NEDD8-activating enzyme E1 regulatory subunit

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Reviewed, UniProtKB/Swiss-Prot Q13564 (ULA1_HUMAN)

Last modified June 16, 2009. Version 79. History...

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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-activating enzyme E1 regulatory subunit
Alternative name(s):
    Amyloid protein-binding protein 1
    Amyloid beta precursor protein-binding protein 1, 59 kDa
      Short name=APP-BP1
    Proto-oncogene protein 1

Gene names

Name:	NAE1
Synonyms:	APPBP1
ORF Names:	HPP1

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	534 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	Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. Ref.6 Ref.7 Ref.8
Enzyme regulation	Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.
Pathway	Protein modification; protein neddylation.
Subunit structure	Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2.
Subcellular location	Cell membrane. Note: Colocalizes with APP in lipid rafts. Ref.9
Tissue specificity	Ubiquitous in fetal tissues. Expressed throughout the adult brain. Ref.1
Miscellaneous	NAE1 and UBA3 correspond to the N-terminal and the C-terminal part of yeast UBA3. In yeast the two subunits form a single polypeptide chain.
Sequence similarities	Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.

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Ontologies

Keywords
Biological process	Apoptosis Cell cycle Ubl conjugation pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA replication Ref.9 Inferred from direct assay. Source: UniProtKB S-M checkpoint Ref.7 Inferred from direct assay. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein neddylation Ref.6 Ref.8 Inferred from direct assay. Source: UniProtKB regulation of apoptosis Ref.7 Ref.9 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.1 Traceable author statement. Source: ProtInc insoluble fraction Ref.9 Inferred from direct assay. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro protein heterodimerization activity Ref.8 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
UBE2M	P61081	1	EBI-718631,EBI-1041660

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 534

534

NEDD8-activating enzyme E1 regulatory subunit

PRO_0000194951

Regions

Region

331 – 344

Interaction with UBA3

Sites

Site

211

Interaction with UBA3

Natural variations

Natural variant

101

S → F: dbSNP rs363212.

VAR_052435

Experimental info

Mutagenesis

331

D → A: Impairs the formation of the NEDD8-UBA3 thioester. Ref.13

Secondary structure

534

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q13564-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 5EC8D3ACE6374F21
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FASTA

534

60,246

        10         20         30         40         50         60 
MAQLGKLLKE QKYDRQLRLW GDHGQEALES AHVCLINATA TGTEILKNLV LPGIGSFTII 

        70         80         90        100        110        120 
DGNQVSGEDA GNNFFLQRSS IGKNRAEAAM EFLQELNSDV SGSFVEESPE NLLDNDPSFF 

       130        140        150        160        170        180 
CRFTVVVATQ LPESTSLRLA DVLWNSQIPL LICRTYGLVG YMRIIIKEHP VIESHPDNAL 

       190        200        210        220        230        240 
EDLRLDKPFP ELREHFQSYD LDHMEKKDHS HTPWIVIIAK YLAQWYSETN GRIPKTYKEK 

       250        260        270        280        290        300 
EDFRDLIRQG ILKNENGAPE DEENFEEAIK NVNTALNTTQ IPSSIEDIFN DDRCINITKQ 

       310        320        330        340        350        360 
TPSFWILARA LKEFVAKEGQ GNLPVRGTIP DMIADSGKYI KLQNVYREKA KKDAAAVGNH 

       370        380        390        400        410        420 
VAKLLQSIGQ APESISEKEL KLLCSNSAFL RVVRCRSLAE EYGLDTINKD EIISSMDNPD 

       430        440        450        460        470        480 
NEIVLYLMLR AVDRFHKQQG RYPGVSNYQV EEDIGKLKSC LTGFLQEYGL SVMVKDDYVH 

       490        500        510        520        530 
EFCRYGAAEP HTIAAFLGGA AAQEVIKIIT KQFVIFNNTY IYSGMSQTSA TFQL

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein." Chow N., Korenberg J.R., Chen X.-N., Neve R.L. J. Biol. Chem. 271:11339-11346(1996) [PubMed: 8626687] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH APP, TISSUE SPECIFICITY. Tissue: Fetal brain and Fetal skeletal muscle.
[2]	"Identification of a new human protooncogene." Kim J.W. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed: 10493829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle.
[6]	"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: FUNCTION.
[7]	"The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons." Chen Y., McPhie D.L., Hirschberg J., Neve R.L. J. Biol. Chem. 275:8929-8935(2000) [PubMed: 10722740] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBA3.
[8]	"Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer." Bohnsack R.N., Haas A.L. J. Biol. Chem. 278:26823-26830(2003) [PubMed: 12740388] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBA3.
[9]	"APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain." Chen Y., Liu W., McPhie D.L., Hassinger L., Neve R.L. J. Cell Biol. 163:27-33(2003) [PubMed: 14557245] [Abstract] Cited for: INTERACTION WITH APP, SUBCELLULAR LOCATION.
[10]	"ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis." Chen Y., Liu W., Naumovski L., Neve R.L. J. Neurochem. 85:801-809(2003) [PubMed: 12694406] [Abstract] Cited for: INTERACTION WITH TP53BP2.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1." Walden H., Podgorski M.S., Huang D.T., Miller D.W., Howard R.J., Minor D.L. Jr., Holton J.M., Schulman B.A. Mol. Cell 12:1427-1437(2003) [PubMed: 14690597] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 5-534 IN COMPLEX WITH UBA3; NEDD8 AND ATP.
[13]	"Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8." Walden H., Podgorski M.S., Schulman B.A. Nature 422:330-334(2003) [PubMed: 12646924] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 5-534 IN COMPLEX WITH UBA3, MUTAGENESIS OF ASP-331.
[14]	"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) IN COMPLEX WITH UBA3 AND UBE2M.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

U50939 mRNA. Translation: AAC50477.1.
AY197612 mRNA. Translation: AAP35030.1.
AC004638 Genomic DNA. Translation: AAC23784.1.
AL136798 mRNA. Translation: CAB66732.1.
BC000480 mRNA. Translation: AAH00480.1.
BC013301 mRNA. Translation: AAH13301.1.

IPI

IPI00018968.

RefSeq

NP_001018169.1.
NP_001018170.1.
NP_003896.1.

UniGene

Hs.460978

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R4M	X-ray	3.00	A/C/E/G	1-534	[»]
1R4N	X-ray	3.60	A/C/E/G	1-534	[»]
1TT5	X-ray	2.60	A/C	1-534	[»]
1YOV	X-ray	2.60	A/C	1-534	[»]
2NVU	X-ray	2.80	A	1-534	[»]
3DBH	X-ray	2.85	A/C/E/G	1-534	[»]
3DBL	X-ray	2.90	A/C/E/G	1-534	[»]
3DBR	X-ray	3.05	A/C/E/G	1-534	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13564. 4 interactions.

PTM databases

PhosphoSite

Q13564.

Proteomic databases

PRIDE

Q13564.

Genome annotation databases

Ensembl

ENSG00000159593. Homo sapiens. [Contig view]

GeneID

8883.

KEGG

hsa:8883.

Organism-specific databases

GeneCards

GC16M065395.

H-InvDB

HIX0013121.

HGNC

HGNC:621. NAE1.

MIM

603385. gene.

PharmGKB

PA24911.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q13564.

Gene expression databases

ArrayExpress

Q13564.

Bgee

Q13564.

CleanEx

HS_NAE1.

GermOnline

ENSG00000159593. Homo sapiens.

Family and domain databases

InterPro

IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD_bd.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

Pfam

PF00899. ThiF. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00171. Adenosine triphosphate.

NextBio

33357.

SOURCE

Search...

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Entry information

Entry name

ULA1_HUMAN

Accession

Primary (citable) accession number: Q13564

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	November 1, 1996
Last modified:	June 16, 2009
This is version 79 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 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents