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Protein

NEDD8-activating enzyme E1 regulatory subunit

Gene

NAE1

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

Functioni

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.3 Publications

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.

Activity regulationi

Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.

Pathwayi: protein neddylation

This protein is involved in the pathway protein neddylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein neddylation and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis, Cell cycle, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000159593-MONOMER
ReactomeiR-HSA-8951664 Neddylation
SIGNORiQ13564
UniPathwayi
UPA00885

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8-activating enzyme E1 regulatory subunit
Alternative name(s):
Amyloid beta precursor protein-binding protein 1, 59 kDa
Short name:
APP-BP1
Amyloid protein-binding protein 1
Proto-oncogene protein 1
Gene namesi
Name:NAE1
Synonyms:APPBP1
ORF Names:HPP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000159593.14
HGNCiHGNC:621 NAE1
MIMi603385 gene
neXtProtiNX_Q13564

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

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi331D → A: Impairs the formation of the NEDD8-UBA3 thioester. 1 Publication1

Organism-specific databases

DisGeNETi8883
OpenTargetsiENSG00000159593
PharmGKBiPA162396730

Chemistry databases

ChEMBLiCHEMBL2016431
DrugBankiDB00171 Adenosine triphosphate

Polymorphism and mutation databases

BioMutaiNAE1
DMDMi50400302

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001949512 – 534NEDD8-activating enzyme E1 regulatory subunitAdd BLAST533

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei6N6-acetyllysineCombined sources1
Modified residuei341N6-acetyllysineBy similarity1

Post-translational modificationi

Ubiquitinated by TRIP12, leading to its degradation by the proteasome.1 Publication

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiQ13564
MaxQBiQ13564
PaxDbiQ13564
PeptideAtlasiQ13564
PRIDEiQ13564
ProteomicsDBi59567
59568 [Q13564-2]

PTM databases

iPTMnetiQ13564
PhosphoSitePlusiQ13564

Expressioni

Tissue specificityi

Ubiquitous in fetal tissues. Expressed throughout the adult brain.1 Publication

Gene expression databases

BgeeiENSG00000159593 Expressed in 235 organ(s), highest expression level in secondary oocyte
CleanExiHS_NAE1
ExpressionAtlasiQ13564 baseline and differential
GenevisibleiQ13564 HS

Organism-specific databases

HPAiHPA041178
HPA042041

Interactioni

Subunit structurei

Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei211Interaction with UBA31

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114402, 43 interactors
CORUMiQ13564
IntActiQ13564, 7 interactors
MINTiQ13564
STRINGi9606.ENSP00000290810

Chemistry databases

BindingDBiQ13564

Structurei

Secondary structure

1534
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13564
SMRiQ13564
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13564

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni331 – 344Interaction with UBA3Add BLAST14

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2016 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00550000074901
HOGENOMiHOG000216537
HOVERGENiHBG079761
InParanoidiQ13564
KOiK04532
OMAiNDDRCIN
OrthoDBiEOG091G05WI
PhylomeDBiQ13564
TreeFamiTF313972

Family and domain databases

InterProiView protein in InterPro
IPR030667 APP-BP1
IPR000594 ThiF_NAD_FAD-bd
IPR035985 Ubiquitin-activating_enz
PANTHERiPTHR10953:SF29 PTHR10953:SF29, 1 hit
PfamiView protein in Pfam
PF00899 ThiF, 1 hit
PIRSFiPIRSF039099 APP-BP1, 1 hit
SUPFAMiSSF69572 SSF69572, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 10 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q13564-1) [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
MAQLGKLLKE QKYDRQLRLW GDHGQEALES AHVCLINATA TGTEILKNLV
60 70 80 90 100
LPGIGSFTII DGNQVSGEDA GNNFFLQRSS IGKNRAEAAM EFLQELNSDV
110 120 130 140 150
SGSFVEESPE NLLDNDPSFF CRFTVVVATQ LPESTSLRLA DVLWNSQIPL
160 170 180 190 200
LICRTYGLVG YMRIIIKEHP VIESHPDNAL EDLRLDKPFP ELREHFQSYD
210 220 230 240 250
LDHMEKKDHS HTPWIVIIAK YLAQWYSETN GRIPKTYKEK EDFRDLIRQG
260 270 280 290 300
ILKNENGAPE DEENFEEAIK NVNTALNTTQ IPSSIEDIFN DDRCINITKQ
310 320 330 340 350
TPSFWILARA LKEFVAKEGQ GNLPVRGTIP DMIADSGKYI KLQNVYREKA
360 370 380 390 400
KKDAAAVGNH VAKLLQSIGQ APESISEKEL KLLCSNSAFL RVVRCRSLAE
410 420 430 440 450
EYGLDTINKD EIISSMDNPD NEIVLYLMLR AVDRFHKQQG RYPGVSNYQV
460 470 480 490 500
EEDIGKLKSC LTGFLQEYGL SVMVKDDYVH EFCRYGAAEP HTIAAFLGGA
510 520 530
AAQEVIKIIT KQFVIFNNTY IYSGMSQTSA TFQL
Length:534
Mass (Da):60,246
Last modified:November 1, 1996 - v1
Checksum:i5EC8D3ACE6374F21
GO
Isoform 2 (identifier: Q13564-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MAQLGKLLKEQKYDRQL → MDAQQTKTNEA

