LIME1

Summary

LIME1 (Lck interacting transmembrane adaptor 1, HGNC:26016) is a protein-coding gene on chromosome 20q13.33, encoding Lck-interacting transmembrane adapter 1 (Q9H400). Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells.

This gene encodes a transmembrane adaptor protein that links the T and B-cell receptor stimulation to downstream signaling pathways via its association with the Src family kinases Lck and Lyn, respectively. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 54923 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_017806

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26016
Approved symbol	LIME1
Name	Lck interacting transmembrane adaptor 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20406, dJ583P15.4, LIME
Ensembl gene	ENSG00000203896
Ensembl biotype	protein_coding
OMIM	609809
Entrez	54923

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000309546, ENST00000444951, ENST00000465591, ENST00000476183, ENST00000480139, ENST00000487026, ENST00000489212, ENST00000493265, ENST00000494776, ENST00000621325, ENST00000899469, ENST00000899470, ENST00000899471, ENST00000899472, ENST00000899473, ENST00000899474, ENST00000899475, ENST00000955191, ENST00000955192

RefSeq mRNA: 3 — MANE Select: NM_017806 NM_001305654, NM_001305655, NM_017806

CCDS: CCDS13536, CCDS82638

Canonical transcript exons

ENST00000309546 — 6 exons

Exon	Start	End
ENSE00001209321	63736664	63736712
ENSE00003465494	63737973	63738060
ENSE00003477059	63738598	63739103
ENSE00003539267	63738183	63738499
ENSE00003543259	63737533	63737647
ENSE00003711187	63737821	63737902

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 97.57.

FANTOM5 (CAGE): breadth broad, TPM avg 11.2533 / max 563.6600, expressed in 323 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185860	7.8056	209
185861	0.9126	121
185858	0.9036	161
185864	0.7840	103
185859	0.7724	139
185862	0.0577	18
185863	0.0174	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.57	gold quality
right lobe of liver	UBERON:0001114	97.30	gold quality
liver	UBERON:0002107	94.45	gold quality
blood	UBERON:0000178	93.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.90	gold quality
cerebellar hemisphere	UBERON:0002245	91.15	gold quality
cerebellar cortex	UBERON:0002129	90.97	gold quality
cerebellum	UBERON:0002037	90.91	gold quality
spleen	UBERON:0002106	90.35	gold quality
putamen	UBERON:0001874	89.85	gold quality
bone marrow cell	CL:0002092	89.82	gold quality
adult mammalian kidney	UBERON:0000082	89.75	gold quality
mucosa of transverse colon	UBERON:0004991	89.71	gold quality
lower esophagus mucosa	UBERON:0035834	87.93	gold quality
caudate nucleus	UBERON:0001873	87.42	gold quality
nucleus accumbens	UBERON:0001882	86.49	gold quality
right frontal lobe	UBERON:0002810	86.28	gold quality
pituitary gland	UBERON:0000007	85.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.20	gold quality
Ammon’s horn	UBERON:0001954	85.15	gold quality
temporal lobe	UBERON:0001871	84.56	gold quality
amygdala	UBERON:0001876	84.56	gold quality
cortex of kidney	UBERON:0001225	84.45	gold quality
anterior cingulate cortex	UBERON:0009835	84.41	gold quality
brain	UBERON:0000955	84.33	gold quality
substantia nigra	UBERON:0002038	84.04	gold quality
adenohypophysis	UBERON:0002196	84.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.97	gold quality
metanephros cortex	UBERON:0010533	83.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.62	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	86.16
E-MTAB-6701	yes	76.36
E-CURD-122	yes	58.20
E-HCAD-6	yes	37.23
E-CURD-46	yes	34.41
E-MTAB-8410	yes	32.91
E-HCAD-11	yes	22.45
E-MTAB-8498	yes	14.69
E-MTAB-9067	yes	13.58
E-ANND-3	yes	10.88
E-HCAD-10	yes	9.41
E-MTAB-9801	yes	6.24
E-CURD-120	no	9.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting LIME1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-1539	92.91	60.97	91

