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Reviewed, UniProtKB/Swiss-Prot Q13564 (ULA1_HUMAN)

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

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length534 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

UBE2MP610811EBI-718631,EBI-1041660

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 534534NEDD8-activating enzyme E1 regulatory subunit
PRO_0000194951

Regions

Region331 – 34414Interaction with UBA3

Sites

Site2111Interaction with UBA3

Natural variations

Natural variant1011S → F: dbSNP rs363212.
VAR_052435

Experimental info

Mutagenesis3311D → A: Impairs the formation of the NEDD8-UBA3 thioester. Ref.13

Secondary structure

................................................................................. 534
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13564-1 [UniParc].

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

FASTA53460,246
        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 

« Hide

References

« Hide '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. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., 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.

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.
IPIIPI00018968.
RefSeqNP_001018169.1.
NP_001018170.1.
NP_003896.1.
UniGeneHs.460978

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1R4MX-ray3.00A/C/E/G1-534[»]
1R4NX-ray3.60A/C/E/G1-534[»]
1TT5X-ray2.60A/C1-534[»]
1YOVX-ray2.60A/C1-534[»]
2NVUX-ray2.80A1-534[»]
3DBHX-ray2.85A/C/E/G1-534[»]
3DBLX-ray2.90A/C/E/G1-534[»]
3DBRX-ray3.05A/C/E/G1-534[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ13564. 4 interactions.

PTM databases

PhosphoSiteQ13564.

Proteomic databases

PRIDEQ13564.

Genome annotation databases

EnsemblENSG00000159593. Homo sapiens. [Contig view]
GeneID8883.
KEGGhsa:8883.

Organism-specific databases

GeneCardsGC16M065395.
H-InvDBHIX0013121.
HGNCHGNC:621. NAE1.
MIM603385. gene.
PharmGKBPA24911.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ13564.

Gene expression databases

ArrayExpressQ13564.
BgeeQ13564.
CleanExHS_NAE1.
GermOnlineENSG00000159593. Homo sapiens.

Family and domain databases

InterProIPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD_bd.
[Graphical view]
Gene3DG3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PfamPF00899. ThiF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00171. Adenosine triphosphate.
NextBio33357.
SOURCESearch...

Entry information

Entry nameULA1_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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 · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents