PAAF1

Summary

PAAF1 (proteasomal ATPase associated factor 1, HGNC:25687) is a protein-coding gene on chromosome 11q13.4, encoding Proteasomal ATPase-associated factor 1 (Q9BRP4). Inhibits proteasome 26S assembly and proteolytic activity by impairing the association of the 19S regulatory complex with the 20S core.

This gene encodes a WD repeat-containing protein involved in regulation of association of proteasome components. During HIV infection, the encoded protein is thought to promote provirus transcription through recruitment of the 19S regulatory complex. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 80227 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_025155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25687
Approved symbol	PAAF1
Name	proteasomal ATPase associated factor 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11848, Rpn14
Ensembl gene	ENSG00000175575
Ensembl biotype	protein_coding
OMIM	619772
Entrez	80227

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000310571, ENST00000376384, ENST00000381783, ENST00000504441, ENST00000535604, ENST00000535936, ENST00000536003, ENST00000536582, ENST00000540659, ENST00000541951, ENST00000542293, ENST00000543079, ENST00000543814, ENST00000544552, ENST00000544909, ENST00000546039, ENST00000861617, ENST00000861618, ENST00000861619, ENST00000928356

RefSeq mRNA: 6 — MANE Select: NM_025155 NM_001267803, NM_001267804, NM_001267805, NM_001267806, NM_001363556, NM_025155

CCDS: CCDS58157, CCDS58158, CCDS8226, CCDS86227

Canonical transcript exons

ENST00000310571 — 12 exons

Exon	Start	End
ENSE00001184405	73924615	73924697
ENSE00001184409	73918950	73919032
ENSE00001184413	73916545	73916660
ENSE00001184415	73914413	73914504
ENSE00001184418	73909399	73909593
ENSE00001184422	73900270	73900420
ENSE00002303709	73876999	73877068
ENSE00003461764	73878779	73878819
ENSE00003483032	73887354	73887457
ENSE00003528087	73891112	73891201
ENSE00003567075	73899146	73899244
ENSE00003771252	73927285	73931114

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7321 / max 97.9453, expressed in 1724 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115830	8.7321	1724

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.34	gold quality
spinal cord	UBERON:0002240	96.36	gold quality
substantia nigra	UBERON:0002038	95.92	gold quality
medial globus pallidus	UBERON:0002477	95.79	gold quality
amygdala	UBERON:0001876	95.70	gold quality
lateral globus pallidus	UBERON:0002476	95.64	gold quality
putamen	UBERON:0001874	95.63	gold quality
globus pallidus	UBERON:0001875	95.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.54	gold quality
nucleus accumbens	UBERON:0001882	95.47	gold quality
midbrain	UBERON:0001891	95.47	gold quality
inferior olivary complex	UBERON:0002127	95.43	gold quality
caudate nucleus	UBERON:0001873	95.15	gold quality
anterior cingulate cortex	UBERON:0009835	94.88	gold quality
hypothalamus	UBERON:0001898	94.86	gold quality
cingulate cortex	UBERON:0003027	94.83	gold quality
right frontal lobe	UBERON:0002810	94.78	gold quality
corpus callosum	UBERON:0002336	94.73	gold quality
substantia nigra pars compacta	UBERON:0001965	94.62	gold quality
buccal mucosa cell	CL:0002336	94.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.28	gold quality
prefrontal cortex	UBERON:0000451	94.04	gold quality
Ammon’s horn	UBERON:0001954	94.00	gold quality
inferior vagus X ganglion	UBERON:0005363	93.61	gold quality
telencephalon	UBERON:0001893	93.55	gold quality
subthalamic nucleus	UBERON:0001906	93.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.47	gold quality
forebrain	UBERON:0001890	93.19	gold quality
frontal cortex	UBERON:0001870	93.18	gold quality
neocortex	UBERON:0001950	93.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting PAAF1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359

Literature-anchored findings (GeneRIF, showing 3)

• Proteasomal ATPase-associated factor 1 (PAAF1) functions as a negative regulator of the proteasome by controlling the assembly/disassembly of the proteasome. (PMID:15831487)
• These results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer. (PMID:22316138)
• Identification of a quality-control factor that monitors failures during proteasome assembly. (PMID:34446601)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
caenorhabditis_elegans	Y39G10AR.9	WBGENE00021467

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), TRAF7 (ENSG00000131653), FBXW9 (ENSG00000132004), FBXO36 (ENSG00000153832), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), WDR86 (ENSG00000187260), FBXO16 (ENSG00000214050), EFCAB8 (ENSG00000215529)

Protein

Protein identifiers

Proteasomal ATPase-associated factor 1 — Q9BRP4 (reviewed: Q9BRP4)

Alternative names: Protein G-16, WD repeat-containing protein 71

All UniProt accessions (8): Q9BRP4, F5H0C4, F5H0F7, F5H103, F5H3E9, F5H3I1, F5H5D4, H0YGB1

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits proteasome 26S assembly and proteolytic activity by impairing the association of the 19S regulatory complex with the 20S core. In case of HIV-1 infection, recruited by viral Tat to the HIV-1 promoter, where it promotes the recruitment of 19S regulatory complex through dissociation of the proteasome 26S. This presumably promotes provirus transcription efficiency. Protects SUPT6H from proteasomal degradation.

Subunit / interactions. Interacts with PSMC1, PSMC2, PSMC3, PSMC4, PSMC5 and PSMC6. Interacts with SUPT6H. (Microbial infection) Interacts with HIV-1 Tat.

Tissue specificity. Ubiquitously expressed, with highest levels in kidney, brain and testis.

Similarity. Belongs to the WD repeat PAAF1/RPN14 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BRP4-1	1	yes
Q9BRP4-2	2
Q9BRP4-3	3

RefSeq proteins (6): NP_001254732, NP_001254733, NP_001254734, NP_001254735, NP_001350485, NP_079431* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051179	WD_repeat_multifunction	Family

Pfam: PF00400

UniProt features (15 total): repeat 7, sequence variant 3, splice variant 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRP4-F1	95.87	0.94

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9907900	Proteasome assembly

MSigDB gene sets: 79 (showing top): chr11q13, DOUGLAS_BMI1_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, HAN_SATB1_TARGETS_DN, CHANDRAN_METASTASIS_UP, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, THUM_SYSTOLIC_HEART_FAILURE_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOCC_PEPTIDASE_COMPLEX, GOCC_ENDOPEPTIDASE_COMPLEX, ARID5B_TARGET_GENES, CBX7_TARGET_GENES, CEBPZ_TARGET_GENES, DLX6_TARGET_GENES, DMRT1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): proteasome complex (GO:0000502), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
cytoplasm	1

Protein interactions and networks

STRING

1371 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAAF1	PSMC4	P43686	976
PAAF1	SLC13A4	Q9UKG4	848
PAAF1	PSMD12	O00232	801
PAAF1	PSMD8	P48556	794
PAAF1	ADRM1	Q16186	794
PAAF1	PSMD14	O00487	771
PAAF1	PSMD10	O75832	762
PAAF1	PSMD3	O43242	759
PAAF1	PSMD9	O00233	743
PAAF1	PSMD4	P55036	739
PAAF1	PSMD7	P51665	732
PAAF1	PSMD11	O00231	723
PAAF1	PSMD6	Q15008	719
PAAF1	PSMD13	Q9UNM6	714
PAAF1	POMP	Q9Y244	701

IntAct

88 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMC4	psi-mi:“MI:0914”(association)	0.970
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
PSMC5	PSMD10	psi-mi:“MI:0914”(association)	0.850
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
PAAF1	PSMC5	psi-mi:“MI:0407”(direct interaction)	0.790
PSMD13	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
PSMD7	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PSMC4	PSMD11	psi-mi:“MI:0914”(association)	0.670
PSMD3	PSMD6	psi-mi:“MI:0914”(association)	0.670
PSMD3	PSMD11	psi-mi:“MI:0914”(association)	0.650
PSMC4	PSMD3	psi-mi:“MI:0914”(association)	0.530
PSMC3	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMD5	PSMD11	psi-mi:“MI:0914”(association)	0.530
CCDC92	PSMD11	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
PAAF1	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
PAAF1	TK1	psi-mi:“MI:0915”(physical association)	0.370
Psmd6	MIF4GD	psi-mi:“MI:0914”(association)	0.350

BioGRID (166): PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Co-fractionation), PAAF1 (Co-fractionation), PAAF1 (Co-fractionation), PAAF1 (Co-fractionation), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS), PAAF1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RUS2, O43379, O60336, P58742, Q08BB3, Q0VBY8, Q148I1, Q15334, Q3MHH0, Q3SZD4, Q3U3T8, Q499N3, Q4R3J7, Q4VBE8, Q5FW06, Q5QP82, Q5RCX2, Q5T6F0, Q5U4D9, Q5U4F6, Q5VW00, Q5ZJL7, Q63ZP7, Q6AX81, Q6AY87, Q6NS57, Q6NWH1, Q6P1M3, Q6P809, Q7Z5U6, Q80Y17, Q86W42, Q8AVS9, Q8BGW4, Q8BGZ3, Q8C5V5, Q8HXL3, Q8K4K5

Diamond homologs: Q148I1, Q5ZK69, Q8MYE8, Q9BRP4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	19	135.7×	3e-36
Vpu mediated degradation of CD4	19	129.4×	4e-36
Autodegradation of the E3 ubiquitin ligase COP1	19	129.4×	4e-36
Ubiquitin-dependent degradation of Cyclin D	19	129.4×	4e-36
Regulation of ornithine decarboxylase (ODC)	18	125.5×	2e-34
Vif-mediated degradation of APOBEC3G	19	123.6×	1e-35
AUF1 (hnRNP D0) binds and destabilizes mRNA	19	121.0×	1e-35
Degradation of AXIN	19	121.0×	1e-35

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	22	23.4×	6e-23
ubiquitin-dependent protein catabolic process	7	10.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2867 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73887350:ATAG:A	acceptor_gain	1.0000
11:73887455:AAGG:A	donor_loss	1.0000
11:73887457:GGT:G	donor_loss	1.0000
11:73887458:G:C	donor_loss	1.0000
11:73887459:T:A	donor_loss	1.0000
11:73889997:A:AG	acceptor_gain	1.0000
11:73891111:GAAAA:G	acceptor_gain	1.0000
11:73891198:GAGT:G	donor_gain	1.0000
11:73891200:GT:G	donor_gain	1.0000
11:73899140:GAACA:G	acceptor_loss	1.0000
11:73899141:AACAG:A	acceptor_loss	1.0000
11:73899142:ACAGA:A	acceptor_loss	1.0000
11:73899143:CAGAT:C	acceptor_loss	1.0000
11:73899144:A:AG	acceptor_gain	1.0000
11:73899144:A:T	acceptor_loss	1.0000
11:73899145:G:GG	acceptor_gain	1.0000
11:73899145:GAT:G	acceptor_gain	1.0000
11:73899145:GATA:G	acceptor_gain	1.0000
11:73899145:GATAA:G	acceptor_gain	1.0000
11:73899243:GG:G	donor_gain	1.0000
11:73899244:GG:G	donor_gain	1.0000
11:73899257:G:GT	donor_gain	1.0000
11:73900269:GAGA:G	acceptor_gain	1.0000
11:73900418:G:GT	donor_gain	1.0000
11:73909394:GCTA:G	acceptor_loss	1.0000
11:73909395:CTA:C	acceptor_loss	1.0000
11:73909396:TAGGT:T	acceptor_loss	1.0000
11:73909398:G:GT	acceptor_loss	1.0000
11:73909398:GGT:G	acceptor_gain	1.0000
11:73909589:GCCCA:G	donor_gain	1.0000

AlphaMissense

2547 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:73900339:A:C	S151R	0.999
11:73900341:T:A	S151R	0.999
11:73900341:T:G	S151R	0.999
11:73899218:T:A	W119R	0.998
11:73899218:T:C	W119R	0.998
11:73900334:T:A	V149D	0.998
11:73900369:T:A	W161R	0.998
11:73900369:T:C	W161R	0.998
11:73909473:T:A	W203R	0.998
11:73909473:T:C	W203R	0.998
11:73918988:T:A	V325D	0.998
11:73916614:G:T	G297W	0.997
11:73909475:G:C	W203C	0.996
11:73909475:G:T	W203C	0.996
11:73914455:C:A	A257D	0.996
11:73914473:T:C	L263P	0.996
11:73916615:G:A	G297E	0.996
11:73919026:A:C	S338R	0.996
11:73919028:C:A	S338R	0.996
11:73919028:C:G	S338R	0.996
11:73877052:T:A	W11R	0.995
11:73877052:T:C	W11R	0.995
11:73887435:T:C	F57S	0.995
11:73899220:G:C	W119C	0.995
11:73899220:G:T	W119C	0.995
11:73900371:G:C	W161C	0.995
11:73900371:G:T	W161C	0.995
11:73916577:C:A	N284K	0.995
11:73916577:C:G	N284K	0.995
11:73916627:G:T	G301V	0.995

dbSNP variants (sampled 300 via entrez): RS1000192265 (11:73900621 A>G), RS1000254941 (11:73877580 T>A), RS1000350842 (11:73897859 G>A), RS1000362923 (11:73912346 C>G), RS1000568787 (11:73878330 A>C,G), RS1000605253 (11:73924771 G>A,C), RS1000647930 (11:73889827 A>G), RS1000686073 (11:73896650 G>A,T), RS1000716531 (11:73893080 T>C), RS1000757793 (11:73896791 C>A), RS1000771972 (11:73885344 A>G), RS1000849950 (11:73908898 C>G,T), RS1000891987 (11:73917942 A>G), RS1000936574 (11:73889201 A>G), RS1000963976 (11:73896302 A>C,T)

Disease associations

OMIM: gene MIM:619772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005760_4	Dimensional psychopathology (Cognitive)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009098	cognitive domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acetaminophen	affects response to substance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance, affects cotreatment	1

Clinical trials (associated diseases)

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