Human Gene NRP1 (uc001ixc.1)
  Description: Homo sapiens neuropilin 1 (NRP1), transcript variant 3, mRNA.
RefSeq Summary (NM_001024629): 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].
Transcript (Including UTRs)
   Position: hg19 chr10:33,500,338-33,624,006 Size: 123,669 Total Exon Count: 10 Strand: -
Coding Region
   Position: hg19 chr10:33,502,134-33,623,310 Size: 121,177 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:33,500,338-33,624,006)mRNA (may differ from genome)Protein (597 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMalacardsMGI
neXtProtOMIMPubMedReactomeTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NRP1_HUMAN
DESCRIPTION: RecName: Full=Neuropilin-1; AltName: Full=Vascular endothelial cell growth factor 165 receptor; AltName: CD_antigen=CD304; Flags: Precursor;
FUNCTION: 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 VEGF-165 isoform of VEGF and VEGF-B. Coexpression with KDR results in increased VEGF-165 binding to KDR as well as increased chemotaxis. It may regulate VEGF-induced angiogenesis.
FUNCTION: 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.
SUBUNIT: Homodimer, and heterodimer with NRP2. Interacts with FER (By similarity). Binds PLXNB1.
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.
SUBCELLULAR LOCATION: Isoform 2: Secreted.
TISSUE SPECIFICITY: The expression of isoforms 1 and 2 does not seem to overlap. Isoform 1 is expressed by the blood vessels of different tissues. In the developing embryo it is found predominantly in the nervous system. In adult tissues, it is highly expressed in heart and placenta; moderately in lung, liver, skeletal muscle, kidney and pancreas; and low in adult brain. Isoform 2 is found in liver hepatocytes, kidney distal and proximal tubules.
DOMAIN: The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding.
SIMILARITY: Belongs to the neuropilin family.
SIMILARITY: Contains 2 CUB domains.
SIMILARITY: Contains 2 F5/8 type C domains.
SIMILARITY: Contains 1 MAM domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): NRP1
CDC HuGE Published Literature: NRP1
Positive Disease Associations: Body Weight , Echocardiography , Hypertrophy, Left Ventricular , Schizophrenia , Triglycerides
Related Studies:
  1. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  2. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Body Weight
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: NRP1
Diseases sorted by gene-association score: acute hemorrhagic leukoencephalitis (11), angiomatous meningioma (8), charcot-marie-tooth disease, type 2d (6), brachial plexus lesion (5), pancreatic cancer (2), breast cancer (2), eye disease (2), tetralogy of fallot (1), exudative vitreoretinopathy 1 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 32.17 RPKM in Cells - Cultured fibroblasts
Total median expression: 387.25 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -203.75547-0.372 Picture PostScript Text
3' UTR -526.771796-0.293 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000421 - Coagulation_fac_5/8-C_type_dom
IPR008985 - ConA-like_lec_gl_sf
IPR000859 - CUB
IPR008979 - Galactose-bd-like
IPR000998 - MAM_dom
IPR014648 - Neuropilin
IPR022579 - Neuropilin1_C

Pfam Domains:
PF00431 - CUB domain
PF00754 - F5/8 type C domain

SCOP Domains:
49785 - Galactose-binding domain-like
49854 - Spermadhesin, CUB domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1KEX - X-ray MuPIT 2QQI - X-ray MuPIT 2QQM - X-ray MuPIT 2QQN - X-ray MuPIT 3I97 - X-ray MuPIT 4DEQ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O14786
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005021 vascular endothelial growth factor-activated receptor activity
GO:0005096 GTPase activator activity
GO:0005515 protein binding
GO:0008201 heparin binding
GO:0015026 coreceptor activity
GO:0017154 semaphorin receptor activity
GO:0019838 growth factor binding
GO:0019901 protein kinase binding
GO:0019955 cytokine binding
GO:0038085 vascular endothelial growth factor binding
GO:0046872 metal ion binding

Biological Process:
GO:0001525 angiogenesis
GO:0001569 branching involved in blood vessel morphogenesis
GO:0001764 neuron migration
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002040 sprouting angiogenesis
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0003148 outflow tract septum morphogenesis
GO:0006930 substrate-dependent cell migration, cell extension
GO:0007165 signal transduction
GO:0007229 integrin-mediated signaling pathway
GO:0007267 cell-cell signaling
GO:0007275 multicellular organism development
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0007413 axonal fasciculation
GO:0007507 heart development
GO:0008045 motor neuron axon guidance
GO:0009611 response to wounding
GO:0009887 animal organ morphogenesis
GO:0010595 positive regulation of endothelial cell migration
GO:0014911 positive regulation of smooth muscle cell migration
GO:0016358 dendrite development
GO:0016477 cell migration
GO:0021612 facial nerve structural organization
GO:0021636 trigeminal nerve morphogenesis
GO:0021637 trigeminal nerve structural organization
GO:0021649 vestibulocochlear nerve structural organization
GO:0021675 nerve development
GO:0021785 branchiomotor neuron axon guidance
GO:0021828 gonadotrophin-releasing hormone neuronal migration to the hypothalamus
GO:0030154 cell differentiation
GO:0030517 negative regulation of axon extension
GO:0031290 retinal ganglion cell axon guidance
GO:0031532 actin cytoskeleton reorganization
GO:0032489 regulation of Cdc42 protein signal transduction
GO:0034446 substrate adhesion-dependent cell spreading
GO:0035729 cellular response to hepatocyte growth factor stimulus
GO:0035767 endothelial cell chemotaxis
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0036486 ventral trunk neural crest cell migration
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0038189 neuropilin signaling pathway
GO:0038190 VEGF-activated neuropilin signaling pathway
GO:0042327 positive regulation of phosphorylation
GO:0043524 negative regulation of neuron apoptotic process
GO:0043542 endothelial cell migration
GO:0043547 positive regulation of GTPase activity
GO:0045766 positive regulation of angiogenesis
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048012 hepatocyte growth factor receptor signaling pathway
GO:0048485 sympathetic nervous system development
GO:0048666 neuron development
GO:0048841 regulation of axon extension involved in axon guidance
GO:0048842 positive regulation of axon extension involved in axon guidance
GO:0048843 negative regulation of axon extension involved in axon guidance
GO:0048844 artery morphogenesis
GO:0048846 axon extension involved in axon guidance
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050918 positive chemotaxis
GO:0051491 positive regulation of filopodium assembly
GO:0051496 positive regulation of stress fiber assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0060301 positive regulation of cytokine activity
GO:0060385 axonogenesis involved in innervation
GO:0060627 regulation of vesicle-mediated transport
GO:0060666 dichotomous subdivision of terminal units involved in salivary gland branching
GO:0060978 angiogenesis involved in coronary vascular morphogenesis
GO:0060982 coronary artery morphogenesis
GO:0061299 retina vasculature morphogenesis in camera-type eye
GO:0061441 renal artery morphogenesis
GO:0061549 sympathetic ganglion development
GO:0061551 trigeminal ganglion development
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071526 semaphorin-plexin signaling pathway
GO:0071679 commissural neuron axon guidance
GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis
GO:0090259 regulation of retinal ganglion cell axon guidance
GO:0097102 endothelial tip cell fate specification
GO:0097374 sensory neuron axon guidance
GO:0097475 motor neuron migration
GO:0097490 sympathetic neuron projection extension
GO:0097491 sympathetic neuron projection guidance
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
GO:1901166 neural crest cell migration involved in autonomic nervous system development
GO:1901998 toxin transport
GO:1902285 semaphorin-plexin signaling pathway involved in neuron projection guidance
GO:1902287 semaphorin-plexin signaling pathway involved in axon guidance
GO:1902336 positive regulation of retinal ganglion cell axon guidance
GO:1902378 VEGF-activated neuropilin signaling pathway involved in axon guidance
GO:1902946 protein localization to early endosome
GO:1903375 facioacoustic ganglion development
GO:1904835 dorsal root ganglion morphogenesis
GO:1905040 otic placode development
GO:2000251 positive regulation of actin cytoskeleton reorganization
GO:2001237 negative regulation of extrinsic apoptotic signaling pathway

Cellular Component:
GO:0002116 semaphorin receptor complex
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005769 early endosome
GO:0005829 cytosol
GO:0005883 neurofilament
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0030426 growth cone
GO:0031410 cytoplasmic vesicle
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0043235 receptor complex
GO:0097443 sorting endosome


