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Protein

E3 ubiquitin-protein ligase TRIM37

Gene

TRIM37

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

Functioni

E3 ubiquitin-protein ligase required to prevent centriole reduplication (PubMed:15885686, PubMed:23769972). Probably acts by ubiquitinating positive regulators of centriole reduplication (PubMed:23769972). Mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression: associates with some Polycomb group (PcG) multiprotein PRC2-like complex and mediates repression of target genes (PubMed:25470042). Has anti-HIV activity (PubMed:24317724).4 Publications

Miscellaneous

Acts as a proto-oncogene via its ability to monoubiquinate 'Lys-119' of histone H2A (H2AK119Ub): overexpressed in a number of breast cancers and promotes transformation of cells by mediating silencing of tumor suppressor genes (PubMed:25470042).1 Publication

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.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.2 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 55RING-type; degeneratePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri90 – 132B box-typePROSITE-ProRule annotationAdd BLAST43

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRepressor, Transferase
Biological processTranscription, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiO94972
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIM37Curated (EC:2.3.2.271 Publication)
Alternative name(s):
Mulibrey nanism protein1 Publication
RING-type E3 ubiquitin transferase TRIM37Curated
Tripartite motif-containing protein 37Curated
Gene namesi
Name:TRIM37Imported
Synonyms:KIAA0898, MUL1 Publication, POB11 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108395.13
HGNCiHGNC:7523 TRIM37
MIMi605073 gene
neXtProtiNX_O94972

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, Peroxisome

Pathology & Biotechi

Involvement in diseasei

Mulibrey nanism (MUL)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive growth disorder characterized by severe growth failure of prenatal onset, constrictive pericardium and progressive cardiomyopathy, facial dysmorphism, and failure of sexual maturation. Additional clinical features include hepatomegaly, muscle hypotonia, J-shaped sella turcica, yellowish dots in the ocular fundi, hypoplasia of various endocrine glands, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor.
See also OMIM:253250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06021776L → P in MUL; decreased ubiquitination and abolishes the formation of perinuclear aggregates. 1 PublicationCorresponds to variant dbSNP:rs386834004EnsemblClinVar.1
Natural variantiVAR_060219109C → S in MUL; no effect on E3 ubiquitin-protein ligase activity. 1 PublicationCorresponds to variant dbSNP:rs121908391EnsemblClinVar.1
Natural variantiVAR_060220322G → V in MUL; no effect on ubiquitination but affects subcellular localization. 2 PublicationsCorresponds to variant dbSNP:rs386834009EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18C → R: Abolishes ability to monoubiquitinate 'Lys-119' of histone H2A (H2AK119Ub). 1 Publication1
Mutagenesisi35 – 36CC → SS: Reduces ubiquitination and abolishes the formation of perinuclear aggregates. 1 Publication2

Keywords - Diseasei

Dwarfism, Proto-oncogene

Organism-specific databases

DisGeNETi4591
MalaCardsiTRIM37
MIMi253250 phenotype
OpenTargetsiENSG00000108395
Orphaneti2576 MULIBREY nanism
PharmGKBiPA35497

Polymorphism and mutation databases

BioMutaiTRIM37

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000562541 – 964E3 ubiquitin-protein ligase TRIM37Add BLAST964

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei454PhosphoserineCombined sources1

Post-translational modificationi

Auto-ubiquitinated.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO94972
MaxQBiO94972
PaxDbiO94972
PeptideAtlasiO94972
PRIDEiO94972
ProteomicsDBi50590
50591 [O94972-2]

PTM databases

iPTMnetiO94972
PhosphoSitePlusiO94972

Expressioni

Tissue specificityi

Ubiquitous (PubMed:10888877). Highly expressed in testis, while it is weakly expressed in other tissues (PubMed:16310976).2 Publications

Inductioni

Overexpressed in a number of breast cancer cell lines.1 Publication

Gene expression databases

BgeeiENSG00000108395 Expressed in 228 organ(s), highest expression level in endometrium epithelium
CleanExiHS_TRIM37
ExpressionAtlasiO94972 baseline and differential
GenevisibleiO94972 HS

Organism-specific databases

HPAiHPA021911

Interactioni

Subunit structurei

Associates with the PRC2/EED-EZH2 complex.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110678, 100 interactors
DIPiDIP-34437N
IntActiO94972, 66 interactors
STRINGi9606.ENSP00000262294

Structurei

Secondary structure

1964
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO94972
SMRiO94972
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94972

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini276 – 403MATHPROSITE-ProRule annotationAdd BLAST128

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili132 – 234Sequence analysisAdd BLAST103
Coiled coili419 – 450Sequence analysisAdd BLAST32
Coiled coili673 – 700Sequence analysisAdd BLAST28

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi534 – 540Poly-Ser7
Compositional biasi578 – 581Poly-Ala4

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri15 – 55RING-type; degeneratePROSITE-ProRule annotationAdd BLAST41
Zinc fingeri90 – 132B box-typePROSITE-ProRule annotationAdd BLAST43

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITG1 Eukaryota
ENOG410YSD5 LUCA
GeneTreeiENSGT00410000025800
HOGENOMiHOG000013010
HOVERGENiHBG057591
InParanoidiO94972
KOiK10608
OMAiTQMAEVR
OrthoDBiEOG091G01C1
PhylomeDBiO94972
TreeFamiTF351092

Family and domain databases

CDDicd00021 BBOX, 1 hit
cd03773 MATH_TRIM37, 1 hit
Gene3Di2.60.210.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR003649 Bbox_C
IPR002083 MATH/TRAF_dom
IPR008974 TRAF-like
IPR037299 TRIM37_MATH
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF00917 MATH, 1 hit
PF00643 zf-B_box, 1 hit
SMARTiView protein in SMART
SM00502 BBC, 1 hit
SM00336 BBOX, 1 hit
SM00061 MATH, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
PROSITEiView protein in PROSITE
PS50144 MATH, 1 hit
PS50119 ZF_BBOX, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 7 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: O94972-1) [UniParc]FASTAAdd to basket
Also known as: TRIM37a1 Publication, TRIM37b1 Publication

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
MDEQSVESIA EVFRCFICME KLRDARLCPH CSKLCCFSCI RRWLTEQRAQ
60 70 80 90 100
CPHCRAPLQL RELVNCRWAE EVTQQLDTLQ LCSLTKHEEN EKDKCENHHE
110 120 130 140 150
KLSVFCWTCK KCICHQCALW GGMHGGHTFK PLAEIYEQHV TKVNEEVAKL
160 170 180 190 200
RRRLMELISL VQEVERNVEA VRNAKDERVR EIRNAVEMMI ARLDTQLKNK
210 220 230 240 250
LITLMGQKTS LTQETELLES LLQEVEHQLR SCSKSELISK SSEILMMFQQ
260 270 280 290 300
VHRKPMASFV TTPVPPDFTS ELVPSYDSAT FVLENFSTLR QRADPVYSPP
310 320 330 340 350
LQVSGLCWRL KVYPDGNGVV RGYYLSVFLE LSAGLPETSK YEYRVEMVHQ
360 370 380 390 400
SCNDPTKNII REFASDFEVG ECWGYNRFFR LDLLANEGYL NPQNDTVILR
410 420 430 440 450
FQVRSPTFFQ KSRDQHWYIT QLEAAQTSYI QQINNLKERL TIELSRTQKS
460 470 480 490 500
RDLSPPDNHL SPQNDDALET RAKKSACSDM LLEGGPTTAS VREAKEDEED
510 520 530 540 550
EEKIQNEDYH HELSDGDLDL DLVYEDEVNQ LDGSSSSASS TATSNTEEND
560 570 580 590 600
IDEETMSGEN DVEYNNMELE EGELMEDAAA AGPAGSSHGY VGSSSRISRR
610 620 630 640 650
THLCSAATSS LLDIDPLILI HLLDLKDRSS IENLWGLQPR PPASLLQPTA
660 670 680 690 700
SYSRKDKDQR KQQAMWRVPS DLKMLKRLKT QMAEVRCMKT DVKNTLSEIK
710 720 730 740 750
SSSAASGDMQ TSLFSADQAA LAACGTENSG RLQDLGMELL AKSSVANCYI
760 770 780 790 800
RNSTNKKSNS PKPARSSVAG SLSLRRAVDP GENSRSKGDC QTLSEGSPGS
810 820 830 840 850
SQSGSRHSSP RALIHGSIGD ILPKTEDRQC KALDSDAVVV AVFSGLPAVE
860 870 880 890 900
KRRKMVTLGA NAKGGHLEGL QMTDLENNSE TGELQPVLPE GASAAPEEGM
910 920 930 940 950
SSDSDIECDT ENEEQEEHTS VGGFHDSFMV MTQPPDEDTH SSFPDGEQIG
960
PEDLSFNTDE NSGR
Length:964
Mass (Da):107,906
Last modified:November 23, 2004 - v2
Checksum:iC0F08D5A5DC3B5AC
GO
Isoform 2 (identifier: O94972-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-122: Missing.
     899-937: Missing.

Note: No experimental confirmation available.
Show »
Length:803
Mass (Da):89,186
Checksum:i43486E1064478477
GO
Isoform 3 (identifier: O94972-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     8-41: Missing.

Show »
Length:930
Mass (Da):103,941
Checksum:i9AD3B427995A9961
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KT90J3KT90_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
194Annotation score:
J3QRK3J3QRK3_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
103Annotation score:
J3QSH5J3QSH5_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
113Annotation score:
J3QSA0J3QSA0_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
58Annotation score:
J3KS72J3KS72_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
67Annotation score:
J3KT32J3KT32_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
54Annotation score:
J3QSF6J3QSF6_HUMAN
E3 ubiquitin-protein ligase TRIM37
TRIM37
117Annotation score:

Sequence cautioni

The sequence BAA74921 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti620I → M in BAF85148 (PubMed:14702039).Curated1
Sequence conflicti624D → A in AAL36460 (Ref. 1) Curated1
Sequence conflicti916E → G in BAG57954 (PubMed:10048485).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06021776L → P in MUL; decreased ubiquitination and abolishes the formation of perinuclear aggregates. 1 PublicationCorresponds to variant dbSNP:rs386834004EnsemblClinVar.1
Natural variantiVAR_060218108T → A1 PublicationCorresponds to variant dbSNP:rs17853504Ensembl.1
Natural variantiVAR_060219109C → S in MUL; no effect on E3 ubiquitin-protein ligase activity. 1 PublicationCorresponds to variant dbSNP:rs121908391EnsemblClinVar.1
Natural variantiVAR_060220322G → V in MUL; no effect on ubiquitination but affects subcellular localization. 2 PublicationsCorresponds to variant dbSNP:rs386834009EnsemblClinVar.1
Natural variantiVAR_075470432Q → R1 Publication1
Natural variantiVAR_052142838V → I. Corresponds to variant dbSNP:rs7222388EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0119191 – 122Missing in isoform 2. 1 PublicationAdd BLAST122
Alternative sequenceiVSP_0574688 – 41Missing in isoform 3. Add BLAST34
Alternative sequenceiVSP_011920899 – 937Missing in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF213365 mRNA Translation: AAL36460.1
AB020705 mRNA Translation: BAA74921.1 Different initiation.
AK289674 mRNA Translation: BAF82363.1
AK294850 mRNA Translation: BAG57954.1
AK292459 mRNA Translation: BAF85148.1
BX537955 mRNA Translation: CAD97922.1
AC005207 Genomic DNA No translation available.
AC036154 Genomic DNA No translation available.
AC099850 Genomic DNA No translation available.
AC100832 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94425.1
CH471109 Genomic DNA Translation: EAW94426.1
BC036012 mRNA Translation: AAH36012.1
CCDSiCCDS32694.1 [O94972-1]
CCDS45746.1 [O94972-1]
CCDS82174.1 [O94972-3]
RefSeqiNP_001005207.1, NM_001005207.3 [O94972-1]
NP_001307916.1, NM_001320987.1 [O94972-3]
NP_001307919.1, NM_001320990.1 [O94972-2]
NP_056109.1, NM_015294.4 [O94972-1]
UniGeneiHs.579079
Hs.605697

Genome annotation databases

EnsembliENST00000262294; ENSP00000262294; ENSG00000108395 [O94972-1]
ENST00000393065; ENSP00000376784; ENSG00000108395 [O94972-3]
ENST00000393066; ENSP00000376785; ENSG00000108395 [O94972-1]
GeneIDi4591
KEGGihsa:4591
UCSCiuc002iwy.5 human [O94972-1]
uc010woc.3 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF213365 mRNA Translation: AAL36460.1
AB020705 mRNA Translation: BAA74921.1 Different initiation.
AK289674 mRNA Translation: BAF82363.1
AK294850 mRNA Translation: BAG57954.1
AK292459 mRNA Translation: BAF85148.1
BX537955 mRNA Translation: CAD97922.1
AC005207 Genomic DNA No translation available.
AC036154 Genomic DNA No translation available.
AC099850 Genomic DNA No translation available.
AC100832 Genomic DNA No translation available.
CH471109 Genomic DNA Translation: EAW94425.1
CH471109 Genomic DNA Translation: EAW94426.1
BC036012 mRNA Translation: AAH36012.1
CCDSiCCDS32694.1 [O94972-1]
CCDS45746.1 [O94972-1]
CCDS82174.1 [O94972-3]
RefSeqiNP_001005207.1, NM_001005207.3 [O94972-1]
NP_001307916.1, NM_001320987.1 [O94972-3]
NP_001307919.1, NM_001320990.1 [O94972-2]
NP_056109.1, NM_015294.4 [O94972-1]
UniGeneiHs.579079
Hs.605697

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3LRQX-ray2.29A/B/C/D1-90[»]
ProteinModelPortaliO94972
SMRiO94972
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110678, 100 interactors
DIPiDIP-34437N
IntActiO94972, 66 interactors
STRINGi9606.ENSP00000262294

PTM databases

iPTMnetiO94972
PhosphoSitePlusiO94972

Polymorphism and mutation databases

BioMutaiTRIM37

Proteomic databases

EPDiO94972
MaxQBiO94972
PaxDbiO94972
PeptideAtlasiO94972
PRIDEiO94972
ProteomicsDBi50590
50591 [O94972-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262294; ENSP00000262294; ENSG00000108395 [O94972-1]
ENST00000393065; ENSP00000376784; ENSG00000108395 [O94972-3]
ENST00000393066; ENSP00000376785; ENSG00000108395 [O94972-1]
GeneIDi4591
KEGGihsa:4591
UCSCiuc002iwy.5 human [O94972-1]
uc010woc.3 human

Organism-specific databases

CTDi4591
DisGeNETi4591
EuPathDBiHostDB:ENSG00000108395.13
GeneCardsiTRIM37
H-InvDBiHIX0014039
HGNCiHGNC:7523 TRIM37
HPAiHPA021911
MalaCardsiTRIM37
MIMi253250 phenotype
605073 gene
neXtProtiNX_O94972
OpenTargetsiENSG00000108395
Orphaneti2576 MULIBREY nanism
PharmGKBiPA35497
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITG1 Eukaryota
ENOG410YSD5 LUCA
GeneTreeiENSGT00410000025800
HOGENOMiHOG000013010
HOVERGENiHBG057591
InParanoidiO94972
KOiK10608
OMAiTQMAEVR
OrthoDBiEOG091G01C1
PhylomeDBiO94972
TreeFamiTF351092

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiO94972

Miscellaneous databases

ChiTaRSiTRIM37 human
EvolutionaryTraceiO94972
GeneWikiiTRIM37
GenomeRNAii4591
PROiPR:O94972
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108395 Expressed in 228 organ(s), highest expression level in endometrium epithelium
CleanExiHS_TRIM37
ExpressionAtlasiO94972 baseline and differential
GenevisibleiO94972 HS

Family and domain databases

CDDicd00021 BBOX, 1 hit
cd03773 MATH_TRIM37, 1 hit
Gene3Di2.60.210.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR003649 Bbox_C
IPR002083 MATH/TRAF_dom
IPR008974 TRAF-like
IPR037299 TRIM37_MATH
IPR000315 Znf_B-box
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF00917 MATH, 1 hit
PF00643 zf-B_box, 1 hit
SMARTiView protein in SMART
SM00502 BBC, 1 hit
SM00336 BBOX, 1 hit
SM00061 MATH, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
PROSITEiView protein in PROSITE
PS50144 MATH, 1 hit
PS50119 ZF_BBOX, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRI37_HUMAN
AccessioniPrimary (citable) accession number: O94972
Secondary accession number(s): A8K0V9
, A8K8U4, A8MZ79, B4DGZ3, F8WEE6, Q7Z3E6, Q8IYF7, Q8WYF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: November 23, 2004
Last modified: September 12, 2018
This is version 172 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
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Main funding by: National Institutes of Health

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