SEMG2

Summary

SEMG2 (semenogelin 2, HGNC:10743) is a protein-coding gene on chromosome 20q13.12, encoding Semenogelin-2 (Q02383). Participates in the formation of a gel matrix (sperm coagulum) entrapping the accessory gland secretions and ejaculated spermatozoa.

The secreted protein encoded by this gene is involved in the formation of a gel matrix that encases ejaculated spermatozoa. Proteolysis by the prostate-specific antigen (PSA) breaks down the gel matrix and allows the spermatozoa to move more freely. The encoded protein is found in lesser abundance than a similar semenogelin protein. An antibacterial activity has been found for a antimicrobial peptide isolated from this protein. The genes encoding these two semenogelin proteins are found in a cluster on chromosome 20.

Source: NCBI Gene 6407 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_003008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10743
Approved symbol	SEMG2
Name	semenogelin 2
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	SGII
Ensembl gene	ENSG00000124157
Ensembl biotype	protein_coding
OMIM	182141
Entrez	6407

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372769

RefSeq mRNA: 1 — MANE Select: NM_003008 NM_003008

CCDS: CCDS13346

Canonical transcript exons

ENST00000372769 — 3 exons

Exon	Start	End
ENSE00000844921	45221709	45223425
ENSE00000844922	45224291	45224458
ENSE00001858311	45221373	45221465

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 65.8511 / max 60755.1035, expressed in 21 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184823	64.4255	18
184828	0.4410	4
184822	0.2847	7
184827	0.2225	3
184824	0.1851	3
184825	0.1725	3
184826	0.1198	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	100.00	gold quality
sperm	CL:0000019	96.69	gold quality
male germ cell	CL:0000015	92.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.32	gold quality
paraflocculus	UBERON:0005351	62.99	gold quality
frontal pole	UBERON:0002795	62.94	gold quality
middle frontal gyrus	UBERON:0002702	62.83	gold quality
endometrium epithelium	UBERON:0004811	62.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.01	gold quality
nasal cavity mucosa	UBERON:0001826	60.04	gold quality
colonic epithelium	UBERON:0000397	56.89	gold quality
tendon of biceps brachii	UBERON:0008188	53.87	gold quality
prostate gland	UBERON:0002367	53.48	gold quality
cerebellar vermis	UBERON:0004720	52.81	gold quality
metanephric glomerulus	UBERON:0004736	52.07	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.99	gold quality
quadriceps femoris	UBERON:0001377	50.44	gold quality
vastus lateralis	UBERON:0001379	49.93	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
kidney epithelium	UBERON:0004819	48.93	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
thymus	UBERON:0002370	48.80	gold quality
metanephros	UBERON:0000081	48.75	silver quality
oviduct epithelium	UBERON:0004804	48.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting SEMG2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-188-5P	97.89	67.01	756

Literature-anchored findings (GeneRIF, showing 11)

• SgII transcripts were demonstrated in several tissues, with the strongest signals coming from seminal vesicles, vas deferens, prostate, epididymis and trachea. (PMID:12200457)
• Seminal plasma motility inhibitor, one of the fragments of Sg, has its inhibitory effect on ejaculated spermatozoa in liquefied semen under physiological conditions. (PMID:14581514)
• structural changes in the semenogelin 1 and 2 proteins that have arisen since the human-chimpanzee-gorilla split may be responsible for the physiological differences between these species ejaculated semen that correlate with their sociosexual behavior (PMID:14629036)
• The binding of Zn2+ to SgI and SgII and their involvment in regulating the activity of PSA are reported. (PMID:15563730)
• SGII is a novel target for protein S-nitrosylation in spermatozoa. (PMID:17683036)
• semenogelins I and II were directly cleaved by KLK14. Semenogelins were also able to reverse KLK14 inhibition by Zn2+, providing a novel regulatory mechanism for KLK14 activity. (PMID:18482984)
• antibacterial activity of the semenogelin-derived peptides generated in seminal plasma was strictly zinc-dependent both at neutral and low pH (PMID:18714013)
• Semenogelins (Sgs) modifies the membrane structure, indirectly inhibiting motility, and provides suggestions for a therapy for male infertility through selection of a functional sperm population using Sgs. (PMID:19089943)
• These results suggest the involvement of semenogelins in prostate cancer and their prognostic values in predicting cancer progression after radical prostatectomy. (PMID:21557275)
• Peptides released by physiological cleavage of Semg1 and Semg2 form amyloids that enhance HIV infection. (PMID:22177559)
• SEMG1/2 augment energy metabolism of tumor cells. (PMID:33311447)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Svs3a	ENSMUSG00000017003
mus_musculus	Semg1	ENSMUSG00000040132
mus_musculus	Svs3b	ENSMUSG00000050383
rattus_norvegicus	Semg1	ENSRNOG00000013776
rattus_norvegicus	Svs3b	ENSRNOG00000036782
rattus_norvegicus	Svs3a	ENSRNOG00000062737

Paralogs (1): SEMG1 (ENSG00000124233)

Protein

Protein identifiers

Semenogelin-2 — Q02383 (reviewed: Q02383)

Alternative names: Semenogelin II

All UniProt accessions (1): Q02383

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the formation of a gel matrix (sperm coagulum) entrapping the accessory gland secretions and ejaculated spermatozoa.

Subunit / interactions. Interacts with SERPINA5.

Subcellular location. Secreted.

Tissue specificity. Seminal vesicles, and to a much lesser extent, epididymis.

Post-translational modifications. Semenogelin-2 is thought to form both the 71 kDa polypeptide and, in its glycosylated form, the 76 kDa polypeptide.

Similarity. Belongs to the semenogelin family.

RefSeq proteins (1): NP_002999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008836	Semenogelin	Family

Pfam: PF05474

UniProt features (33 total): compositionally biased region 14, region of interest 7, sequence variant 5, repeat 4, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02383-F1	30.69	0.00

Functional residue map

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

Glycosylation sites (1): 272

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOCC_SECRETORY_GRANULE, MODULE_151, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT

GO Biological Process (5): antibacterial humoral response (GO:0019731), sperm capacitation (GO:0048240), coagulation (GO:0050817), positive regulation of serine-type endopeptidase activity (GO:1900005), negative regulation of flagellated sperm motility (GO:1901318)

GO Molecular Function (3): protease binding (GO:0002020), zinc ion binding (GO:0008270), protein binding (GO:0005515)

GO Cellular Component (5): acrosomal vesicle (GO:0001669), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antimicrobial humoral response	1
defense response to bacterium	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
multicellular organismal process	1
serine-type endopeptidase activity	1
positive regulation of endopeptidase activity	1
regulation of serine-type endopeptidase activity	1
negative regulation of cilium movement	1
flagellated sperm motility	1
regulation of flagellated sperm motility	1
negative regulation of cilium-dependent cell motility	1
negative regulation of reproductive process	1
enzyme binding	1
transition metal ion binding	1
binding	1
secretory granule	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMG2	WFDC12	Q8WWY7	871
SEMG2	KLK3	P07288	744
SEMG2	PI3	P19957	735
SEMG2	SLPI	P03973	670
SEMG2	ZAN	Q9Y493	667
SEMG2	SEMG1	P04279	640
SEMG2	SERPINA5	P05154	597
SEMG2	FN1	P02751	596
SEMG2	KLK2	P20151	595
SEMG2	WFDC8	Q8IUA0	582
SEMG2	OR8U3	Q8NH85	582
SEMG2	LGALS3BP	Q08380	575
SEMG2	TGM4	P49221	570
SEMG2	SPINT4	Q6UDR6	568
SEMG2	WFDC5	Q8TCV5	568

IntAct

71 interactions, top by confidence:

A	B	Type	Score
SNTB2	CASK	psi-mi:“MI:0914”(association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
SYT16	DUSP14	psi-mi:“MI:0914”(association)	0.530
HACD1	SEMG1	psi-mi:“MI:0914”(association)	0.530
NUPR1	SEMG1	psi-mi:“MI:0914”(association)	0.530
MSS51	SEMG1	psi-mi:“MI:0914”(association)	0.530
LINC02908	SEMG1	psi-mi:“MI:0914”(association)	0.530
LSM14B	SEMG1	psi-mi:“MI:0914”(association)	0.530
SEMG2	VSIG8	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
PIK3R2	BCR/ABL fusion	psi-mi:“MI:0914”(association)	0.460
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
SEMG2	CDK10	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
POLL	SULT1C2	psi-mi:“MI:0914”(association)	0.350
BSPRY	DEAF1	psi-mi:“MI:0914”(association)	0.350
SLC22A13	SEMG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Proximity Label-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SMURF2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUY1, A6NJ88, A6QL64, B3KS81, E9Q6E9, O43493, O48582, O77733, P04279, P0C7A4, P0C7A5, P0CV57, P0DKJ7, P10322, P16225, P48997, P48998, Q02383, Q06990, Q08AG5, Q0ZNK1, Q5JPF3, Q5JRC9, Q5SRN2, Q5U7M7, Q5U7M8, Q5U7M9, Q5U7N0, Q5U7N1, Q5U7N3, Q5U7N4, Q5XHX6, Q659K0, Q6AYN3, Q6JHY2, Q6P902, Q6SJ82, Q6X2M3, Q6XPR3, Q80Y39

Diamond homologs: O77733, P04279, P0C7A4, P0C7A5, Q02383, Q5U7M7, Q5U7M8, Q5U7M9, Q5U7N0, Q5U7N1, Q5U7N3, Q5U7N4, Q6X2M3, Q95196, P22006, F2Z472

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

180 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45221463:AAGG:A	donor_loss	1.0000
20:45221466:GTGA:G	donor_loss	1.0000
20:45221467:T:G	donor_loss	1.0000
20:45221466:G:GG	donor_gain	0.9900
20:45224285:CCCTA:C	acceptor_loss	0.9900
20:45224286:CCTA:C	acceptor_loss	0.9900
20:45224287:CTAG:C	acceptor_loss	0.9900
20:45224288:TAGG:T	acceptor_loss	0.9900
20:45224289:A:G	acceptor_loss	0.9900
20:45224290:GGT:G	acceptor_gain	0.9800
20:45221464:AG:A	donor_gain	0.9600
20:45221465:GG:G	donor_gain	0.9600
20:45224289:A:AG	acceptor_gain	0.9600
20:45224290:G:GG	acceptor_gain	0.9600
20:45221463:AAG:A	donor_gain	0.9300
20:45221467:T:A	donor_gain	0.9300
20:45221468:G:GG	donor_loss	0.9300
20:45221462:AAAGG:A	donor_gain	0.9200
20:45221465:GGT:G	donor_gain	0.9200
20:45221466:GTG:G	donor_gain	0.9200
20:45221463:AAGGT:A	donor_gain	0.9100
20:45221464:AGGTG:A	donor_gain	0.9100
20:45221469:AGTGG:A	donor_gain	0.9100
20:45221462:AAAG:A	donor_gain	0.9000
20:45221468:GAGTG:G	donor_gain	0.8900
20:45221470:G:C	donor_gain	0.8900
20:45221461:AAAAG:A	donor_gain	0.8700
20:45224289:AG:A	acceptor_gain	0.8600
20:45224290:GG:G	acceptor_gain	0.8600
20:45224290:GGTGT:G	acceptor_gain	0.8400

AlphaMissense

3896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45221436:A:T	E16V	0.943
20:45221421:T:C	L11P	0.917
20:45222392:T:C	F254L	0.911
20:45222394:T:A	F254L	0.911
20:45222394:T:G	F254L	0.911
20:45221444:G:C	A19P	0.907
20:45221412:T:A	V8D	0.903
20:45221437:G:C	E16D	0.898
20:45221437:G:T	E16D	0.898
20:45221747:T:C	F39L	0.890
20:45221749:T:A	F39L	0.890
20:45221749:T:G	F39L	0.890
20:45221999:T:C	F123L	0.887
20:45222001:T:A	F123L	0.887
20:45222001:T:G	F123L	0.887
20:45221427:T:C	L13P	0.876
20:45221447:G:C	A20P	0.874
20:45221408:T:C	F7L	0.869
20:45221410:T:A	F7L	0.869
20:45221410:T:G	F7L	0.869
20:45221440:G:C	K17N	0.865
20:45221440:G:T	K17N	0.865
20:45221436:A:C	E16A	0.860
20:45221443:A:C	Q18H	0.849
20:45221443:A:T	Q18H	0.849
20:45221415:T:G	L9R	0.837
20:45221421:T:G	L11R	0.835
20:45221424:T:C	L12P	0.828
20:45221424:T:G	L12R	0.826
20:45221819:T:C	F63L	0.823

dbSNP variants (sampled 300 via entrez): RS1001057447 (20:45224299 C>T), RS1001330971 (20:45224394 T>A,C), RS1001966331 (20:45220979 A>C), RS1002034264 (20:45219707 T>A,C), RS1003112003 (20:45221234 T>C), RS1003298655 (20:45219898 G>C), RS1003395339 (20:45220126 T>A), RS1005400261 (20:45220159 C>A,T), RS1005763576 (20:45220589 T>A,C), RS1005894935 (20:45224800 T>G), RS1006384084 (20:45224727 C>T), RS1007190932 (20:45219423 G>A), RS1007271347 (20:45220896 C>T), RS1009210050 (20:45220618 C>A,T), RS1009262500 (20:45220938 A>G)

Disease associations

OMIM: gene MIM:182141 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005212_22	Asthma	3.000000e-06
GCST008103_143	Bipolar disorder	3.000000e-06
GCST010725_40	Malaria	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Zinc	decreases reaction, affects binding, affects reaction, decreases activity	2
Benzo(a)pyrene	affects methylation, increases methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Dextran Sulfate	affects binding, affects reaction	1

Clinical trials (associated diseases)

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