NEDD8-conjugating enzyme Ubc12 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P61081 (UBC12_HUMAN)

Last modified June 16, 2009. Version 63. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    NEDD8-conjugating enzyme Ubc12
    EC=6.3.2.-
Alternative name(s):
    Ubiquitin-conjugating enzyme E2 M
    NEDD8 protein ligase
    NEDD8 carrier protein

Gene names

Name:	UBE2M
Synonyms:	UBC12

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	183 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation. Ref.2 Ref.9
Catalytic activity	ATP + NEDD8 + protein lysine = AMP + diphosphate + protein N-NEDD8yllysine.
Pathway	Protein modification; protein neddylation.
Subunit structure	Interacts with UBA3 and RBX1.
Domain	Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8.
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.

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Ontologies

Keywords
Biological process	Ubl conjugation pathway
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein neddylation Ref.7 Inferred from direct assay. Source: UniProtKB regulation of protein metabolic process Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NEDD8 ligase activity Ref.7 Inferred from direct assay. Source: UniProtKB protein binding Ref.7 Ref.9 Inferred from physical interaction. Source: UniProtKB ribosomal S6-glutamic acid ligase activity Ref.9 Inferred from direct assay. Source: UniProtKB ubiquitin-protein ligase activity Ref.1 Ref.10 Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct
CDK2	P24941	1	EBI-1041660,EBI-375096
FAM113A	Q9H1Q7	1	EBI-1041660,EBI-748452
NAE1	Q13564	1	EBI-1041660,EBI-718631
NEDD8	Q15843	1	EBI-1041660,EBI-716247
PRKAR1A	P10644	1	EBI-1041660,EBI-476431
TUSC4	Q8WTW4	1	EBI-1041660,EBI-1043552
UBA3	Q8TBC4	2	EBI-1041660,EBI-717567

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 183

183

NEDD8-conjugating enzyme Ubc12

PRO_0000082488

Regions

Region

1 – 26

Interaction with UBA3

Region

27 – 57

Interaction with UBA3

Sites

Active site

111

Glycyl thioester intermediate

Amino acid modifications

Modified residue

Phosphoserine Ref.6

Experimental info

Mutagenesis

M → A: No effect on thioester intermediate formation. Ref.9

Mutagenesis

L → A: Impairs thioester intermediate formation. Ref.9

Mutagenesis

F → A: Strongly impairs thioester intermediate formation. Ref.9

Mutagenesis

S → A: Slightly impairs thioester intermediate formation. Ref.9

Mutagenesis

L → A: Strongly impairs thioester intermediate formation. Ref.9

Mutagenesis

Q → A: Impairs thioester intermediate formation. Ref.9

Mutagenesis

Q → A: No effect on thioester intermediate formation. Ref.9

Mutagenesis

K → A: No effect on thioester intermediate formation. Ref.9

Mutagenesis

K → A: Impairs thioester intermediate formation. Ref.9

Mutagenesis

L → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

Q → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

K → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

I → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

N → A: No effect on thioester intermediate formation. Ref.10

Mutagenesis

L → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

F → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

D → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

L → A: Strongly impairs thioester intermediate formation. Ref.10

Mutagenesis

111

C → S: Forms a stable complex with NEDD8, which prevents subsequent NEDD8 conjugation to cullins. Ref.5

Secondary structure

183

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P61081-1 [UniParc].

Last modified April 26, 2004. Version 1.
Checksum: E3C288CA6A98BC5C
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FASTA

183

20,900

        10         20         30         40         50         60 
MIKLFSLKQQ KKEEESAGGT KGSSKKASAA QLRIQKDINE LNLPKTCDIS FSDPDDLLNF 

        70         80         90        100        110        120 
KLVICPDEGF YKSGKFVFSF KVGQGYPHDP PKVKCETMVY HPNIDLEGNV CLNILREDWK 

       130        140        150        160        170        180 
PVLTINSIIY GLQYLFLEPN PEDPLNKEAA EVLQNNRRLF EQNVQRSMRG GYIGSTYFER 


