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Protein

E3 ubiquitin-protein ligase HECW2

Gene

HECW2

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

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370).2 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1540Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ubiquitin protein ligase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9P2P5
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HECW2 (EC:2.3.2.26)
Alternative name(s):
HECT, C2 and WW domain-containing protein 2
HECT-type E3 ubiquitin transferase HECW2
NEDD4-like E3 ubiquitin-protein ligase 2
Gene namesi
Name:HECW2
Synonyms:KIAA1301, NEDL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138411.10
HGNCiHGNC:29853 HECW2
MIMi617245 gene
neXtProtiNX_Q9P2P5

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

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodevelopmental disorder characterized by severely delayed psychomotor development, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles, and white matter abnormalities.
See also OMIM:617268
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0779051191R → Q in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854416EnsemblClinVar.1
Natural variantiVAR_0779061193F → V in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854422EnsemblClinVar.1
Natural variantiVAR_0779071330R → W in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854417EnsemblClinVar.1
Natural variantiVAR_0779081445E → G in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854424EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi57520
MalaCardsiHECW2
MIMi617268 phenotype
OpenTargetsiENSG00000138411
PharmGKBiPA134925001

Polymorphism and mutation databases

BioMutaiHECW2
DMDMi126215718

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002776671 – 1572E3 ubiquitin-protein ligase HECW2Add BLAST1572

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei48PhosphoserineCombined sources1
Modified residuei852PhosphoserineCombined sources1
Modified residuei909PhosphoserineCombined sources1
Modified residuei1175PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9P2P5
MaxQBiQ9P2P5
PaxDbiQ9P2P5
PeptideAtlasiQ9P2P5
PRIDEiQ9P2P5
ProteomicsDBi83874
83875 [Q9P2P5-2]

PTM databases

iPTMnetiQ9P2P5
PhosphoSitePlusiQ9P2P5

Expressioni

Tissue specificityi

Predominantly expressed in adult brain, lung and heart.1 Publication

Gene expression databases

BgeeiENSG00000138411 Expressed in 176 organ(s), highest expression level in corpus callosum
CleanExiHS_HECW2
ExpressionAtlasiQ9P2P5 baseline and differential
GenevisibleiQ9P2P5 HS

Organism-specific databases

HPAiHPA034609

Interactioni

Subunit structurei

Interacts with TP73 (PubMed:12890487). Interacts with FZR1 (PubMed:24163370).2 Publications

Protein-protein interaction databases

BioGridi121581, 301 interactors
IntActiQ9P2P5, 1 interactor
MINTiQ9P2P5
STRINGi9606.ENSP00000260983

Structurei

Secondary structure

11572
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9P2P5
SMRiQ9P2P5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini172 – 282C2PROSITE-ProRule annotationAdd BLAST111
Domaini807 – 840WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini985 – 1018WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini1237 – 1572HECTPROSITE-ProRule annotationAdd BLAST336

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni737 – 1068Interaction with TP731 PublicationAdd BLAST332

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili847 – 874Sequence analysisAdd BLAST28

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000069940
HOVERGENiHBG057414
InParanoidiQ9P2P5
KOiK12168
OMAiEDMPGGH
OrthoDBiEOG091G0A54
PhylomeDBiQ9P2P5
TreeFamiTF313938

Family and domain databases

CDDicd08691 C2_NEDL1-like, 1 hit
cd00078 HECTc, 1 hit
cd00201 WW, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037795 C2_HECW
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR032348 HECW_N
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF16562 HECW_N, 1 hit
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 2 hits
PS50020 WW_DOMAIN_2, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9P2P5-1) [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
MASSAREHLL FVRRRNPQMR YTLSPENLQS LAAQSSMPEN MTLQRANSDT
60 70 80 90 100
DLVTSESRSS LTASMYEYTL GQAQNLIIFW DIKEEVDPSD WIGLYHIDEN
110 120 130 140 150
SPANFWDSKN RGVTGTQKGQ IVWRIEPGPY FMEPEIKICF KYYHGISGAL
160 170 180 190 200
RATTPCITVK NPAVMMGAEG MEGGASGNLH SRKLVSFTLS DLRAVGLKKG
210 220 230 240 250
MFFNPDPYLK MSIQPGKKSS FPTCAHHGQE RRSTIISNTT NPIWHREKYS
260 270 280 290 300
FFALLTDVLE IEIKDKFAKS RPIIKRFLGK LTIPVQRLLE RQAIGDQMLS
310 320 330 340 350
YNLGRRLPAD HVSGYLQFKV EVTSSVHEDA SPEAVGTILG VNSVNGDLGS
360 370 380 390 400
PSDDEDMPGS HHDSQVCSNG PVSEDSAADG TPKHSFRTSS TLEIDTEELT
410 420 430 440 450
STSSRTSPPR GRQDSLNDYL DAIEHNGHSR PGTATCSERS MGASPKLRSS
460 470 480 490 500
FPTDTRLNAM LHIDSDEEDH EFQQDLGYPS SLEEEGGLIM FSRASRADDG
510 520 530 540 550
SLTSQTKLED NPVENEEAST HEAASFEDKP ENLPELAESS LPAGPAPEEG
560 570 580 590 600
EGGPEPQPSA DQGSAELCGS QEVDQPTSGA DTGTSDASGG SRRAVSETES
610 620 630 640 650
LDQGSEPSQV SSETEPSDPA RTESVSEAST RPEGESDLEC ADSSCNESVT
660 670 680 690 700
TQLSSVDTRC SSLESARFPE TPAFSSQEEE DGACAAEPTS SGPAEGSQES
710 720 730 740 750
VCTAGSLPVV QVPSGEDEGP GAESATVPDQ EELGEVWQRR GSLEGAAAAA
760 770 780 790 800
ESPPQEEGSA GEAQGTCEGA TAQEEGATGG SQANGHQPLR SLPSVRQDVS
810 820 830 840 850
RYQRVDEALP PNWEARIDSH GRIFYVDHVN RTTTWQRPTA PPAPQVLQRS
860 870 880 890 900
NSIQQMEQLN RRYQSIRRTM TNERPEENTN AIDGAGEEAD FHQASADFRR
910 920 930 940 950
ENILPHSTSR SRITLLLQSP PVKFLISPEF FTVLHSNPSA YRMFTNNTCL
960 970 980 990 1000
KHMITKVRRD THHFERYQHN RDLVGFLNMF ANKQLELPRG WEMKHDHQGK
1010 1020 1030 1040 1050
AFFVDHNSRT TTFIDPRLPL QSSRPTSALV HRQHLTRQRS HSAGEVGEDS
1060 1070 1080 1090 1100
RHAGPPVLPR PSSTFNTVSR PQYQDMVPVA YNDKIVAFLR QPNIFEILQE
1110 1120 1130 1140 1150
RQPDLTRNHS LREKIQFIRT EGTPGLVRLS SDADLVMLLS LFEEEIMSYV
1160 1170 1180 1190 1200
PPHALLHPSY CQSPRGSPVS SPQNSPGTQR ANARAPAPYK RDFEAKLRNF
1210 1220 1230 1240 1250
YRKLETKGYG QGPGKLKLII RRDHLLEDAF NQIMGYSRKD LQRNKLYVTF
1260 1270 1280 1290 1300
VGEEGLDYSG PSREFFFLVS RELFNPYYGL FEYSANDTYT VQISPMSAFV
1310 1320 1330 1340 1350
DNHHEWFRFS GRILGLALIH QYLLDAFFTR PFYKALLRIL CDLSDLEYLD
1360 1370 1380 1390 1400
EEFHQSLQWM KDNDIHDILD LTFTVNEEVF GQITERELKP GGANIPVTEK
1410 1420 1430 1440 1450
NKKEYIERMV KWRIERGVVQ QTESLVRGFY EVVDARLVSV FDARELELVI
1460 1470 1480 1490 1500
AGTAEIDLSD WRNNTEYRGG YHDNHIVIRW FWAAVERFNN EQRLRLLQFV
1510 1520 1530 1540 1550
TGTSSIPYEG FASLRGSNGP RRFCVEKWGK ITALPRAHTC FNRLDLPPYP
1560 1570
SFSMLYEKLL TAVEETSTFG LE
Length:1,572
Mass (Da):175,769
Last modified:February 20, 2007 - v2
Checksum:iDCFF0146ADFAF8BE
GO
Isoform 2 (identifier: Q9P2P5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-131: Missing.
     191-213: DLRAVGLKKGMFFNPDPYLKMSI → ARKEEQFPHLCPPRAGETVYYHQ
     214-1572: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:82
Mass (Da):9,041
Checksum:i954974F23D7CB9F5
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2C9F2N4A0A2C9F2N4_HUMAN
E3 ubiquitin-protein ligase HECW2
HECW2
1,216Annotation score:
A0A2R8Y6F3A0A2R8Y6F3_HUMAN
E3 ubiquitin-protein ligase HECW2
HECW2
1,579Annotation score:
A0A2R8YE75A0A2R8YE75_HUMAN
E3 ubiquitin-protein ligase HECW2
HECW2
814Annotation score:
C9JHL2C9JHL2_HUMAN
E3 ubiquitin-protein ligase HECW2
HECW2
120Annotation score:

Sequence cautioni

The sequence BAA92539 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAH18262 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1074Q → H in CAH18262 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0779051191R → Q in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854416EnsemblClinVar.1
Natural variantiVAR_0779061193F → V in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854422EnsemblClinVar.1
Natural variantiVAR_0779071330R → W in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854417EnsemblClinVar.1
Natural variantiVAR_0779081445E → G in NDHSAL. 1 PublicationCorresponds to variant dbSNP:rs878854424EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0591061 – 131Missing in isoform 2. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_059107191 – 213DLRAV…LKMSI → ARKEEQFPHLCPPRAGETVY YHQ in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_059108214 – 1572Missing in isoform 2. 1 PublicationAdd BLAST1359

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037722 mRNA Translation: BAA92539.1 Different initiation.
AL390186 mRNA Translation: CAB99103.1
CR749424 mRNA Translation: CAH18262.1 Sequence problems.
AC020571 Genomic DNA No translation available.
AC068544 Genomic DNA No translation available.
AC073905 Genomic DNA No translation available.
AC074090 Genomic DNA No translation available.
AC093379 Genomic DNA No translation available.
BC117194 mRNA Translation: AAI17195.1
BC117198 mRNA Translation: AAI17199.1
CCDSiCCDS33354.1 [Q9P2P5-1]
PIRiT51886
RefSeqiNP_065811.1, NM_020760.2 [Q9P2P5-1]
XP_016860052.1, XM_017004563.1
UniGeneiHs.633212
Hs.654742

Genome annotation databases

EnsembliENST00000260983; ENSP00000260983; ENSG00000138411 [Q9P2P5-1]
ENST00000644256; ENSP00000494649; ENSG00000138411 [Q9P2P5-1]
ENST00000644978; ENSP00000495418; ENSG00000138411 [Q9P2P5-1]
ENST00000647236; ENSP00000494800; ENSG00000138411 [Q9P2P5-2]
GeneIDi57520
KEGGihsa:57520
UCSCiuc002utl.2 human [Q9P2P5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB037722 mRNA Translation: BAA92539.1 Different initiation.
AL390186 mRNA Translation: CAB99103.1
CR749424 mRNA Translation: CAH18262.1 Sequence problems.
AC020571 Genomic DNA No translation available.
AC068544 Genomic DNA No translation available.
AC073905 Genomic DNA No translation available.
AC074090 Genomic DNA No translation available.
AC093379 Genomic DNA No translation available.
BC117194 mRNA Translation: AAI17195.1
BC117198 mRNA Translation: AAI17199.1
CCDSiCCDS33354.1 [Q9P2P5-1]
PIRiT51886
RefSeqiNP_065811.1, NM_020760.2 [Q9P2P5-1]
XP_016860052.1, XM_017004563.1
UniGeneiHs.633212
Hs.654742

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LFENMR-A43-162[»]
ProteinModelPortaliQ9P2P5
SMRiQ9P2P5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121581, 301 interactors
IntActiQ9P2P5, 1 interactor
MINTiQ9P2P5
STRINGi9606.ENSP00000260983

PTM databases

iPTMnetiQ9P2P5
PhosphoSitePlusiQ9P2P5

Polymorphism and mutation databases

BioMutaiHECW2
DMDMi126215718

Proteomic databases

EPDiQ9P2P5
MaxQBiQ9P2P5
PaxDbiQ9P2P5
PeptideAtlasiQ9P2P5
PRIDEiQ9P2P5
ProteomicsDBi83874
83875 [Q9P2P5-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260983; ENSP00000260983; ENSG00000138411 [Q9P2P5-1]
ENST00000644256; ENSP00000494649; ENSG00000138411 [Q9P2P5-1]
ENST00000644978; ENSP00000495418; ENSG00000138411 [Q9P2P5-1]
ENST00000647236; ENSP00000494800; ENSG00000138411 [Q9P2P5-2]
GeneIDi57520
KEGGihsa:57520
UCSCiuc002utl.2 human [Q9P2P5-1]

Organism-specific databases

CTDi57520
DisGeNETi57520
EuPathDBiHostDB:ENSG00000138411.10
GeneCardsiHECW2
HGNCiHGNC:29853 HECW2
HPAiHPA034609
MalaCardsiHECW2
MIMi617245 gene
617268 phenotype
neXtProtiNX_Q9P2P5
OpenTargetsiENSG00000138411
PharmGKBiPA134925001
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000069940
HOVERGENiHBG057414
InParanoidiQ9P2P5
KOiK12168
OMAiEDMPGGH
OrthoDBiEOG091G0A54
PhylomeDBiQ9P2P5
TreeFamiTF313938

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9P2P5

Miscellaneous databases

ChiTaRSiHECW2 human
GenomeRNAii57520
PROiPR:Q9P2P5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138411 Expressed in 176 organ(s), highest expression level in corpus callosum
CleanExiHS_HECW2
ExpressionAtlasiQ9P2P5 baseline and differential
GenevisibleiQ9P2P5 HS

Family and domain databases

CDDicd08691 C2_NEDL1-like, 1 hit
cd00078 HECTc, 1 hit
cd00201 WW, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037795 C2_HECW
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR032348 HECW_N
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00632 HECT, 1 hit
PF16562 HECW_N, 1 hit
PF00397 WW, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 2 hits
SUPFAMiSSF51045 SSF51045, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 2 hits
PS50020 WW_DOMAIN_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiHECW2_HUMAN
AccessioniPrimary (citable) accession number: Q9P2P5
Secondary accession number(s): B8ZZB4
, Q17RT5, Q68DF8, Q9NPS9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: February 20, 2007
Last modified: November 7, 2018
This is version 142 of the entry and version 2 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 2
    Human chromosome 2: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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