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

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: 570.45   (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: 570.45   (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 Ligand: 1

Tclin

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

Active Drug: 0

Active Ligands (1)

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1 – 1 of 1

EG01377

NRP1Tchem

Kd: 5.88000011

Protein Data Bank (17)

1 – 5 of 17

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (20)

Reactome (14)

KEGG (2)

PathwayCommons (4)

Axon guidance (R-HSA-422475)

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1 – 5 of 14

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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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)

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1 – 10 of 192

• See Interactions on String-DB

KCTD9

Tbio

Novelty: 0.30071599

p_int: 0.999999986

p_ni: 1.4e-8

Score: 0.175

Data Source: BioPlex,STRINGDB

BCS1L

Tbio

Family: Enzyme

Novelty: 0.00258512

p_int: 0.999999721

p_ni: 2.79e-7

Data Source: BioPlex

ODF2

Tbio

Novelty: 0.03275361

p_int: 0.999901227

p_ni: 0.000012282

p_wrong: 0.000086491

Score: 0.19

Data Source: BioPlex,STRINGDB

FAM241A

Tdark

Novelty: 2.7184466

p_int: 0.999164276

p_ni: 0.000835688

p_wrong: 3.6e-8

Data Source: BioPlex

TNFAIP1

Tbio

Novelty: 0.04871082

p_int: 0.998269354

p_ni: 0.001720834

p_wrong: 0.000009811

Score: 0.313

Data Source: BioPlex,STRINGDB

TMX1

Tbio

Novelty: 0.01558923

p_int: 0.997279754

p_ni: 0.002720246

Data Source: BioPlex

UBR2

Tbio

Family: Enzyme

Novelty: 0.03319944

p_int: 0.99315068

p_ni: 0.00684932

Data Source: BioPlex

CSNK2A1

Tchem

Family: Kinase

Novelty: 0.00124949

p_int: 0.9900044

p_ni: 0.0099956

Score: 0.231

Data Source: BioPlex,STRINGDB

UBR1

Tbio

Family: Enzyme

Novelty: 0.00742688

p_int: 0.988982702

p_ni: 0.011017298

Data Source: BioPlex

PIP5K1A

Tbio

Family: Kinase

Novelty: 0.08213456

p_int: 0.988472897

p_ni: 0.011527102

p_wrong: 1e-9

Data Source: BioPlex

Publication Statistics

PubMed Score  570.45

PubMed score by year

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PubTator Score  652.88

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Alternative splicing
Angiogenesis
Calcium
Cell membrane
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Developmental protein
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Disulfide bond

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mathematical ability
migraine disorder
waist-hip ratio

MGI Phenotype Find Similar Targets

cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
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hematopoietic system phenotype
immune system phenotype
mortality/aging
muscle phenotype
neoplasm