NRP2 neuropilin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NRP2provided by HGNC
Official Full Name: neuropilin 2provided by HGNC
Primary source: HGNC:HGNC:8005
See related: Ensembl:ENSG00000118257 MIM:602070
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NP2; NPN2; PRO2714; VEGF165R2
Summary: This gene encodes a member of the neuropilin family of receptor proteins. The encoded transmembrane protein binds to SEMA3C protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C} and SEMA3F protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F}, and interacts with vascular endothelial growth factor (VEGF). This protein may play a role in cardiovascular development, axon guidance, and tumorigenesis. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in placenta (RPKM 10.6), ovary (RPKM 9.8) and 20 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q33.3

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
109.20190607	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (205682500..205798131)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (206547184..206662857)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

neuropilin-2 (Nrp2) is the receptor for HCMV-pentamer infection in epithelial/endothelial cells
Title: An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor.
The article highlights the diverse NRP1 and NRP2 ligands and interacting partners on endothelial cells, which are relevant in the context of the tumor vasculature and the tumor microenvironment. (Review)
Title: Neuropilins in the Context of Tumor Vasculature.
NRP2 protein was highly expressed in HPV (-) group compared to that in HPV (+) group. E7-HOTAIR-miR-331-3p-NRP2-E7 formed a regulatory loop, and could be involved in the pathogenesis of cervical cancer.
Title: ARFHPV E7 oncogene, lncRNA HOTAIR, miR-331-3p and its target, NRP2, form a negative feedback loop to regulate the apoptosis in the tumorigenesis in HPV positive cervical cancer.
Neuropilin-2 (NRP-2) induces lymphatic endothelial cells (LECs)proliferation, reconstruction and lymphangiogenesis and subsequently promotes tumor cell migration, invasion and lymphatic metastasis via VEGF-C/D-NRP-2 axis [Review]
Title: NRP-2 in tumor lymphangiogenesis and lymphatic metastasis.
Overexpression of NRP2 is associated with spitzoid melanocytic lesions.
Title: Quantitative assessment of neuropilin-2 as a simple and sensitive diagnostic assay for spitzoid melanocytic lesions.
The results of this study showed that there is a significant association betweenNPR2 rs849563 polymorphism and autism in the studied population
Title: Neuropilin-2 rs849563 gene variations and susceptibility to autism in Iranian population: A case-control study.
The authors also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus in hepatitis C virus-infected patients, respectively.
Title: Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.
Authors found that NRP2 gene silencing in metastatic melanoma cell lines inhibited tumor cell growth in vitro; furthermore, knockdown of NRP2 expression in the metastatic melanoma cell line 1205Lu significantly inhibited in-vivo tumor growth and metastasis.
Title: Neuropilin-2 promotes melanoma growth and progression in vivo.
Study identifies NRP2 and ESL-1 as targets for polysialylation in murine microglia and human THP-1 macrophages and reveals a striking convergence in the regulation of the two polysialylated acceptors in the course of inflammatory activation. A pool of polysialylated NRP2 and ESL-1 is assembled after injury or in culture and its shedding is an early response to lipopolysaccharide-induced activation of microglia.
Title: Polysialylation and lipopolysaccharide-induced shedding of E-selectin ligand-1 and neuropilin-2 by microglia and THP-1 macrophages.
Neuropilin 2 isoform NRP2b contributed to the oncogenic response to transforming growth factor-beta (TGFbeta) and correlated with tumor progression in non-small cell lung cancer (NSCLC) patients.
Title: The neuropilin 2 isoform NRP2b uniquely supports TGFβ-mediated progression in lung cancer.

Submit: New GeneRIF Correction See all GeneRIFs (78)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of neuropilin 2 (NRP2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of neuropilin 2 (NRP2) in human B cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Axon guidance, organism-specific biosystem (from REACTOME)
Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
L1CAM interactions, organism-specific biosystem (from REACTOME)
L1CAM interactions, organism-specific biosystemThe L1 family of cell adhesion molecules (L1CAMs) are a subfamily of the immunoglobulin superfamily of transmembrane receptors, comprised of four structurally related proteins: L1, Close Homolog of L...
Neurophilin interactions with VEGF and VEGFR, organism-specific biosystem (from REACTOME)
Neurophilin interactions with VEGF and VEGFR, organism-specific biosystemThe plasma membrane-associated Neuropilin receptors NRP-1 and -2 bind some of the VEGF proteins and associate with VEGF receptor proteins. NRP-1 binds VEGF-A165, -B, and PLGF-2; NRP-2 also binds VEGF...
NrCAM interactions, organism-specific biosystem (from REACTOME)
NrCAM interactions, organism-specific biosystemThe NgCAM-related cell adhesion molecule (NrCAM) is member of the L1 family involved in the eye development and node of Ranvier. Like all the other members of L1 family NrCAM also has the ability to...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by VEGF, organism-specific biosystem (from REACTOME)
Signaling by VEGF, organism-specific biosystemIn normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angioge...
Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem
Signaling events mediated by VEGFR1 and VEGFR2
VEGFR1 specific signals, organism-specific biosystem (from Pathway Interaction Database)
VEGFR1 specific signals, organism-specific biosystem
VEGFR1 specific signals

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-80012 (e-PCR)
- UniSTS:102144

SGC31090 (e-PCR)
- UniSTS:44054

STS-AA009628 (e-PCR)
- UniSTS:2328

NRP2_1404 (e-PCR)
- UniSTS:277541

NRP2_v462 (e-PCR)
- UniSTS:277541

D8S2279 (e-PCR)
- UniSTS:473907

D2S2128 (e-PCR)
- UniSTS:154175

RH99006 (e-PCR)
- UniSTS:92750

D2S1846 (e-PCR)
- UniSTS:28759

SHGC-146056 (e-PCR)
- UniSTS:174968

RH36188 (e-PCR)
- UniSTS:57471

RH68921 (e-PCR)
- UniSTS:52363

D16S325 (e-PCR)
- UniSTS:147089

SHGC-105157 (e-PCR)
- UniSTS:169169

Homology

Homologs of the NRP2 gene: The NRP2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 262 organisms have orthologs with human gene NRP2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine binding	NAS Non-traceable Author Statement more info	PubMed
growth factor binding	TAS Traceable Author Statement more info	PubMed
heparin binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
semaphorin receptor activity	NAS Non-traceable Author Statement more info	PubMed
signaling receptor activity	TAS Traceable Author Statement more info	PubMed
vascular endothelial growth factor-activated receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
angiogenesis	NAS Non-traceable Author Statement more info	PubMed
axon extension involved in axon guidance	ISS Inferred from Sequence or Structural Similarity more info
axon guidance	NAS Non-traceable Author Statement more info	PubMed
cell adhesion	NAS Non-traceable Author Statement more info	PubMed
cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
dorsal root ganglion morphogenesis	IEA Inferred from Electronic Annotation more info
facial nerve structural organization	IEA Inferred from Electronic Annotation more info
facioacoustic ganglion development	IEA Inferred from Electronic Annotation more info
gonadotrophin-releasing hormone neuronal migration to the hypothalamus	IEA Inferred from Electronic Annotation more info
negative chemotaxis	IEA Inferred from Electronic Annotation more info
nerve development	ISS Inferred from Sequence or Structural Similarity more info
neural crest cell migration involved in autonomic nervous system development	IEA Inferred from Electronic Annotation more info
outflow tract septum morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of endothelial cell migration	TAS Traceable Author Statement more info	PubMed
positive regulation of endothelial cell proliferation	TAS Traceable Author Statement more info	PubMed
regulation of postsynapse organization	IEA Inferred from Electronic Annotation more info
semaphorin-plexin signaling pathway involved in neuron projection guidance	ISS Inferred from Sequence or Structural Similarity more info
sensory neuron axon guidance	IEA Inferred from Electronic Annotation more info
sympathetic ganglion development	ISS Inferred from Sequence or Structural Similarity more info
sympathetic neuron projection extension	ISS Inferred from Sequence or Structural Similarity more info
sympathetic neuron projection guidance	ISS Inferred from Sequence or Structural Similarity more info
trigeminal ganglion development	IEA Inferred from Electronic Annotation more info
vascular endothelial growth factor receptor signaling pathway	TAS Traceable Author Statement more info
vascular endothelial growth factor signaling pathway	IEA Inferred from Electronic Annotation more info
ventral trunk neural crest cell migration	IEA Inferred from Electronic Annotation more info
vestibulocochlear nerve structural organization	IEA Inferred from Electronic Annotation more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
axon	IEA Inferred from Electronic Annotation more info
extracellular region	IEA Inferred from Electronic Annotation more info
glutamatergic synapse	IEA Inferred from Electronic Annotation more info
integral component of membrane	NAS Non-traceable Author Statement more info	PubMed
integral component of postsynaptic membrane	IEA Inferred from Electronic Annotation more info
membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
semaphorin receptor complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: neuropilin-2

Names: neuropilin-2a(17); neuropilin-2a(22); neuropilin-2b(0); receptor for VEGF165 and semaphorins class3; vascular endothelial cell growth factor 165 receptor 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029567.1 RefSeqGene

Range

5001..120634

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003872.3 → NP_003863.2 neuropilin-2 isoform 2 precursor

See identical proteins and their annotated locations for NP_003863.2

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as NRP2a(17), lacks an alternate in-frame segment, compared to variant 1. This results in a shorter isoform (2), compared to isoform 1.