Literature-anchored findings (GeneRIF, showing 2)

• these results establish LIME as a transmembrane adaptor protein linking TCR stimulation to IS formation and integrin activation through activation of Vav(Vav guanine nucleotide exchange factor) (PMID:22395814)
• Results identified one differentially methylated region associated with cerebral palsy within the transcription start site of the LIME1 gene, which plays a key role in inflammatory pathways. (PMID:29484035)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lime1	ENSMUSG00000090077
rattus_norvegicus	Lime1	ENSRNOG00000049336
drosophila_melanogaster	CG4709	FBGN0032169
caenorhabditis_elegans		WBGENE00016383

Paralogs (2): TFIP11 (ENSG00000100109), ZGPAT (ENSG00000197114)

Protein

Protein identifiers

Lck-interacting transmembrane adapter 1 — Q9H400 (reviewed: Q9H400)

Alternative names: Lck-interacting molecule

All UniProt accessions (6): A0A087WT39, A0A087WUJ1, A0A087WZP9, Q9H400, V9GYI1, X6RKG5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules.

Subunit / interactions. When phosphorylated in response to BCR activation, interacts with LYN, PIK3R1, PLCG2, and GRB2. When phosphorylated in response to TCR stimulation and/or CD4 co-stimulation, interacts with LCK, CSK, FYN, PTPN11/SHP2, GRB2, PIK3R1 and GRAP2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in peripheral blood lymphocytes, lymphoid tissues, and liver. Present in T-cells and plasma cells, and in various hematopoietic cell lines (at protein level).

Post-translational modifications. Palmitoylation of Cys-28 and Cys-31 is required for raft targeting. Phosphorylated on tyrosines upon TCR activation and/or CD4 coreceptor stimulation, or upon BCR stimulation; which leads to the recruitment of SH2-containing proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H400-1	1	yes
Q9H400-2	2

RefSeq proteins (3): NP_001292583, NP_001292584, NP_060276* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026072	Lime1	Family

Pfam: PF15332

UniProt features (29 total): region of interest 8, modified residue 6, mutagenesis site 5, topological domain 2, lipid moiety-binding region 2, chain 1, compositionally biased region 1, transmembrane region 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H400-F1	54.39	0.04

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 (8): 145, 167, 200, 235, 254, 256, 28, 31

Mutagenesis-validated functional residues (5):

Position	Phenotype
145	no change in binding to lck, csk or fyn.
167	abolishes binding to csk.
200	reduces binding to csk.
235	no change in binding to lck, csk or fyn.
254	abolishes binding to lck and reduces binding to fyn.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): RNGTGGGC_UNKNOWN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MAINTENANCE_OF_LOCATION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, RYTTCCTG_ETS2_B, GOBP_MONOATOMIC_ION_HOMEOSTASIS

GO Biological Process (9): adaptive immune response (GO:0002250), regulation of transcription by RNA polymerase II (GO:0006357), regulation of canonical NF-kappaB signal transduction (GO:0043122), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), regulation of release of sequestered calcium ion into cytosol (GO:0051279), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), regulation of non-canonical NF-kappaB signal transduction (GO:1901222), immune system process (GO:0002376)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), B cell receptor complex (GO:0019815), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of intracellular signal transduction	3
antigen receptor-mediated signaling pathway	2
immune response	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
canonical NF-kappaB signal transduction	1
release of sequestered calcium ion into cytosol	1
regulation of calcium ion transmembrane transport	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
non-canonical NF-kappaB signal transduction	1
biological_process	1
kinase binding	1
binding	1
immunoglobulin complex	1
plasma membrane signaling receptor complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIME1	LCK	P06239	951
LIME1	GRAP2	O75791	771
LIME1	LYN	P07948	770
LIME1	GRAP	Q13588	756
LIME1	GRB2	P29354	745
LIME1	ZGPAT	Q8N5A5	620
LIME1	ZNF461	Q8TAF7	602
LIME1	CSK	P41240	580
LIME1	SLC2A4RG	Q9NR83	570
LIME1	EBLN2	Q6P2I7	543
LIME1	FYN	P06241	521
LIME1	EBLN1	P0CF75	518
LIME1	LAT2	Q9GZY6	479
LIME1	ARFRP1	Q13795	460
LIME1	TMC6	Q7Z403	450

