SSB

Summary

SSB (small RNA binding exonuclease protection factor La, HGNC:11316) is a protein-coding gene on chromosome 2q31.1, encoding Lupus La protein (P05455). Binds to the 3’ poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation. It is a selective cancer dependency (DepMap: 74.8% of cell lines).

The protein encoded by this gene is involved in diverse aspects of RNA metabolism, including binding and protecting poly(U) termini of nascent RNA polymerase III transcripts from exonuclease digestion, processing 5’ and 3’ ends of pre-tRNA precursors, acting as an RNA chaperone, and binding viral RNAs associated with hepatitis C virus. Autoantibodies reacting with this protein are found in the sera of patients with Sjogren syndrome and systemic lupus erythematosus. Alternative promoter usage results in two different transcript variants which encode the same protein.

Source: NCBI Gene 6741 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 60 total
• GTEx eGene: eQTL in 14 tissues, sQTL in 9 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 74.8% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.41 (moderately constrained)
• MANE Select transcript: NM_003142
• Interaction hub: 2,462 STRING partners (top 4% of genes corpus-wide)
• Notable: 60 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11316
Approved symbol	SSB
Name	small RNA binding exonuclease protection factor La
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	SSB/La, LARP3, La, La/SSB
Ensembl gene	ENSG00000138385
Ensembl biotype	protein_coding
OMIM	109090
Entrez	6741

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 22 protein_coding, 8 nonsense_mediated_decay, 7 retained_intron

MANE Select: ENST00000260956

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 4, TSL 5: 2

ENST00000260956, ENST00000409333, ENST00000413002, ENST00000417292, ENST00000422006, ENST00000461708, ENST00000465871, ENST00000468600, ENST00000470621, ENST00000474273, ENST00000490914, ENST00000494051, ENST00000906406, ENST00000906407, ENST00000906408, ENST00000938524, ENST00000938525, ENST00000938526, ENST00000938527, ENST00000938528, ENST00000938529, ENST00000949512, ENST00000997727, ENST00001088050, ENST00001088052, ENST00001088053, ENST00001088054, ENST00001088055, ENST00001088063, ENST00001093690, ENST00001093691, ENST00001093692, ENST00001093693, ENST00001093694, ENST00001111282, ENST00001130564, ENST00001144909

RefSeq mRNA: 2 — MANE Select: NM_003142 NM_001294145, NM_003142

CCDS: CCDS2237

Canonical transcript exons

ENST00000260956 — 12 exons

Exon	Start	End
ENSE00000782045	169811183	169811323
ENSE00001588653	169811668	169812064
ENSE00001893329	169798871	169798976
ENSE00002471090	169805665	169805839
ENSE00002496741	169806785	169806892
ENSE00003510639	169800952	169801026
ENSE00003562426	169810858	169811044
ENSE00003578824	169810283	169810423
ENSE00003606885	169808482	169808553
ENSE00003607377	169808860	169808902
ENSE00003620133	169805474	169805577
ENSE00003787270	169806971	169807071

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.8853 / max 3387.4530, expressed in 1821 samples.

Highest expression (Bgee): tendon of biceps brachii, tendon, calcaneal tendon, ventricular zone, mucosa of paranasal sinus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SSB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	3.0e-14	-0.33	2:169799894:TAC:T
Esophagus Muscularis	sqtl	1.9e-09	+0.59	2:169755736:A:G
Colon Sigmoid	sqtl	4.5e-09	-0.68	2:169774127:A:G
Artery Aorta	eqtl	6.6e-07	+0.15	2:169807404:T:C
Adipose Subcutaneous	eqtl	4.9e-06	-0.26	2:169799745:C:T
Cells EBV-transformed lymphocytes	eqtl	5.7e-06	-0.46	2:170077458:T:C
Brain Cerebellar Hemisphere	sqtl	9.4e-06	-0.50	2:169743898:A:G
Colon Transverse	sqtl	1.3e-05	+0.53	2:169751316:C:T
Thyroid	eqtl	8.8e-05	+0.11	2:169776459:C:A
Nerve Tibial	eqtl	9.3e-05	+0.10	2:169797755:A:G
Artery Tibial	eqtl	2.3e-04	-0.22	2:170038280:T:C
Adipose Visceral Omentum	eqtl	3.3e-04	-0.23	2:169819092:A:G
Esophagus Gastroesophageal Junction	sqtl	5.7e-04	+0.54	2:169752327:G:A
Cells EBV-transformed lymphocytes	sqtl	7.1e-03	-0.53	2:170170310:T:C
Brain Cerebellum	sqtl	9.3e-03	+0.88	2:170076190:A:G
Small Intestine Terminal Ileum	eqtl	1.1e-02	+0.89	2:168816413:C:T
Muscle Skeletal	eqtl	2.3e-02	+0.51	2:169767057:G:T
Cells Cultured fibroblasts	sqtl	2.4e-02	-0.48	2:169799745:C:T
Lung	eqtl	2.4e-02	+0.39	2:170186659:C:T
Uterus	sqtl	2.7e-02	+0.82	2:169752327:G:A

FANTOM5 promoters

9 alternative TSS:

Promoter ID	TPM avg	Samples expressed
23572	104.2044	1821
23574	3.8475	1344
23573	2.1911	1141
23575	1.7421	802
23576	0.9577	513
23580	0.7895	132
23581	0.0969	40
23579	0.0356	16
23578	0.0205	8

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.33	gold quality
tendon	UBERON:0000043	98.79	gold quality
calcaneal tendon	UBERON:0003701	98.66	gold quality
ventricular zone	UBERON:0003053	98.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.24	gold quality
monocyte	CL:0000576	98.10	gold quality
epithelium of nasopharynx	UBERON:0001951	97.95	gold quality
nasopharynx	UBERON:0001728	97.94	gold quality
ganglionic eminence	UBERON:0004023	97.87	gold quality
cortical plate	UBERON:0005343	97.81	gold quality
mononuclear cell	CL:0000842	97.75	gold quality
peritoneum	UBERON:0002358	97.71	gold quality
omental fat pad	UBERON:0010414	97.71	gold quality
left coronary artery	UBERON:0001626	97.68	gold quality
endometrium	UBERON:0001295	97.65	gold quality
adenohypophysis	UBERON:0002196	97.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.61	gold quality
right uterine tube	UBERON:0001302	97.58	gold quality
descending thoracic aorta	UBERON:0002345	97.58	gold quality
leukocyte	CL:0000738	97.56	gold quality
coronary artery	UBERON:0001621	97.56	gold quality
embryo	UBERON:0000922	97.54	gold quality
medial globus pallidus	UBERON:0002477	97.54	gold quality
islet of Langerhans	UBERON:0000006	97.52	gold quality
left ovary	UBERON:0002119	97.49	gold quality
right ovary	UBERON:0002118	97.48	gold quality
thoracic aorta	UBERON:0001515	97.47	gold quality
ascending aorta	UBERON:0001496	97.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.45	gold quality
adipose tissue	UBERON:0001013	97.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.42	gold quality
lymph node	UBERON:0000029	97.40	gold quality
aorta	UBERON:0000947	97.39	gold quality
ovary	UBERON:0000992	97.37	gold quality
connective tissue	UBERON:0002384	97.36	gold quality
pituitary gland	UBERON:0000007	97.35	gold quality
popliteal artery	UBERON:0002250	97.35	gold quality
tibial artery	UBERON:0007610	97.35	gold quality
buccal mucosa cell	CL:0002336	97.25	gold quality
right coronary artery	UBERON:0001625	97.24	gold quality
adrenal tissue	UBERON:0018303	97.18	gold quality
mucosa of stomach	UBERON:0001199	97.17	gold quality
smooth muscle tissue	UBERON:0001135	97.13	gold quality
body of uterus	UBERON:0009853	97.11	gold quality
left uterine tube	UBERON:0001303	97.05	gold quality
left lobe of thyroid gland	UBERON:0001120	97.03	gold quality
thyroid gland	UBERON:0002046	96.99	gold quality
cerebellar hemisphere	UBERON:0002245	96.99	gold quality
cerebellar cortex	UBERON:0002129	96.97	gold quality
oocyte	CL:0000023	96.96	gold quality
endocervix	UBERON:0000458	96.96	gold quality
rectum	UBERON:0001052	96.96	gold quality
globus pallidus	UBERON:0001875	96.96	gold quality
right lobe of thyroid gland	UBERON:0001119	96.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.93	gold quality
amniotic fluid	UBERON:0000173	96.90	gold quality
vermiform appendix	UBERON:0001154	96.90	gold quality
left adrenal gland cortex	UBERON:0035825	96.89	gold quality
left adrenal gland	UBERON:0001234	96.88	gold quality
cingulate cortex	UBERON:0003027	96.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.87	gold quality
anterior cingulate cortex	UBERON:0009835	96.86	gold quality
nucleus accumbens	UBERON:0001882	96.85	gold quality
prostate gland	UBERON:0002367	96.84	gold quality
cerebellar vermis	UBERON:0004720	96.84	gold quality
uterus	UBERON:0000995	96.83	gold quality
metanephros cortex	UBERON:0010533	96.83	gold quality
lower esophagus	UBERON:0013473	96.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.82	gold quality
adrenal cortex	UBERON:0001235	96.79	gold quality
gall bladder	UBERON:0002110	96.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.77	gold quality
pericardium	UBERON:0002407	96.73	gold quality
caudate nucleus	UBERON:0001873	96.72	gold quality
right adrenal gland cortex	UBERON:0035827	96.72	gold quality
amygdala	UBERON:0001876	96.71	gold quality
right adrenal gland	UBERON:0001233	96.70	gold quality
stromal cell of endometrium	CL:0002255	96.68	gold quality
adrenal gland	UBERON:0002369	96.68	gold quality
ectocervix	UBERON:0012249	96.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.59	gold quality
caecum	UBERON:0001153	96.58	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.58	gold quality
tibial nerve	UBERON:0001323	96.55	gold quality
right lung	UBERON:0002167	96.52	gold quality
putamen	UBERON:0001874	96.51	gold quality
cerebellum	UBERON:0002037	96.51	gold quality
female reproductive system	UBERON:0000474	96.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.49	gold quality
substantia nigra pars compacta	UBERON:0001965	96.48	gold quality
bronchial epithelial cell	CL:0002328	96.36	gold quality
right frontal lobe	UBERON:0002810	96.35	gold quality
pons	UBERON:0000988	96.27	gold quality
myometrium	UBERON:0001296	96.26	gold quality
sigmoid colon	UBERON:0001159	96.25	gold quality
right atrium auricular region	UBERON:0006631	96.25	gold quality
spinal cord	UBERON:0002240	96.19	gold quality
corpus callosum	UBERON:0002336	96.16	gold quality
superior vestibular nucleus	UBERON:0007227	96.15	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	20.36
E-MTAB-7052	no	411.89
E-CURD-135	no	334.51
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Adipose tissue	tissue	107.1	medium
Frontal cortex	tissue	106.1
Caudate putamen	tissue	99.4
Bone marrow	tissue	99.3	low
Lymph node	tissue	87.2	medium
Urinary bladder	tissue	82.5	high
Epididymis	tissue	77.4	high
Thyroid gland	tissue	76.5	high
Tonsil	tissue	76.1	high
Parathyroid gland	tissue	75.2	high
Prostate	tissue	73.3	high
Appendix	tissue	71.5	high
Adrenal gland	tissue	71.3	high
Ovary	tissue	69.6	high
Kidney	tissue	69.5	high
Placenta	tissue	69.1	high
Choroid plexus	tissue	67.1
Thymus	tissue	65.5
Heart muscle	tissue	64.6	medium
Breast	tissue	64.4	high
Endometrium 1	tissue	64.2	high
Liver	tissue	64.0	high
Pituitary gland	tissue	63.8
Postcentral gyrus	tissue	59.2
Spleen	tissue	59.1	high
Smooth muscle	tissue	57.4	medium
Fallopian tube	tissue	57.3	high
Seminal vesicle	tissue	55.3	high
Cervix	tissue	55.1	high
Gallbladder	tissue	54.4	high
Rectum	tissue	53.6	high
Lung	tissue	52.6	high
Retina	tissue	51.1
Vagina	tissue	51.0	high
Colon	tissue	50.5	high
Locus coeruleus	tissue	50.2
Tongue	tissue	49.5
Esophagus	tissue	47.9	high
Salivary gland	tissue	47.1	high
Stomach 1	tissue	46.9	high
Skeletal muscle	tissue	46.6	medium
Small intestine	tissue	46.4	high
Duodenum	tissue	46.3	medium
Skin 1	tissue	44.0	high
Hippocampus	tissue	44.0	high
Nucleus accumbens	tissue	43.8
Olfactory bulb	tissue	39.2
Testis	tissue	38.5	high
Cerebellum	tissue	37.4	high
Putamen	tissue	37.1
Corpus callosum	tissue	36.5
Septum	tissue	35.9
Periaqueductal gray	tissue	34.8
Ventral forebrain	tissue	34.5
Spinal cord	tissue	34.3
Prefrontal cortex	tissue	34.2
Cerebral cortex	tissue	34.2	high
Pancreas	tissue	34.2	high
Pons	tissue	33.9
Midbrain	tissue	33.9

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (85.2), Median raphe nucleus (56.6), Orbitofrontal gyrus, anterior (55.9), Arcuate nucleus (54.5), Paraventricular nucleus (54.4).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets:

Target	Regulation
HAP1	Repression
LAMB1	Activation
XIAP	Unknown

miRNA regulators (miRDB)

Targeting SSB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 40 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-452-3P	99.01	66.25	1241

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.405, missense Z 2.76 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000260956 — one region, missense o/e 0.68. DepMap (CRISPR cell-line fitness): dependent in 74.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): U-251 MG (-1.352), F-36P (-1.318), SF767 (-1.193), BHY (-1.188), SNU-626 (-1.185), YKG1 (-1.182), NCI-H2452 (-1.163), SW 1088 (-1.155), LN-443 (-1.131), D341 Med (-1.105), LN382 (-1.104), A-375 (-1.098), SKM-1 (-1.081), JVM-2 (-1.079), LS123 (-1.068).

Literature-anchored findings (GeneRIF, showing 40)

• inhibits tRNA 3’ processing (PMID:11580243)
• nuclear trafficking by La affects the normal order of pre-tRNA processing (PMID:12049746)
• molecular characterization of the human La protein.hepatitis B virus RNA.B interaction in vitro (PMID:12121976)
• La autoantigen is required for the internal ribosome entry site-mediated translation of Coxsackievirus B3 RNA (PMID:12384597)
• binds differentially to multiple sites within the 5’ untranslated region of Coxsackievirus B3 RNA (PMID:12457960)
• in addition to full-length La protein, both N- and C-terminal halves were able to interact with hepatitis C virus internal ribosome entry site in vivo. (PMID:12540850)
• Dengue 4 virus minus strand 3’UTR RNA binds with La protein in human monocytes (PMID:12584332)
• Results suggest that La ribonucleoproteins (RNP) exist in distinct states that differ in subcellular localization, serine 366 phosphorylation, and associated RNAs. (PMID:14636586)
• La motif adopts an alpha/beta fold that comprises a winged-helix motif elaborated by the insertion of three helices (PMID:15004549)
• La protein binds to the 5’ end and with the 3’ UTR of Dengue virus RNA; interacts with the dengue virus nonstructural proteins NS5 and NS3 (PMID:15084396)
• NMR assignment and secondary structure of the La motif (PMID:15213463)
• Composition of La/hepatitis B virus ribonucleoprotein particles as well as interacting cellular factors, are critical determinants in the regulation of the stability of the HBV RNA. (PMID:15302879)
• RRM1 and La motifs bind pre-tRNA (PMID:15371415)
• CK2 is responsible for La S(366) phosphorylation in vivo (PMID:15485924)
• Nonphosphorylated SSB interacts with nucleolin at nucleolar sites involved in rRNA biogenesis. (PMID:15572691)
• This protein is s host factors responsible for the regulation of the hepatitis C virus internal ribosome entry site. (PMID:15685555)
• essential for efficient hepatitis C virus replication (PMID:15823607)
• In vitro RNA chaperone activity pf SSB was studied. (PMID:15928345)
• nuclear retention of peptidylglycine alpha-amidating monooxygenase (PAM) mRNA is lost upon expressing the La proteins that lack a conserved nuclear retention element, suggesting a direct association between PAM mRNA and La protein in vivo (PMID:16107699)
• Anti-La antibodies bound to immunodominant epitopes of La within the NH(2)-terminus and the RNA recognition motif (RRM) region of apoptotic human cells (PMID:16320341)
• Here, we show by chromatin immunoprecipitation (ChIP) that La is associated with pol III-transcribed genes in vivo (PMID:16344466)
