Q969M7 (UBE2F_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NEDD8-conjugating enzyme UBE2F
EC=6.3.2.-

Alternative name(s):
NEDD8 carrier protein UBE2F
NEDD8 protein ligase UBE2F
NEDD8-conjugating enzyme 2
Ubiquitin-conjugating enzyme E2 F

Gene names

Name:	UBE2F
Synonyms:	NCE2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	185 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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 RBX2, but not RBX1, suggests that the RBX2-UBE2F complex neddylates specific target proteins, such as CUL5. Ref.6
Catalytic activity	ATP + NEDD8 + protein lysine = AMP + diphosphate + protein N-NEDD8yllysine.
Pathway	Protein modification; protein neddylation.
Subunit structure	Interacts with UBA3 and RBX2. Ref.6
Tissue specificity	Widely expressed (at protein level). Ref.6
Post-translational modification	The acetylation of Met-1 increases affinity for DCUN1D3 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins. Ref.8
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family. UBE2F subfamily.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein neddylation Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NEDD8 ligase activity Inferred from direct assay Ref.6. Source: UniProtKB protein binding Inferred from physical interaction Ref.6. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q969M7-1)

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.

Isoform 2 (identifier: Q969M7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     170-185: EDFRNKVDDYIKRYAR → SPMLLLHRRTSGIKWMTTSNVMPDNKRGRLQAHGLCYSLSLT

Note: No experimental confirmation available.

Isoform 3 (identifier: Q969M7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     40-71: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q969M7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     118-120: SLL → RIF
     121-185: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q969M7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     72-185: DEGYYQGGKF...VDDYIKRYAR → ASQSEMPDQDLAPQHHRDRGNMSEFIERTFN

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 185

185

NEDD8-conjugating enzyme UBE2F

PRO_0000263077

Regions

Region

1 – 29

29

Interaction with UBA3

Sites

Active site

116

1

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.8

Natural variations

Alternative sequence

40 – 71

32

Missing in isoform 3.

VSP_037270

Alternative sequence

72 – 185

114

DEGYY…KRYAR → ASQSEMPDQDLAPQHHRDRG NMSEFIERTFN in isoform 5.

VSP_037271

Alternative sequence

118 – 120

3

SLL → RIF in isoform 4.

VSP_037272

Alternative sequence

121 – 185

65

Missing in isoform 4.

VSP_037273

Alternative sequence

170 – 185

16

EDFRN…KRYAR → SPMLLLHRRTSGIKWMTTSN VMPDNKRGRLQAHGLCYSLS LT in isoform 2.

VSP_037274

Experimental info

Sequence conflict

181

1

K → E in BAF82752. Ref.2

Secondary structure

1

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185

Helix Strand Turn

Details...

Helix

4 – 8

5

Helix

32 – 44

13

Helix

45 – 47

3

Beta strand

52 – 55

4

Beta strand

57 – 60

4

Beta strand

64 – 69

6

Beta strand

72 – 74

3

Turn

75 – 78

4

Beta strand

81 – 86

6

Beta strand

97 – 100

4

Beta strand

107 – 109

3

Beta strand

111 – 113

3

Helix

118 – 120

3

Beta strand

124 – 126

3

Helix

136 – 145

10

Turn

146 – 150

5

Beta strand

153 – 155

3

Helix

159 – 167

9

Helix

169 – 183

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: B22C86238D13216E	FASTA	185	21,077
	10 20 30 40 50 60 MLTLASKLKR DDGLKGSRTA ATASDSTRRV SVRDKLLVKE VAELEANLPC TCKVHFPDPN 70 80 90 100 110 120 KLHCFQLTVT PDEGYYQGGK FQFETEVPDA YNMVPPKVKC LTKIWHPNIT ETGEICLSLL 130 140 150 160 170 180 REHSIDGTGW APTRTLKDVV WGLNSLFTDL LNFDDPLNIE AAEHHLRDKE DFRNKVDDYI KRYAR
	Isoform 2 [UniParc]. Checksum: 26D6D083CACA07ED	FASTA	211	23,760
	10 20 30 40 50 60 MLTLASKLKR DDGLKGSRTA ATASDSTRRV SVRDKLLVKE VAELEANLPC TCKVHFPDPN 70 80 90 100 110 120 KLHCFQLTVT PDEGYYQGGK FQFETEVPDA YNMVPPKVKC LTKIWHPNIT ETGEICLSLL 130 140 150 160 170 180 REHSIDGTGW APTRTLKDVV WGLNSLFTDL LNFDDPLNIE AAEHHLRDKS PMLLLHRRTS 190 200 210 GIKWMTTSNV MPDNKRGRLQ AHGLCYSLSL T
	Isoform 3 [UniParc]. Checksum: 738B62CEF923150C	FASTA	153	17,500
	10 20 30 40 50 60 MLTLASKLKR DDGLKGSRTA ATASDSTRRV SVRDKLLVKD EGYYQGGKFQ FETEVPDAYN 70 80 90 100 110 120 MVPPKVKCLT KIWHPNITET GEICLSLLRE HSIDGTGWAP TRTLKDVVWG LNSLFTDLLN 130 140 150 FDDPLNIEAA EHHLRDKEDF RNKVDDYIKR YAR
	Isoform 4 [UniParc]. Checksum: B7A58924FDDB46AF	FASTA	120	13,513
	10 20 30 40 50 60 MLTLASKLKR DDGLKGSRTA ATASDSTRRV SVRDKLLVKE VAELEANLPC TCKVHFPDPN 70 80 90 100 110 120 KLHCFQLTVT PDEGYYQGGK FQFETEVPDA YNMVPPKVKC LTKIWHPNIT ETGEICLRIF
	Isoform 5 [UniParc]. Checksum: 676F8ABBE02435AE	FASTA	102	11,450
	10 20 30 40 50 60 MLTLASKLKR DDGLKGSRTA ATASDSTRRV SVRDKLLVKE VAELEANLPC TCKVHFPDPN 70 80 90 100 KLHCFQLTVT PASQSEMPDQ DLAPQHHRDR GNMSEFIERT FN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NEDD8-conjugating enzyme." Gladysheva T., Chau V. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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; 3; 4 AND 5). Tissue: Brain, Brain cortex, Glial tumor, Substantia nigra and 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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] (ISOFORM 1). Tissue: Brain.
[6]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 22-185 IN COMPLEX WITH UBA3, FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH UBA3; NAE1 AND RBX2.
[7]	"Solution structure of the UQ_CON domain from human NEDD8-conjugating enzyme NCE2." RIKEN structural genomics initiative (RSGI) Submitted (AUG-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 23-185.
[8]	"Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes." Monda J.K., Scott D.C., Miller D.J., Lydeard J., King D., Harper J.W., Bennett E.J., Schulman B.A. Structure 21:42-53(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-25 IN COMPLEX WITH DCUN1D3, ACETYLATION AT MET-1.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF310723 mRNA. Translation: AAL26792.1.
AK290063 mRNA. Translation: BAF82752.1.
AK293334 mRNA. Translation: BAG56850.1.
AK294107 mRNA. Translation: BAG57442.1.
AK297502 mRNA. Translation: BAG59915.1.
AK303094 mRNA. Translation: BAG64204.1.
AC016776 Genomic DNA. Translation: AAY24220.1.
CH471063 Genomic DNA. Translation: EAW71129.1.
CH471063 Genomic DNA. Translation: EAW71132.1.
BC010549 mRNA. Translation: AAH10549.1.

CCDS

CCDS2523.1. [Q969M7-1]
CCDS63177.1. [Q969M7-3]

RefSeq

NP_001265234.1. NM_001278305.1. [Q969M7-1]
NP_001265235.1. NM_001278306.1.
NP_001265236.1. NM_001278307.1. [Q969M7-3]
NP_001265237.1. NM_001278308.1.
NP_542409.1. NM_080678.2. [Q969M7-1]

UniGene

Hs.471785.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EDI	NMR	-	A	26-185	[»]
3FN1	X-ray	2.50	B	21-185	[»]
4GBA	X-ray	2.40	F/G	1-25	[»]

ProteinModelPortal

Q969M7.

SMR

Q969M7. Positions 26-185.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

126682. 11 interactions.

IntAct

Q969M7. 6 interactions.

STRING

9606.ENSP00000272930.

PTM databases

PhosphoSite

Q969M7.

Polymorphism databases

DMDM

74751725.

Proteomic databases

MaxQB

Q969M7.

PaxDb

Q969M7.

PeptideAtlas

Q969M7.

PRIDE

Q969M7.

Protocols and materials databases

DNASU

140739.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000272930; ENSP00000272930; ENSG00000184182. [Q969M7-1]
ENST00000414443; ENSP00000399183; ENSG00000184182. [Q969M7-3]
ENST00000433241; ENSP00000393515; ENSG00000184182. [Q969M7-4]
ENST00000441728; ENSP00000409749; ENSG00000184182. [Q969M7-5]

GeneID

140739.

KEGG

hsa:140739.

UCSC

uc002vxk.3. human. [Q969M7-1]
uc010znn.2. human. [Q969M7-3]
uc010znp.2. human. [Q969M7-4]

Organism-specific databases

CTD

140739.

GeneCards

GC02P238875.

HGNC

HGNC:12480. UBE2F.

HPA

HPA037444.

neXtProt

NX_Q969M7.

PharmGKB

PA37130.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5078.

HOVERGEN

HBG098591.

InParanoid

Q969M7.

KO

K10687.

OMA

WHPNISE.

PhylomeDB

Q969M7.

TreeFam

TF101125.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

SignaLink

Q969M7.

UniPathway

UPA00885.

Gene expression databases

ArrayExpress

Q969M7.

Bgee

Q969M7.

CleanEx

HS_UBE2F.

Genevestigator

Q969M7.

Family and domain databases

Gene3D

3.10.110.10. 1 hit.

InterPro

IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

SUPFAM

SSF54495. SSF54495. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

Q969M7.

GenomeRNAi

140739.

NextBio

84333.

PRO

Q969M7.

Entry information

Entry name

UBE2F_HUMAN

Accession

Primary (citable) accession number: Q969M7
Secondary accession number(s): A8K1Z8 , B4DDT9, B4DFI1, B4DMK3, B4DZU2, B8ZZG2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	December 1, 2001
Last modified:	July 9, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.