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STRAP

gene
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Also known as UNRIPpt-wdMAWD

Summary

STRAP (serine/threonine kinase receptor associated protein, HGNC:30796) is a protein-coding gene on chromosome 12p12.3, encoding Serine-threonine kinase receptor-associated protein (Q9Y3F4). The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs.

Enables RNA binding activity. Involved in maintenance of gastrointestinal epithelium and spliceosomal snRNP assembly. Acts upstream of with a positive effect on negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytosol. Part of SMN complex. Implicated in adenocarcinoma; colorectal carcinoma; large cell carcinoma; lung carcinoma; and squamous cell neoplasm.

Source: NCBI Gene 11171 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

  • Clinical variants (ClinVar): 45 total
  • Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈18% of expected missense variation)
  • GTEx eGene: eQTL in 25 tissues, sQTL in 1 (q < 0.05)
  • Constraint (gnomAD): pLI 0.84 (intermediate), LOEUF 0.57 (moderately constrained)
  • MANE Select transcript: NM_007178

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:30796
Approved symbolSTRAP
Nameserine/threonine kinase receptor associated protein
Location12p12.3
Locus typegene with protein product
StatusApproved
AliasesUNRIP, pt-wd, MAWD
Ensembl geneENSG00000023734
Ensembl biotypeprotein_coding
OMIM605986
Entrez11171

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 19 protein_coding, 14 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000419869

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

ENST00000419869, ENST00000025399, ENST00000536737, ENST00000538718, ENST00000539887, ENST00000541731, ENST00000888770, ENST00000888771, ENST00000927387, ENST00000927388, ENST00000927389, ENST00000927390, ENST00000927391, ENST00000956572, ENST00000991393, ENST00000991394, ENST00001033302, ENST00001033303, ENST00001033306, ENST00001033309, ENST00001033311, ENST00001033313, ENST00001092516, ENST00001092517, ENST00001092518, ENST00001092519, ENST00001092520, ENST00001092521, ENST00001092522, ENST00001092523, ENST00001092524, ENST00001092525, ENST00001092526, ENST00001107118, ENST00001141796

RefSeq mRNA: 1 — MANE Select: NM_007178 NM_007178

CCDS: CCDS8676

Canonical transcript exons

ENST00000419869 — 10 exons

ExonStartEnd
ENSE000007240911588354115883676
ENSE000022973071588238715882819
ENSE000034795971589788215898018
ENSE000034942281589404715894143
ENSE000035376681590291715903478
ENSE000035964441590094715901012
ENSE000035969101588992815890009
ENSE000036025591589990415900053
ENSE000036045501589059715890669
ENSE000036941951589535915895496

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 172.2765 / max 1290.3241, expressed in 1828 samples.

Highest expression (Bgee): secondary oocyte, oocyte, corpus epididymis, pons, cauda epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STRAP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Nerve Tibialeqtl2.7e-09+0.2412:15821046:T:C
Artery Tibialeqtl7.2e-09+0.2412:15874060:C:T
Thyroideqtl6.8e-07-0.3512:15836444:C:A
Adipose Subcutaneouseqtl2.5e-06+0.2412:15915510:T:G
Skin Sun Exposed Lower legeqtl1.6e-05-0.4312:16003965:G:T
Artery Aortaeqtl2.2e-04+0.2712:15897577:G:A
Brain Caudate basal gangliaeqtl2.2e-04-0.6412:15836444:C:A
Cells Cultured fibroblastseqtl4.2e-04+0.1512:15764754:A:G
Pancreaseqtl2.0e-03-0.5112:15542270:C:T
Esophagus Musculariseqtl3.0e-03+0.1512:15736221:T:C
Brain Amygdalaeqtl3.9e-03-0.7512:16010500:C:T
Esophagus Gastroesophageal Junctioneqtl5.2e-03+0.1812:15823326:A:G
Brain Cerebellumeqtl5.4e-03-0.5212:16003965:G:T
Colon Transverseeqtl9.1e-03+0.1012:15883327:C:G
Spleeneqtl9.5e-03+0.2812:15923578:C:T
Brain Hippocampuseqtl9.5e-03-0.4712:16003965:G:T
Testiseqtl1.5e-02-0.5112:15706089:C:A
Adipose Visceral Omentumeqtl1.7e-02-0.1612:15550245:A:G
Esophagus Mucosaeqtl2.0e-02-0.2312:16187125:A:G
Colon Sigmoideqtl2.4e-02-0.2412:15172900:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter IDTPM avgSamples expressed
124503167.91111828
1245044.30721495
1245020.058217

Top tissues by expression

showing 100 of 305 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065599.52gold quality
oocyteCL:000002399.36gold quality
corpus epididymisUBERON:000435998.99gold quality
ponsUBERON:000098898.81gold quality
cauda epididymisUBERON:000436098.81gold quality
type B pancreatic cellCL:000016998.72gold quality
caput epididymisUBERON:000435898.71gold quality
adenohypophysisUBERON:000219698.67gold quality
embryoUBERON:000092298.64gold quality
ventricular zoneUBERON:000305398.59gold quality
ganglionic eminenceUBERON:000402398.57gold quality
cortical plateUBERON:000534398.55gold quality
adult organismUBERON:000702398.51gold quality
pituitary glandUBERON:000000798.49gold quality
Brodmann (1909) area 46UBERON:000648398.49gold quality
hypothalamusUBERON:000189898.45gold quality
amniotic fluidUBERON:000017398.44gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451198.33gold quality
lateral nuclear group of thalamusUBERON:000273698.32gold quality
germinal epithelium of ovaryUBERON:000130498.31gold quality
substantia nigra pars compactaUBERON:000196598.31gold quality
lower lobe of lungUBERON:000894998.30gold quality
right frontal lobeUBERON:000281098.29gold quality
Brodmann (1909) area 9UBERON:001354098.29gold quality
dorsolateral prefrontal cortexUBERON:000983498.23gold quality
gingivaUBERON:000182898.20gold quality
gingival epitheliumUBERON:000194998.20gold quality
amygdalaUBERON:000187698.16gold quality
substantia nigra pars reticulataUBERON:000196698.16gold quality
middle temporal gyrusUBERON:000277198.12gold quality
oral cavityUBERON:000016798.11gold quality
orbitofrontal cortexUBERON:000416798.09gold quality
superior vestibular nucleusUBERON:000722798.08gold quality
mucosa of sigmoid colonUBERON:000499398.05gold quality
Ammon’s hornUBERON:000195498.04gold quality
body of pancreasUBERON:000115098.01gold quality
nucleus accumbensUBERON:000188298.01gold quality
caudate nucleusUBERON:000187397.97gold quality
forebrainUBERON:000189097.97gold quality
body of tongueUBERON:001187697.97gold quality
heart right ventricleUBERON:000208097.96gold quality
tongue squamous epitheliumUBERON:000691997.96gold quality
Brodmann (1909) area 23UBERON:001355497.94gold quality
putamenUBERON:000187497.93gold quality
cerebral cortexUBERON:000095697.92gold quality
epithelium of nasopharynxUBERON:000195197.92gold quality
postcentral gyrusUBERON:000258197.91gold quality
nasopharynxUBERON:000172897.90gold quality
dorsal root ganglionUBERON:000004497.89gold quality
telencephalonUBERON:000189397.89gold quality
hair follicleUBERON:000207397.89gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450297.89gold quality
endometriumUBERON:000129597.87gold quality
choroid plexus epitheliumUBERON:000391197.87gold quality
right adrenal gland cortexUBERON:003582797.86gold quality
deciduaUBERON:000245097.85gold quality
cingulate cortexUBERON:000302797.85gold quality
nephron tubuleUBERON:000123197.84gold quality
islet of LangerhansUBERON:000000697.82gold quality
brainUBERON:000095597.81gold quality
stromal cell of endometriumCL:000225597.80gold quality
central nervous systemUBERON:000101797.80gold quality
right adrenal glandUBERON:000123397.79gold quality
primary visual cortexUBERON:000243697.79gold quality
prefrontal cortexUBERON:000045197.78gold quality
seminal vesicleUBERON:000099897.78gold quality
temporal lobeUBERON:000187197.78gold quality
anterior cingulate cortexUBERON:000983597.78gold quality
parietal lobeUBERON:000187297.77gold quality
neocortexUBERON:000195097.77gold quality
smooth muscle tissueUBERON:000113597.76gold quality
vena cavaUBERON:000408797.76gold quality
lower esophagusUBERON:001347397.75gold quality
lower esophagus muscularis layerUBERON:003583397.75gold quality
gluteal muscleUBERON:000200097.74gold quality
right atrium auricular regionUBERON:000663197.74gold quality
biceps brachiiUBERON:000150797.73gold quality
tongueUBERON:000172397.73gold quality
mammary ductUBERON:000176597.73gold quality
tibial arteryUBERON:000761097.73gold quality
popliteal arteryUBERON:000225097.72gold quality
hindlimb stylopod muscleUBERON:000425297.72gold quality
frontal cortexUBERON:000187097.71gold quality
mucosa of transverse colonUBERON:000499197.71gold quality
frontal lobeUBERON:001652597.71gold quality
diaphragmUBERON:000110397.70gold quality
left adrenal glandUBERON:000123497.70gold quality
triceps brachiiUBERON:000150997.70gold quality
occipital lobeUBERON:000202197.70gold quality
tibiaUBERON:000097997.69gold quality
arteryUBERON:000163797.69gold quality
adipose tissueUBERON:000101397.68gold quality
cortex of kidneyUBERON:000122597.68gold quality
adrenal cortexUBERON:000123597.68gold quality
colonic mucosaUBERON:000031797.66gold quality
left adrenal gland cortexUBERON:003582597.66gold quality
renal glomerulusUBERON:000007497.65gold quality
sigmoid colonUBERON:000115997.65gold quality
cardiac ventricleUBERON:000208297.65gold quality
heart left ventricleUBERON:000208497.65gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