Source sequence(s)

AC007362, AC007561, KF459587

Consensus CDS

CCDS46496.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

Q7LBX6, Q7Z3T9

Related

ENSP00000350432.5, ENST00000357785.9

Conserved Domains (4) summary

smart00137
Location:641 → 794

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

pfam11980
Location:845 → 926

DUF3481; C-terminal domain of neuropilin glycoprotein
NM_018534.4 → NP_061004.3 neuropilin-2 isoform 4 precursor

See identical proteins and their annotated locations for NP_061004.3

Status: REVIEWED

Description

Transcript Variant: This variant (4), also known as NRP2b(5), lacks the last two 3' exons and includes an alternate 3' exon, compared to variant 1. This results in a shorter isoform (4) with a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC007362, KF459587

Consensus CDS

CCDS2365.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

Q7Z3T9

Related

ENSP00000272849.3, ENST00000272849.7

Conserved Domains (6) summary

cd06263
Location:646 → 793

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam11980
Location:822 → 901

DUF3481; Domain of unknown function (DUF3481)

smart00137
Location:641 → 794

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

smart00231
Location:277 → 427

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
NM_201264.1 → NP_957716.1 neuropilin-2 isoform 6 precursor

See identical proteins and their annotated locations for NP_957716.1

Status: REVIEWED

Description

Transcript Variant: This variant (6), also known as S9NRP2b, lacks several 3' exons and uses an alternate segment in the 3' coding region and 3' UTR, compared to variant 1. This results in a shorter, potentially soluble isoform (6) with a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AF280546, AL833606, BX537423

Consensus CDS

CCDS46499.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

Q7Z3T9

Related

ENSP00000387519.1, ENST00000417189.5

Conserved Domains (3) summary

smart00231
Location:277 → 427

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
NM_201266.2 → NP_957718.1 neuropilin-2 isoform 1 precursor

See identical proteins and their annotated locations for NP_957718.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as NRP2a(22), represents the longest transcript, and encodes the longest isoform (1).

Source sequence(s)

AC007362, AC007561, KF459587

Consensus CDS

CCDS2364.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

Q7Z3T9, X5D2Q8

Related

ENSP00000353582.3, ENST00000360409.7

Conserved Domains (4) summary

smart00137
Location:641 → 794

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

pfam11980
Location:850 → 931

DUF3481; C-terminal domain of neuropilin glycoprotein
NM_201267.2 → NP_957719.1 neuropilin-2 isoform 5 precursor

See identical proteins and their annotated locations for NP_957719.1

Status: REVIEWED

Description

Transcript Variant: This variant (5), also known as NRP2b(0), includes an alternate 3' sequence, compared to variant 1. This results in a shorter isoform (5) with a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC007362, KF459587

Consensus CDS

CCDS46498.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

A0A024R412, Q7Z3T9

Related

ENSP00000349632.4, ENST00000357118.8

Conserved Domains (6) summary

cd06263
Location:646 → 793

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam11980
Location:817 → 896

DUF3481; Domain of unknown function (DUF3481)

smart00137
Location:641 → 794

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

smart00231
Location:277 → 427

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
NM_201279.2 → NP_958436.1 neuropilin-2 isoform 3 precursor

See identical proteins and their annotated locations for NP_958436.1

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as NRP2a(0), lacks an in-frame segment and a following in-frame exon in the coding region, compared to variant 1. This results in a shorter isoform (3), compared to isoform 1.

Source sequence(s)

AC007362, AC007561, KF459587

Consensus CDS

CCDS46497.1

UniProtKB/Swiss-Prot

O60462

UniProtKB/TrEMBL

A0A024R3W6, Q7Z3T9

Related

ENSP00000407626.2, ENST00000412873.2

Conserved Domains (6) summary

cd06263
Location:646 → 793

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

pfam11980
Location:832 → 906

DUF3481; Domain of unknown function (DUF3481)

smart00137
Location:641 → 794

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

smart00231
Location:277 → 427

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain

cd00041
Location:28 → 141

CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

cd00057
Location:280 → 426

FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.