• Results report the crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to RNA. (PMID:16387655)
• Changes in salivary production rate are associated with aging and SSB antibodies. (PMID:16467037)
• La protein undergoes nucleocytoplasmic shuttling whereas EBER1 and EBER2 noncoding RNA’s are confined to the nucleus. (PMID:16682524)
• In mice transgenic for the mutant form of La autoantigen, mutant La mRNAs are not only repressed and translated to mutant La protein but, unexpectedly, expression of mutant La favors the development of systemic autoimmunity. (PMID:16849479)
• Nuclear injury and the translocation of SSA/Ro and SSB/La antigens to the fetal cardiocyte plasma membrane were common downstream events of Fas and TNF receptor ligation. (PMID:16906225)
• There is a correlation between La protein and HBV mRNA and the expression of HBV protein. (PMID:17064465)
• suggest that conserved elements mediate nuclear retention, nuclear export, and RNA-binding activities of the multifunctional La protein (PMID:17308035)
• La autoantigen can interact with both the 3’ and 5’UTRs of coxsackievirus B3 independently of the poly(A) tail and may share the same binding site on the La protein. (PMID:17346312)
• Increased Ro/SSA 60 and La/SSB mRNA expression in minor salivary glands in primary Sjogren’s syndrome (pSS) suggest that these these 2 autoantigens, but not Ro/SSA 52, are involved in the tissue-specific autoimmune response in pSS. (PMID:17552056)
• Overexpression of La autoantigen is associated with neoplasms (PMID:17875783)
• Results suggest that La protein is cleaved by granzyme B and N-terminal La fragment (27 kD) translocated to the cytoplasm, thus leading to a novel autoantibody production during granzyme B-mediated cytotoxicity. (PMID:17945310)
• the autoantibodies to SSB/La may modulate neutrophils function in systemic lupus erythematosis (PMID:17985193)
• The La-mediated suppression of HAV translation and stimulation of poliovirus translation implies unexpected mechanistic differences between viral internal ribosomal entry site elements. (PMID:18282467)
• Identification of a conserved set of interactions with the last two nucleotides at the 3’ end of the RNA ligand that are key to binding by the La protein. (PMID:18547518)
• La supports the growth of nonsegmented negative-strand RNA viruses by both IFN suppression and a potentially novel IFN-independent mechanism (PMID:18550659)
• the frequency of La/SSB antibodies was higher in sporadic systemic lupus erythematosus (P = 0.048) than in those with familial SLE, although this was not significant after application of Bonferroni’s correction for the number of comparisons (PMID:19074175)
• Using electrophoretic mobility-shift and UV cross-linking assays, as well as a yeast three-hybrid system, it was shown here that La protein binds to the 3’ stem-loop (SL) structure of Japanese encephalitis virus genome. (PMID:19264640)
• The authors show that La preferentially binds pre-tRNAs over processed tRNAs or 3’ trailer products through coupled use of two sites: one on the La motif and another on the RRM1 beta-surface that binds elsewhere on tRNA. (PMID:19287396)
• Nine of the 45 consecutive CHB cases (20%) were anti-Ro/La-negative with no known cause; they were less stable and complete than the anti-Ro/La positive cases (PMID:19567621)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ssb	ENSDARG00000029252
mus_musculus	Ssb	ENSMUSG00000068882
rattus_norvegicus	Ssb	ENSRNOG00000007998
rattus_norvegicus	Ssbl1	ENSRNOG00000011606
drosophila_melanogaster	La	FBGN0011638
caenorhabditis_elegans	ssb-1	WBGENE00016653

Paralogs (6): LARP4B (ENSG00000107929), LARP1B (ENSG00000138709), LARP1 (ENSG00000155506), LARP4 (ENSG00000161813), LARP6 (ENSG00000166173), LARP7 (ENSG00000174720)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98423) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
small spleen	1
forebrain hypoplasia	1
abnormal cerebral cortex morphology	1
arrested B cell differentiation	1
decreased IgG level	1
decreased IgM level	1
decreased brain weight	1
neurodegeneration	1
abnormal neuron morphology	1
decreased spleen weight	1
inner cell mass degeneration	1
decreased B cell number	1
abnormal trophoblast giant cell morphology	1
thin cerebral cortex	1
hippocampus pyramidal cell degeneration	1
embryonic lethality, complete penetrance	1
embryonic lethality before implantation, complete penetrance	1
decreased forebrain size	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q4R627	95.7%	Diamond
Bos taurus	P10881	90.9%	Diamond
Oryctolagus cuniculus	Q04504	86.8%	Diamond
Xenopus laevis	P28048	85.7%	Diamond
Xenopus tropicalis	Q28G87	61.9%	Diamond
Arabidopsis thaliana	Q94K80	55.3%	Diamond
Cryptococcus neoformans H99	J9VT60	49.3%	Diamond
Aedes albopictus	Q26457	48.0%	Diamond
Schizosaccharomyces pombe 972h-	P87058	43.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
METTL5	protein-coding	29081
SNORD3K	snoRNA	109617017
UBR3	protein-coding	130507
MYO3B	protein-coding	140469

Protein

Protein identifiers

Lupus La protein — P05455 (reviewed: P05455)

Alternative names: La autoantigen, La ribonucleoprotein, Sjoegren syndrome type B antigen

All UniProt accessions (4): E7ERC4, E9PFL9, E9PGX9, P05455

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the 3’ poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation. In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation.

Subunit / interactions. Interacts with DDX15. May interact with RUFY1.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated. The phosphorylation sites are at the C-terminal part of the protein. The N-terminus is blocked.

Miscellaneous. Sera from patients with systemic lupus erythematosus (SLE) often contain antibodies that react with the normal cellular La protein as if this antigen was foreign.

RefSeq proteins (2): NP_001281074, NP_003133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002344	Lupus_La	Family
IPR006630	La_HTH	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR014886	La_xRRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045180	La_dom_prot	Family

Pfam: PF00076, PF05383, PF08777

UniProt features (50 total): helix 14, strand 13, modified residue 11, turn 4, domain 3, compositionally biased region 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
2VOO	Crystal structure of N-terminal domains of Human La protein complexed with RNA oligomer …	X-RAY DIFFRACTION	1.8
1ZH5	Structural basis for recognition of UUUOH 3’-terminii of nascent RNA pol III transcripts …	X-RAY DIFFRACTION	1.85
2VOD	Crystal structure of N-terminal domains of Human La protein complexed with RNA oligomer …	X-RAY DIFFRACTION	2.1
2VON	Crystal structure of N-terminal domains of Human La protein complexed with RNA oligomer …	X-RAY DIFFRACTION	2.1
1YTY	Structural basis for recognition of UUUOH 3’-terminii of nascent RNA pol III transcripts …	X-RAY DIFFRACTION	2.29
9NFA	Cryo-EM structure of Ro60/La/minimal misfolded pre-5S rRNA complex with Fab, composite map	ELECTRON MICROSCOPY	2.7
2VOP	Crystal structure of N-terminal domains of Human La protein complexed with RNA oligomer …	X-RAY DIFFRACTION	2.8
9NF8	Cryo-EM structure of Ro60/La/truncated misfolded human pre-5S rRNA complex with Fab …	ELECTRON MICROSCOPY	3.1
1OWX	Solution structure of the C-terminal RRM of human La (La225-334)	SOLUTION NMR
1S79	Solution structure of the central RRM of human La protein	SOLUTION NMR
1S7A	NMR structure of the La motif of human La protein	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05455-F1	75.19	0.37

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF approved

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 (11)

Type	Positions
Phosphothreonine	120, 362
N6-acetyllysine	128, 328, 341, 360, 116
Phosphoserine	225, 366, 92, 94

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation	electronic
R-HSA-74158	RNA Polymerase III Transcription	—
R-HSA-73980	RNA Polymerase III Transcription Termination	electronic

MSigDB gene sets: 261 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT

GO Biological Process (11): tRNA 5’-leader removal (GO:0001682), tRNA modification (GO:0006400), tRNA export from nucleus (GO:0006409), tRNA processing (GO:0008033), histone mRNA metabolic process (GO:0008334), tRNA 3’-end processing (GO:0042780), positive regulation of translation (GO:0045727), nuclear histone mRNA catabolic process (GO:0071045), IRES-dependent viral translational initiation (GO:0075522), protein localization to cytoplasmic stress granule (GO:1903608), RNA processing (GO:0006396)

GO Molecular Function (7): tRNA binding (GO:0000049), RNA binding (GO:0003723), mRNA binding (GO:0003729), poly(U) RNA binding (GO:0008266), sequence-specific mRNA binding (GO:1990825), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

2 top-level categories:

Category	Pathways
RNA Polymerase III Transcription	2
Gene expression (Transcription)	1

GO top-level categories

32 GO namespaces:

Category	Terms
tRNA processing	2
RNA binding	2
binding	2
cellular anatomical structure	2
tRNA 5’-end processing	1
RNA modification	1
RNA export from nucleus	1
tRNA transport	1
RNA processing	1
tRNA metabolic process	1
mRNA metabolic process	1
RNA 3’-end processing	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
histone mRNA catabolic process	1
viral process	1
viral translation	1
protein localization to organelle	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
poly-pyrimidine tract binding	1
mRNA binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoplasmic ribonucleoprotein granule	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
IRES-dependent viral translational initiation	BP	direct assay
nuclear histone mRNA catabolic process	BP	mutant phenotype
protein localization to cytoplasmic stress granule	BP	direct assay
tRNA 3’-end processing	BP	genetic interaction
tRNA 5’-leader removal	BP	genetic interaction
tRNA export from nucleus	BP	mutant phenotype
tRNA processing	BP	mutant phenotype
chromosome, telomeric region	CC	high-throughput assay
cytoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	mutant phenotype
poly(U) RNA binding	MF	mutant phenotype
sequence-specific mRNA binding	MF	mutant phenotype
tRNA binding	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,462 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSB	TRIM21	P19474	979
SSB	RO60	P10155	773
SSB	SNRNP70	P08621	717
SSB	FTL	P02792	535
SSB	TNFSF13B	Q9Y275	491
SSB	CENPB	P07199	470
SSB	EXOSC10	Q01780	465
SSB	APOH	P02749	451
SSB	B2M	P01884	448
SSB	PRTN3	P15637	445
SSB	SPTAN1	Q13813	436
SSB	CRP	P02741	435
SSB	PCBP2	Q15366	427
SSB	SYNCRIP	O60506	409
SSB	MVP	Q14764	389

IntAct

Human interaction partners of SSB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 34 partners by confidence:

Partner	Interaction type	MIscore	Records
YBX1	association	0.710	1
HSPA2	physical association	0.560	3
HTT	physical association	0.560	3
NDUFB10	physical association	0.560	3
RAPGEF4	physical association	0.560	3
HSD17B10	association	0.530	1
RO60	association	0.530	1
PRPF31	association	0.510	2
CSNK2A1	phosphorylation reaction	0.440	1
CCDC71	physical association	0.400	1
DST	physical association	0.400	1
H2BC21	physical association	0.400	1
NCL	physical association	0.400	1
OXER1	physical association	0.400	1
TCOF1	physical association	0.400	1
YWHAZ	physical association	0.400	1
SPIB	physical association	0.370	1
ARFGEF1	association	0.350	1
GTF3A	association	0.350	1
IFIT5	association	0.350	1
RPS3A	association	0.350	1
IKBKE	physical association	0.000	1
LYAR	physical association	0.000	1
MAP3K14	physical association	0.000	1
NME2	physical association	0.000	1
NR3C1	physical association	0.000	1
PMVK	physical association	0.000	1
PRKAB1	physical association	0.000	1
PUF60	physical association	0.000	1
RXRB	physical association	0.000	1