IntAct

132 interactions, top by confidence:

A	B	Type	Score
LIME1	TRAF7	psi-mi:“MI:0915”(physical association)	0.620
TRAF3IP3	LIME1	psi-mi:“MI:0915”(physical association)	0.560
LPAR3	LIME1	psi-mi:“MI:0915”(physical association)	0.560
AGR3	LIME1	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	LIME1	psi-mi:“MI:0915”(physical association)	0.560
MEST	LIME1	psi-mi:“MI:0915”(physical association)	0.560
PBX3	LIME1	psi-mi:“MI:0915”(physical association)	0.560
AQP1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
BNIP2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
TMEM243	LIME1	psi-mi:“MI:0915”(physical association)	0.560
LIME1	MAN2B2	psi-mi:“MI:0915”(physical association)	0.560
MIEF2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
UPK2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
TBRG4	LIME1	psi-mi:“MI:0915”(physical association)	0.560
PKMYT1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
NRAC	LIME1	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	LIME1	psi-mi:“MI:0915”(physical association)	0.560
LIME1	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
RTP2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
NINJ1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
FRMD8	LIME1	psi-mi:“MI:0915”(physical association)	0.560
SNX1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
SEC22C	LIME1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	LIME1	psi-mi:“MI:0915”(physical association)	0.560
LIME1	ARFGAP3	psi-mi:“MI:0915”(physical association)	0.560
LIME1	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.560
GAD2	LIME1	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	LIME1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): TRAF7 (Affinity Capture-MS), LIME1 (Affinity Capture-MS), LIME1 (Reconstituted Complex), LIME1 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), IDE (Affinity Capture-MS), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid), LIME1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GW64, A0A5F4BST2, A0PJX4, A8MVS5, A8MWV9, B0FP48, E5RIL1, E9PGG2, O14836, O60320, O95998, P09564, Q01113, Q01114, Q13477, Q2KI80, Q2T9R2, Q3TS39, Q3UPR0, Q3URD2, Q4V9L6, Q5FVJ4, Q5M869, Q6A044, Q6UWJ8, Q75VT8, Q864V4, Q8BRJ3, Q8BX43, Q8C503, Q8IVY1, Q8K5A9, Q8N112, Q8NC24, Q8NDY8, Q8QZT4, Q8R138, Q969Z4, Q9BUF7, Q9CQM1

Diamond homologs: Q9EQR5, Q9H400

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

887 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63737900:GCG:G	donor_gain	1.0000
20:63738058:GGG:G	donor_gain	1.0000
20:63738059:GGG:G	donor_gain	1.0000
20:63738497:CAG:C	donor_loss	1.0000
20:63738498:AG:A	donor_loss	1.0000
20:63738499:GG:G	donor_loss	1.0000
20:63738500:GTAA:G	donor_loss	1.0000
20:63738501:T:A	donor_loss	1.0000
20:63736708:GCTTG:G	donor_gain	0.9900
20:63736710:TTGGT:T	donor_loss	0.9900
20:63736711:TGG:T	donor_loss	0.9900
20:63736712:GGTA:G	donor_loss	0.9900
20:63736713:G:GG	donor_gain	0.9900
20:63736713:G:T	donor_loss	0.9900
20:63736714:T:A	donor_loss	0.9900
20:63737807:C:G	acceptor_gain	0.9900
20:63737812:A:AG	acceptor_gain	0.9900
20:63737813:C:G	acceptor_gain	0.9900
20:63737817:CAAG:C	acceptor_loss	0.9900
20:63737818:AAG:A	acceptor_gain	0.9900
20:63737819:A:G	acceptor_gain	0.9900
20:63737819:A:T	acceptor_loss	0.9900
20:63737820:G:GT	acceptor_loss	0.9900
20:63737899:AGCGG:A	donor_loss	0.9900
20:63737901:CGGT:C	donor_loss	0.9900
20:63737903:G:C	donor_loss	0.9900
20:63737903:G:GG	donor_gain	0.9900
20:63737904:T:G	donor_loss	0.9900
20:63737971:A:AG	acceptor_gain	0.9900
20:63737972:G:GG	acceptor_gain	0.9900