Note: No experimental confirmation available.
Show »
Length:528
Mass (Da):59,420
Checksum:iF3732BF1F365C633
GO
Isoform 3 (identifier: Q13564-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-89: Missing.

Note: No experimental confirmation available.
Show »
Length:445
Mass (Da):50,624
Checksum:i0E6DF500733F61E6
GO
Isoform 4 (identifier: Q13564-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: G → GNVG

Show »
Length:537
Mass (Da):60,517
Checksum:i9F3D01503E29A668
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BSS8H3BSS8_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
85Annotation score:
J3KRK3J3KRK3_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
162Annotation score:
H3BQW6H3BQW6_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
167Annotation score:
J3QRA5J3QRA5_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
124Annotation score:
H3BMR3H3BMR3_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
109Annotation score:
J3QLH4J3QLH4_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
112Annotation score:
J3KTE3J3KTE3_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
129Annotation score:
H3BS69H3BS69_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
64Annotation score:
H3BQ16H3BQ16_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
25Annotation score:
H3BMN8H3BMN8_HUMAN
NEDD8-activating enzyme E1 regulato...
NAE1
23Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti268A → V in BAG53511 (PubMed:14702039).Curated1
Sequence conflicti285I → T in BAG53511 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052435101S → F. Corresponds to variant dbSNP:rs363212Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0542581 – 89Missing in isoform 3. CuratedAdd BLAST89
Alternative sequenceiVSP_0428951 – 17MAQLG…YDRQL → MDAQQTKTNEA in isoform 2. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_05425953G → GNVG in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U50939 mRNA Translation: AAC50477.1
AY197612 mRNA Translation: AAP35030.1
AK097680 mRNA Translation: BAG53511.1
AK298159 mRNA Translation: BAH12735.1
AK312784 mRNA Translation: BAG35647.1
AC004638 Genomic DNA Translation: AAC23784.1
AC044802 Genomic DNA No translation available.
AL136798 mRNA Translation: CAB66732.1
CH471092 Genomic DNA Translation: EAW83042.1
BC000480 mRNA Translation: AAH00480.1
BC013301 mRNA Translation: AAH13301.1
CCDSiCCDS10820.1 [Q13564-1]
CCDS42171.1 [Q13564-2]
CCDS42172.1 [Q13564-3]
CCDS67050.1 [Q13564-4]
RefSeqiNP_001018169.1, NM_001018159.1 [Q13564-2]
NP_001018170.1, NM_001018160.1 [Q13564-3]
NP_001273429.1, NM_001286500.1 [Q13564-4]
NP_003896.1, NM_003905.3 [Q13564-1]
XP_005256272.1, XM_005256215.1 [Q13564-3]
XP_011521724.1, XM_011523422.2 [Q13564-3]
UniGeneiHs.460978

Genome annotation databases

EnsembliENST00000290810; ENSP00000290810; ENSG00000159593 [Q13564-1]
ENST00000359087; ENSP00000351990; ENSG00000159593 [Q13564-4]
ENST00000379463; ENSP00000368776; ENSG00000159593 [Q13564-2]
ENST00000394074; ENSP00000377637; ENSG00000159593 [Q13564-3]
GeneIDi8883
KEGGihsa:8883
UCSCiuc002eqe.4 human [Q13564-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiULA1_HUMAN
AccessioniPrimary (citable) accession number: Q13564
Secondary accession number(s): A6NCK0
, A6NFN4, A8MU28, B2R700, B3KUP9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 172 of the entry and version 1 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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