BioGRID (620 interactions; top human partners by supporting records in a sample of 600 records): TROVE2 (Affinity Capture-MS; 5 records), LARP7 (Co-fractionation; 4 records), HIST1H2BD (Cross-Linking-MS (XL-MS); 3 records), HIST1H2BK (Cross-Linking-MS (XL-MS); 3 records), RPL31 (Co-fractionation; 3 records), SERBP1 (Affinity Capture-MS; 3 records), SRSF6 (Affinity Capture-MS; 3 records), SURF2 (Affinity Capture-MS; 3 records), TRMT2A (Affinity Capture-MS; 3 records), ACTC1 (Affinity Capture-MS; 2 records), BYSL (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-MS; 2 records), CDC37 (Co-fractionation; 2 records), CUL2 (Co-fractionation; 2 records), CUL3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	up-regulates	SSB	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Emerin complex 25	16	EMD, G3BP1, SAP130, SSB, BCCIP, LMNB1, LSM8, SNRPD1, YWHAE, BANF1, CDC37, LSM2, ACTB, HNRNPK, YWHAB, ZRANB2
★ H2AX complex, without IR exposure	13	H2BC26, SSB, SSRP1, SUPT16H, CALM1, H4C1, HNRNPR, HSPA5, NPM1, PABPC1, CALR, EIF3L, H2AX

Disease & clinical

Genetic variants

Variant evidence for SSB: 60 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 817):

Position(s)	Effect	Δscore	Sites
2:169798977	donor_loss	1.0000
2:169801027–169801028	donor_loss	1.0000	4
2:169805472–169805473	acceptor_loss	1.0000	5
2:169805578–169805579	donor_loss	1.0000	6
2:169805663–169805664	acceptor_loss	1.0000	5
2:169805799	donor_gain	1.0000
2:169806775	acceptor_gain	1.0000
2:169806893–169806894	donor_loss	1.0000	5
2:169806968	acceptor_gain	1.0000
2:169806970	acceptor_loss	1.0000	2

AlphaMissense

1,094 missense substitutions predicted likely pathogenic (of 2,741 scored), across 258 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M142	9	0.906	0.998
D33	8	1.000	1.000
F55	8	0.997	1.000
F25	8	0.993	0.999
F150	8	0.988	0.999
N29	8	0.984	0.999
F118	8	0.982	1.000
F155	8	0.980	0.998
F35	8	0.975	1.000
D27	8	0.968	0.998
D125	8	0.961	0.995
D248	8	0.950	0.983
F253	8	0.948	0.991
F158	8	0.938	0.993
F275	8	0.934	0.991
F236	8	0.927	0.998
F167	8	0.859	0.989
D43	8	0.778	0.934
W46	7	0.998	1.000
R91	7	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.13e-07
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	9.44e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000119
Lung Adenocarcinoma (TCGA)	unfavorable	0.000244

Disease associations

OMIM: gene MIM:109090 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST005891_5	Glomerular filtration rate in diabetes	1e-6
GCST008504_9	Fasting glucose change (long-term)	4e-6
GCST005184_8	Common carotid intima-media thickness in HIV infection	5e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2040701 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	MOLIBRESIB
7.55	Kd	27.85	nM	CHEMBL5653589
7.55	ED50	27.85	nM	CHEMBL5653589
5.71	Kd	1940	nM	CHEMBL3752910
5.71	ED50	1940	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 24 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178552: Inhibition of SSB (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0100	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149496: Binding affinity to human SSB incubated for 45 mins by Kinobead based pull down assay	kd	0.0278	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149496: Binding affinity to human SSB incubated for 45 mins by Kinobead based pull down assay	kd	1.9399	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
coumarin	increases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
SB 203580	decreases reaction, increases secretion	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases secretion, decreases reaction	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Aminoglutethimide	decreases expression	1
Ammonium Chloride	decreases reaction, increases expression, increases secretion	1
Arsenic	increases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Chloroquine	decreases reaction, increases expression, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2046250	ADMET	Binding affinity to human La antigen by NMR based ALARM assay	A novel class of highly potent irreversible hepatitis C virus NS5B polymerase inhibitors. — *J Med Chem*
CHEMBL3419563	Binding	Induction of thiol reactivity with La protein (unknown origin) using 13C labeled compound assessed as protein reactivity by ALARM NMR	PAINS in the assay: chemical mechanisms of assay interference and promiscuous enzymatic inhibition observed during a sulfhydryl-scavenging HTS. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SSB across ~30M SureChEMBL compounds — explore on Sugi Predict.