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Reviewed, UniProtKB/Swiss-Prot O14786 (NRP1_HUMAN)

Last modified June 16, 2009. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Neuropilin-1
Alternative name(s):
    Vascular endothelial cell growth factor 165 receptor
    CD_antigen=CD304
Gene names
Name: NRP1
Synonyms: NRP, VEGF165R
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length923 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

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.

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 structure

Heterodimer with NRP2 Probable. Binds PLXNB1.

Subcellular location

Cell membrane; Single-pass type I membrane protein.

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.

Sequence similarities

Belongs to the neuropilin family.

Contains 2 CUB domains.

Contains 2 F5/8 type C domains.

Contains 1 MAM domain.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14786-1)

Also known as: Membrane-bound;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14786-2)

Also known as: Soluble; SNRP1;

The sequence of this isoform differs from the canonical sequence as follows:
     642-644: EFP → GIK
     645-923: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.2 Ref.3
Chain22 – 923902Neuropilin-1
PRO_0000021859

Regions

Topological domain22 – 856835Extracellular Potential
Transmembrane857 – 87923 Potential
Topological domain880 – 92344Cytoplasmic Potential
Domain27 – 141115CUB 1
Domain147 – 265119CUB 2
Domain275 – 424150F5/8 type C 1
Domain431 – 583153F5/8 type C 2
Domain645 – 811167MAM

Amino acid modifications

Modified residue9201Phosphotyrosine Ref.11
Glycosylation1501N-linked (GlcNAc...) Ref.9
Glycosylation2611N-linked (GlcNAc...)
Glycosylation3001N-linked (GlcNAc...) Potential
Glycosylation5221N-linked (GlcNAc...)
Glycosylation6121O-linked (Xyl...) (chondroitin sulfate); alternate Ref.10
Glycosylation6121O-linked (Xyl...) (heparan sulfate); alternate Ref.10
Glycosylation8421N-linked (GlcNAc...) Potential
Disulfide bond27 ↔ 54 Probable
Disulfide bond82 ↔ 104 Probable
Disulfide bond147 ↔ 173 Probable
Disulfide bond206 ↔ 228 Probable
Disulfide bond275 ↔ 424 By similarity
Disulfide bond431 ↔ 583 By similarity

Natural variations

Alternative sequence642 – 6443EFP → GIK in isoform 2.
VSP_004339
Alternative sequence645 – 923279Missing in isoform 2.
VSP_004340
Natural variant1791V → A: dbSNP rs7079053. Ref.2 Ref.3 Ref.1 Ref.4 Ref.6
VAR_046536
Natural variant5611F → L: dbSNP rs2228637.
VAR_046537
Natural variant7331V → I: dbSNP rs2228638.
VAR_056957

Experimental info

Sequence conflict261K → E in AAC51759. Ref.1
Sequence conflict7491D → H in AAC12921. Ref.2
Sequence conflict8551D → E in AAC51759. Ref.1

Secondary structure

...................................................................... 923
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Membrane-bound) [UniParc].

Last modified September 23, 2008. Version 3.
Checksum: 1EAC2FA6C8FD6A0B

FASTA923103,134
        10         20         30         40         50         60 
MERGLPLLCA VLALVLAPAG AFRNDKCGDT IKIESPGYLT SPGYPHSYHP SEKCEWLIQA 

        70         80         90        100        110        120 
PDPYQRIMIN FNPHFDLEDR DCKYDYVEVF DGENENGHFR GKFCGKIAPP PVVSSGPFLF 

       130        140        150        160        170        180 
IKFVSDYETH GAGFSIRYEI FKRGPECSQN YTTPSGVIKS PGFPEKYPNS LECTYIVFVP 

       190        200        210        220        230        240 
KMSEIILEFE SFDLEPDSNP PGGMFCRYDR LEIWDGFPDV GPHIGRYCGQ KTPGRIRSSS 

       250        260        270        280        290        300 
GILSMVFYTD SAIAKEGFSA NYSVLQSSVS EDFKCMEALG MESGEIHSDQ ITASSQYSTN 

       310        320        330        340        350        360 
WSAERSRLNY PENGWTPGED SYREWIQVDL GLLRFVTAVG TQGAISKETK KKYYVKTYKI 

       370        380        390        400        410        420 
DVSSNGEDWI TIKEGNKPVL FQGNTNPTDV VVAVFPKPLI TRFVRIKPAT WETGISMRFE 

       430        440        450        460        470        480 
VYGCKITDYP CSGMLGMVSG LISDSQITSS NQGDRNWMPE NIRLVTSRSG WALPPAPHSY 

       490        500        510        520        530        540 
INEWLQIDLG EEKIVRGIII QGGKHRENKV FMRKFKIGYS NNGSDWKMIM DDSKRKAKSF 

       550        560        570        580        590        600 
EGNNNYDTPE LRTFPALSTR FIRIYPERAT HGGLGLRMEL LGCEVEAPTA GPTTPNGNLV 

       610        620        630        640        650        660 
DECDDDQANC HSGTGDDFQL TGGTTVLATE KPTVIDSTIQ SEFPTYGFNC EFGWGSHKTF 

       670        680        690        700        710        720 
CHWEHDNHVQ LKWSVLTSKT GPIQDHTGDG NFIYSQADEN QKGKVARLVS PVVYSQNSAH 

       730        740        750        760        770        780 
CMTFWYHMSG SHVGTLRVKL RYQKPEEYDQ LVWMAIGHQG DHWKEGRVLL HKSLKLYQVI 

       790        800        810        820        830        840 
FEGEIGKGNL GGIAVDDISI NNHISQEDCA KPADLDKKNP EIKIDETGST PGYEGEGEGD 

       850        860        870        880        890        900 
KNISRKPGNV LKTLDPILIT IIAMSALGVL LGAVCGVVLY CACWHNGMSE RNLSALENYN 

       910        920 
FELVDGVKLK KDKLNTQSTY SEA 

« Hide

Isoform 2 (Soluble) (SNRP1).

Checksum: 1F055D9E6DD9BE70
Show »

FASTA64471,935

References

« Hide 'large scale' references
[1]"Neuropilin is a receptor for the axonal chemorepellent semaphorin III."
He Z., Tessier-Lavigne M.
Cell 90:739-751(1997) [PubMed: 9288753] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ALA-179.
[2]"Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor."
Soker S., Takashima S., Miao H.-Q., Neufeld G., Klagsbrun M.
Cell 92:735-745(1998) [PubMed: 9529250] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 22-39, VARIANT ALA-179.
Tissue: Mammary gland.
[3]"Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity."
Gagnon M.L., Bielenberg D.R., Gechtman Z., Miao H.-Q., Takashima S., Soker S., Klagsbrun M.
Proc. Natl. Acad. Sci. U.S.A. 97:2573-2578(2000) [PubMed: 10688880] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 22-31, VARIANT ALA-179.
Tissue: Prostatic adenocarcinoma.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-179.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ALA-179.
Tissue: Kidney.
[7]"Plexins are a large family of receptors for transmembrane, secreted and GPI-anchored semaphorins in vertebrates."
Tamagnone L., Artigiani S., Chen H., He Z., Ming G.-L., Song H.-L., Chedotal A., Winberg M.L., Goodman C.S., Poo M.-M., Tessier-Lavigne M., Comoglio P.M.
Cell 99:71-80(1999) [PubMed: 10520995] [Abstract]
Cited for: INTERACTION WITH PLXNB1.
[8]"Neuropilin-2 and neuropilin-1 are receptors for the 165-amino acid form of vascular endothelial growth factor (VEGF) and of placenta growth factor-2, but only neuropilin-2 functions as a receptor for the 145-amino acid form of VEGF."
Gluzman-Poltorak Z., Cohen T., Herzog Y., Neufeld G.
J. Biol. Chem. 275:18040-18045(2000) [PubMed: 10748121] [Abstract]
Cited for: CHARACTERIZATION.
[9]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-150, MASS SPECTROMETRY.
Tissue: Plasma.
[10]"Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling."
Shintani Y., Takashima S., Asano Y., Kato H., Liao Y., Yamazaki S., Tsukamoto O., Seguchi O., Yamamoto H., Fukushima T., Sugahara K., Kitakaze M., Hori M.
EMBO J. 25:3045-3055(2006) [PubMed: 16763549] [Abstract]
Cited for: GLYCOSYLATION AT SER-612.
[11]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-920, MASS SPECTROMETRY.
[12]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-150; ASN-261 AND ASN-522, MASS SPECTROMETRY.
Tissue: Liver.
[13]"Crystal structure of the human neuropilin-1 b1 domain."
Lee C.C., Kreusch A., McMullan D., Ng K., Spraggon G.
Structure 11:99-108(2003) [PubMed: 12517344] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 273-427.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF018956 mRNA. Translation: AAC51759.1.
AF016050 mRNA. Translation: AAC12921.1.
AF145712 mRNA. Translation: AAF44344.1.
BT006995 mRNA. Translation: AAP35641.1.
AL353600, AL121748 Genomic DNA. Translation: CAI16997.1.
AL121748, AL353600 Genomic DNA. Translation: CAI40248.1.
BC007533 mRNA. Translation: AAH07533.1.
IPIIPI00299594.
IPI00607733.
UniGeneHs.131704
Hs.714624

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1KEXX-ray1.90A273-427[»]
2QQIX-ray1.80A273-586[»]
2QQMX-ray2.00A141-586[»]
2QQNX-ray2.20A273-427[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:5743N.
IntActO14786. 2 interactions.

PTM databases

PhosphoSiteO14786.

Proteomic databases

PRIDEO14786.

Genome annotation databases

EnsemblENSG00000099250. Homo sapiens. [Contig view]

Organism-specific databases

GeneCardsGC10M033506.
H-InvDBHIX0008755.
HGNCHGNC:8004. NRP1.
HPACAB004511.
MIM602069. gene.
PharmGKBPA31783.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO14786.
HOVERGENO14786.
OMAO14786. LECTYII.

Enzyme and pathway databases

Pathway_Interaction_DBvegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
vegfr1_pathway. VEGFR1 specific signals.
ReactomeREACT_12529. Signaling by VEGF.

Gene expression databases

ArrayExpressO14786.
BgeeO14786.
CleanExHS_NRP1.
GermOnlineENSG00000099250. Homo sapiens.

Family and domain databases

InterProIPR000421. Coagulation_factor_5/8-type_C.
IPR000859. CUB.
IPR000998. MAM.
IPR014648. Neuropilin.
[Graphical view]
Gene3DG3DSA:2.60.120.290. CUB. 2 hits.
PfamPF00431. CUB. 2 hits.
PF00754. F5_F8_type_C. 2 hits.
PF00629. MAM. 1 hit.
[Graphical view]
PIRSFPIRSF036960. Neuropilin. 1 hit.
PRINTSPR00020. MAMDOMAIN.
SMARTSM00042. CUB. 2 hits.
SM00231. FA58C. 2 hits.
SM00137. MAM. 1 hit.
[Graphical view]
PROSITEPS01180. CUB. 2 hits.
PS01285. FA58C_1. 2 hits.
PS01286. FA58C_2. 2 hits.
PS50022. FA58C_3. 2 hits.
PS00740. MAM_1. 1 hit.
PS50060. MAM_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00039. Palifermin.
DB04895. Pegaptanib.
SOURCESearch...

Entry information

Entry nameNRP1_HUMAN
AccessionPrimary (citable) accession number: O14786
Secondary accession number(s): O60461, Q5T7F3, Q96IH5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 23, 2008
Last modified: June 16, 2009
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents