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Protein

Ephrin type-B receptor 2

Gene

EPHB2

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

Functioni

Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei653ATPPROSITE-ProRule annotation1
Active sitei746Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi627 – 635ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processNeurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-2682334 EPH-Ephrin signaling
R-HSA-373760 L1CAM interactions
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-3928664 Ephrin signaling
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
SignaLinkiP29323
SIGNORiP29323

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-B receptor 2 (EC:2.7.10.1)
Alternative name(s):
Developmentally-regulated Eph-related tyrosine kinase
ELK-related tyrosine kinase
EPH tyrosine kinase 3
EPH-like kinase 5
Short name:
EK5
Short name:
hEK5
Renal carcinoma antigen NY-REN-47
Tyrosine-protein kinase TYRO5
Tyrosine-protein kinase receptor EPH-3
Gene namesi
Name:EPHB2
Synonyms:DRT, EPHT3, EPTH3, ERK, HEK5, TYRO5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000133216.16
HGNCiHGNC:3393 EPHB2
MIMi600997 gene
neXtProtiNX_P29323

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 domaini19 – 543ExtracellularSequence analysisAdd BLAST525
Transmembranei544 – 564HelicalSequence analysisAdd BLAST21
Topological domaini565 – 1055CytoplasmicSequence analysisAdd BLAST491

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Prostate cancer (PC)2 Publications
The gene represented in this entry may be involved in disease pathogenesis. EPHB2 mutations have been found in a prostate cancer cell line derived from a brain metastasis.
Disease descriptionA malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
See also OMIM:176807

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi2048
MalaCardsiEPHB2
MIMi176807 phenotype
603688 phenotype
OpenTargetsiENSG00000133216
Orphaneti1331 Familial prostate cancer
PharmGKBiPA27825

Chemistry databases

ChEMBLiCHEMBL3290
DrugBankiDB04395 Phosphoaminophosphonic Acid-Adenylate Ester
GuidetoPHARMACOLOGYi1831

Polymorphism and mutation databases

BioMutaiEPHB2
DMDMi76803654

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001682719 – 1055Ephrin type-B receptor 2Add BLAST1037

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi62 ↔ 1841 Publication
Disulfide bondi97 ↔ 1071 Publication
Glycosylationi265N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi336N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi428N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi482N-linked (GlcNAc...) asparagineSequence analysis1
Isoform 2 (identifier: P29323-2)
Modified residuei983PhosphoserineCombined sources1
Isoform 3 (identifier: P29323-3)
Modified residuei984PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP29323
MaxQBiP29323
PaxDbiP29323
PeptideAtlasiP29323
PRIDEiP29323
ProteomicsDBi54540
54541 [P29323-2]
54542 [P29323-3]

PTM databases

iPTMnetiP29323
PhosphoSitePlusiP29323
SwissPalmiP29323

Expressioni

Tissue specificityi

Brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. Preferentially expressed in fetal brain.

Gene expression databases

BgeeiENSG00000133216
CleanExiHS_EPHB2
ExpressionAtlasiP29323 baseline and differential
GenevisibleiP29323 HS

Organism-specific databases

HPAiCAB013647
HPA071200

Interactioni

Subunit structurei

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (By similarity). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome. Interacts with AQP1; involved in endolymph production in the inner ear.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NUP153P497902EBI-1059294,EBI-286779

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108362, 23 interactors
DIPiDIP-1162N
IntActiP29323, 6 interactors
MINTiP29323
STRINGi9606.ENSP00000363763