ExperimentMarker?Max mean expression
E-HCAD-4yes19.68
E-HCAD-10yes16.94
E-MTAB-7249no37194.32
E-MTAB-6075no696.64
E-MTAB-7303no438.65
E-ANND-3no0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 159 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Skeletal muscletissue122.6low
Ponstissue113.9
Thalamustissue109.7
Locus coeruleustissue108.8
Superior colliculitissue108.1
Tonguetissue106.9
Caudate putamentissue104.6
Midbraintissue101.5
Frontal cortextissue101.2
Spinal cordtissue94.8
Medulla oblongatatissue94.4
Hippocampal formationtissue94.4
Hypothalamustissue93.0
Substantia nigratissue91.1
Putamentissue90.3
Septumtissue89.3
Postcentral gyrustissue88.8
Cerebral cortextissue87.8medium
Somatosensory cortextissue87.8
Heart muscletissue87.1high
Periaqueductal graytissue85.7
Motor cortextissue83.6
Occipital cortextissue80.8
Ventral forebraintissue79.5
Kidneytissue79.3high
Retinatissue79.2
Parathyroid glandtissue78.9low
Retrosplenial and cingulate cortextissue77.1
Prefrontal cortextissue75.9
Basal gangliatissue75.1low
Livertissue75.1medium
Hippocampustissue74.1medium
Entorhinal cortextissue73.9
Nucleus accumbenstissue73.8
Corpus callosumtissue73.2
Temporal cortextissue73.2
Retrosplenial cortextissue72.9
Thyroid glandtissue72.7high
Cerebellumtissue71.0medium
Amygdalatissue70.7
Pancreastissue67.9medium
Adrenal glandtissue66.2high
Adipose tissuetissue66.0medium
Urinary bladdertissue65.8medium
Choroid plexustissue64.7
Insular cortextissue64.4
Smooth muscletissue64.3high
Thymustissue61.9
Placentatissue60.8high
Olfactory bulbtissue59.5
Esophagustissue57.2medium
Tonsiltissue53.6high
Pituitary glandtissue53.5
Colontissue52.0high
Appendixtissue51.7medium
Lymph nodetissue51.3high
Rectumtissue49.7medium
Endometrium 1tissue48.9medium
Bone marrowtissue48.9medium
Cervixtissue48.7medium

