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Protein

Protein-lysine methyltransferase METTL21D

Gene

VCPKMT

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

Functioni

Protein-lysine N-methyltransferase that specifically trimethylates 'Lys-315' of VCP/p97; this modification may decrease VCP ATPase activity.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43S-adenosyl-L-methionine; via amide nitrogen1 Publication1
Binding sitei96S-adenosyl-L-methionine1 Publication1
Binding sitei126S-adenosyl-L-methionine; via amide nitrogen1 Publication1
Binding sitei143S-adenosyl-L-methionine; via carbonyl oxygen1 Publication1
Binding sitei148S-adenosyl-L-methionine1 Publication1

GO - Molecular functioni

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

GO - Biological processi

  • negative regulation of ATPase activity Source: UniProtKB
  • peptidyl-lysine methylation Source: UniProtKB
  • peptidyl-lysine trimethylation Source: UniProtKB
  • protein methylation Source: Reactome

Keywordsi

Molecular functionMethyltransferase, Transferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-HSA-8876725 Protein methylation
SIGNORiQ9H867

Names & Taxonomyi

Protein namesi
Recommended name:
Protein-lysine methyltransferase METTL21D (EC:2.1.1.-)
Alternative name(s):
Methyltransferase-like protein 21D
VCP lysine methyltransferase
Short name:
VCP-KMT
Valosin-containing protein lysine methyltransferase
Gene namesi
Name:VCPKMT
Synonyms:C14orf138, METTL21D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100483.13
HGNCiHGNC:20352 VCPKMT
MIMi615260 gene
neXtProtiNX_Q9H867

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73E → Q: Loss of methyltransferase activity. 1 Publication1
Mutagenesisi96D → A or V: Loss of methyltransferase activity. 1 Publication1
Mutagenesisi144D → V: Loss of methyltransferase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000100483
PharmGKBiPA134866014

Chemistry databases

ChEMBLiCHEMBL3588742

Polymorphism and mutation databases

BioMutaiMETTL21D
DMDMi152031572

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000899372 – 229Protein-lysine methyltransferase METTL21DAdd BLAST228

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei8PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H867
PaxDbiQ9H867
PeptideAtlasiQ9H867
PRIDEiQ9H867
ProteomicsDBi81183
81184 [Q9H867-1]
81185 [Q9H867-2]
81186 [Q9H867-3]
81187 [Q9H867-5]

PTM databases

iPTMnetiQ9H867
PhosphoSitePlusiQ9H867

Expressioni

Gene expression databases

BgeeiENSG00000100483 Expressed in 216 organ(s), highest expression level in endothelial cell
CleanExiHS_C14orf138
GenevisibleiQ9H867 HS

Organism-specific databases

HPAiHPA001146
HPA076561

Interactioni

Subunit structurei

Interacts with ALKBH6. Interacts with ASPSCR1 and UBXN6; interaction with ASPSCR1, but not with UBXN6, enhances VCP methylation.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122744, 15 interactors
IntActiQ9H867, 1 interactor
STRINGi9606.ENSP00000379201

Structurei

Secondary structure

1229
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H867
SMRiQ9H867
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni75 – 77S-adenosyl-L-methionine binding1 Publication3

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410ISZE Eukaryota
ENOG4111MAT LUCA
GeneTreeiENSGT00550000074572
HOGENOMiHOG000007089
HOVERGENiHBG054931
InParanoidiQ9H867
KOiK21806
OMAiEDIHILY
OrthoDBiEOG091G0NXA
PhylomeDBiQ9H867
TreeFamiTF352990

Family and domain databases

InterProiView protein in InterPro
IPR019410 Methyltransf_16
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF10294 Methyltransf_16, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 4 (identifier: Q9H867-4) [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
MADTLESSLE DPLRSFVRVL EKRDGTVLRL QQYSSGGVGC VVWDAAIVLS
60 70 80 90 100
KYLETPEFSG DGAHALSRRS VLELGSGTGA VGLMAATLGA DVVVTDLEEL
110 120 130 140 150
QDLLKMNINM NKHLVTGSVQ AKVLKWGEEI EGFPSPPDFI LMADCIYYEE
160 170 180 190 200
SLEPLLKTLK DISGFETCII CCYEQRTMGK NPEIEKKYFE LLQLDFDFEK
210 220
IPLEKHDEEY RSEDIHIIYI RKKKSKFPS
Length:229
Mass (Da):25,807
Last modified:July 10, 2007 - v2
Checksum:i73B22FC1D14F12C7
GO
Isoform 1 (identifier: Q9H867-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     123-144: VLKWGEEIEGFPSPPDFILMAD → GGRNRRLSFSTRLHTDGRLHIL
     145-229: Missing.

Show »
Length:144
Mass (Da):15,565
Checksum:iA9570313CE131B75
GO
Isoform 2 (identifier: Q9H867-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: MADTLESSLE...AVGLMAATLG → MWGRLLQAFPPVPTPQSTLFYR
     191-229: Missing.

Note: No experimental confirmation available.
Show »
Length:123
Mass (Da):14,211
Checksum:i879E819E309F8610
GO
Isoform 3 (identifier: Q9H867-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     90-229: Missing.

Note: No experimental confirmation available.
Show »
Length:89
Mass (Da):9,371
Checksum:i1E7A543768BB6488
GO
Isoform 5 (identifier: Q9H867-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     191-225: Missing.

Note: No experimental confirmation available.
Show »
Length:194
Mass (Da):21,435
Checksum:i34E94BD4A4DB2EE7
GO

Sequence cautioni

The sequence CAD62329 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05962163A → D. Corresponds to variant dbSNP:rs11157729Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0088141 – 89MADTL…AATLG → MWGRLLQAFPPVPTPQSTLF YR in isoform 2. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_00881590 – 229Missing in isoform 3. 1 PublicationAdd BLAST140
Alternative sequenceiVSP_026586123 – 144VLKWG…ILMAD → GGRNRRLSFSTRLHTDGRLH IL in isoform 1. 2 PublicationsAdd BLAST22
Alternative sequenceiVSP_026587145 – 229Missing in isoform 1. 2 PublicationsAdd BLAST85
Alternative sequenceiVSP_008816191 – 229Missing in isoform 2. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_043258191 – 225Missing in isoform 5. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK023982 mRNA Translation: BAB14752.1
AK129564 mRNA Translation: BAC85183.1
BX247997 mRNA Translation: CAD62329.1 Different initiation.
AL109758 Genomic DNA No translation available.
BC027585 mRNA No translation available.
BC105118 mRNA Translation: AAI05119.1
BC143673 mRNA Translation: AAI43674.1
BC143674 mRNA Translation: AAI43675.1
CCDSiCCDS41951.1 [Q9H867-5]
CCDS9696.2 [Q9H867-4]
RefSeqiNP_001035752.1, NM_001040662.1 [Q9H867-5]
NP_078834.2, NM_024558.2 [Q9H867-4]
UniGeneiHs.558541

Genome annotation databases

EnsembliENST00000395859; ENSP00000379200; ENSG00000100483 [Q9H867-5]
ENST00000395860; ENSP00000379201; ENSG00000100483 [Q9H867-4]
ENST00000491402; ENSP00000437113; ENSG00000100483 [Q9H867-1]
GeneIDi79609
KEGGihsa:79609
UCSCiuc001wxo.2 human [Q9H867-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK023982 mRNA Translation: BAB14752.1
AK129564 mRNA Translation: BAC85183.1
BX247997 mRNA Translation: CAD62329.1 Different initiation.
AL109758 Genomic DNA No translation available.
BC027585 mRNA No translation available.
BC105118 mRNA Translation: AAI05119.1
BC143673 mRNA Translation: AAI43674.1
BC143674 mRNA Translation: AAI43675.1
CCDSiCCDS41951.1 [Q9H867-5]
CCDS9696.2 [Q9H867-4]
RefSeqiNP_001035752.1, NM_001040662.1 [Q9H867-5]
NP_078834.2, NM_024558.2 [Q9H867-4]
UniGeneiHs.558541

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LG1X-ray1.80A/B/C7-229[»]
ProteinModelPortaliQ9H867
SMRiQ9H867
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122744, 15 interactors
IntActiQ9H867, 1 interactor
STRINGi9606.ENSP00000379201

Chemistry databases

ChEMBLiCHEMBL3588742

PTM databases

iPTMnetiQ9H867
PhosphoSitePlusiQ9H867

Polymorphism and mutation databases

BioMutaiMETTL21D
DMDMi152031572

Proteomic databases

EPDiQ9H867
PaxDbiQ9H867
PeptideAtlasiQ9H867
PRIDEiQ9H867
ProteomicsDBi81183
81184 [Q9H867-1]
81185 [Q9H867-2]
81186 [Q9H867-3]
81187 [Q9H867-5]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395859; ENSP00000379200; ENSG00000100483 [Q9H867-5]
ENST00000395860; ENSP00000379201; ENSG00000100483 [Q9H867-4]
ENST00000491402; ENSP00000437113; ENSG00000100483 [Q9H867-1]
GeneIDi79609
KEGGihsa:79609
UCSCiuc001wxo.2 human [Q9H867-4]

Organism-specific databases

CTDi79609
EuPathDBiHostDB:ENSG00000100483.13
GeneCardsiVCPKMT
HGNCiHGNC:20352 VCPKMT
HPAiHPA001146
HPA076561
MIMi615260 gene
neXtProtiNX_Q9H867
OpenTargetsiENSG00000100483
PharmGKBiPA134866014
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ISZE Eukaryota
ENOG4111MAT LUCA
GeneTreeiENSGT00550000074572
HOGENOMiHOG000007089
HOVERGENiHBG054931
InParanoidiQ9H867
KOiK21806
OMAiEDIHILY
OrthoDBiEOG091G0NXA
PhylomeDBiQ9H867
TreeFamiTF352990

Enzyme and pathway databases

ReactomeiR-HSA-8876725 Protein methylation
SIGNORiQ9H867

Miscellaneous databases

ChiTaRSiVCPKMT human
GenomeRNAii79609
PROiPR:Q9H867
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100483 Expressed in 216 organ(s), highest expression level in endothelial cell
CleanExiHS_C14orf138
GenevisibleiQ9H867 HS

Family and domain databases

InterProiView protein in InterPro
IPR019410 Methyltransf_16
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF10294 Methyltransf_16, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMT21D_HUMAN
AccessioniPrimary (citable) accession number: Q9H867
Secondary accession number(s): B7ZLA3
, B7ZLA4, Q2M2X3, Q86T12
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: July 10, 2007
Last modified: September 12, 2018
This is version 128 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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