Chemistry databases

BindingDBiP29323

Structurei

Secondary structure

11055
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi21 – 25Combined sources5
Helixi26 – 28Combined sources3
Beta strandi36 – 39Combined sources4
Beta strandi44 – 49Combined sources6
Beta strandi55 – 61Combined sources7
Beta strandi66 – 68Combined sources3
Beta strandi71 – 74Combined sources4
Beta strandi84 – 94Combined sources11
Helixi97 – 99Combined sources3
Beta strandi111 – 120Combined sources10
Beta strandi130 – 132Combined sources3
Beta strandi135 – 141Combined sources7
Beta strandi148 – 152Combined sources5
Beta strandi155 – 166Combined sources12
Beta strandi171 – 183Combined sources13
Beta strandi185 – 194Combined sources10
Helixi618 – 620Combined sources3
Beta strandi621 – 626Combined sources6
Beta strandi635 – 640Combined sources6
Beta strandi648 – 655Combined sources8
Helixi661 – 674Combined sources14
Beta strandi685 – 689Combined sources5
Beta strandi691 – 700Combined sources10
Helixi707 – 712Combined sources6
Turni713 – 716Combined sources4
Helixi720 – 739Combined sources20
Helixi749 – 751Combined sources3
Beta strandi752 – 754Combined sources3
Beta strandi760 – 762Combined sources3
Helixi790 – 792Combined sources3
Helixi795 – 800Combined sources6
Helixi805 – 820Combined sources16
Turni826 – 829Combined sources4
Helixi832 – 840Combined sources9
Helixi853 – 862Combined sources10
Helixi873 – 885Combined sources13
Helixi887 – 890Combined sources4
Helixi918 – 924Combined sources7
Helixi928 – 930Combined sources3
Helixi931 – 936Combined sources6
Helixi942 – 945Combined sources4
Helixi950 – 955Combined sources6
Helixi961 – 982Combined sources22

3D structure databases

ProteinModelPortaliP29323
SMRiP29323
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29323

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 202Eph LBDPROSITE-ProRule annotationAdd BLAST183
Domaini324 – 434Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini435 – 530Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini621 – 884Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini913 – 977SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi984 – 986PDZ-binding (in isoform 2)Sequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi184 – 324Cys-richAdd BLAST141

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP29323
KOiK05111
OMAiVCRGCPS
OrthoDBiEOG091G00W0
PhylomeDBiP29323
TreeFamiTF315608

Family and domain databases

CDDicd10477 EphR_LBD_B2, 1 hit
cd00063 FN3, 2 hits
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034238 EphB2_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR011641 Tyr-kin_ephrin_A/B_rcpt-like
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016257 Tyr_kinase_ephrin_rcpt
IPR001426 Tyr_kinase_rcpt_V_CS
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF07699 Ephrin_rec_like, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 2 hits
PROSITEiView protein in PROSITE
PS51550 EPH_LBD, 1 hit
PS50853 FN3, 2 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00790 RECEPTOR_TYR_KIN_V_1, 1 hit
PS00791 RECEPTOR_TYR_KIN_V_2, 1 hit
PS50105 SAM_DOMAIN, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P29323-1) [UniParc]FASTAAdd to basket
Also known as: EPHB2v, Long

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
MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD
60 70 80 90 100
ENMNTIRTYQ VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI
110 120 130 140 150
PSVPGSCKET FNLYYYEADF DSATKTFPNW MENPWVKVDT IAADESFSQV
160 170 180 190 200
DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD YGGCMSLIAV RVFYRKCPRI
210 220 230 240 250
IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY CNGDGEWLVP
260 270 280 290 300
IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA
310 320 330 340 350
TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS
360 370 380 390 400
GGREDLVYNI ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA
410 420 430 440 450
HTQYTFEIQA VNGVTDQSPF SPQFASVNIT TNQAAPSAVS IMHQVSRTVD
460 470 480 490 500
SITLSWSQPD QPNGVILDYE LQYYEKELSE YNATAIKSPT NTVTVQGLKA
510 520 530 540 550
GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK LPLIIGSSAA
560 570 580 590 600
GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF
610 620 630 640 650
TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV
660 670 680 690 700
AIKTLKSGYT EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE
710 720 730 740 750
FMENGSLDSF LRQNDGQFTV IQLVGMLRGI AAGMKYLADM NYVHRDLAAR
760 770 780 790 800
NILVNSNLVC KVSDFGLSRF LEDDTSDPTY TSALGGKIPI RWTAPEAIQY
810 820 830 840 850
RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE QDYRLPPPMD
860 870 880 890 900
CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI
910 920 930 940 950
NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM
960 970 980 990 1000
EDILRVGVTL AGHQKKILNS IQVMRAQMNQ IQSVEGQPLA RRPRATGRTK
1010 1020 1030 1040 1050
RCQPRDVTKK TCNSNDGKKK GMGKKKTDPG RGREIQGIFF KEDSHKESND

CSCGG
Length:1,055
Mass (Da):117,493
Last modified:September 27, 2005 - v5
Checksum:i4F8BFEDC45986483
GO
Isoform 2 (identifier: P29323-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     986-986: G → V
     987-1055: Missing.

Show »
Length:986
Mass (Da):109,874
Checksum:i4B9B532A48B754A6
GO
Isoform 3 (identifier: P29323-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     568-568: R → RR
     986-986: G → V
     987-1055: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:987
Mass (Da):110,030
Checksum:iEF6DA7A63D894E47
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 20MALRR…LAAVE → MWVPVLALPVCTYA in BAA06506 (PubMed:8033077).CuratedAdd BLAST20
Sequence conflicti154G → D in BAA06506 (PubMed:8033077).Curated1
Sequence conflicti476K → KQ in BAA06506 (PubMed:8033077).Curated1
Sequence conflicti495 – 496Missing in AAA74244 (PubMed:7898931).Curated2
Sequence conflicti532E → D in BAA06506 (PubMed:8033077).Curated1
Sequence conflicti589M → I in AAA74244 (PubMed:7898931).Curated1
Sequence conflicti671A → R in BAA03537 (PubMed:7688222).Curated1
Sequence conflicti788I → F in AAA74244 (PubMed:7898931).Curated1
Sequence conflicti853S → A in BAA06506 (PubMed:8033077).Curated1
Sequence conflicti853S → A in BAA07073 (PubMed:7601466).Curated1
Sequence conflicti853S → A in BAA03537 (PubMed:7688222).Curated1
Sequence conflicti923E → K in BAA06506 (PubMed:8033077).Curated1
Sequence conflicti923E → K in BAA07073 (PubMed:7601466).Curated1
Sequence conflicti923E → K in BAA03537 (PubMed:7688222).Curated1
Sequence conflicti958V → L in AAA99310 (PubMed:8589679).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032853199R → H in prostate cancer. 1 PublicationCorresponds to variant dbSNP:rs201754821Ensembl.1
Natural variantiVAR_032854279A → S in prostate cancer. 3 PublicationsCorresponds to variant dbSNP:rs35882952EnsemblClinVar.1
Natural variantiVAR_042172289C → G1 Publication1
Natural variantiVAR_042173361I → V1 PublicationCorresponds to variant dbSNP:rs56180036Ensembl.1
Natural variantiVAR_032855650V → A in prostate cancer. 1 PublicationCorresponds to variant dbSNP:rs142173175Ensembl.1
Natural variantiVAR_042174678D → N1 PublicationCorresponds to variant dbSNP:rs28936395Ensembl.1
Natural variantiVAR_032856679H → N in prostate cancer. 1 Publication1
Natural variantiVAR_042175844R → W1 PublicationCorresponds to variant dbSNP:rs55826626Ensembl.1
Natural variantiVAR_032857883M → V in prostate cancer. 1 PublicationCorresponds to variant dbSNP:rs372653137Ensembl.1
Natural variantiVAR_032858909I → M in prostate cancer. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015713568R → RR in isoform 3. 1 Publication1
Alternative sequenceiVSP_003016986G → V in isoform 2 and isoform 3. 5 Publications1
Alternative sequenceiVSP_003017987 – 1055Missing in isoform 2 and isoform 3. 5 PublicationsAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31661 mRNA Translation: BAA06506.1
L41939 mRNA Translation: AAA99310.1
AF025304 mRNA Translation: AAB94602.1
AL035704 Genomic DNA No translation available.
AL158086 Genomic DNA No translation available.
AL512444 Genomic DNA No translation available.
L36643 mRNA Translation: AAA74244.1
D37827 mRNA Translation: BAA07073.1
D14717 mRNA Translation: BAA03537.1
X59292 Genomic DNA Translation: CAA41981.1
CCDSiCCDS229.2 [P29323-2]
CCDS230.1 [P29323-3]
CCDS81279.1 [P29323-1]
PIRiA57174
I78842
RefSeqiNP_001296122.1, NM_001309193.1 [P29323-1]
NP_004433.2, NM_004442.7 [P29323-3]
NP_059145.2, NM_017449.4 [P29323-2]
UniGeneiHs.380705
Hs.523329

Genome annotation databases

EnsembliENST00000374630; ENSP00000363761; ENSG00000133216 [P29323-2]
ENST00000374632; ENSP00000363763; ENSG00000133216 [P29323-3]
ENST00000400191; ENSP00000383053; ENSG00000133216 [P29323-1]
GeneIDi2048
KEGGihsa:2048
UCSCiuc001bge.4 human [P29323-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEPHB2_HUMAN
AccessioniPrimary (citable) accession number: P29323
Secondary accession number(s): O43477
, Q5T0U6, Q5T0U7, Q5T0U8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: September 27, 2005
Last modified: July 18, 2018
This is version 221 of the entry and version 5 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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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