Brain sub-regions (HPA Brain Atlas): detected in 483; highest nTPM — Arcuate nucleus (115.1), Lateral hypothalamic area (111.0), Ventromedial nucleus (100.7), Supraoptic nucleus (95.2), Ventral spinal cord (94.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 54 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-223-3P99.9970.141140
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-548P99.9872.253784
HSA-MIR-480399.9871.993117
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-LET-7C-3P99.9573.422862
HSA-MIR-4778-3P99.9370.401818
HSA-MIR-10523-5P99.9169.222038
HSA-MIR-652-5P99.9167.49505
HSA-MIR-10527-5P99.9172.283754
HSA-MIR-6499-3P99.9066.381212
HSA-MIR-6715A-3P99.8368.051473
HSA-MIR-4659A-3P99.8072.624248
HSA-MIR-4659B-3P99.8072.624248
HSA-MIR-4645-3P99.7669.33993
HSA-MIR-3059-5P99.7069.932491
HSA-MIR-6892-3P99.6866.401178
HSA-MIR-3177-5P99.6570.381174
HSA-MIR-130399.6569.771662
HSA-MIR-549A-3P99.5468.17825
HSA-MIR-1212399.5271.792990
HSA-MIR-642A-5P99.5165.101152
HSA-MIR-942-5P99.4168.401977
HSA-MIR-6719-3P99.2967.781387
HSA-MIR-664A-3P99.2271.082696
HSA-MIR-122B-3P99.2168.901333
HSA-MIR-21-3P99.2168.951312

Functional genomics

gnomAD constraint: pLI 0.844, LOEUF 0.567, missense Z 2.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000419869 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈18% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
12:15,882,708–15,882,79831 / 39.20.79no
12:15,882,799–15,889,95432 / 76.10.42no
12:15,889,955–15,897,968152 / 183.00.83no
12:15,897,969–15,900,95026 / 76.70.34yes (p 7.1e-09)
12:15,900,951–15,902,97552 / 45.01.16no

Literature-anchored findings (GeneRIF, showing 27)

