TISIDB

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Secreted.
Domain	PF06607 Prokineticin
Function	May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts gastrointestinal (GI) smooth muscle.

> Gene Ontology [ TOP ]
Biological Process	GO:0000187 activation of MAPK activity GO:0001525 angiogenesis GO:0003012 muscle system process GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006936 muscle contraction GO:0006937 regulation of muscle contraction GO:0006939 smooth muscle contraction GO:0006940 regulation of smooth muscle contraction GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007218 neuropeptide signaling pathway GO:0007283 spermatogenesis GO:0007623 circadian rhythm GO:0019233 sensory perception of pain GO:0032147 activation of protein kinase activity GO:0033674 positive regulation of kinase activity GO:0043405 regulation of MAP kinase activity GO:0043406 positive regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0044057 regulation of system process GO:0045765 regulation of angiogenesis GO:0045860 positive regulation of protein kinase activity GO:0045933 positive regulation of muscle contraction GO:0045987 positive regulation of smooth muscle contraction GO:0048232 male gamete generation GO:0048511 rhythmic process GO:0048514 blood vessel morphogenesis GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0071900 regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0090257 regulation of muscle system process GO:1901342 regulation of vasculature development
Molecular Function	GO:0001664 G-protein coupled receptor binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PROK2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between PROK2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24496457	Merkel Cell Carcinoma	Promote immunity (infiltration)	Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients.

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of PROK2 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of PROK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.33	0.287
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.762	0.182
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.029	0.944
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.036	0.278
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.648	0.0876
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.026	0.505
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.227	0.763
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.318	0.768
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.497	0.713
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.592	0.428
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.039	0.968
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.079	0.783

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PROK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PROK2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PROK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PROK2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PROK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PROK2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PROK2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PROK2
Name	prokineticin 2
Aliases	PK2; BV8; MIT1; KAL4; protein Bv8 homolog; HH4; Prokineticin-2
Chromosomal Location	3p21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PROK2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse PROK2