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Protein

Protein N-lysine methyltransferase METTL21A

Gene

METTL21A

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

Functioni

Protein-lysine methyltransferase that selectively trimethylates residues in heat shock protein 70 (HSP70) family members. Contributes to the in vivo trimethylation of Lys residues in HSPA1 and HSPA8. In vitro methylates 'Lys-561' in HSPA1, 'Lys-564' in HSPA2, 'Lys-585' in HSPA5, 'Lys-563' in HSPA6 and 'Lys-561' in HSPA8.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei47 – 471S-adenosyl-L-methionine; via amide nitrogen1 Publication
Binding sitei94 – 941S-adenosyl-L-methionine1 Publication
Binding sitei125 – 1251S-adenosyl-L-methionine; via amide nitrogen1 Publication
Binding sitei143 – 1431S-adenosyl-L-methionine; via carbonyl oxygen1 Publication

GO - Molecular functioni

  • ATPase binding Source: BHF-UCL
  • Hsp70 protein binding Source: BHF-UCL
  • protein-lysine N-methyltransferase activity Source: UniProtKB

GO - Biological processi

  • peptidyl-lysine methylation Source: BHF-UCL
  • protein methylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
Protein N-lysine methyltransferase METTL21A (EC:2.1.1.-)
Alternative name(s):
HSPA lysine methyltransferase
HSPA-KMT
Hepatocellular carcinoma-associated antigen 557b
Methyltransferase-like protein 21A
Gene namesi
Name:METTL21A
Synonyms:FAM119A, HCA557B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:30476. METTL21A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi94 – 941D → A: Abolishes methyltransferase activity. 1 Publication

Organism-specific databases

PharmGKBiPA145008433.

Polymorphism and mutation databases

BioMutaiMETTL21A.
DMDMi150382834.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 218218Protein N-lysine methyltransferase METTL21APRO_0000292033Add
BLAST

Proteomic databases

EPDiQ8WXB1.
MaxQBiQ8WXB1.
PaxDbiQ8WXB1.
PRIDEiQ8WXB1.

PTM databases

iPTMnetiQ8WXB1.
PhosphoSiteiQ8WXB1.

Expressioni

Gene expression databases

BgeeiQ8WXB1.
CleanExiHS_FAM119A.
ExpressionAtlasiQ8WXB1. baseline and differential.
GenevisibleiQ8WXB1. HS.

Organism-specific databases

HPAiHPA034712.

Interactioni

Subunit structurei

Interacts with heat shock protein 70 family members; at least some of these proteins are methylation substrates (PubMed:23349634 and PubMed:23921388).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATRIPQ8WXE13EBI-8652459,EBI-747353
LNX1Q8TBB13EBI-8652459,EBI-739832

GO - Molecular functioni

  • ATPase binding Source: BHF-UCL
  • Hsp70 protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi127352. 20 interactions.
IntActiQ8WXB1. 3 interactions.
STRINGi9606.ENSP00000385481.

Structurei

Secondary structure

1
218
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi16 – 183Combined sources
Beta strandi19 – 268Combined sources
Beta strandi29 – 346Combined sources
Turni37 – 404Combined sources
Helixi42 – 443Combined sources
Helixi48 – 5811Combined sources
Beta strandi68 – 736Combined sources
Helixi78 – 858Combined sources
Beta strandi89 – 946Combined sources
Helixi96 – 10712Combined sources
Helixi112 – 1154Combined sources
Beta strandi119 – 1224Combined sources
Helixi129 – 1313Combined sources
Beta strandi138 – 1447Combined sources
Helixi149 – 1513Combined sources
Helixi152 – 16211Combined sources
Beta strandi168 – 1736Combined sources
Helixi178 – 19013Combined sources
Beta strandi191 – 1999Combined sources
Turni200 – 2034Combined sources
Beta strandi204 – 2129Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LECX-ray2.28A/B8-218[»]
ProteinModelPortaliQ8WXB1.
SMRiQ8WXB1. Positions 15-216.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni73 – 753S-adenosyl-L-methionine binding1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2793. Eukaryota.
ENOG4111IJ0. LUCA.
GeneTreeiENSGT00550000074572.
HOVERGENiHBG059353.
InParanoidiQ8WXB1.
PhylomeDBiQ8WXB1.
TreeFamiTF313206.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR019410. Methyltransf_16.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF10294. Methyltransf_16. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8WXB1-1) [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
MALVPYEETT EFGLQKFHKP LATFSFANHT IQIRQDWRHL GVAAVVWDAA
60 70 80 90 100
IVLSTYLEMG AVELRGRSAV ELGAGTGLVG IVAALLGAHV TITDRKVALE
110 120 130 140 150
FLKSNVQANL PPHIQTKTVV KELTWGQNLG SFSPGEFDLI LGADIIYLEE
160 170 180 190 200
TFTDLLQTLE HLCSNHSVIL LACRIRYERD NNFLAMLERQ FTVRKVHYDP
210
EKDVHIYEAQ KRNQKEDL
Length:218
Mass (Da):24,600
Last modified:June 26, 2007 - v2
Checksum:i18E7E39A1CDCC56E
GO
Isoform 2 (identifier: Q8WXB1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     88-90: AHV → GGI
     91-218: Missing.

Show »
Length:90
Mass (Da):9,609
Checksum:i4A8C7FFF7CDB4C1C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti33 – 331I → T in BAC04229 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti192 – 1921T → I.3 Publications
Corresponds to variant rs2551949 [ dbSNP | Ensembl ].
VAR_032935

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei88 – 903AHV → GGI in isoform 2. 1 PublicationVSP_026379
Alternative sequencei91 – 218128Missing in isoform 2. 1 PublicationVSP_026380Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF455817 mRNA. Translation: AAL66295.1.
AK093812 mRNA. Translation: BAC04229.1.
AC079767 Genomic DNA. Translation: AAX93175.1.
BC009462 mRNA. Translation: AAH09462.1.
BC033720 mRNA. Translation: AAH33720.1.
CCDSiCCDS2376.1. [Q8WXB1-1]
RefSeqiNP_001120867.1. NM_001127395.2. [Q8WXB1-1]
NP_001294950.1. NM_001308021.1.
NP_660323.3. NM_145280.5. [Q8WXB1-1]
XP_005246396.1. XM_005246339.2. [Q8WXB1-1]
XP_005246397.1. XM_005246340.2. [Q8WXB1-1]
XP_005246398.1. XM_005246341.2. [Q8WXB1-1]
XP_006712392.1. XM_006712329.2. [Q8WXB1-1]
UniGeneiHs.664764.
Hs.734938.

Genome annotation databases

EnsembliENST00000406927; ENSP00000385481; ENSG00000144401. [Q8WXB1-1]
ENST00000411432; ENSP00000415115; ENSG00000144401. [Q8WXB1-1]
ENST00000425132; ENSP00000400730; ENSG00000144401. [Q8WXB1-2]
ENST00000426075; ENSP00000403317; ENSG00000144401. [Q8WXB1-1]
ENST00000442521; ENSP00000392062; ENSG00000144401. [Q8WXB1-1]
ENST00000448007; ENSP00000407622; ENSG00000144401. [Q8WXB1-1]
ENST00000458426; ENSP00000389684; ENSG00000144401. [Q8WXB1-2]
GeneIDi151194.
KEGGihsa:151194.
UCSCiuc002vce.4. human. [Q8WXB1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF455817 mRNA. Translation: AAL66295.1.
AK093812 mRNA. Translation: BAC04229.1.
AC079767 Genomic DNA. Translation: AAX93175.1.
BC009462 mRNA. Translation: AAH09462.1.
BC033720 mRNA. Translation: AAH33720.1.
CCDSiCCDS2376.1. [Q8WXB1-1]
RefSeqiNP_001120867.1. NM_001127395.2. [Q8WXB1-1]
NP_001294950.1. NM_001308021.1.
NP_660323.3. NM_145280.5. [Q8WXB1-1]
XP_005246396.1. XM_005246339.2. [Q8WXB1-1]
XP_005246397.1. XM_005246340.2. [Q8WXB1-1]
XP_005246398.1. XM_005246341.2. [Q8WXB1-1]
XP_006712392.1. XM_006712329.2. [Q8WXB1-1]
UniGeneiHs.664764.
Hs.734938.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LECX-ray2.28A/B8-218[»]
ProteinModelPortaliQ8WXB1.
SMRiQ8WXB1. Positions 15-216.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127352. 20 interactions.
IntActiQ8WXB1. 3 interactions.
STRINGi9606.ENSP00000385481.