AlphaMissense

1860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63738197:A:C	S95R	0.973
20:63738199:C:A	S95R	0.973
20:63738199:C:G	S95R	0.973
20:63738006:A:C	S72R	0.959
20:63738008:C:A	S72R	0.959
20:63738008:C:G	S72R	0.959
20:63738016:A:T	D75V	0.958
20:63738007:G:T	S72I	0.947
20:63738413:T:C	Y167H	0.946
20:63738011:G:C	K73N	0.944
20:63738011:G:T	K73N	0.944
20:63738610:T:G	Y200D	0.943
20:63738627:G:C	K205N	0.942
20:63738627:G:T	K205N	0.942
20:63738782:T:C	I257T	0.942
20:63738768:C:A	N252K	0.938
20:63738768:C:G	N252K	0.938
20:63738778:A:C	S256R	0.936
20:63738780:C:A	S256R	0.936
20:63738780:C:G	S256R	0.936
20:63737595:G:A	G16R	0.932
20:63737595:G:C	G16R	0.932
20:63738017:C:A	D75E	0.932
20:63738017:C:G	D75E	0.932
20:63738414:A:G	Y167C	0.926
20:63738015:G:C	D75H	0.920
20:63738016:A:G	D75G	0.920
20:63738016:A:C	D75A	0.916
20:63738198:G:A	S95N	0.915
20:63738610:T:A	Y200N	0.911

dbSNP variants (sampled 300 via entrez): RS1000543965 (20:63735691 C>A,G,T), RS1001033902 (20:63736350 C>T), RS1001490462 (20:63737092 C>G,T), RS1003950709 (20:63735125 C>T), RS1004278575 (20:63735051 G>A,T), RS1004898140 (20:63737039 C>G,T), RS1004995681 (20:63736752 C>G), RS1005018219 (20:63733712 G>A), RS1005235630 (20:63736013 C>A), RS1006481569 (20:63737391 G>T), RS1006729999 (20:63736052 CGGGGTCCCATCT>C), RS1007554039 (20:63736619 A>G), RS1008325456 (20:63739258 C>A,G,T), RS1008628684 (20:63739059 G>A), RS1009784831 (20:63736323 G>A,T)

Disease associations

OMIM: gene MIM:609809 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001725_68	Inflammatory bowel disease	1.000000e-23
GCST001942_22	Prostate cancer	4.000000e-16
GCST004131_34	Inflammatory bowel disease	3.000000e-26
GCST004132_110	Crohn’s disease	3.000000e-13
GCST004133_15	Ulcerative colitis	9.000000e-17
GCST007563_15	Allergic disease (asthma, hay fever or eczema)	3.000000e-08
GCST007564_6	Asthma or allergic disease (pleiotropy)	3.000000e-10
GCST007876_130	Estimated glomerular filtration rate	2.000000e-09
GCST008916_69	Asthma	3.000000e-09
GCST010002_71	Refractive error	1.000000e-14
GCST010143_12	Meat-related diet	7.000000e-09
GCST011354_34	Bell’s palsy	2.000000e-08
GCST012232_38	Lipoprotein (a) levels	4.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0006925	lipoprotein A measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects methylation, increases abundance	2
Valproic Acid	decreases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Ozone	affects methylation, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
S-Nitrosoglutathione	decreases expression	1
Particulate Matter	affects methylation, increases abundance	1

Clinical trials (associated diseases)

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