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Protein

Neuropilin-2

Gene

NRP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi197CalciumCombined sources1 Publication1
Metal bindingi211CalciumCombined sources1 Publication1
Metal bindingi252CalciumCombined sources1 Publication1

GO - Molecular functioni

  • cytokine binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL
  • heparin binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • receptor activity Source: ProtInc
  • semaphorin receptor activity Source: UniProtKB
  • vascular endothelial growth factor-activated receptor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Heparin-binding, Receptor
Biological processDifferentiation, Neurogenesis
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-194306 Neurophilin interactions with VEGF and VEGFR
R-HSA-447038 NrCAM interactions
SIGNORiO60462

Names & Taxonomyi

Protein namesi
Recommended name:
Neuropilin-2
Alternative name(s):
Vascular endothelial cell growth factor 165 receptor 2
Gene namesi
Name:NRP2
Synonyms:VEGF165R2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000118257.16
HGNCiHGNC:8005 NRP2
MIMi602070 gene
neXtProtiNX_O60462

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 864ExtracellularSequence analysisAdd BLAST844
Transmembranei865 – 889HelicalSequence analysisAdd BLAST25
Topological domaini890 – 931CytoplasmicSequence analysisAdd BLAST42

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi8828
OpenTargetsiENSG00000118257
PharmGKBiPA31784

Polymorphism and mutation databases

BioMutaiNRP2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Or 22Sequence analysisAdd BLAST20
ChainiPRO_000002186321 – 931Neuropilin-2Add BLAST911

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 551 Publication
Disulfide bondi83 ↔ 1051 Publication
Disulfide bondi149 ↔ 1751 Publication
Glycosylationi152N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi157N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi208 ↔ 2301 Publication
Disulfide bondi277 ↔ 4271 Publication
Disulfide bondi434 ↔ 5921 Publication
Glycosylationi629N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi839N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO60462
MaxQBiO60462
PaxDbiO60462
PeptideAtlasiO60462
PRIDEiO60462

PTM databases

iPTMnetiO60462
PhosphoSitePlusiO60462
SwissPalmiO60462

Expressioni

Gene expression databases

BgeeiENSG00000118257
CleanExiHS_NRP2
ExpressionAtlasiO60462 baseline and differential
GenevisibleiO60462 HS

Organism-specific databases

HPAiHPA039980
HPA054974

Interactioni

Subunit structurei

Heterodimer with NRP1. Binds PLXNB1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
VegfcP97953-13EBI-12586256,EBI-16148671From a different organism.

GO - Molecular functioni

  • cytokine binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL
  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi114355, 19 interactors
CORUMiO60462
DIPiDIP-5745N
IntActiO60462, 2 interactors
STRINGi9606.ENSP00000353582

Structurei

Secondary structure

1931
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 33Combined sources4
Beta strandi38 – 41Combined sources4
Turni43 – 46Combined sources4
Beta strandi55 – 60Combined sources6
Beta strandi66 – 72Combined sources7
Beta strandi83 – 95Combined sources13
Beta strandi98 – 104Combined sources7
Beta strandi116 – 125Combined sources10
Beta strandi136 – 142Combined sources7
Beta strandi151 – 153Combined sources3
Beta strandi155 – 161Combined sources7
Turni163 – 166Combined sources4
Beta strandi174 – 180Combined sources7
Beta strandi186 – 195Combined sources10
Beta strandi210 – 219Combined sources10
Turni220 – 222Combined sources3
Beta strandi225 – 229Combined sources5
Beta strandi231 – 233Combined sources3
Beta strandi238 – 240Combined sources3
Beta strandi242 – 250Combined sources9
Beta strandi255 – 257Combined sources3
Beta strandi259 – 267Combined sources9
Turni283 – 285Combined sources3
Beta strandi286 – 288Combined sources3
Helixi290 – 292Combined sources3
Beta strandi293 – 296Combined sources4
Beta strandi302 – 304Combined sources3
Helixi306 – 308Combined sources3
Beta strandi324 – 326Combined sources3
Beta strandi329 – 345Combined sources17
Turni350 – 352Combined sources3
Beta strandi355 – 371Combined sources17
Beta strandi376 – 381Combined sources6
Beta strandi388 – 391Combined sources4
Beta strandi394 – 417Combined sources24
Beta strandi420 – 428Combined sources9
Helixi429 – 431Combined sources3
Beta strandi432 – 434Combined sources3
Turni440 – 442Combined sources3
Beta strandi443 – 445Combined sources3
Helixi447 – 449Combined sources3
Beta strandi450 – 453Combined sources4
Beta strandi456 – 459Combined sources4
Helixi462 – 465Combined sources4
Turni467 – 469Combined sources3
Beta strandi470 – 472Combined sources3
Beta strandi477 – 480Combined sources4
Turni483 – 485Combined sources3
Beta strandi488 – 504Combined sources17
Helixi515 – 517Combined sources3
Beta strandi521 – 534Combined sources14
Turni541 – 544Combined sources4
Beta strandi553 – 557Combined sources5
Beta strandi559 – 578Combined sources20
Beta strandi585 – 593Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QQJX-ray1.95A275-595[»]
2QQKX-ray2.75A23-595[»]
2QQLX-ray3.10A23-595[»]
2QQOX-ray2.30A/B145-595[»]
4QDQX-ray1.95A/B276-595[»]
4QDRX-ray2.40A276-595[»]
4QDSX-ray2.40A/B275-457[»]
5DN2X-ray1.95A/B/C/D275-429[»]
5DQ0X-ray1.80A275-430[»]
ProteinModelPortaliO60462
SMRiO60462
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60462

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 142CUB 1PROSITE-ProRule annotationAdd BLAST115
Domaini149 – 267CUB 2PROSITE-ProRule annotationAdd BLAST119
Domaini277 – 427F5/8 type C 1PROSITE-ProRule annotationAdd BLAST151
Domaini434 – 592F5/8 type C 2PROSITE-ProRule annotationAdd BLAST159
Domaini642 – 802MAMPROSITE-ProRule annotationAdd BLAST161

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi671 – 674Poly-Ser4

Domaini

The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding.

Sequence similaritiesi

Belongs to the neuropilin family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHB5 Eukaryota
ENOG410ZPIE LUCA
GeneTreeiENSGT00910000143988
HOVERGENiHBG000502
InParanoidiO60462
KOiK06819
OMAiEYEVDWS
OrthoDBiEOG091G01LI
PhylomeDBiO60462
TreeFamiTF316506

Family and domain databases

CDDicd00041 CUB, 2 hits
cd06263 MAM, 1 hit
Gene3Di2.60.120.260, 2 hits
2.60.120.290, 2 hits
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR000859 CUB_dom
IPR000421 FA58C
IPR008979 Galactose-bd-like_sf
IPR000998 MAM_dom
IPR014648 Neuropilin
IPR027143 Neuropilin-2
IPR022579 Neuropilin_C
IPR035914 Sperma_CUB_dom_sf
PANTHERiPTHR44185 PTHR44185, 1 hit
PTHR44185:SF2 PTHR44185:SF2, 1 hit
PfamiView protein in Pfam
PF00431 CUB, 2 hits
PF11980 DUF3481, 1 hit
PF00754 F5_F8_type_C, 2 hits
PF00629 MAM, 1 hit
PIRSFiPIRSF036960 Neuropilin, 1 hit
PRINTSiPR00020 MAMDOMAIN
SMARTiView protein in SMART
SM00042 CUB, 2 hits
SM00231 FA58C, 2 hits
SM00137 MAM, 1 hit
SUPFAMiSSF49785 SSF49785, 2 hits
SSF49854 SSF49854, 2 hits
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS01180 CUB, 2 hits
PS01285 FA58C_1, 2 hits
PS01286 FA58C_2, 2 hits
PS50022 FA58C_3, 2 hits
PS50060 MAM_2, 1 hit