PTM databases

iPTMnetiQ8WXB1.
PhosphoSiteiQ8WXB1.

Polymorphism and mutation databases

BioMutaiMETTL21A.
DMDMi150382834.

Proteomic databases

EPDiQ8WXB1.
MaxQBiQ8WXB1.
PaxDbiQ8WXB1.
PRIDEiQ8WXB1.

Protocols and materials databases

DNASUi151194.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000406927; ENSP00000385481; ENSG00000144401. [Q8WXB1-1]
ENST00000411432; ENSP00000415115; ENSG00000144401. [Q8WXB1-1]
ENST00000425132; ENSP00000400730; ENSG00000144401. [Q8WXB1-2]
ENST00000426075; ENSP00000403317; ENSG00000144401. [Q8WXB1-1]
ENST00000442521; ENSP00000392062; ENSG00000144401. [Q8WXB1-1]
ENST00000448007; ENSP00000407622; ENSG00000144401. [Q8WXB1-1]
ENST00000458426; ENSP00000389684; ENSG00000144401. [Q8WXB1-2]
GeneIDi151194.
KEGGihsa:151194.
UCSCiuc002vce.4. human. [Q8WXB1-1]

Organism-specific databases

CTDi151194.
GeneCardsiMETTL21A.
HGNCiHGNC:30476. METTL21A.
HPAiHPA034712.
MIMi615257. gene.
neXtProtiNX_Q8WXB1.
PharmGKBiPA145008433.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2793. Eukaryota.
ENOG4111IJ0. LUCA.
GeneTreeiENSGT00550000074572.
HOVERGENiHBG059353.
InParanoidiQ8WXB1.
PhylomeDBiQ8WXB1.
TreeFamiTF313206.

Miscellaneous databases

ChiTaRSiMETTL21A. human.
GenomeRNAii151194.
PROiQ8WXB1.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WXB1.
CleanExiHS_FAM119A.
ExpressionAtlasiQ8WXB1. baseline and differential.
GenevisibleiQ8WXB1. HS.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR019410. Methyltransf_16.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF10294. Methyltransf_16. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "HCA557b, a transcription factor associated with hepatocellular carcinoma."
    Dong X.-Y., Chen W.-F.
    Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-192.
  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] (ISOFORM 1), VARIANT ILE-192.
    Tissue: Thymus.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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 1 AND 2), VARIANT ILE-192.
    Tissue: Brain and Lymph.
  5. "Lysine methylation of VCP by a member of a novel human protein methyltransferase family."
    Kernstock S., Davydova E., Jakobsson M., Moen A., Pettersen S., Maelandsmo G.M., Egge-Jacobsen W., Falnes P.O.
    Nat. Commun. 3:1038-1038(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ASP-94.
  6. "Identification and characterization of a novel human methyltransferase modulating Hsp70 function through lysine methylation."
    Jakobsson M.E., Moen A., Bousset L., Egge-Jacobsen W., Kernstock S., Melki R., Falnes P.O.
    J. Biol. Chem. 288:27752-27763(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT.
  7. "A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity."
    Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.
    PLoS Genet. 9:E1003210-E1003210(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HSP70 FAMILY MEMBERS, SUBCELLULAR LOCATION.
  8. "The crystal structure of human methyltransferase-like protein 21A in complex with SAH."
    Structural genomics consortium (SGC)
    Submitted (JUL-2013) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 8-218 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.

Entry informationi

Entry nameiMT21A_HUMAN
AccessioniPrimary (citable) accession number: Q8WXB1
Secondary accession number(s): Q53RV0, Q8N1Z9, Q96GH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 26, 2007
Last sequence update: June 26, 2007
Last modified: June 8, 2016
This is version 102 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

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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
  7. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.