  • unrip functions in the pathway of small nuclear ribonucleoproteins biogenesis (PMID:15848170)
  • biochemical evidence for the existence of another, yet atypical, SMN complex component, termed unr-interacting protein (unrip) (PMID:16159890)
  • STRAP acts as an intermediate signaling molecule linking between the phosphatidylinositol 3-kinase/PDK1 and the TGF-beta signaling pathways (PMID:16251192)
  • Gemin8 has an essential role in the proper structural organization of the SMN complex and the involvement of the heteromeric subunit containing Gemin6, Gemin7, Gemin8, and Unrip in the recruitment of Sm proteins to the snRNP assembly pathway (PMID:17023415)
  • the direct interaction of NM23-H1 and STRAP is important for the regulation of TGF-beta-dependent biological activity as well as NM23-H1 activity (PMID:17314099)
  • These results indicate that upregulation of STRAP might play a role in tumor development as an early event for colorectal cancers. (PMID:17316412)
  • an interplay between PPM1G and unrip determine compartment-specific phosphorylation patterns, localization, and function of the SMN complex (PMID:17984321)
  • Strap regulation reflects the coordinated interplay between different DNA damage-activated protein kinases, ATM and Chk2 (Checkpoint kinase 2), where phosphorylation by each kinase provides a distinct functional consequence on the activity of Strap. (PMID:18833288)
  • STRAP can act as a negative regulator of ASK1. (PMID:19880523)
  • gonucleotide pulldown identified STRAP (serine/threonine kinase receptor-associated protein) as a further protein recruited to the MMP28 promoter and acting functionally with Sp1. (PMID:20144149)
  • B-MYB acts as a positive regulator of STRAP (PMID:21148321)
  • STRAP protein decreases ubiquitination of intracellular domain of Notch3 and may help to stabilize it. (PMID:21502811)
  • both of the TPR and OB-fold domains localize to the chromatin of p53 target genes and exhibit intrinsic regulatory activity necessary for the Strap-dependent p53 response (PMID:22362889)
  • Coexpression of MAWBP and MAWD inhibited epithelial mesenchymal transformation, and EMT-aided malignant cell progression was suppressed in gastric cancer. (PMID:23687415)
  • Data indicate serine-threonine kinase receptor-associated protein (STRAP) as a novel regulator of the coordinated translation of collagen alpha1(I) and alpha2(I) mRNAs. (PMID:23918805)
  • Strap augments the apoptotic effects of mitochondrial p53. (PMID:25168243)
  • STRAP inhibits the transactivation function of Sp1 either by directly blocking its DNA binding domain or destabilizing Sp1 protein through ubiquitin-proteasome pathway in cell cycle G1 phase. (PMID:25483064)
  • MAWD and MAWBP were downregulated and associated with the differentiation grade in GC tissues. (PMID:26373288)
  • these results suggest that STRAP increases invasion and metastasis of colorectal cancer partly through inhibiting ubiquitin-dependent degradation of beta-catenin and promoting Wnt/beta-catenin signaling (PMID:26910283)
  • Findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in colorectal cancer. (PMID:28827371)
  • STRAP plays an inhibitory role in hepatocellular carcinoma via regulating PTEN expression.STRAP is down-regulated in the hepatocellular carcinoma tissues. (PMID:29283497)
  • Study found that STRAP and MELK were overexpressed and highly phosphorylated in samples form colorectal adenocarcinoma patients and their expression were significantly correlated with tumor stages. (PMID:29783958)
  • Strap associates with Csde1 and affects expression of select Csde1-bound transcripts (PMID:30138317)
  • Results show that the increased STRAP protein levels observed in HCC provide growth advantage among others by enhancing Wnt/beta-catenin signaling. (PMID:30257989)
  • SIRT7 Deacetylates STRAP to Regulate p53 Activity and Stability. (PMID:32527012)
  • Serine-threonine Kinase Receptor-Associated Protein is a Critical Mediator of APC Mutation-Induced Intestinal Tumorigenesis Through a Feed-Forward Mechanism. (PMID:34520730)
  • Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK). (PMID:35272839)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriostrapENSDARG00000007405
mus_musculusStrapENSMUSG00000030224
rattus_norvegicusStrapENSRNOG00000007134
drosophila_melanogasterwmdFBGN0034876

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1329037) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)Records
abnormal angiogenesis1
abnormal heart development1
abnormal somite development1
abnormal embryo turning1
abnormal neural tube closure1
decreased incidence of tumors by chemical induction1
embryonic lethality during organogenesis, complete penetrance1

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.

OrganismUniProtIdentityMethod
Bos taurusQ5E95999.1%Diamond
Aspergillus fischeri NRRL 181A1DMI896.5%Diamond
Pyricularia oryzae 70-15G4MQX394.0%Diamond
Neurospora crassa OR74AQ0136994.0%Diamond
Aspergillus clavatus NRRL 1A1CTE691.8%Diamond
Gallus gallusQ5ZL3389.4%Diamond
Coccidioides immitis RSQ1DRB678.1%Diamond
Oryza sativa Japonica GroupQ9AYE477.0%Diamond
Schizosaccharomyces pombe 972h-O7418465.2%Diamond
Arabidopsis thalianaQ9SXY163.6%Diamond
Yarrowia lipolytica CLIB122Q6C4I963.3%Diamond
Saccharomyces cerevisiae S288CP2563555.7%Diamond
Dictyostelium discoideumQ54LT848.5%Diamond
Caenorhabditis elegansG5EFW739.7%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).

SymbolTypeEntrez
MGST1protein-coding4257
DERAprotein-coding51071
SLC15A5protein-coding729025
EPS8protein-coding2059
PTPROprotein-coding5800

Protein

Protein identifiers

Serine-threonine kinase receptor-associated protein — Q9Y3F4 (reviewed: Q9Y3F4)

Alternative names: MAP activator with WD repeats, UNR-interacting protein, WD-40 repeat protein PT-WD

All UniProt accessions (3): Q9Y3F4, F5H1G1, H0YH33

UniProt curated annotations — full annotation on UniProt →

Function. The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein.

Subunit / interactions. Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Associates with the SMN complex in the cytoplasm but not in the nucleus. Interacts with GEMIN6; the interaction is direct. Interacts with GEMIN7; the interaction is direct. Interacts with CSDE1/UNR and MAWBP. Interacts with PDPK1. Interacts with TRIM48.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the WD repeat STRAP family.

Isoforms (2)

UniProt IDNamesCanonical?
Q9Y3F4-11yes
Q9Y3F4-22

RefSeq proteins (1): NP_009109* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001680WD40_rptRepeat
IPR015943WD40/YVTN_repeat-like_dom_sfHomologous_superfamily
IPR020472WD40_PAC1Repeat
IPR036322WD40_repeat_dom_sfHomologous_superfamily
IPR056551Beta-prop_NOL10_NDomain

Pfam: PF00400, PF23098

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

Structure

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9Y3F4-F189.750.84

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; cell junctions

Antibody reliability (HPA): IH approved · IF supported

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 (3)

TypePositions
Phosphoserine338, 312, 335

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 14; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

IDPathwayEvidence
R-HSA-9764790Positive Regulation of CDH1 Gene Transcriptioncurated
R-HSA-418990Adherens junctions interactions—
R-HSA-446728Cell junction organization—
R-HSA-1500931Cell-Cell communication—
R-HSA-421270Cell-cell junction organization—
R-HSA-2173788Downregulation of TGF-beta receptor signalingelectronic
R-HSA-9764265Regulation of CDH1 Expression and Function—
R-HSA-9764560Regulation of CDH1 Gene Transcription—
R-HSA-9764274Regulation of Expression and Function of Type I Classical Cadherins—
R-HSA-9759476Regulation of Homotypic Cell-Cell Adhesion—
R-HSA-162582Signal Transduction—
R-HSA-170834Signaling by TGF-beta Receptor Complex—
R-HSA-9006936Signaling by TGFB family members—
R-HSA-2173789TGF-beta receptor signaling activates SMADs—

MSigDB gene sets: 196 (showing top): GOBP_DIGESTION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, PAL_PRMT5_TARGETS_UP, MODULE_151, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (9): alternative mRNA splicing, via spliceosome (GO:0000380), spliceosomal snRNP assembly (GO:0000387), cell differentiation (GO:0030154), maintenance of gastrointestinal epithelium (GO:0030277), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380), protein-RNA complex assembly (GO:0022618)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA binding (GO:0003729), signaling receptor binding (GO:0005102), U2 snRNP binding (GO:1990447), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), SMN complex (GO:0032797), SMN-Sm protein complex (GO:0034719)

Reactome top-level categories

12 top-level categories:

CategoryPathways
TGF-beta receptor signaling activates SMADs1
Regulation of CDH1 Gene Transcription1
Signaling by TGFB family members1
Signaling by TGF-beta Receptor Complex1
Cell-cell junction organization1
Cell junction organization1
Cell-Cell communication1
Signal Transduction1
Adherens junctions interactions1
Regulation of Expression and Function of Type I Classical Cadherins1
Regulation of Homotypic Cell-Cell Adhesion1
Regulation of CDH1 Expression and Function1

GO top-level categories

27 GO namespaces:

CategoryTerms
mRNA splicing, via spliceosome2
RNA processing2
cellular anatomical structure2
cytoplasm2
Sm-like protein family complex2
protein-RNA complex assembly1
cellular developmental process1
epithelial structure maintenance1
digestive system process1
transforming growth factor beta receptor signaling pathway1
regulation of transforming growth factor beta receptor signaling pathway1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile1
mRNA processing1
mRNA metabolic process1
ribonucleoprotein complex biogenesis1
protein-containing complex assembly1
protein-RNA complex organization1
nucleic acid binding1
RNA binding1
protein binding1
snRNP binding1
binding1
intracellular membrane-bounded organelle1
intracellular anatomical structure1
SMN-Sm protein complex1
SMN complex1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO termNSEvidence
maintenance of gastrointestinal epitheliumBPmutant phenotype
negative regulation of transforming growth factor beta receptor signaling pathwayBPmutant phenotype
spliceosomal snRNP assemblyBPdirect assay
SMN complexCCdirect assay
SMN-Sm protein complexCCdirect assay
cytoplasmCCdirect assay
cytosolCCdirect assay
RNA bindingMFhigh-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,648 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
STRAPPBLDP30039948
STRAPGEMIN2O14893908
STRAPGEMIN7Q9H840902
STRAPCSDE1O75534846
STRAPLSM2Q9Y333815
STRAPSMN1Q16637754
STRAPGEMIN8Q9NWZ8741
STRAPDDX20Q9UHI6712
STRAPGEMIN5Q8TEQ6673
STRAPGEMIN6Q8WXD5651
STRAPGEMIN4P57678606
STRAPLARP6Q9BRS8598
STRAPSNRPD1P13641551
STRAPCLNS1AP54105470
STRAPLSM10Q969L4455

IntAct

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

29 partners by confidence:

PartnerInteraction typeMIscoreRecords
GEMIN6direct interaction0.7602
GEMIN7direct interaction0.7602
NME1physical association0.6709
HTTphysical association0.6703
SNRPBdirect interaction0.5901
SNRPD2direct interaction0.5901
SZRD1physical association0.5603
CDK2AP1association0.5301
CHEK2phosphorylation reaction0.4401
SNRPD3direct interaction0.4401
SNRPEdirect interaction0.4401
SGTAphysical association0.4001
TGFBR1physical association0.4001
GEMIN2association0.3502
RAPH1association0.3501
ACTR6physical association0.0001
EIF1Bphysical association0.0001
GH1physical association0.0001
GSK3Bphysical association0.0001
HLA-Bphysical association0.0001
HUS1physical association0.0001
IKBKEphysical association0.0001
MTRES1physical association0.0001
NME2physical association0.0001
PRKAB1physical association0.0001
PTP4A3physical association0.0001
RNPS1physical association0.0001
TNIKphysical association0.0001
TRAF6physical association0.0001

BioGRID (428 interactions; top human partners by supporting records): CSDE1 (Affinity Capture-MS; 14 records), GEMIN7 (Affinity Capture-MS; 7 records), SMN1 (Affinity Capture-Western; 7 records), DDX20 (Affinity Capture-MS; 6 records), GEMIN2 (Affinity Capture-MS; 5 records), GEMIN6 (Affinity Capture-MS; 5 records), GEMIN8 (Affinity Capture-MS; 5 records), SZRD1 (Affinity Capture-MS; 5 records), GEMIN4 (Affinity Capture-MS; 4 records), GEMIN5 (Affinity Capture-MS; 4 records), SMAD3 (Phenotypic Suppression; 4 records), SMAD7 (Phenotypic Enhancement; 4 records), EGFR (Negative Genetic; 3 records), EP300 (Affinity Capture-MS; 3 records), GSK3B (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

AEffectBMechanism
SMAD7up-regulatesSTRAPbinding

Protein complexes (CORUM) (5)

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

5 complexes by size:

ComplexSubunitsMembers
Spliceosome, E complex129RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
SMN complex (16 subunits)16SNRPD3, SNRPG, GEMIN4, GEMIN5, SNRPB, SNRPF, DDX20, GEMIN7, SMN1, STRAP, SNRPD1, SNRPD2, SNRPE, GEMIN2, GEMIN6, GEMIN8
SMN complex10DDX20, GEMIN5, GEMIN6, GEMIN7, SNRPA, SNRPB, STRAP, GEMIN2, GEMIN4, SMN1
★ AXIN1-GSK3B-STRAP complex3AXIN1, GSK3B, STRAP
GEMIN6-GEMIN7-STRAP complex, SMN-independent intermediate3GEMIN6, GEMIN7, STRAP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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:

PathwayPartnersFoldFDR
SARS-CoV-2 modulates host translation machinery765.3×1e-09
snRNP Assembly761.7×1e-09
mRNA Splicing522.9×6e-05
Processing of Capped Intron-Containing Pre-mRNA517.1×2e-04
mRNA Splicing - Major Pathway511.4×9e-04
Dengue Virus-Host Interactions59.5×2e-03
Metabolism of RNA58.7×2e-03

GO biological processes:

GO termPartnersFoldFDR
spliceosomal snRNP assembly7145.3×9e-12
mRNA splicing, via spliceosome722.9×2e-06
RNA splicing515.8×8e-04

Disease & clinical

Genetic variants

Variant evidence for STRAP: 45 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance23
Likely benign0
Benign0

AlphaMissense

1,272 missense substitutions predicted likely pathogenic (of 2,300 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:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M4290.9800.999
H1381.0001.000
D8081.0001.000
D28681.0001.000
D3880.9991.000
D5080.9991.000
H5880.9991.000
H26480.9991.000
H26980.9971.000
H10180.9960.999
F26580.9941.000
F5580.9931.000
D24480.9931.000
H9980.9910.998
D27680.9900.999
D16380.9860.999
S27480.9861.000
F2280.9841.000
H14280.9820.997
S3480.9781.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

11 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable1.56e-06
Lung Adenocarcinoma (TCGA)unfavorable5.72e-06
Kidney Renal Clear Cell Carcinoma (TCGA)favorable5.89e-06
Liver Hepatocellular Carcinoma (validation)unfavorable1.41e-05
Kidney Renal Clear Cell Carcinoma (TCGA)favorable3.28e-05
Liver Hepatocellular Carcinoma (TCGA)unfavorable3.55e-05
Ovary Serous Cystadenocarcinoma (TCGA)unfavorable0.000107
Ovary Serous Cystadenocarcinoma (validation)unfavorable0.00011
Pancreatic Adenocarcinoma (validation)unfavorable0.000159
Kidney Chromophobe (TCGA)unfavorable0.000526
Bladder Urothelial Carcinoma (TCGA)unfavorable0.000832

Disease associations

OMIM: gene MIM:605986 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067330 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
CHEMBL5653589KD1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.75Kd17.7nMCHEMBL5653589
7.75ED5017.7nMCHEMBL5653589
6.64Kd231.2nMCHEMBL3752910
6.64ED50231.2nMCHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149517: Binding affinity to human STRAP incubated for 45 mins by Kinobead based pull down assaykd0.0177uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149517: Binding affinity to human STRAP incubated for 45 mins by Kinobead based pull down assaykd0.2312uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects expression, decreases expression, decreases methylation4
Tobacco Smoke Pollutionaffects expression, increases expression2
aristolochic acid Iincreases expression1
FR900359increases phosphorylation1
bisphenol Fincreases expression1
moringinincreases expression1
TAK-243increases sumoylation1
deoxynivalenolincreases expression1
trichostatin Aincreases expression1
sodium arsenitedecreases expression1
tetrabromobisphenol Adecreases expression1
2-bromopalmitateincreases palmitoylation, decreases reaction, increases abundance1
perfluorooctanoic aciddecreases expression1
ochratoxin Aincreases expression1
chloropicrinincreases expression1
bisphenol Bincreases expression1
bisphenol Sincreases expression1
bisphenol AFincreases expression1
Arsenic Trioxideincreases expression1
Vorinostatdecreases expression1
Acetaminophendecreases expression1
Air Pollutants, Occupationalaffects expression1
Benztropinedecreases expression1
Cadmiumincreases abundance, increases palmitoylation, decreases reaction1
Cannabidiolincreases expression1
Clozapinedecreases expression1
Doxorubicinaffects expression1
Enzyme Inhibitorsdecreases activity, increases O-linked glycosylation1
Ivermectindecreases expression1
Phthalic Acidsincreases methylation1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5652559BindingBinding affinity to human STRAP incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B3IIAbcam HEK293T STRAP KOTransformed cell lineFemale

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.