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A22 (identifier: O60462-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDMFPLTWVF LALYFSRHQV RGQPDPPCGG RLNSKDAGYI TSPGYPQDYP
60 70 80 90 100
SHQNCEWIVY APEPNQKIVL NFNPHFEIEK HDCKYDFIEI RDGDSESADL
110 120 130 140 150
LGKHCGNIAP PTIISSGSML YIKFTSDYAR QGAGFSLRYE IFKTGSEDCS
160 170 180 190 200
KNFTSPNGTI ESPGFPEKYP HNLDCTFTIL AKPKMEIILQ FLIFDLEHDP
210 220 230 240 250
LQVGEGDCKY DWLDIWDGIP HVGPLIGKYC GTKTPSELRS STGILSLTFH
260 270 280 290 300
TDMAVAKDGF SARYYLVHQE PLENFQCNVP LGMESGRIAN EQISASSTYS
310 320 330 340 350
DGRWTPQQSR LHGDDNGWTP NLDSNKEYLQ VDLRFLTMLT AIATQGAISR
360 370 380 390 400
ETQNGYYVKS YKLEVSTNGE DWMVYRHGKN HKVFQANNDA TEVVLNKLHA
410 420 430 440 450
PLLTRFVRIR PQTWHSGIAL RLELFGCRVT DAPCSNMLGM LSGLIADSQI
460 470 480 490 500
SASSTQEYLW SPSAARLVSS RSGWFPRIPQ AQPGEEWLQV DLGTPKTVKG
510 520 530 540 550
VIIQGARGGD SITAVEARAF VRKFKVSYSL NGKDWEYIQD PRTQQPKLFE
560 570 580 590 600
GNMHYDTPDI RRFDPIPAQY VRVYPERWSP AGIGMRLEVL GCDWTDSKPT
610 620 630 640 650
VETLGPTVKS EETTTPYPTE EEATECGENC SFEDDKDLQL PSGFNCNFDF
660 670 680 690 700
LEEPCGWMYD HAKWLRTTWA SSSSPNDRTF PDDRNFLRLQ SDSQREGQYA
710 720 730 740 750
RLISPPVHLP RSPVCMEFQY QATGGRGVAL QVVREASQES KLLWVIREDQ
760 770 780 790 800
GGEWKHGRII LPSYDMEYQI VFEGVIGKGR SGEIAIDDIR ISTDVPLENC
810 820 830 840 850
MEPISAFAGE NFKVDIPEIH EREGYEDEID DEYEVDWSNS SSATSGSGAP
860 870 880 890 900
STDKEKSWLY TLDPILITII AMSSLGVLLG ATCAGLLLYC TCSYSGLSSR
910 920 930
SCTTLENYNF ELYDGLKHKV KMNHQKCCSE A
Length:931
Mass (Da):104,831
Last modified:March 28, 2018 - v3
Checksum:i270CBAE69A0A797C
GO
Isoform A0 (identifier: O60462-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     809-830: Missing.

Show »
Length:909
Mass (Da):102,215
Checksum:i983E34FD23E3B3FB
GO
Isoform A17 (identifier: O60462-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     809-813: Missing.

Show »
Length:926
Mass (Da):104,255
Checksum:i40000DC73D237AF6
GO
Isoform B0 (identifier: O60462-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     809-813: Missing.
     814-931: VDIPEIHERE...MNHQKCCSEA → GGTLLPGTEP...KLEQDRGSHC

Show »
Length:901
Mass (Da):101,381
Checksum:iA1310304AFD086AB
GO
Isoform B5 (identifier: O60462-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     814-931: VDIPEIHERE...MNHQKCCSEA → GGTLLPGTEP...KLEQDRGSHC

Show »
Length:906
Mass (Da):101,957
Checksum:iEB183F265457B0B9
GO
Isoform s9 (identifier: O60462-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     548-555: LFEGNMHY → VGCSWRPL
     556-931: Missing.

