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A4FU01

- MTMRB_HUMAN

UniProt

A4FU01 - MTMRB_HUMAN

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Protein

Myotubularin-related protein 11

Gene

MTMR11

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at transcript leveli

Functioni

Probable pseudophosphatase. Contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase (Potential).Curated

GO - Molecular functioni

  1. phosphatase activity Source: InterPro
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Myotubularin-related protein 11
Alternative name(s):
Cisplatin resistance-associated protein
Short name:
hCRA
Gene namesi
Name:MTMR11
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:24307. MTMR11.

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142671303.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 709709Myotubularin-related protein 11PRO_0000337098Add
BLAST

Proteomic databases

PaxDbiA4FU01.
PRIDEiA4FU01.

PTM databases

PhosphoSiteiA4FU01.

Expressioni

Tissue specificityi

Expressed in bone marrow, spleen and thymus.1 Publication

Gene expression databases

BgeeiA4FU01.
CleanExiHS_MTMR11.
GenevestigatoriA4FU01.

Organism-specific databases

HPAiHPA030351.

Interactioni

Protein-protein interaction databases

BioGridi116109. 1 interaction.
IntActiA4FU01. 1 interaction.
MINTiMINT-1186094.

Structurei

3D structure databases

ProteinModelPortaliA4FU01.
SMRiA4FU01. Positions 46-535.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini196 – 639444Myotubularin phosphatasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 myotubularin phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG299000.
GeneTreeiENSGT00760000118832.
HOVERGENiHBG108155.
InParanoidiA4FU01.
KOiK18085.
OMAiGPRLSWH.
OrthoDBiEOG7K0ZBZ.
PhylomeDBiA4FU01.
TreeFamiTF315197.

Family and domain databases

InterProiIPR010569. Myotubularin-like_Pase_dom.
IPR022587. Myotubularin_assoc.
IPR029021. Prot-tyrosine_phosphatase-like.
[Graphical view]
PfamiPF12578. 3-PAP. 1 hit.
PF06602. Myotub-related. 1 hit.
[Graphical view]
SUPFAMiSSF52799. SSF52799. 2 hits.
PROSITEiPS51339. PPASE_MYOTUBULARIN. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: A4FU01-1) [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
MWWGGRGQSF NIAPQKEEPE MGSVQENRMP EPRSRQPSSC LASRCLPGEQ
60 70 80 90 100
ILAWAPGVRK GLEPELSGTL ICTNFRVTFQ PCGWQWNQDT PLNSEYDFAL
110 120 130 140 150
VNIGRLEAVS GLSRVQLLRP GSLHKFIPEE ILIHGRDFRL LRVGFEAGGL
160 170 180 190 200
EPQAFQVTMA IVQARAQSNQ AQQYSGITLS KAGQGSGSRK PPIPLMETAE
210 220 230 240 250
DWETERKKQA ARGWRVSTVN ERFDVATSLP RYFWVPNRIL DSEVRRAFGH
260 270 280 290 300
FHQGRGPRLS WHHPGGSDLL RCGGFYTASD PNKEDIRAVE LMLQAGHSDV
310 320 330 340 350
VLVDTMDELP SLADVQLAHL RLRALCLPDS SVAEDKWLSA LEGTRWLDYV
360 370 380 390 400
RACLRKASDI SVLVTSRVRS VILQERGDRD LNGLLSSLVQ LLSAPEARTL
410 420 430 440 450
FGFQSLVQRE WVAAGHPFLT RLGGTGASEE APVFLLFLDC VWQLLQQFPA
460 470 480 490 500
DFEFSEFFLL ALHDSVRVPD TLTFLRNTPW ERGKQSGQLN SYTQVYTPGY
510 520 530 540 550
SQPPAGNSFN LQLSVWDWDL RYSNAQILQF QNPGYDPEHC PDSWLPRPQP
560 570 580 590 600
SFMVPGPPSS VWLFSRGALT PLNQLCPWRD SPSLLAVSSR WLPRPAISSE
610 620 630 640 650
SLADQEWGLP SHWGACPLPP GLLLPGYLGP QIRLWRRCYL RGRPEVQMGL
660 670 680 690 700
SAPTISGLQD ELSHLQELLR KWTPRISPED HSKKRDPHTI LNPTEIAGIL

KGRAEGDLG
Length:709
Mass (Da):79,545
Last modified:May 20, 2008 - v2
Checksum:iAC07581E26364D1F
GO
Isoform 2 (identifier: A4FU01-2) [UniParc]FASTAAdd to Basket

