”(physical association)	0.550
TRIM5	TRIM32	psi-mi:“MI:0915”(physical association)	0.510
ZWINT		psi-mi:“MI:0915”(physical association)	0.400
TRIM5	SNAI1	psi-mi:“MI:0915”(physical association)	0.400
SNAI1	TRIM5	psi-mi:“MI:0915”(physical association)	0.400
HIP2	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
UBE2D3	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
UBE2H	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2N	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2V1	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2V2	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	UBE2U	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
PCBD1	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
LZTR1	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
TRIM5	MNAT1	psi-mi:“MI:0915”(physical association)	0.370
MKRN3	TRIM5	psi-mi:“MI:0915”(physical association)	0.370
Ppp2ca	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (161): TRIM5 (Biochemical Activity), UBE2D2 (Reconstituted Complex), TRIM5 (Biochemical Activity), UBE2D3 (Reconstituted Complex), TRIM5 (Affinity Capture-MS), TRIM5 (Affinity Capture-MS), UL123 (Affinity Capture-Western), TRIM5 (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D3 (Reconstituted Complex), TRIM5 (Reconstituted Complex), TRIM5 (Co-crystal Structure), SUMO1 (Co-localization), TRIM5 (Biochemical Activity), CUEDC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, C9J1S8, I1YAP6, K7N6K2, P0CI25, P0CI26, P15533, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T6, Q5C8T8, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0

Diamond homologs: A0JN74, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, B1H278, C9J1S8, K7N6K2, O00635, O15553, O19085, O77666, P0CI25, P0CI26, P14373, P15533, P18892, P19474, Q02084, Q0PF16, Q12899, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58DK8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM5	ubiquitination
UBE2D2	“up-regulates activity”	TRIM5	binding
TRIM5	“up-regulates quantity”	TRIM5	monoubiquitination
TRIM21	“up-regulates quantity”	TRIM5	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen processing: Ubiquitination & Proteasome degradation	9	14.6×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein K63-linked ubiquitination	5	46.1×	7e-06
protein polyubiquitination	9	35.8×	4e-10
ubiquitin-dependent protein catabolic process	5	12.8×	8e-04
protein ubiquitination	8	11.4×	1e-05
proteasome-mediated ubiquitin-dependent protein catabolic process	5	9.0×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

122 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	14
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4999 predictions. Top by Δscore:

Variant	Effect	Δscore
11:5679018:T:TA	donor_gain	1.0000
11:5679019:C:A	donor_gain	1.0000
11:5679047:A:AC	donor_gain	1.0000
11:5679048:C:CC	donor_gain	1.0000
11:5679050:C:CA	donor_gain	1.0000
11:5679064:AT:A	donor_gain	1.0000
11:5679065:T:TA	donor_gain	1.0000
11:5679076:T:A	donor_gain	1.0000
11:5679759:A:AC	donor_gain	1.0000
11:5679760:C:CC	donor_gain	1.0000
11:5679769:C:CA	donor_gain	1.0000
11:5697340:G:GT	donor_gain	1.0000
11:5697348:G:GT	donor_gain	1.0000
11:5697366:GGA:G	donor_gain	1.0000
11:5697367:G:T	donor_gain	1.0000
11:5697380:G:GT	donor_gain	1.0000
11:5698306:A:AG	acceptor_gain	1.0000
11:5698310:CCAA:C	acceptor_loss	1.0000
11:5698312:A:AG	acceptor_gain	1.0000
11:5698313:A:AG	acceptor_gain	1.0000
11:5698314:G:GG	acceptor_gain	1.0000
11:5698314:G:GT	acceptor_loss	1.0000
11:5698314:GA:G	acceptor_gain	1.0000
11:5698314:GAA:G	acceptor_gain	1.0000
11:5698314:GAAT:G	acceptor_gain	1.0000
11:5698314:GAATT:G	acceptor_gain	1.0000
11:5698544:AGGT:A	donor_loss	1.0000
11:5698546:G:A	donor_loss	1.0000
11:5709051:A:AG	acceptor_gain	1.0000
11:5709052:G:GG	acceptor_gain	1.0000

