SPAG11B

Summary

SPAG11B (sperm associated antigen 11B, HGNC:14534) is a protein-coding gene on chromosome 8p23.1, encoding Sperm-associated antigen 11B (Q08648). Has antimicrobial activity against E.coli.

This gene encodes several androgen-dependent, epididymis-specific secretory proteins. The specific functions of these proteins have not been determined, but they are thought to be involved in sperm maturation. Some of the isoforms contain regions of similarity to beta-defensins, a family of antimicrobial peptides. The gene is located on chromosome 8p23 near the defensin gene cluster. Alternative splicing of this gene results in seven transcript variants encoding different isoforms. Two different N-terminal and five different C-terminal protein sequences are encoded by the splice variants. Two additional variants have been described, but their full length sequences have not been determined.

Source: NCBI Gene 10407 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_058201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14534
Approved symbol	SPAG11B
Name	sperm associated antigen 11B
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	HE2, EP2, EP2C, EP2D, EDDM2B
Ensembl gene	ENSG00000164871
Ensembl biotype	protein_coding
OMIM	606560
Entrez	10407

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000297498, ENST00000317900, ENST00000359758, ENST00000361111, ENST00000398462, ENST00000458665, ENST00000528168, ENST00000528767, ENST00000528943

RefSeq mRNA: 7 — MANE Select: NM_058201 NM_016512, NM_058200, NM_058201, NM_058202, NM_058203, NM_058206, NM_058207

CCDS: CCDS47774, CCDS5964, CCDS5965, CCDS5966, CCDS5967

Canonical transcript exons

ENST00000398462 — 3 exons

Exon	Start	End
ENSE00001763075	7462707	7462859
ENSE00002152493	7463443	7463542
ENSE00002157151	7450603	7450900

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 88.02.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.02	gold quality
monocyte	CL:0000576	42.85	gold quality
leukocyte	CL:0000738	41.48	gold quality
endometrium	UBERON:0001295	41.31	gold quality
left uterine tube	UBERON:0001303	40.59	gold quality
ganglionic eminence	UBERON:0004023	38.87	gold quality
fallopian tube	UBERON:0003889	37.57	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
lower esophagus mucosa	UBERON:0035834	36.76	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
uterine cervix	UBERON:0000002	33.56	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
esophagus mucosa	UBERON:0002469	33.37	gold quality
ectocervix	UBERON:0012249	32.68	gold quality
corpus callosum	UBERON:0002336	32.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
calcaneal tendon	UBERON:0003701	31.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.73	silver quality
duodenum	UBERON:0002114	28.14	gold quality
blood	UBERON:0000178	27.94	silver quality
esophagus	UBERON:0001043	27.76	gold quality
lymph node	UBERON:0000029	27.57	gold quality
nucleus accumbens	UBERON:0001882	27.25	silver quality
tonsil	UBERON:0002372	27.05	gold quality
kidney	UBERON:0002113	26.62	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	11146.28
E-ANND-3	no	0.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

39 targeting SPAG11B, 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-3120-5P	100.00	65.56	965
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-34B-3P	98.70	67.40	1171
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-6784-3P	98.39	64.88	662

Literature-anchored findings (GeneRIF, showing 9)

• In the chimpanzee epididymis, several mRNA HE2/EP2 variants are produced. Of these, three cDNAs code for two different protein sequences that have a cysteine distribution characteristic for beta-defensins. (PMID:10819450)
• The human HE2/EP2 gene is the fusion product of two ancestral beta-defensin genes. During its evolution, the gene has acquired additional exons whose inclusion produces new message variants that encode peptides unrelated to defensins. (PMID:11259252)
• HE2 peptides were detected in human epididymal epithelium, epididymal fluid, and ejaculate (PMID:12193388)
• HE2 transcriptional and translational products normally expressed in the caput epididymidis were not affected by vasectomy. (PMID:14662784)
• EP2 expression is more widespread in male reproductive tract than realized previously. Activity of every EP2 variant tested is antibacterial. Further investigation may reveal additional roles for EP2 peptides in primate male reproductive tract. (PMID:15229135)
• Isoform C of SPAG11B encodes a peptide with antimicrobial activity against E. coli. (PMID:16411022)
• SPAG11B/D is both a substrate and a potent inhibitor of TPSAB1 activity. (PMID:19535787)
• Combination of two proteins, SPAG11B and TEX101, can be used for differential diagnosis of azoospermia (PMID:21933954)
• we report the three dimensional structure of the human SPAG11B proteins and their C-terminal peptides. web-based hydropathy, amphipathicity, and topology (WHAT) analyses and grand average of hydropathy (PMID:25573789)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spag11b	ENSMUSG00000059463
rattus_norvegicus		ENSRNOG00000081099
rattus_norvegicus		ENSRNOG00000083831

Paralogs (1): SPAG11A (ENSG00000178287)

Protein

Protein identifiers

Sperm-associated antigen 11B — Q08648 (reviewed: Q08648)

Alternative names: Human epididymis-specific protein 2, Protein EP2, Sperm antigen HE2

All UniProt accessions (4): A0A0A0MRG4, A0A0B4J218, Q08648, H0YF39

UniProt curated annotations — full annotation on UniProt →

Function. Has antimicrobial activity against E.coli. Plays a role in the defense response in the male reproductive tract, contributing to sperm maturation, storage and protection.

Subcellular location. Secreted.

Tissue specificity. Specifically expressed in caput and proximal corpus of epididymis (at protein level). Present in the epididymal epithelium and on the sperm surface, with a subacrosomal equatorial distribution on the sperm head (at protein level).

Similarity. Belongs to the SPAG11 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q08648-1	EP2A, HE2 alpha1	yes
Q08648-2	EP2B
Q08648-3	EP2C, HE2C
Q08648-4	EP2D, HE2 beta1
Q08648-5	EP2E
Q08648-6	EP2F

RefSeq proteins (7): NP_057596, NP_478107, NP_478108, NP_478109, NP_478110, NP_478113, NP_478114 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007988	Sperm_Ag_11A_B	Family

Pfam: PF05324

UniProt features (13 total): splice variant 5, sequence conflict 3, sequence variant 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08648-F1	64.23	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): 29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MALE_GAMETE_GENERATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_CELL_KILLING, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, YAGI_AML_WITH_11Q23_REARRANGED, GOBP_RESPONSE_TO_BACTERIUM, OKUMURA_INFLAMMATORY_RESPONSE_LPS, GOBP_ANTIMICROBIAL_HUMORAL_IMMUNE_RESPONSE_MEDIATED_BY_ANTIMICROBIAL_PEPTIDE, RAO_BOUND_BY_SALL4_ISOFORM_B, GSE13522_WT_VS_IFNG_KO_SKIN_UP

GO Biological Process (5): spermatogenesis (GO:0007283), defense response to bacterium (GO:0042742), obsolete cytolysis by host of symbiont cells (GO:0051838), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response (GO:0006952)

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
defense response	1
response to bacterium	1
antimicrobial humoral response	1
response to stress	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SRPK1	SPAG11B	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SPAG11B	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): SPAG11B (Synthetic Lethality), SPAG11B (Two-hybrid), UBQLN2 (Two-hybrid)

ESM2 similar proteins: A0A0B4J1N3, A0A1B0GTK4, A0A1B0GTR0, A0JNL8, A2RUT3, A4IFR0, C9JUS6, D3ZKM3, E9PXB6, F2Z3F1, O70899, O71302, O93195, O95411, P03165, P04610, P0C7M3, P12912, P13206, P20976, P20977, P29560, P47939, P47940, P69714, Q02919, Q08648, Q1RN00, Q1WG82, Q5PR19, Q66669, Q67923, Q69027, Q69604, Q6PDA7, Q6UWK7, Q80IU5, Q80IU8, Q8N5N4, Q913A9

Diamond homologs: Q08648, Q3UW43, Q6PDA7, Q9MZ28, Q8K4N2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

200 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7461532:GTTC:G	acceptor_loss	1.0000
8:7461533:TTC:T	acceptor_loss	1.0000
8:7461534:TC:T	acceptor_loss	1.0000
8:7461535:C:CA	acceptor_loss	1.0000
8:7461535:C:CC	acceptor_gain	1.0000
8:7461540:T:TC	acceptor_gain	1.0000
8:7462703:TCACC:T	donor_loss	1.0000
8:7462704:CAC:C	donor_loss	1.0000
8:7462705:ACCT:A	donor_loss	1.0000
8:7462859:CCTG:C	acceptor_gain	1.0000
8:7461530:AGGTT:A	acceptor_gain	0.9900
8:7461532:GTT:G	acceptor_gain	0.9900
8:7461533:TT:T	acceptor_gain	0.9900
8:7461536:T:C	acceptor_loss	0.9900
8:7461538:C:CT	acceptor_gain	0.9900
8:7461539:A:C	acceptor_gain	0.9900
8:7461540:T:C	acceptor_gain	0.9900
8:7462855:CGATC:C	acceptor_gain	0.9900
8:7462858:TC:T	acceptor_gain	0.9900
8:7462860:C:CC	acceptor_gain	0.9900
8:7462861:T:A	acceptor_loss	0.9900
8:7462862:G:C	acceptor_gain	0.9900
8:7462862:G:GC	acceptor_gain	0.9900
8:7461531:GGTT:G	acceptor_gain	0.9800
8:7461539:A:AC	acceptor_gain	0.9800
8:7462705:A:AC	donor_gain	0.9800
8:7462705:AC:A	donor_gain	0.9800
8:7462706:C:CC	donor_gain	0.9800
8:7462706:CC:C	donor_gain	0.9800
8:7462856:GATC:G	acceptor_gain	0.9800

AlphaMissense

858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7463471:G:C	S11R	0.934
8:7463471:G:T	S11R	0.934
8:7463473:T:G	S11R	0.934
8:7463457:G:T	A16D	0.823
8:7463463:A:T	L14H	0.767
8:7463466:A:T	L13H	0.767
8:7462744:T:A	K59N	0.764
8:7462744:T:G	K59N	0.764
8:7450895:C:G	C99S	0.747
8:7450896:A:T	C99S	0.747
8:7462768:A:C	F51L	0.747
8:7462768:A:T	F51L	0.747
8:7462770:A:G	F51L	0.747
8:7463466:A:C	L13R	0.715
8:7463469:A:T	L12H	0.703
8:7463460:A:T	V15E	0.698
8:7462745:T:A	K59I	0.670
8:7463463:A:C	L14R	0.667
8:7462725:G:T	R66S	0.655
8:7450894:A:C	C99W	0.649
8:7463469:A:C	L12R	0.646
8:7463443:C:G	G21R	0.621
8:7463443:C:T	G21R	0.621
8:7463472:C:T	S11N	0.616
8:7463478:A:T	V9D	0.605
8:7462834:G:C	N29K	0.600
8:7462834:G:T	N29K	0.600
8:7450895:C:T	C99Y	0.582
8:7463454:A:C	L17R	0.578

dbSNP variants (sampled 300 via entrez): RS1000646281 (8:7449544 G>A), RS1000909932 (8:7447805 C>T), RS1005162578 (8:7451660 G>A,T), RS1005541408 (8:7454425 T>C), RS1007931434 (8:7447739 G>C), RS1008935883 (8:7459335 G>A,C), RS1008967220 (8:7454644 A>G), RS1011888756 (8:7451379 G>A,C), RS1011920113 (8:7449915 A>C,G), RS1015499015 (8:7451858 A>G), RS1018895198 (8:7455360 A>C), RS1018949216 (8:7459346 A>G), RS1020623742 (8:7447742 G>A), RS1023522582 (8:7463101 A>C), RS1024662416 (8:7451430 G>C)

Disease associations

OMIM: gene MIM:606560 | 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: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
hydroxyhydroquinone	increases expression	1
Polychlorinated Biphenyls	affects expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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