Show »
Length:555
Mass (Da):62,430
Checksum:iB67B7C992AB0546F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047754123K → R1 PublicationCorresponds to variant dbSNP:rs849541Ensembl.1
Natural variantiVAR_067537334R → C Rare variant; may act as a phenotype modifier in EIEE13 patients carrying SCN8A mutations. 1 PublicationCorresponds to variant dbSNP:rs114144673Ensembl.1
Natural variantiVAR_067538428R → W Rare variant; may act as a phenotype modifier in EIEE13 patients carrying SCN8A mutations. 1 PublicationCorresponds to variant dbSNP:rs139711818Ensembl.1
Natural variantiVAR_065167602E → K2 PublicationsCorresponds to variant dbSNP:rs1128169Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044908548 – 555LFEGNMHY → VGCSWRPL in isoform s9. 1 Publication8
Alternative sequenceiVSP_044909556 – 931Missing in isoform s9. 1 PublicationAdd BLAST376
Alternative sequenceiVSP_004342809 – 830Missing in isoform A0. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_004341809 – 813Missing in isoform A17 and isoform B0. 3 Publications5
Alternative sequenceiVSP_041160814 – 931VDIPE…CCSEA → GGTLLPGTEPTVDTVPMQPI PAYWYYVMAAGGAVLVLVSV ALALVLHYHRFRYAAKKTDH SITYKTSHYTNGAPLAVEPT LTIKLEQDRGSHC in isoform B0 and isoform B5. 2 PublicationsAdd BLAST118

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022859 mRNA Translation: AAC51788.1
AF022860 mRNA Translation: AAC51789.1
AF016098 mRNA Translation: AAC12922.1
AF280544 mRNA Translation: AAG41403.1
AF280545 mRNA Translation: AAG41404.1
AF280546 mRNA Translation: AAG41405.1
KJ534899 mRNA Translation: AHW56539.1
AF281074 Genomic DNA Translation: AAG41897.1
AF281074 Genomic DNA Translation: AAG41898.1
AF281074 Genomic DNA Translation: AAG41899.1
AF281074 Genomic DNA Translation: AAG41900.1
AC007362 Genomic DNA Translation: AAX93216.1
AC007561 Genomic DNA Translation: AAY14875.1
KF459587 Genomic DNA No translation available.
CH471063 Genomic DNA Translation: EAW70362.1
CH471063 Genomic DNA Translation: EAW70363.1
CH471063 Genomic DNA Translation: EAW70364.1
CH471063 Genomic DNA Translation: EAW70366.1
CH471063 Genomic DNA Translation: EAW70368.1
CH471063 Genomic DNA Translation: EAW70369.1
CH471063 Genomic DNA Translation: EAW70371.1
CH471063 Genomic DNA Translation: EAW70372.1
CH471063 Genomic DNA Translation: EAW70373.1
BC101525 mRNA Translation: AAI01526.1
BC104770 mRNA Translation: AAI04771.1
BC143238 mRNA Translation: AAI43239.1
BC117413 mRNA Translation: AAI17414.1
CCDSiCCDS2364.1 [O60462-1]
CCDS2365.1 [O60462-5]
CCDS46496.1 [O60462-3]
CCDS46497.1 [O60462-2]
CCDS46498.1 [O60462-4]
CCDS46499.1 [O60462-6]
RefSeqiNP_003863.2, NM_003872.2
NP_061004.3, NM_018534.3
NP_957716.1, NM_201264.1
NP_957718.1, NM_201266.1
NP_957719.1, NM_201267.1
NP_958436.1, NM_201279.1
XP_005246990.2, XM_005246933.3
XP_005246991.2, XM_005246934.3
XP_016860674.1, XM_017005185.1
XP_016860675.1, XM_017005186.1
UniGeneiHs.471200
Hs.660596

Genome annotation databases

EnsembliENST00000272849; ENSP00000272849; ENSG00000118257 [O60462-5]
ENST00000357118; ENSP00000349632; ENSG00000118257 [O60462-4]
ENST00000357785; ENSP00000350432; ENSG00000118257 [O60462-3]
ENST00000360409; ENSP00000353582; ENSG00000118257 [O60462-1]
ENST00000412873; ENSP00000407626; ENSG00000118257 [O60462-2]
ENST00000417189; ENSP00000387519; ENSG00000118257 [O60462-6]
GeneIDi8828
KEGGihsa:8828
UCSCiuc002vau.4 human [O60462-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNRP2_HUMAN
AccessioniPrimary (citable) accession number: O60462
Secondary accession number(s): A0A024R3W6
, A0A024R412, E9PF66, O14820, O14821, Q53TQ4, Q53TS3, Q7LBX6, Q7LBX7, Q9H2D4, Q9H2D5, Q9H2E2, Q9H2E3, Q9H2E4, X5D2Q8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: March 28, 2018
Last modified: April 25, 2018
This is version 170 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health