-  Descriptions from all associated GenBank mRNAs
  BX648250 - Homo sapiens mRNA; cDNA DKFZp686E15115 (from clone DKFZp686E15115).
JA482200 - Sequence 183 from Patent WO2011072091.
JE980492 - Sequence 183 from Patent EP2862929.
BX510902 - Homo sapiens mRNA; cDNA DKFZp451L152 (from clone DKFZp451L152); complete cds.
AL833608 - Homo sapiens mRNA; cDNA DKFZp686M1967 (from clone DKFZp686M1967).
CR749333 - Homo sapiens mRNA; cDNA DKFZp781F1414 (from clone DKFZp781F1414).
AB209641 - Homo sapiens mRNA for Neuropilin-1 precursor variant protein.
AK292822 - Homo sapiens cDNA FLJ77207 complete cds.
AF016050 - Homo sapiens vascular endothelial cell growth factor 165 receptor/neuropilin (VEGF165) mRNA, complete cds.
AF018956 - Homo sapiens neuropilin mRNA, complete cds.
AY249243 - Homo sapiens neuropilin-1 (NRP1) mRNA, complete cds; alternatively spliced.
EU831654 - Synthetic construct Homo sapiens clone HAIB:100066683; DKFZo007G0519 neuropilin 1 protein (NRP1) gene, encodes complete protein.
EU831737 - Synthetic construct Homo sapiens clone HAIB:100066766; DKFZo003G0520 neuropilin 1 protein (NRP1) gene, encodes complete protein.
JA482201 - Sequence 184 from Patent WO2011072091.
JA482202 - Sequence 185 from Patent WO2011072091.
JE980493 - Sequence 184 from Patent EP2862929.
JE980494 - Sequence 185 from Patent EP2862929.
AF145712 - Homo sapiens soluble neuropilin-1 mRNA, complete cds.
BC007737 - Homo sapiens neuropilin 1, mRNA (cDNA clone MGC:12920 IMAGE:4122289), complete cds.
BC007533 - Homo sapiens neuropilin 1, mRNA (cDNA clone MGC:15383 IMAGE:2958475), complete cds.
KJ892632 - Synthetic construct Homo sapiens clone ccsbBroadEn_02026 NRP1 gene, encodes complete protein.
KJ892633 - Synthetic construct Homo sapiens clone ccsbBroadEn_02027 NRP1 gene, encodes complete protein.
BT006995 - Homo sapiens neuropilin 1 mRNA, complete cds.
AF280547 - Homo sapiens neuropilin-1 soluble isoform 11 (NRP1) mRNA, complete cds, alternatively spliced.
AF268691 - Homo sapiens muscle type neuropilin 1 (NRP1) mRNA, complete cds, alternatively spliced.
BX648025 - Homo sapiens mRNA; cDNA DKFZp686A03134 (from clone DKFZp686A03134).
CU675785 - Synthetic construct Homo sapiens gateway clone IMAGE:100017428 5' read NRP1 mRNA.
JD333764 - Sequence 314788 from Patent EP1572962.
JD369680 - Sequence 350704 from Patent EP1572962.
JD382870 - Sequence 363894 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04360 - Axon guidance

Reactome (by CSHL, EBI, and GO)

Protein O14786 (Reactome details) participates in the following event(s):

R-HSA-195408 NRP-1 forms a ternary complex with VEGF165 and VEGFR1
R-HSA-374669 L1 binds NRP1
R-HSA-399942 Plexin-A1-4 binds NRP1
R-HSA-445083 CHL1 interacts with NRP1
R-HSA-9010951 ROBO1 binds NRP1
R-HSA-399933 Sema3A binds Nrp-1 bound to PlexinA
R-HSA-399931 Activation of Fyn
R-HSA-399934 Phosphorylation of Plexin-A
R-HSA-399944 Phosphorylation of CRMPs by Cdk5
R-HSA-399946 Recruitment and activation of Cdk5
R-HSA-399951 Phosphorylation of CRMPs by GSK3beta
R-HSA-399941 Rac1 binds PlexinA
R-HSA-399947 Tyrosine phosphorylation of CRMPs by Fes
R-HSA-399928 Recruitment of Rnd1 to Plexin A
R-HSA-399930 Activation of PAK by Rac1
R-HSA-399939 Autophosphorylation of PAK
R-HSA-399952 Phosphorylation of LIMK-1 by PAK
R-HSA-399935 Inactivation of R-Ras by Sema3A-Plexin-A GAP activity
R-HSA-194306 Neurophilin interactions with VEGF and VEGFR
R-HSA-445144 Signal transduction by L1
R-HSA-399955 SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
R-HSA-447041 CHL1 interactions
R-HSA-376176 Signaling by ROBO receptors
R-HSA-399956 CRMPs in Sema3A signaling
R-HSA-194138 Signaling by VEGF
R-HSA-373760 L1CAM interactions
R-HSA-373755 Semaphorin interactions
R-HSA-422475 Axon guidance
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1266738 Developmental Biology
R-HSA-162582 Signal Transduction
R-HSA-399954 Sema3A PAK dependent Axon repulsion

-  Other Names for This Gene
  Alternate Gene Symbols: B0LPG9, BX648025, NM_001024629, NP_001019800, NRP, NRP1_HUMAN, O14786, O60461, Q5T7F2, Q5T7F3, Q86T59, Q96IH5, VEGF165R
UCSC ID: uc001ixc.1
RefSeq Accession: NM_001024629
Protein: O14786 (aka NRP1_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: BX648025.1
exon count: 10CDS single in 3' UTR: no RNA size: 4155
ORF size: 1794CDS single in intron: no Alignment % ID: 99.85
txCdsPredict score: 3561.50frame shift in genome: no % Coverage: 99.49
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 1976# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.