CLK

« Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new NEDD8-ligating system for cullin-4A." Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S., Tanaka K., Kato S. Genes Dev. 12:2263-2268(1998) [PubMed: 9694792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway." Gong L., Yeh E.T.H. J. Biol. Chem. 274:12036-12042(1999) [PubMed: 10207026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Placenta.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[5]	"A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo." Wada H., Yeh E.T.H., Kamitani T. J. Biol. Chem. 275:17008-17015(2000) [PubMed: 10828074] [Abstract] Cited for: MUTAGENESIS OF CYS-111.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, MASS SPECTROMETRY.
[7]	"E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification." Huang D.T., Ayrault O., Hunt H.W., Taherbhoy A.M., Duda D.M., Scott D.C., Borg L.A., Neale G., Murray P.J., Roussel M.F., Schulman B.A. Mol. Cell 33:483-495(2009) [PubMed: 19250909] [Abstract] Cited for: INTERACTION WITH RBX1.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8." Huang D.T., Miller D.W., Mathew R., Cassell R., Holton J.M., Roussel M.F., Schulman B.A. Nat. Struct. Mol. Biol. 11:927-935(2004) [PubMed: 15361859] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-26 IN COMPLEX WITH UBA3 AND NAE1, MUTAGENESIS OF MET-1; LEU-4; PHE-5; SER-6; LEU-7; GLN-9; GLN-10; LYS-11 AND LYS-12, FUNCTION.
[10]	"Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1." Huang D.T., Paydar A., Zhuang M., Waddell M.B., Holton J.M., Schulman B.A. Mol. Cell 17:341-350(2005) [PubMed: 15694336] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 27-183 IN COMPLEX WITH UBA3 AND NAE1, MUTAGENESIS OF LEU-32; GLN-35; LYS-36; ILE-38; ASN-39; LEU-41; PHE-51; ASP-55 AND LEU-57.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

AB012191 mRNA. Translation: BAA33145.1.
AF075599 mRNA. Translation: AAC26141.1.
BT006754 mRNA. Translation: AAP35400.1.
BC058924 mRNA. Translation: AAH58924.1.

IPI

IPI00022597.

RefSeq

NP_003960.1.

UniGene

Hs.406068

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TT5	X-ray	2.60	E/F	1-26	[»]
1Y8X	X-ray	2.40	A	27-183	[»]
2NVU	X-ray	2.80	C	1-178	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P61081. 18 interactions.

PTM databases

PhosphoSite

P61081.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00022597.

Proteomic databases

PeptideAtlas

P61081.

PRIDE

P61081.

Genome annotation databases

Ensembl

ENSG00000130725. Homo sapiens. [Contig view]

GeneID

9040.

KEGG

hsa:9040.

Organism-specific databases

GeneCards

GC19M063758.

H-InvDB

HIX0039921.

HGNC

HGNC:12491. UBE2M.

HPA

CAB004993.

MIM

603173. gene.

PharmGKB

PA37140.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P61081.

HOVERGEN

P61081.

OMA

P61081. LEPNASD.

Gene expression databases

ArrayExpress

P61081.

Bgee

P61081.

CleanEx

HS_UBE2M.

GermOnline

ENSG00000130725. Homo sapiens.

Family and domain databases

InterPro

IPR015580. RUB1_conj_enz_Ubc12.
IPR016135. UBQ-conjugat/RWD-like.
IPR000608. UBQ-conjugat_E2.
[Graphical view]

Gene3D

G3DSA:3.10.110.10. UBQ-conjugat_E2. 1 hit.

PANTHER

PTHR11621:SF17. Ubc12. 1 hit.

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

ProDom

PD000461. UBQ_conjugat. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00212. UBCc. 1 hit.
[Graphical view]

PROSITE

PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

33867.

SOURCE

Search...

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Entry information

Entry name

UBC12_HUMAN

Accession

Primary (citable) accession number: P61081
Secondary accession number(s): O76069, Q8VC50

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	June 16, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2-D gel databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents