SERF2

Summary

SERF2 (small EDRK-rich factor 2, HGNC:10757) is a protein-coding gene on chromosome 15q15.3, encoding Small EDRK-rich factor 2 (P84101). Positive regulator of amyloid protein aggregation and proteotoxicity. It is a selective cancer dependency (DepMap: 13.0% of cell lines).

Involved in protein destabilization. Predicted to be located in cytosol and nucleus.

Source: NCBI Gene 10169 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 13.0% of screened cell lines
• MANE Select transcript: NM_001018108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10757
Approved symbol	SERF2
Name	small EDRK-rich factor 2
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Aliases	FAM2C, Hero7, 4F5REL, H4F5rel, HsT17089
Ensembl gene	ENSG00000140264
Ensembl biotype	protein_coding
OMIM	605054
Entrez	10169

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000249786, ENST00000339624, ENST00000381359, ENST00000402131, ENST00000403425, ENST00000409291, ENST00000409614, ENST00000409617, ENST00000409646, ENST00000409960, ENST00000430901, ENST00000445816, ENST00000448830, ENST00000474290, ENST00000475927, ENST00000486144, ENST00000630046, ENST00000914900, ENST00000914901, ENST00000914902, ENST00000914903

RefSeq mRNA: 5 — MANE Select: NM_001018108 NM_001018108, NM_001199875, NM_001199876, NM_001199877, NM_001199878

CCDS: CCDS32218, CCDS55963, CCDS55964, CCDS55965

Canonical transcript exons

ENST00000249786 — 3 exons

Exon	Start	End
ENSE00003559739	43792975	43793083
ENSE00003907559	43793710	43796079
ENSE00003908400	43792320	43792383

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 433.8425 / max 2689.0986, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146349	432.0438	1828
146351	0.6139	285
146346	0.5433	299
146347	0.2816	60
146348	0.1909	62
146352	0.1691	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.80	gold quality
right adrenal gland	UBERON:0001233	99.76	gold quality
right adrenal gland cortex	UBERON:0035827	99.76	gold quality
stromal cell of endometrium	CL:0002255	99.75	gold quality
left adrenal gland	UBERON:0001234	99.73	gold quality
left adrenal gland cortex	UBERON:0035825	99.73	gold quality
right testis	UBERON:0004534	99.69	gold quality
right lobe of thyroid gland	UBERON:0001119	99.68	gold quality
left testis	UBERON:0004533	99.68	gold quality
prostate gland	UBERON:0002367	99.67	gold quality
adult mammalian kidney	UBERON:0000082	99.66	gold quality
left lobe of thyroid gland	UBERON:0001120	99.66	gold quality
placenta	UBERON:0001987	99.66	gold quality
metanephros cortex	UBERON:0010533	99.66	gold quality
granulocyte	CL:0000094	99.65	gold quality
pituitary gland	UBERON:0000007	99.65	gold quality
thyroid gland	UBERON:0002046	99.65	gold quality
adenohypophysis	UBERON:0002196	99.65	gold quality
adrenal gland	UBERON:0002369	99.65	gold quality
right atrium auricular region	UBERON:0006631	99.65	gold quality
cortex of kidney	UBERON:0001225	99.63	gold quality
ascending aorta	UBERON:0001496	99.63	gold quality
thoracic aorta	UBERON:0001515	99.63	gold quality
body of stomach	UBERON:0001161	99.62	gold quality
left coronary artery	UBERON:0001626	99.62	gold quality
apex of heart	UBERON:0002098	99.62	gold quality
descending thoracic aorta	UBERON:0002345	99.62	gold quality
transverse colon	UBERON:0001157	99.61	gold quality
heart left ventricle	UBERON:0002084	99.61	gold quality
right lobe of liver	UBERON:0001114	99.60	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	16205.70
E-MTAB-6505	yes	8976.28
E-CURD-98	yes	3610.51
E-HCAD-4	yes	2945.70
E-HCAD-5	yes	2425.94
E-ANND-2	yes	1237.86
E-CURD-122	yes	77.32
E-MTAB-7316	yes	27.07
E-GEOD-130148	yes	21.45
E-MTAB-9221	yes	21.23
E-CURD-46	yes	19.94
E-MTAB-8142	yes	15.92
E-CURD-88	yes	13.31
E-MTAB-10042	yes	13.10
E-HCAD-35	yes	7.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAX

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• The human orthologs of MOAG-4, SERF2 and SERF1A, are ubiquitously expressed, consistent with a role in a general cellular pathway. (PMID:20723760)
• Atomistic molecular-dynamic simulations predict spontaneous unfolding of SERF2, and computational large-scale protein-protein interactions predict its stable binding to ubiquitins. SERF2 is also predicted to bind to most proteins screened at random, although with lower average stability than to ubiquitins, suggesting roles in aggregation initiation and/or progression. (PMID:30291272)
• The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation. (PMID:34617299)
• Backbone 1H, 13C, and 15N chemical shift assignments for human SERF2. (PMID:38466543)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	serf2b	ENSDARG00000074340
danio_rerio	serf2a	ENSDARG00000075881

Protein

Protein identifiers

Small EDRK-rich factor 2 — P84101 (reviewed: P84101)

Alternative names: Gastric cancer-related protein VRG107, Protein 4F5-related

All UniProt accessions (6): P84101, B8ZZY7, B9A031, C9JQZ0, F8WBN3, F8WBV6

UniProt curated annotations — full annotation on UniProt →

Function. Positive regulator of amyloid protein aggregation and proteotoxicity. Induces conformational changes in amyloid proteins, such as HTT, driving them into compact formations preceding the formation of aggregates.

Similarity. Belongs to the SERF family.

Isoforms (4)

UniProt ID	Names	Canonical?
P84101-1	1	yes
P84101-2	2
P84101-3	3
P84101-4	4

RefSeq proteins (5): NP_001018118, NP_001186804, NP_001186805, NP_001186806, NP_001186807 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007513	SERF-like_N	Domain
IPR040211	SERF1/2-like	Family

Pfam: PF04419

UniProt features (8 total): splice variant 3, compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9DT0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P84101-F1	81.46	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): PAL_PRMT5_TARGETS_UP, GCANCTGNY_MYOD_Q6, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AREB6_03, CAGGTCC_MIR492, CAGCTG_AP4_Q5, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_PROTEIN_DESTABILIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GARY_CD5_TARGETS_DN, GOBP_REGULATION_OF_PROTEIN_STABILITY, PARK_HSC_AND_MULTIPOTENT_PROGENITORS, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, MARKEY_RB1_ACUTE_LOF_UP

GO Biological Process (1): protein destabilization (GO:0031648)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein stability	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERF2	HYPK	Q9NX55	620
SERF2	PRNP	P04156	460
SERF2	SERINC4	A6NH21	449
SERF2	PRR29	P0C7W0	433
SERF2	LRRC57	Q8N9N7	426
SERF2	MFAP1	P55081	412
SERF2	SYT8	Q8NBV8	384
SERF2	UBE2R2	Q712K3	378
SERF2	ZFYVE19	Q96K21	373
SERF2	TMEM54	Q969K7	373
SERF2	RUSF1	Q96GQ5	370
SERF2	PIP5K1A	Q99755	359
SERF2	NFS1	Q9Y697	353
SERF2	C19orf53	Q9UNZ5	349
SERF2	EIF2B2	P49770	347

IntAct

22 interactions, top by confidence:

A	B	Type	Score
NAV3	SERF2	psi-mi:“MI:0915”(physical association)	0.400
POLR3B	SERF2	psi-mi:“MI:0915”(physical association)	0.400
SERF2	BOLL	psi-mi:“MI:0915”(physical association)	0.370
SERF2	PTPN11	psi-mi:“MI:0915”(physical association)	0.370
SERF2	WT1	psi-mi:“MI:0915”(physical association)	0.370
SERF2	RHOXF2	psi-mi:“MI:0915”(physical association)	0.370
MDFI	SERF2	psi-mi:“MI:0915”(physical association)	0.370
SERF2	PSME3	psi-mi:“MI:0915”(physical association)	0.370
SERF2	RBPMS	psi-mi:“MI:0915”(physical association)	0.370
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
MYORG	CLGN	psi-mi:“MI:0914”(association)	0.350
alsS	SERF2	psi-mi:“MI:0915”(physical association)	0.000
GC	SERF2	psi-mi:“MI:0915”(physical association)	0.000
SERF2	CHD3	psi-mi:“MI:0915”(physical association)	0.000
NELFCD	SERF2	psi-mi:“MI:0915”(physical association)	0.000
SERF2	QKI	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (90): SERF2 (Two-hybrid), SERF2 (Two-hybrid), SERF2 (Two-hybrid), THAP1 (Two-hybrid), BOLL (Two-hybrid), KRTAP10-3 (Two-hybrid), RHOXF2 (Two-hybrid), SERF2 (Two-hybrid), PSME3 (Two-hybrid), RBPMS (Two-hybrid), SERF2 (Two-hybrid), SERF2 (Two-hybrid), SERF2 (Affinity Capture-MS), SERF2 (Affinity Capture-RNA), RBPMS (Two-hybrid)

ESM2 similar proteins: A5JSS4, B1MTI8, O88892, P02641, P06398, P09739, P0C0A9, P12620, P45378, P84101, P84102, Q05310, Q0UVD1, Q148I0, Q1E554, Q28HN4, Q28IN9, Q2KIT1, Q2TBR9, Q2TBV6, Q32P76, Q3E7B7, Q4I5Z5, Q5R5J3, Q5R6N0, Q5R7C4, Q5R8X8, Q5REM2, Q5ZHK9, Q68EY7, Q6DD17, Q6GNG8, Q6NVR5, Q6PHE8, Q75NG9, Q7SDA6, Q7ZY35, Q8MKI3, Q8NHG7, Q8R1F0

Diamond homologs: A5JSS4, B1MTI8, O75920, O88892, P84101, P84102, Q32P76, Q5R7C4, Q9BKU8, Q9VEW2, Q3E7B7, Q9UTF0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3926 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43792972:TA:T	acceptor_loss	1.0000
15:43792973:A:AG	acceptor_gain	1.0000
15:43792973:AGGC:A	acceptor_gain	1.0000
15:43792974:G:GG	acceptor_gain	1.0000
15:43792974:G:T	acceptor_loss	1.0000
15:43792974:GGC:G	acceptor_gain	1.0000
15:43792974:GGCG:G	acceptor_gain	1.0000
15:43793038:G:T	donor_gain	1.0000
15:43793039:A:T	donor_gain	1.0000
15:43793081:G:GT	donor_gain	1.0000
15:43793081:GAG:G	donor_gain	1.0000
15:43796656:G:C	donor_gain	1.0000
15:43798030:A:T	acceptor_gain	1.0000
15:43800781:GACG:G	donor_gain	1.0000
15:43800783:CGG:C	donor_loss	1.0000
15:43800785:G:GG	donor_gain	1.0000
15:43800785:GT:G	donor_loss	1.0000
15:43800786:T:A	donor_loss	1.0000
15:43801184:AGCGG:A	donor_loss	1.0000
15:43801185:GCG:G	donor_gain	1.0000
15:43801188:G:C	donor_loss	1.0000
15:43801188:G:GG	donor_gain	1.0000
15:43801189:T:A	donor_loss	1.0000
15:43801512:TTGCA:T	acceptor_loss	1.0000
15:43801513:TGCA:T	acceptor_loss	1.0000
15:43801514:GCA:G	acceptor_loss	1.0000
15:43801516:A:AG	acceptor_gain	1.0000
15:43801516:A:AT	acceptor_loss	1.0000
15:43801516:AG:A	acceptor_gain	1.0000
15:43801517:G:GA	acceptor_loss	1.0000

AlphaMissense

391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43792986:C:T	R7C	0.999
15:43793073:C:A	R36S	0.999
15:43793711:G:C	D40H	0.999
15:43792977:G:C	G4R	0.998
15:43792978:G:T	G4V	0.998
15:43792986:C:A	R7S	0.998
15:43792998:C:A	R11S	0.998
15:43793070:G:C	A35P	0.998
15:43793078:G:C	K37N	0.998
15:43793078:G:T	K37N	0.998
15:43793083:G:T	R39M	0.998
15:43793712:A:C	D40A	0.998
15:43793712:A:T	D40V	0.998
15:43793730:A:C	Q46P	0.998
15:43792977:G:T	G4C	0.997
15:43792978:G:A	G4D	0.997
15:43792982:C:A	N5K	0.997
15:43792982:C:G	N5K	0.997
15:43792985:G:C	Q6H	0.997
15:43792985:G:T	Q6H	0.997
15:43792993:T:C	L9P	0.997
15:43793074:G:C	R36P	0.997
15:43793083:G:C	R39T	0.997
15:43793710:G:C	R39S	0.997
15:43793710:G:T	R39S	0.997
15:43793711:G:A	D40N	0.997
15:43793712:A:G	D40G	0.997
15:43793713:C:A	D40E	0.997
15:43793713:C:G	D40E	0.997
15:43793714:T:C	S41P	0.997

dbSNP variants (sampled 300 via entrez): RS1000304083 (15:43796488 T>G), RS1000521898 (15:43776887 C>G,T), RS1000849516 (15:43778702 C>A,T), RS1000977658 (15:43777189 AAG>A), RS1000991580 (15:43778880 C>T), RS1001032210 (15:43784777 G>A,T), RS1001485890 (15:43785229 C>T), RS1001486755 (15:43775202 A>G), RS1001520787 (15:43781415 A>G), RS1001656497 (15:43781695 G>A,T), RS1001688292 (15:43793408 G>A,T), RS1001725480 (15:43791127 G>A), RS1001857699 (15:43779972 C>T), RS1002020765 (15:43792300 C>A,T), RS1002093965 (15:43786538 C>T)

Disease associations

OMIM: gene MIM:605054 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742282 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
chloropicrin	affects expression, decreases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Valproic Acid	decreases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
bisphenol A	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression, affects cotreatment	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Fluorouracil	decreases expression	1
Methotrexate	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Plant Extracts	decreases expression, affects cotreatment	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Mifepristone	increases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713780	Binding	Protac activity at CRBN/SERF2 in human BxPC-3 cells assessed as SERF2 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Clinical trials (associated diseases)

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