STRIT1

Summary

STRIT1 (small transmembrane regulator of ion transport 1, HGNC:52297) is a protein-coding gene on chromosome 3q25.2, encoding Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF (P0DN84). Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a key regulator of skeletal muscle activity.

Predicted to enable enzyme activator activity. Predicted to be involved in regulation of calcium ion transport and regulation of striated muscle contraction. Predicted to act upstream of or within positive regulation of ATPase-coupled calcium transmembrane transporter activity and positive regulation of calcium ion import. Predicted to be located in sarcoplasmic reticulum membrane.

Source: NCBI Gene 100507537 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001352129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:52297
Approved symbol	STRIT1
Name	small transmembrane regulator of ion transport 1
Location	3q25.2
Locus type	gene with protein product
Status	Approved
Aliases	DWORF
Ensembl gene	ENSG00000240045
Ensembl biotype	protein_coding
OMIM	616891
Entrez	100507537

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000489090

RefSeq mRNA: 1 — MANE Select: NM_001352129 NM_001352129

CCDS: CCDS87158

Canonical transcript exons

ENST00000489090 — 3 exons

Exon	Start	End
ENSE00001828305	155293620	155293683
ENSE00001882056	155290940	155291038
ENSE00001944442	155290227	155290846

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 99.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8791 / max 907.2394, expressed in 69 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45219	1.3087	45
45220	0.2411	34
45218	0.1646	16
45222	0.0756	25
45221	0.0663	24
45223	0.0227	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	99.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.54	gold quality
tibialis anterior	UBERON:0001385	99.43	gold quality
vastus lateralis	UBERON:0001379	99.42	gold quality
quadriceps femoris	UBERON:0001377	99.40	gold quality
deltoid	UBERON:0001476	99.22	gold quality
skeletal muscle tissue	UBERON:0001134	99.16	gold quality
biceps brachii	UBERON:0001507	99.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.91	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.77	gold quality
muscle of leg	UBERON:0001383	97.59	gold quality
body of tongue	UBERON:0011876	91.37	gold quality
muscle tissue	UBERON:0002385	89.54	gold quality
putamen	UBERON:0001874	86.38	gold quality
tongue	UBERON:0001723	85.45	gold quality
jejunal mucosa	UBERON:0000399	84.69	gold quality
jejunum	UBERON:0002115	82.17	gold quality
caudate nucleus	UBERON:0001873	75.95	gold quality
superior surface of tongue	UBERON:0007371	75.17	gold quality
apex of heart	UBERON:0002098	72.12	gold quality
buccal mucosa cell	CL:0002336	71.09	silver quality
heart left ventricle	UBERON:0002084	68.34	gold quality
cardiac ventricle	UBERON:0002082	67.40	gold quality
duodenum	UBERON:0002114	65.96	gold quality
trabecular bone tissue	UBERON:0002483	63.95	silver quality
minor salivary gland	UBERON:0001830	62.65	gold quality
lower lobe of lung	UBERON:0008949	61.75	silver quality
mucosa of paranasal sinus	UBERON:0005030	61.34	silver quality
mouth mucosa	UBERON:0003729	60.72	gold quality
heart	UBERON:0000948	59.97	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• The transmembrane peptide DWORF activates SERCA2a via dual mechanisms. (PMID:33581112)
• Dwarf open reading frame (DWORF) is a direct activator of the sarcoplasmic reticulum calcium pump SERCA. (PMID:34075877)
• Inhibitory and stimulatory micropeptides preferentially bind to different conformations of the cardiac calcium pump. (PMID:35605666)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Strit1	ENSMUSG00000103476

Protein

Protein identifiers

Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF — P0DN84 (reviewed: P0DN84)

Alternative names: Dwarf open reading frame, Small transmembrane regulator of ion transport 1

All UniProt accessions (1): P0DN84

UniProt curated annotations — full annotation on UniProt →

Function. Enhances the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by displacing ATP2A1/SERCA1 inhibitors, thereby acting as a key regulator of skeletal muscle activity. Also enhances the activity of the ATP2A2/SERCA2 ATPase. Does not directly stimulate SERCA pump activity. Binds preferentially to the phosphorylated E1 and E2 conformational forms of ATP2A2 which predominate at high Ca(2+) concentrations during the systolic phase of the cardiac cycle. Competes with ATP2A2 inhibitor phospholamban (PLN) for binding to ATP2A2 and displaces PLN. Can activate ATP2A2 directly in the absence of PLN. Also enhances sarcoplasmic reticulum Ca(2+) uptake and myocyte contractility by displacing the SERCA inhibitory peptides sarcolipin (SLN) and myoregulin (MRLN).

Subunit / interactions. Homooligomer. Can also form heterooligomers with other sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) regulators ARLN, ERLN, PLN and SLN. Monomer. Interacts with ATP2A1/SERCA1; the interaction results in activation of ATP2A1. Interacts as a monomer with ATP2A2/SERCA2; the interaction results in activation of ATP2A2.

Subcellular location. Sarcoplasmic reticulum membrane.

Domain organisation. The transmembrane domain is sufficient to compete with phospholamban (PLN) for binding to ATP2A2.

RefSeq proteins (1): NP_001339058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR044529	DWORF	Family

Pfam: PF22030

UniProt features (5 total): mutagenesis site 2, chain 1, transmembrane region 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7MPA	SOLID-STATE NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DN84-F1	85.41	0.62

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
15	significant reduction in binding to atp2a and reduced atp2a2 activation; when associated with a-22.
22	significant reduction in binding to atp2a and reduced atp2a2 activation; when associated with a-15.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, GOBP_SKELETAL_MUSCLE_CONTRACTION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, GOBP_CALCIUM_ION_IMPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_REGULATION_OF_CALCIUM_ION_IMPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_CARDIAC_MUSCLE_CELL_CONTRACTION

GO Biological Process (5): regulation of slow-twitch skeletal muscle fiber contraction (GO:0031449), positive regulation of calcium ion import (GO:0090280), positive regulation of cardiac muscle cell contraction (GO:0106134), regulation of ATPase-coupled calcium transmembrane transporter activity (GO:1901894), positive regulation of calcium ion import into sarcoplasmic reticulum (GO:1902082)

GO Molecular Function (2): enzyme activator activity (GO:0008047), protein binding (GO:0005515)

GO Cellular Component (3): sarcoplasmic reticulum membrane (GO:0033017), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of calcium ion transport	2
regulation of twitch skeletal muscle contraction	1
slow-twitch skeletal muscle fiber contraction	1
calcium ion import	1
regulation of calcium ion import	1
cardiac muscle cell contraction	1
regulation of cardiac muscle cell contraction	1
positive regulation of actin filament-based movement	1
P-type calcium transporter activity	1
regulation of transmembrane transporter activity	1
regulation of ATP-dependent activity	1
positive regulation of intracellular transport	1
regulation of calcium ion import into sarcoplasmic reticulum	1
calcium ion import into sarcoplasmic reticulum	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
binding	1
endoplasmic reticulum membrane	1
sarcoplasmic reticulum	1
bounding membrane of organelle	1
cellular anatomical structure	1
endoplasmic reticulum	1
sarcoplasm	1

Protein interactions and networks

STRING

158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRIT1	MRLN	P0DMT0	871
STRIT1	SLN	O00631	848
STRIT1	ERLN	P0DI80	729
STRIT1	ARLN	Q8WVX3	684
STRIT1	SPAAR	A0A1B0GVQ0	666
STRIT1	MTLN	Q8NCU8	545
STRIT1	MYMX	A0A1B0GTQ4	534
STRIT1	SMIM38	A0A286YFK9	520
STRIT1	NBDY	A0A0U1RRE5	507
STRIT1	TMDD1	P0DPE3	506
STRIT1	FAM240C	A0A1B0GVR7	479
STRIT1	SMIM30	A4D0T7	419
STRIT1	SMIM28	A0A1B0GU29	417
STRIT1	ATP2A1	O14983	377
STRIT1	SMIM22	K7EJ46	353

IntAct

138 interactions, top by confidence:

A	B	Type	Score
STRIT1	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	SPNS3	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	TMEM101	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	PDZK1IP1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	IFNGR2	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	TMEM51	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	SLC14A1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	KCNJ6	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	MOG	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	MFF	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	STRIT1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	STX1A	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	STX2	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	JPH1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	EDA2R	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	CMTM2	psi-mi:“MI:0915”(physical association)	0.560

ESM2 similar proteins: A0A1B0GWH6, A0A7H0DN68, A0A7H0DNB3, A0T0B1, A0T0B4, A0T0P6, A2BVK2, A4ZUB9, A4ZUC7, A5A617, B7K767, C0HJH3, C0HJH4, C7J0R5, O00631, O78448, P0C2G8, P0CAJ2, P0CAJ3, P0CAJ4, P0CK21, P0CK22, P0DN84, P0DPN0, P0DPO4, P0DPO8, P0DTF1, P0DTI0, P11339, P15911, P30396, P37256, P48109, P49487, P49516, P64442, P64443, P64444, P9WEJ6, Q06J23

Diamond homologs: P0DN83, P0DN84

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

219 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:155290979:C:G	G25R	0.971
3:155290988:A:G	W22R	0.970
3:155290988:A:T	W22R	0.970
3:155290991:C:G	G21R	0.948
3:155290978:C:T	G25D	0.941
3:155290976:A:G	C26R	0.934
3:155290969:A:T	I28K	0.932
3:155290990:C:T	G21D	0.930
3:155290969:A:C	I28R	0.899
3:155290999:A:T	L18H	0.870
3:155291002:A:T	L17H	0.868
3:155290950:G:C	F34L	0.863
3:155290950:G:T	F34L	0.863
3:155290952:A:G	F34L	0.863
3:155291002:A:C	L17R	0.857
3:155290981:A:T	V24E	0.844
3:155290996:A:C	L19R	0.830
3:155290954:A:T	V33D	0.823
3:155290999:A:G	L18P	0.818
3:155290999:A:C	L18R	0.811
3:155291011:A:T	V14D	0.784
3:155290986:C:A	W22C	0.775
3:155290986:C:G	W22C	0.775
3:155290957:A:T	V32D	0.760
3:155290966:A:T	M29K	0.757
3:155290984:A:T	I23N	0.753
3:155290966:A:C	M29R	0.748
3:155290996:A:G	L19P	0.713
3:155291008:G:T	P15H	0.695
3:155290993:A:T	I20N	0.671

dbSNP variants (sampled 300 via entrez): RS1000710615 (3:155292903 G>A,T), RS1001358352 (3:155295247 T>A,C), RS1001515847 (3:155292261 G>A), RS1001592975 (3:155291844 A>G), RS1001851238 (3:155293636 T>C), RS1001924767 (3:155293203 G>A), RS1002113987 (3:155291041 T>C), RS1002457312 (3:155292520 C>T), RS1003074126 (3:155292068 A>C,T), RS1003457562 (3:155293994 A>G), RS1003541904 (3:155294993 T>C,G), RS1003573240 (3:155294687 A>G,T), RS1004718736 (3:155295196 A>G), RS1004787905 (3:155294058 C>T), RS1005031322 (3:155294666 C>A,T)

Disease associations

OMIM: gene MIM:616891 | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases expression	1

Clinical trials (associated diseases)

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