PEAK3

Summary

PEAK3 (PEAK family member 3, HGNC:24793) is a protein-coding gene on chromosome 19p13.3, encoding Protein PEAK3 (Q6ZS72). Probable catalytically inactive kinase.

Predicted to enable protein kinase activity. Involved in regulation of actin cytoskeleton organization and regulation of cell shape. Predicted to be active in actin cytoskeleton and focal adhesion.

Source: NCBI Gene 374872 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_198532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24793
Approved symbol	PEAK3
Name	PEAK family member 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45778
Ensembl gene	ENSG00000188305
Ensembl biotype	protein_coding
OMIM	618526
Entrez	374872

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342063

RefSeq mRNA: 1 — MANE Select: NM_198532 NM_198532

CCDS: CCDS12087

Canonical transcript exons

ENST00000342063 — 4 exons

Exon	Start	End
ENSE00001385263	2278584	2279113
ENSE00001389541	2280850	2280935
ENSE00001389676	2274631	2276489
ENSE00001390555	2282087	2282175

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 86.31.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4169 / max 128.8878, expressed in 359 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178155	0.7544	264
178154	0.6625	184

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	86.31	gold quality
granulocyte	CL:0000094	78.48	gold quality
bone marrow cell	CL:0002092	78.01	gold quality
leukocyte	CL:0000738	75.84	gold quality
monocyte	CL:0000576	75.52	gold quality
sural nerve	UBERON:0015488	74.97	gold quality
bone marrow	UBERON:0002371	71.26	gold quality
spleen	UBERON:0002106	67.78	gold quality
vermiform appendix	UBERON:0001154	61.76	gold quality
stromal cell of endometrium	CL:0002255	58.90	gold quality
right lung	UBERON:0002167	57.55	gold quality
upper lobe of left lung	UBERON:0008952	57.35	gold quality
mucosa of transverse colon	UBERON:0004991	56.67	gold quality
right atrium auricular region	UBERON:0006631	55.76	gold quality
apex of heart	UBERON:0002098	55.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.40	gold quality
right adrenal gland cortex	UBERON:0035827	55.07	gold quality
left uterine tube	UBERON:0001303	54.41	gold quality
right adrenal gland	UBERON:0001233	54.13	gold quality
lung	UBERON:0002048	53.59	gold quality
small intestine	UBERON:0002108	52.76	gold quality
lymph node	UBERON:0000029	52.53	gold quality
small intestine Peyer’s patch	UBERON:0003454	52.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	51.55	gold quality
heart	UBERON:0000948	51.43	gold quality
left adrenal gland	UBERON:0001234	51.27	gold quality
muscle tissue	UBERON:0002385	51.00	gold quality
skeletal muscle tissue	UBERON:0001134	50.83	gold quality
right coronary artery	UBERON:0001625	50.53	gold quality
tonsil	UBERON:0002372	50.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PEAK3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-2681-3P	98.18	65.28	577
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-597-5P	96.82	67.57	732
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-139-3P	95.24	63.10	316

Literature-anchored findings (GeneRIF, showing 1)

• by binding to CrkII, PEAK3 prevents the formation of CrkII-dependent membrane ruffling. (PMID:31311869)

Cross-species orthologs

0 orthologs

Paralogs (3): PINK1 (ENSG00000158828), PEAK1 (ENSG00000173517), PRAG1 (ENSG00000275342)

Protein

Protein identifiers

Protein PEAK3 — Q6ZS72 (reviewed: Q6ZS72)

All UniProt accessions (1): Q6ZS72

UniProt curated annotations — full annotation on UniProt →

Function. Probable catalytically inactive kinase. Interacts with CRK-II and antagonizes CRK-II-signaling. Prevents the formation of CRK-II-dependent membrane ruffling and lamellipodia-like extensions.

Subunit / interactions. Homodimerizes. Interacts with CRK isoform CRK-II; the interaction requires PEAK3 homodimerization.

Similarity. Belongs to the protein kinase superfamily.

RefSeq proteins (1): NP_940934* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051511	MitoQC_Scaffold_Kinases	Family

UniProt features (33 total): helix 12, strand 10, mutagenesis site 5, region of interest 2, compositionally biased region 2, chain 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8DGO	X-RAY DIFFRACTION	2.3
8DGP	X-RAY DIFFRACTION	2.7
8DP5	ELECTRON MICROSCOPY	3.1
8DS6	ELECTRON MICROSCOPY	4.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZS72-F1	77.28	0.48

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 (5):

Position	Phenotype
56–60	abolishes interaction with crk isoform crk-ii. abolishes inhibition of crk-ii-dependent membrane ruffling.
146	abolishes homodimerization and interaction with crk isoform crk-ii.
330	strongly decreases homodimerization and interaction with crk isoform crk-ii.
436	abolishes homodimerization and interaction with crk isoform crk-ii.
453	abolishes homodimerization and interaction with crk isoform crk-ii.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_REGULATION_OF_CELL_SHAPE, GOCC_ANCHORING_JUNCTION, chr19p13, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, NCOA2_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR1303, GOBP_CELL_MORPHOGENESIS

GO Biological Process (3): regulation of cell shape (GO:0008360), regulation of actin cytoskeleton organization (GO:0032956), regulation of cell motility (GO:2000145)

GO Molecular Function (2): protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (2): focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cell morphogenesis	1
regulation of biological quality	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
regulation of locomotion	1
cell motility	1
regulation of cellular process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
cell-substrate junction	1
cytoskeleton	1

Protein interactions and networks

STRING

362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEAK3	CCDC200	A0A1B0GVQ3	571
PEAK3	PAN3	Q58A45	491
PEAK3	FAM20A	Q96MK3	474
PEAK3	SELENOO	Q9BVL4	456
PEAK3	STKLD1	Q8NE28	453
PEAK3	PSKH2	Q96QS6	451
PEAK3	CCDC57	Q2TAC2	447
PEAK3	TRRAP	Q9Y4A5	405
PEAK3	LHFPL7	Q6ICI0	370
PEAK3	IQCN	Q9H0B3	370
PEAK3	PRAG1	Q86YV5	365
PEAK3	CNRIP1	Q96F85	352
PEAK3	XKR6	Q5GH73	348
PEAK3	PEAK1	Q9H792	339
PEAK3	ASAP1	Q9ULH1	335

IntAct

0 interactions, top by confidence:

BioGRID (18): PEAK1 (Affinity Capture-Western), SGK223 (Affinity Capture-Western), EGFR (Affinity Capture-Western), ASAP1 (Affinity Capture-Western), PTK2B (Affinity Capture-Western), CBL (Affinity Capture-Western), SHC1 (Affinity Capture-Western), CRK (Affinity Capture-Western), GRB2 (Affinity Capture-Western), ASAP1 (Affinity Capture-MS), ASAP2 (Affinity Capture-MS), CRK (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), CRKL (Affinity Capture-MS), PTK2B (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

582 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2278582:ACCT:A	donor_loss	1.0000
19:2278583:C:CT	donor_loss	1.0000
19:2280936:C:CC	acceptor_gain	1.0000
19:2276486:GCACC:G	acceptor_loss	0.9900
19:2276489:CCTGC:C	acceptor_loss	0.9900
19:2276490:CTG:C	acceptor_loss	0.9900
19:2276491:T:G	acceptor_loss	0.9900
19:2278582:A:AC	donor_gain	0.9900
19:2278583:C:CC	donor_gain	0.9900
19:2279109:CTGAC:C	acceptor_gain	0.9900
19:2279110:TGAC:T	acceptor_gain	0.9900
19:2279111:GACCT:G	acceptor_loss	0.9900
19:2279114:C:CC	acceptor_gain	0.9900
19:2280844:GCTTA:G	donor_loss	0.9900
19:2280845:CTTAC:C	donor_loss	0.9900
19:2280846:TTAC:T	donor_loss	0.9900
19:2280847:TACCA:T	donor_loss	0.9900
19:2280848:A:AC	donor_gain	0.9900
19:2280849:C:CC	donor_gain	0.9900
19:2280849:C:CG	donor_loss	0.9900
19:2280849:CCAAG:C	donor_gain	0.9900
19:2280931:TGTTG:T	acceptor_gain	0.9900
19:2280933:T:TC	acceptor_gain	0.9900
19:2280933:TTGC:T	acceptor_loss	0.9900
19:2280934:TG:T	acceptor_gain	0.9900
19:2280935:GC:G	acceptor_loss	0.9900
19:2280937:T:G	acceptor_loss	0.9900
19:2278582:AC:A	donor_gain	0.9800
19:2278583:CC:C	donor_gain	0.9800
19:2278586:TGGCG:T	donor_gain	0.9800

AlphaMissense

2934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2278584:C:A	K204N	0.956
19:2278584:C:G	K204N	0.956
19:2276415:A:C	N229K	0.955
19:2276415:A:T	N229K	0.955
19:2276109:A:C	F331L	0.950
19:2276109:A:T	F331L	0.950
19:2276111:A:G	F331L	0.950
19:2276418:G:C	F228L	0.943
19:2276418:G:T	F228L	0.943
19:2276420:A:G	F228L	0.943
19:2276235:G:C	S289R	0.942
19:2276235:G:T	S289R	0.942
19:2276237:T:G	S289R	0.942
19:2278634:A:C	Y188D	0.937
19:2278588:G:T	A203D	0.930
19:2278650:G:C	S182R	0.920
19:2278650:G:T	S182R	0.920
19:2278652:T:G	S182R	0.920
19:2275902:C:A	W400C	0.912
19:2275902:C:G	W400C	0.912
19:2278637:A:C	Y187D	0.906
19:2276173:A:G	L310S	0.903
19:2275904:A:G	W400R	0.901
19:2275904:A:T	W400R	0.901
19:2276188:A:G	L305S	0.899
19:2278683:G:C	F171L	0.894
19:2278683:G:T	F171L	0.894
19:2278685:A:G	F171L	0.894
19:2276363:A:G	W247R	0.891
19:2276363:A:T	W247R	0.891

dbSNP variants (sampled 300 via entrez): RS1000050406 (19:2275130 G>C), RS1000119915 (19:2282493 C>T), RS1000340300 (19:2278767 C>G,T), RS1000845893 (19:2283823 A>G), RS1000921005 (19:2274347 T>C), RS1000951796 (19:2278941 C>A,T), RS1001125245 (19:2283558 A>G), RS1001434807 (19:2277683 T>C), RS1001456873 (19:2282775 G>A), RS1001615463 (19:2282653 G>A), RS1001795450 (19:2281150 T>G), RS1002215019 (19:2281578 C>G), RS1002453136 (19:2281988 G>A,T), RS1003224211 (19:2280245 CAG>C), RS1003305551 (19:2274743 C>A,T)

Disease associations

OMIM: gene MIM:618526 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001263_14	Height	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Arsenic	decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0QT	U2OS GFP-PEAK3	Cancer cell line	Female
CVCL_C0QU	U2OS ST-PEAK3	Cancer cell line	Female
CVCL_C0QV	HeLa GFP-PEAK3	Cancer cell line	Female
CVCL_C0QW	HeLa ST-PEAK3	Cancer cell line	Female
CVCL_C0QX	THP1 GFP-PEAK3	Cancer cell line	Male
CVCL_C0QY	THP1 ST-PEAK3	Cancer cell line	Male

Clinical trials (associated diseases)

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