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Q9WVS7

- MP2K5_MOUSE

UniProt

Q9WVS7 - MP2K5_MOUSE

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Protein

Dual specificity mitogen-activated protein kinase kinase 5

Gene

Map2k5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei195 – 1951ATPPROSITE-ProRule annotation
Active sitei283 – 2831Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi172 – 1809ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein serine/threonine kinase activity Source: UniProtKB-KW
  4. protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

  1. activation of MAPK activity Source: Ensembl
  2. cellular response to growth factor stimulus Source: Ensembl
  3. ERK5 cascade Source: Ensembl
  4. heart development Source: MGI
  5. MAPK cascade Source: MGI
  6. negative regulation of cell migration involved in sprouting angiogenesis Source: Ensembl
  7. negative regulation of chemokine (C-X-C motif) ligand 2 production Source: Ensembl
  8. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  9. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  10. negative regulation of heterotypic cell-cell adhesion Source: Ensembl
  11. negative regulation of interleukin-8 biosynthetic process Source: Ensembl
  12. negative regulation of NF-kappaB transcription factor activity Source: Ensembl
  13. negative regulation of response to cytokine stimulus Source: Ensembl
  14. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  15. positive regulation of cell growth Source: Ensembl
  16. positive regulation of epithelial cell proliferation Source: Ensembl
  17. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_216232. Signalling to ERK5.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 5 (EC:2.7.12.2)
Short name:
MAP kinase kinase 5
Short name:
MAPKK 5
Alternative name(s):
MAPK/ERK kinase 5
Short name:
MEK 5
Gene namesi
Name:Map2k5
Synonyms:Mek5, Mkk5, Prkmk5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1346345. Map2k5.

Subcellular locationi

Cytoplasm By similarity

GO - Cellular componenti

  1. cytosol Source: Ensembl
  2. nucleus Source: Ensembl
  3. spindle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi20 – 201R → A: Loss of MAPK7 binding; when associated with A-21. 1 Publication
Mutagenesisi21 – 211I → A: Loss of MAPK7 binding; when associated with A-20. 1 Publication
Mutagenesisi64 – 641D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-65. 1 Publication
Mutagenesisi65 – 651E → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-64. 1 Publication
Mutagenesisi67 – 671G → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-68. 1 Publication
Mutagenesisi68 – 681D → A: Loss of MAP3K2/MAP3K3 binding; when associated with A-67. 1 Publication
Mutagenesisi311 – 3111S → A: Dominant negative form; when associated with V-315. 1 Publication
Mutagenesisi311 – 3111S → D: Dominant active form; when associated with D-315. 1 Publication
Mutagenesisi315 – 3151T → D: Dominant active form; when associated with D-311. 1 Publication
Mutagenesisi315 – 3151T → V: Dominant negative form; when associated with A-311. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 448448Dual specificity mitogen-activated protein kinase kinase 5PRO_0000086384Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei311 – 3111PhosphoserineBy similarity
Modified residuei315 – 3151PhosphothreonineBy similarity

Post-translational modificationi

Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9WVS7.
PaxDbiQ9WVS7.
PRIDEiQ9WVS7.

PTM databases

PhosphoSiteiQ9WVS7.

Expressioni

Gene expression databases

BgeeiQ9WVS7.
CleanExiMM_MAP2K5.
GenevestigatoriQ9WVS7.

Interactioni

Subunit structurei

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Map3k2Q610834EBI-446144,EBI-446134
Map3k3Q6108415EBI-446144,EBI-446250
Nap1l1P2865620EBI-446144,EBI-645055
Sqstm1Q643373EBI-446144,EBI-645025

Protein-protein interaction databases

IntActiQ9WVS7. 10 interactions.
MINTiMINT-1728345.

Structurei

Secondary structure

1
448
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi17 – 226
Beta strandi28 – 347
Beta strandi36 – 383
Helixi41 – 5111
Beta strandi60 – 623
Beta strandi70 – 745
Helixi75 – 9521
Beta strandi102 – 1065

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WI0NMR-A8-107[»]
ProteinModelPortaliQ9WVS7.
SMRiQ9WVS7. Positions 16-438.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9WVS7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 9780OPRAdd
BLAST
Domaini166 – 419254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni18 – 258Interaction with MAPK7
Regioni64 – 685Interaction with MAP3K2/MAP3K3
Regioni117 – 13115Interaction with MAPK7Add
BLAST

Domaini

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the OPR domain. This domain also mediates interactions with SQSTM1 and PARD6A.2 Publications

Sequence similaritiesi

Contains 1 OPR domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ9WVS7.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG7HF1KZ.
PhylomeDBiQ9WVS7.
TreeFamiTF106468.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9WVS7-1) [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
MLWLALGPFC AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ
60 70 80 90 100
VLPEATTTAF EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE
110 120 130 140 150
PLQIFPRACK PPGERNIHGL KVNTRAGPSQ HTSPVVSDSL PSNSLKKSSA
160 170 180 190 200
ELRKILANGQ MNEQDIRYRD TLGHGNGGTV YKAHHVPSGK ILAVKVILLD
210 220 230 240 250
ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC TEFMDGGSLD
260 270 280 290 300
VYRKIPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTGGQVKLC
310 320 330 340 350
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA
360 370 380 390 400
LGRFPYPQIQ KNQGSLMPLQ LLQCIVDEDS PVLPLGEFSE PFVHFITQCM
410 420 430 440
RKQPKERPAP EELMGHPFIV QFNDGNSTVV SMWVCRALEE RRSQQGPP
Length:448
Mass (Da):50,105
Last modified:November 1, 1999 - v1
Checksum:i50C50E8F0F712BE7
GO
Isoform 2 (identifier: Q9WVS7-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-367: Missing.

Show »
Length:439
Mass (Da):49,105
Checksum:iABAFCC35482F0EF6
GO
Isoform 3 (identifier: Q9WVS7-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     183-186: AHHV → LLHI
     187-448: Missing.

Show »
Length:186
Mass (Da):20,737
Checksum:i9978D2D647198D15
GO
Isoform 4 (identifier: Q9WVS7-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     108-118: ACKPPGERNIH → GYRRGSRLREY
     119-448: Missing.

Show »
Length:118
Mass (Da):13,589
Checksum:iCACEC8FE6518544A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei108 – 11811ACKPPGERNIH → GYRRGSRLREY in isoform 4. 1 PublicationVSP_015836Add
BLAST
Alternative sequencei119 – 448330Missing in isoform 4. 1 PublicationVSP_015837Add
BLAST
Alternative sequencei183 – 1864AHHV → LLHI in isoform 3. 1 PublicationVSP_015838
Alternative sequencei187 – 448262Missing in isoform 3. 1 PublicationVSP_015839Add
BLAST
Alternative sequencei359 – 3679Missing in isoform 2. 1 PublicationVSP_015840

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB019374 mRNA. Translation: BAA82040.1.
AK020716 mRNA. Translation: BAB32187.1.
BC013697 mRNA. Translation: AAH13697.1.
BC028260 mRNA. Translation: AAH28260.1.
CCDSiCCDS23269.1. [Q9WVS7-1]
RefSeqiNP_035970.1. NM_011840.2. [Q9WVS7-1]
XP_006511208.1. XM_006511145.1. [Q9WVS7-2]
UniGeneiMm.325746.

Genome annotation databases

EnsembliENSMUST00000034920; ENSMUSP00000034920; ENSMUSG00000058444. [Q9WVS7-1]
GeneIDi23938.
KEGGimmu:23938.
UCSCiuc009qaw.1. mouse. [Q9WVS7-1]
uc009qaz.1. mouse. [Q9WVS7-4]
uc012guv.1. mouse. [Q9WVS7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB019374 mRNA. Translation: BAA82040.1 .
AK020716 mRNA. Translation: BAB32187.1 .
BC013697 mRNA. Translation: AAH13697.1 .
BC028260 mRNA. Translation: AAH28260.1 .
CCDSi CCDS23269.1. [Q9WVS7-1 ]
RefSeqi NP_035970.1. NM_011840.2. [Q9WVS7-1 ]
XP_006511208.1. XM_006511145.1. [Q9WVS7-2 ]
UniGenei Mm.325746.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1WI0 NMR - A 8-107 [» ]
ProteinModelPortali Q9WVS7.
SMRi Q9WVS7. Positions 16-438.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q9WVS7. 10 interactions.
MINTi MINT-1728345.

PTM databases

PhosphoSitei Q9WVS7.

Proteomic databases

MaxQBi Q9WVS7.
PaxDbi Q9WVS7.
PRIDEi Q9WVS7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000034920 ; ENSMUSP00000034920 ; ENSMUSG00000058444 . [Q9WVS7-1 ]
GeneIDi 23938.
KEGGi mmu:23938.
UCSCi uc009qaw.1. mouse. [Q9WVS7-1 ]
uc009qaz.1. mouse. [Q9WVS7-4 ]
uc012guv.1. mouse. [Q9WVS7-2 ]

Organism-specific databases

CTDi 5607.
MGIi MGI:1346345. Map2k5.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119199.
HOGENOMi HOG000234206.
HOVERGENi HBG108518.
InParanoidi Q9WVS7.
KOi K04463.
OMAi EVVSMWV.
OrthoDBi EOG7HF1KZ.
PhylomeDBi Q9WVS7.
TreeFami TF106468.

Enzyme and pathway databases

Reactomei REACT_216232. Signalling to ERK5.

Miscellaneous databases

ChiTaRSi MAP2K5. mouse.
EvolutionaryTracei Q9WVS7.
NextBioi 303741.
PROi Q9WVS7.
SOURCEi Search...

Gene expression databases

Bgeei Q9WVS7.
CleanExi MM_MAP2K5.
Genevestigatori Q9WVS7.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus."
    Kamakura S., Moriguchi T., Nishida E.
    J. Biol. Chem. 274:26563-26571(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF SER-311 AND THR-315.
    Tissue: Brain.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
    Strain: C57BL/6J.
    Tissue: Head and Hypothalamus.
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Strain: Czech II.
    Tissue: Mammary gland.
  4. "Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins."
    Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T.
    J. Biol. Chem. 278:34568-34581(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SQSTM1; PRKCZ; PRKCI; PARD6A AND MAP3K3, DOMAIN.
  5. "PB1 domain-dependent signaling complex is required for extracellular signal-regulated kinase 5 activation."
    Nakamura K., Uhlik M.T., Johnson N.L., Hahn K.M., Johnson G.L.
    Mol. Cell. Biol. 26:2065-2079(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DOMAIN, INTERACTION WITH MAP3K2 AND MAPK7, MUTAGENESIS OF ARG-20; ILE-21; ASP-64; GLU-65; GLY-67 AND ASP-68.
  6. "Solution structure of the PB1 domain of mouse mitogen activated protein kinase kinase 5 (MAP2K5)."
    RIKEN structural genomics initiative (RSGI)
    Submitted (JAN-2006) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 7-107.

Entry informationi

Entry nameiMP2K5_MOUSE
AccessioniPrimary (citable) accession number: Q9WVS7
Secondary accession number(s): Q8CFM3, Q8K360, Q9D222
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: November 1, 1999
Last modified: October 29, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3