Tchem NRP1 Neuropilin-1

Protein Summary

Description

The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system. It mediates the chemorepulsant activity of semaphorins. It binds to semaphorin 3A, The PLGF-2 isoform of PGF, The VEGF165 isoform of VEGFA and VEGFB. Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulate VEGF-induced angiogenesis. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). The soluble isoform 2 binds VEGF-165 and appears to inhibit its binding to cells. It may also induce apoptosis by sequestering VEGF-165. May bind as well various members of the semaphorin family. Its expression has an averse effect on blood vessel number and integrity. This gene encodes one of two neuropilins, which contain specific protein domains which allow them to participate in several different types of signaling pathways that control cell migration. Neuropilins contain a large N-terminal extracellular domain, made up of complement-binding, coagulation factor V/VIII, and meprin domains. These proteins also contains a short membrane-spanning domain and a small cytoplasmic domain. Neuropilins bind many ligands and various types of co-receptors; they affect cell survival, migration, and attraction. Some of the ligands and co-receptors bound by neuropilins are vascular endothelial growth factor (VEGF) and semaphorin family members. Several alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

Uniprot Accession IDs

• O14786
• B0LPG9
• O60461
• Q5T7F1
• Q5T7F2
• Q5T7F3
• Q86T59
• Q96I90
• Q96IH5

Gene Name

• NRP1

Ensembl ID

• ENST00000265371
• ENSP00000265371
• ENSG00000099250
• ENST00000374821
• ENSP00000363954
• ENST00000374822
• ENSP00000363955
• ENST00000374867
• ENSP00000364001

Symbol

• NRP
• VEGF165R
• NP1
• NRP
• BDCA4
• CD304
• VEGF165R

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
protein complex	1
transcription factor perturbation	1
gene perturbation	0.99
protein domain	0.97

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GENEVA

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 777.57   (req: < 5)

Gene RIFs: 219   (req: <= 3)

Antibodies: 810   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 777.57   (req: >= 5)

Gene RIFs: 219   (req: > 3)

Antibodies: 810   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 94

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 6

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (6)

Explore Active Ligands

1 – 6 of 6

EG01377

NRP1Tchem

Kd : 5.88000011

CHEMBL4207210

NRP1Tchem

Kd : 7.12

CHEMBL4205347

NRP1Tchem

Kd : 6.39

CHEMBL4208692

NRP1Tchem

Kd : 6.17

CHEMBL4279036

NRP1Tchem

IC50 : 6.1

CHEMBL4204363

NRP1Tchem

Kd : 6.08

GWAS Traits (8)

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5

1 – 5 of 8

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
high density lipoprotein cholesterol measurement	EFO_0004612	1	2	2		64.8
waist-hip ratio	EFO_0004343	3	4	4		60.2
biological sex	PATO_0000047	1	1	1		48.5
BMI-adjusted waist-hip ratio	EFO_0007788	1	2	2		37.3
migraine disorder	EFO_0003821	1	1	0	1.1	33.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
high density lipoprotein cholesterol measurement	EFO_0004612	2		64.8
waist-hip ratio	EFO_0004343	4		60.2
biological sex	PATO_0000047	1		48.5
BMI-adjusted waist-hip ratio	EFO_0007788	2		37.3
migraine disorder	EFO_0003821	0	1.1	33.1

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Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	neuropilin 1	VGNC:4969	450397
Macaque	neuropilin 1		697755
Mouse	neuropilin 1	MGI:106206	18186
Rat	neuropilin 1	RGD:621588	246331
Dog	neuropilin 1	VGNC:43974	477955

Species	Name	OMA	EggNOG	Inparanoid
Chimp	neuropilin 1
Macaque	neuropilin 1
Mouse	neuropilin 1
Rat	neuropilin 1
Dog	neuropilin 1

Protein Structure (17 Structures, 1 AlphaFold Model)

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Representation

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Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

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More information can be found at RCSB PDB

AF-O14786-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 17

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (20)

Reactome (14)

KEGG (2)

PathwayCommons (4)

Axon guidance (R-HSA-422475)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	CHL1 interactions	9 targets	R-HSA-447041
Reactome	CRMPs in Sema3A signaling	16 targets	R-HSA-399956
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	L1CAM interactions	100 targets	R-HSA-373760

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
CHL1 interactions	9 targets	R-HSA-447041
CRMPs in Sema3A signaling	16 targets	R-HSA-399956
Developmental Biology	1055 targets	R-HSA-1266738
L1CAM interactions	100 targets	R-HSA-373760

Gene Ontology Terms (111)

Functions (10)

Components (17)

Processes (84)

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Items per page:

10

1 – 10 of 10

GO Term	Evidence	Assigned by
growth factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
vascular endothelial growth factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL
GTPase activator activity	Inferred from Mutant Phenotype (IMP)	BHF-UCL
vascular endothelial growth factor-activated receptor activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
coreceptor activity	Traceable Author Statement (TAS)	BHF-UCL
cytokine binding	Non-traceable Author Statement (NAS)	BHF-UCL
semaphorin receptor activity	Non-traceable Author Statement (NAS)	BHF-UCL
heparin binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein kinase binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (192)

Explore Interacting Targets

1 – 10 of 192

• See Interactions on String-DB

KCTD9

Tbio

Novelty:  0.22841768

p_int:  0.999999986

p_ni:  1.4e-8

Score:  0.175

Data Source:  BioPlex,STRINGDB

BCS1L

Tbio

Family:  Enzyme

Novelty:  0.01764582

p_int:  0.999999721

p_ni:  2.79e-7

Data Source:  BioPlex

ODF2

Tbio

Novelty:  0.03203587

p_int:  0.999901227

p_ni:  0.000012282

p_wrong:  0.000086491

Score:  0.19

Data Source:  BioPlex,STRINGDB

FAM241A

Tdark

Novelty:  1.04041354

p_int:  0.999164276

p_ni:  0.000835688

p_wrong:  3.6e-8

Data Source:  BioPlex

TNFAIP1

Tbio

Novelty:  0.04006419

p_int:  0.998269354

p_ni:  0.001720834

p_wrong:  0.000009811

Score:  0.313

Data Source:  BioPlex,STRINGDB

TMX1

Tbio

Novelty:  0.03444237

p_int:  0.997279754

p_ni:  0.002720246

Data Source:  BioPlex

UBR2

Tbio

Family:  Enzyme

Novelty:  0.03126228

p_int:  0.99315068

p_ni:  0.00684932

Data Source:  BioPlex

CSNK2A1

Tchem

Family:  Kinase

Novelty:  0.00187855

p_int:  0.9900044

p_ni:  0.0099956

Score:  0.231

Data Source:  BioPlex,STRINGDB

UBR1

Tbio

Family:  Enzyme

Novelty:  0.00998888

p_int:  0.988982702

p_ni:  0.011017298

Data Source:  BioPlex

PIP5K1A

Tbio

Family:  Kinase

Novelty:  0.05039085

p_int:  0.988472897

p_ni:  0.011527102

p_wrong:  1e-9

Data Source:  BioPlex

Publication Statistics

PubMed Score  777.57

PubMed score by year

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PubTator Score  652.88

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

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3D-structure
Alternative splicing
Angiogenesis
Calcium
Cell membrane
Complete proteome
Developmental protein
Differentiation
Direct protein sequencing
Disulfide bond

GWAS Trait Find Similar Targets

No Header	No Header
apolipoprotein A 1 measurement
biological sex
BMI-adjusted waist-hip ratio
high density lipoprotein cholesterol measurement
mathematical ability
migraine disorder
reticulocyte count
waist-hip ratio

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
muscle phenotype
neoplasm