Also known as: hCRA alpha

The sequence of this isoform differs from the canonical sequence as follows:
     258-268: RLSWHHPGGSD → VSVMVRVMAVD
     269-709: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Show »
Length:268
Mass (Da):30,116
Checksum:i3767F7815C94AAE0
GO
Isoform 3 (identifier: A4FU01-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.
     258-268: RLSWHHPGGSD → VSVMVRVMAVD
     269-709: 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:240
Mass (Da):26,885
Checksum:iE8D6FA7FD8657504
GO
Isoform 4 (identifier: A4FU01-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-72: Missing.
     73-75: TNF → MPP
     703-709: RAEGDLG → QSHPFWITRC

Show »
Length:640
Mass (Da):72,117
Checksum:iDB67312F79750231
GO
Isoform 5 (identifier: A4FU01-5) [UniParc]FASTAAdd to Basket

Also known as: hCRA beta

The sequence of this isoform differs from the canonical sequence as follows:
     228-272: SLPRYFWVPN...HPGGSDLLRC → RLRCFSSSLI...VSGFLTPLPS
     273-709: Missing.

Note: No experimental confirmation available.

Show »
Length:272
Mass (Da):30,195
Checksum:i24FE481676EF146D
GO
Isoform 6 (identifier: A4FU01-6) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: Missing.
     375-382: ERGDRDLN → GSGVSPLP
     383-709: Missing.

Note: No experimental confirmation available.

Show »
Length:354
Mass (Da):39,372
Checksum:i2032989C2E856CAA
GO

Sequence cautioni

The sequence AAB36952.1 differs from that shown. Reason: Frameshift at position 8. Curated
The sequence AAB36953.1 differs from that shown. Reason: Frameshift at position 8. Curated
The sequence AAH94756.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti86 – 861W → R in BAG60917. (PubMed:14702039)Curated
Sequence conflicti165 – 1651R → G in BAG60917. (PubMed:14702039)Curated
Sequence conflicti263 – 2631H → R in BAG53406. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti159 – 1591M → V.1 Publication
Corresponds to variant rs11205303 [ dbSNP | Ensembl ].
VAR_043598
Natural varianti531 – 5311Q → P.
Corresponds to variant rs16836857 [ dbSNP | Ensembl ].
VAR_043599

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7272Missing in isoform 4. 1 PublicationVSP_033883Add
BLAST
Alternative sequencei1 – 2828Missing in isoform 3 and isoform 6. 2 PublicationsVSP_033884Add
BLAST
Alternative sequencei73 – 753TNF → MPP in isoform 4. 1 PublicationVSP_033885
Alternative sequencei228 – 27245SLPRY…DLLRC → RLRCFSSSLIVSGSSSSSFQ LILNSLSFSFLLFMTVSGFL TPLPS in isoform 5. 1 PublicationVSP_033886Add
BLAST
Alternative sequencei258 – 26811RLSWHHPGGSD → VSVMVRVMAVD in isoform 2 and isoform 3. 3 PublicationsVSP_033887Add
BLAST
Alternative sequencei269 – 709441Missing in isoform 2 and isoform 3. 3 PublicationsVSP_033888Add
BLAST
Alternative sequencei273 – 709437Missing in isoform 5. 1 PublicationVSP_033889Add
BLAST
Alternative sequencei375 – 3828ERGDRDLN → GSGVSPLP in isoform 6. 1 PublicationVSP_035725
Alternative sequencei383 – 709327Missing in isoform 6. 1 PublicationVSP_035726Add
BLAST
Alternative sequencei703 – 7097RAEGDLG → QSHPFWITRC in isoform 4. 1 PublicationVSP_033890

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78556 mRNA. Translation: AAB36952.1. Frameshift.
U78557 mRNA. Translation: AAB36953.1. Frameshift.
AK097000 mRNA. Translation: BAG53406.1.
AK296094 mRNA. Translation: BAG58848.1.
AK298775 mRNA. Translation: BAG60917.1.
AK304820 mRNA. Translation: BAG65568.1.
AL590487 Genomic DNA. Translation: CAI12649.1.
CH471121 Genomic DNA. Translation: EAW53589.1.
CH471121 Genomic DNA. Translation: EAW53590.1.
CH471121 Genomic DNA. Translation: EAW53594.1.
BC064372 mRNA. No translation available.
BC094756 mRNA. Translation: AAH94756.1. Different initiation.
BC100818 mRNA. Translation: AAI00819.1.
BC100819 mRNA. Translation: AAI00820.1.
BC100820 mRNA. Translation: AAI00821.1.
CCDSiCCDS72901.1. [A4FU01-4]
CCDS72902.1. [A4FU01-1]
RefSeqiNP_001139334.1. NM_001145862.1. [A4FU01-1]
NP_870988.2. NM_181873.3. [A4FU01-4]
UniGeneiHs.425144.

Genome annotation databases

EnsembliENST00000369140; ENSP00000358136; ENSG00000014914. [A4FU01-4]
ENST00000439741; ENSP00000391668; ENSG00000014914. [A4FU01-1]
GeneIDi10903.
KEGGihsa:10903.
UCSCiuc001etl.4. human. [A4FU01-1]
uc001etm.2. human. [A4FU01-4]
uc010pbm.1. human. [A4FU01-6]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78556 mRNA. Translation: AAB36952.1 . Frameshift.
U78557 mRNA. Translation: AAB36953.1 . Frameshift.
AK097000 mRNA. Translation: BAG53406.1 .
AK296094 mRNA. Translation: BAG58848.1 .
AK298775 mRNA. Translation: BAG60917.1 .
AK304820 mRNA. Translation: BAG65568.1 .
AL590487 Genomic DNA. Translation: CAI12649.1 .
CH471121 Genomic DNA. Translation: EAW53589.1 .
CH471121 Genomic DNA. Translation: EAW53590.1 .
CH471121 Genomic DNA. Translation: EAW53594.1 .
BC064372 mRNA. No translation available.
BC094756 mRNA. Translation: AAH94756.1 . Different initiation.
BC100818 mRNA. Translation: AAI00819.1 .
BC100819 mRNA. Translation: AAI00820.1 .
BC100820 mRNA. Translation: AAI00821.1 .
CCDSi CCDS72901.1. [A4FU01-4 ]
CCDS72902.1. [A4FU01-1 ]
RefSeqi NP_001139334.1. NM_001145862.1. [A4FU01-1 ]
NP_870988.2. NM_181873.3. [A4FU01-4 ]
UniGenei Hs.425144.

3D structure databases

ProteinModelPortali A4FU01.
SMRi A4FU01. Positions 46-535.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116109. 1 interaction.
IntActi A4FU01. 1 interaction.
MINTi MINT-1186094.

PTM databases

PhosphoSitei A4FU01.

Proteomic databases

PaxDbi A4FU01.
PRIDEi A4FU01.

Protocols and materials databases

DNASUi 10903.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000369140 ; ENSP00000358136 ; ENSG00000014914 . [A4FU01-4 ]
ENST00000439741 ; ENSP00000391668 ; ENSG00000014914 . [A4FU01-1 ]
GeneIDi 10903.
KEGGi hsa:10903.
UCSCi uc001etl.4. human. [A4FU01-1 ]
uc001etm.2. human. [A4FU01-4 ]
uc010pbm.1. human. [A4FU01-6 ]

Organism-specific databases

CTDi 10903.
GeneCardsi GC01M149900.
H-InvDB HIX0001007.
HGNCi HGNC:24307. MTMR11.
HPAi HPA030351.
neXtProti NX_A4FU01.
PharmGKBi PA142671303.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG299000.
GeneTreei ENSGT00760000118832.
HOVERGENi HBG108155.
InParanoidi A4FU01.
KOi K18085.
OMAi GPRLSWH.
OrthoDBi EOG7K0ZBZ.
PhylomeDBi A4FU01.
TreeFami TF315197.

Miscellaneous databases

ChiTaRSi MTMR11. human.
GenomeRNAii 10903.
NextBioi 41411.
PROi A4FU01.

Gene expression databases

Bgeei A4FU01.
CleanExi HS_MTMR11.
Genevestigatori A4FU01.

Family and domain databases

InterProi IPR010569. Myotubularin-like_Pase_dom.
IPR022587. Myotubularin_assoc.
IPR029021. Prot-tyrosine_phosphatase-like.
[Graphical view ]
Pfami PF12578. 3-PAP. 1 hit.
PF06602. Myotub-related. 1 hit.
[Graphical view ]
SUPFAMi SSF52799. SSF52799. 2 hits.
PROSITEi PS51339. PPASE_MYOTUBULARIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Tanimura H., Ledakis P., Fojo T.
    Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5).
    Tissue: Ovary tumor, Small intestine, Thalamus and Uterus.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 4 AND 6).
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-709 (ISOFORM 1), VARIANT VAL-159.
    Tissue: Ovary.
  6. "A common 93-kb duplicated DNA sequence at 1q21.2 in acute lymphoblastic leukemia and Burkitt lymphoma."
    La Starza R., Crescenzi B., Pierini V., Romoli S., Gorello P., Brandimarte L., Matteucci C., Kropp M.G., Barba G., Martelli M.F., Mecucci C.
    Cancer Genet. Cytogenet. 175:73-76(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiMTMRB_HUMAN
AccessioniPrimary (citable) accession number: A4FU01
Secondary accession number(s): B3KUE4
, B4DJI6, B4DQF5, B4E3Q6, Q3ZCP7, Q5SZ62, Q6P2Q8, Q99752, Q99753
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: November 26, 2014
This is version 65 of the entry and version 2 of the sequence. [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

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3