AlphaMissense

3253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:5665210:A:G	W361R	0.990
11:5665210:A:T	W361R	0.990
11:5665180:A:G	W371R	0.987
11:5665180:A:T	W371R	0.987
11:5664938:G:C	F451L	0.986
11:5664938:G:T	F451L	0.986
11:5664940:A:G	F451L	0.986
11:5665208:C:A	W361C	0.986
11:5665208:C:G	W361C	0.986
11:5664899:A:C	F464L	0.983
11:5664899:A:T	F464L	0.983
11:5664901:A:G	F464L	0.983
11:5665171:C:A	G374W	0.983
11:5664968:G:C	F441L	0.981
11:5664968:G:T	F441L	0.981
11:5664970:A:G	F441L	0.981
11:5664945:A:T	V449D	0.978
11:5665170:C:T	G374E	0.976
11:5679863:G:C	F105L	0.972
11:5679863:G:T	F105L	0.972
11:5679865:A:G	F105L	0.972
11:5665209:C:G	W361S	0.970
11:5664939:A:G	F451S	0.968
11:5665171:C:G	G374R	0.968
11:5665171:C:T	G374R	0.968
11:5665213:A:C	Y360D	0.967
11:5664932:A:C	N453K	0.964
11:5664932:A:T	N453K	0.964
11:5679838:A:G	C114R	0.964
11:5664972:A:T	V440D	0.960

dbSNP variants (sampled 300 via entrez): RS1000011327 (11:5630522 G>T), RS1000043628 (11:5630215 A>T), RS1000045375 (11:5613101 C>T), RS1000081513 (11:5659020 G>C), RS1000111751 (11:5675453 C>A,T), RS1000135029 (11:5593280 T>C), RS1000137673 (11:5598084 T>A,C), RS1000139707 (11:5629996 G>A), RS1000165634 (11:5627135 T>G), RS1000172583 (11:5588774 G>A), RS1000190275 (11:5598418 A>C,G), RS1000191669 (11:5673784 G>A,T), RS1000205321 (11:5636909 G>A), RS1000218152 (11:5642596 C>A,T), RS1000227735 (11:5675185 C>G,T)

Disease associations

OMIM: gene MIM:608487 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST002058_10	DNA methylation (variation)	3.000000e-06
GCST004286_5	Midgestational circulating levels of PBDEs (fetal genetic effect)	6.000000e-07
GCST004599_17	Mean platelet volume	2.000000e-12
GCST004599_18	Mean platelet volume	6.000000e-19
GCST004599_19	Mean platelet volume	6.000000e-24
GCST005194_105	Coronary artery disease	2.000000e-12
GCST005195_51	Coronary artery disease	6.000000e-13
GCST005196_41	Coronary artery disease	3.000000e-06
GCST005196_42	Coronary artery disease	2.000000e-12
GCST005991_18	Platelet count	9.000000e-10
GCST006016_20	Serum alkaline phosphatase levels	1.000000e-09
GCST010204_112	Low density lipoprotein cholesterol levels	3.000000e-24
GCST010241_20	Apolipoprotein A1 levels	7.000000e-18
GCST010242_162	HDL cholesterol levels	9.000000e-12
GCST010243_199	Apolipoprotein B levels	9.000000e-25
GCST010243_232	Apolipoprotein B levels	4.000000e-10
GCST010245_174	LDL cholesterol levels	2.000000e-15
GCST010245_89	LDL cholesterol levels	2.000000e-08
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST010866_150	Coronary artery disease	4.000000e-15
GCST011353_9	Serum alkaline phosphatase levels	2.000000e-11
GCST011365_142	Myocardial infarction	2.000000e-06
GCST90000255_12	Severe COVID-19 infection with respiratory failure (analysis I)	4.000000e-06
GCST90002395_73	Mean platelet volume	2.000000e-09
GCST90002395_74	Mean platelet volume	3.000000e-14
GCST90002395_75	Mean platelet volume	4.000000e-20
GCST90002395_76	Mean platelet volume	1.000000e-16
GCST90002395_77	Mean platelet volume	1.000000e-18

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0022599	DNA methylation
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0004309	platelet count
EFO:0004533	alkaline phosphatase measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7950311	TRIM5		0.00	0

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Acetaminophen	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases expression	2
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression, increases expression	1
arsenite	decreases reaction, affects binding	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
eprenetapopt	affects expression, affects reaction	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	increases abundance, increases expression	1
Cytarabine	decreases expression	1
Diethylstilbestrol	increases expression	1
Succimer	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TU32	HAP1 TRIM5 (-) 1	Cancer cell line	Male
CVCL_TU33	HAP1 TRIM5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer