UniProtKB - Q13564 (ULA1_HUMAN)
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Protein
NEDD8-activating enzyme E1 regulatory subunit
Gene
NAE1
Organism
Homo sapiens (Human)
Status
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.
Enzyme regulationi
Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.
: protein neddylation Pathwayi
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
- NEDD8 activating enzyme activity Source: InterPro
- protein heterodimerization activity Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- mitotic DNA replication checkpoint Source: UniProtKB
- neuron apoptotic process Source: UniProtKB
- post-translational protein modification Source: Reactome
- protein neddylation Source: UniProtKB
- regulation of apoptotic process Source: UniProtKB
- regulation of neuron apoptotic process Source: UniProtKB
- signal transduction Source: ProtInc
Keywordsi
Biological process | Apoptosis, Cell cycle, Ubl conjugation pathway |
Enzyme and pathway databases
BioCyci | MetaCyc:ENSG00000159593-MONOMER. |
Reactomei | R-HSA-8951664. Neddylation. |
SIGNORi | Q13564. |
UniPathwayi | UPA00885. |
Names & Taxonomyi
Protein namesi | Recommended name: NEDD8-activating enzyme E1 regulatory subunitAlternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000159593.14. |
HGNCi | HGNC:621. NAE1. |
MIMi | 603385. gene. |
neXtProti | NX_Q13564. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 331 | D → A: Impairs the formation of the NEDD8-UBA3 thioester. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8883. |
OpenTargetsi | ENSG00000159593. |
PharmGKBi | PA162396730. |
Chemistry databases
ChEMBLi | CHEMBL2016431. |
DrugBanki | DB00171. Adenosine triphosphate. |
Polymorphism and mutation databases
BioMutai | NAE1. |
DMDMi | 50400302. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000194951 | 2 – 534 | NEDD8-activating enzyme E1 regulatory subunitAdd BLAST | 533 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 6 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 341 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Ubiquitinated by TRIP12, leading to its degradation by the proteasome.1 Publication
Keywords - PTMi
Acetylation, Ubl conjugationProteomic databases
EPDi | Q13564. |
MaxQBi | Q13564. |
PaxDbi | Q13564. |
PeptideAtlasi | Q13564. |
PRIDEi | Q13564. |
PTM databases
iPTMneti | Q13564. |
PhosphoSitePlusi | Q13564. |
Expressioni
Tissue specificityi
Ubiquitous in fetal tissues. Expressed throughout the adult brain.1 Publication
Gene expression databases
Bgeei | ENSG00000159593. |
CleanExi | HS_NAE1. |
ExpressionAtlasi | Q13564. baseline and differential. |
Genevisiblei | Q13564. HS. |
Organism-specific databases
HPAi | HPA041178. HPA042041. |
Interactioni
Subunit structurei
Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2.3 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 211 | Interaction with UBA3 | 1 |
GO - Molecular functioni
- protein heterodimerization activity Source: UniProtKB
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 114402. 43 interactors. |
CORUMi | Q13564. |
IntActi | Q13564. 8 interactors. |
MINTi | Q13564. |
STRINGi | 9606.ENSP00000290810. |
Chemistry databases
BindingDBi | Q13564. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 3 – 12 | Combined sources | 10 | |
Helixi | 14 – 30 | Combined sources | 17 | |
Beta strandi | 32 – 36 | Combined sources | 5 | |
Helixi | 40 – 50 | Combined sources | 11 | |
Turni | 51 – 53 | Combined sources | 3 | |
Beta strandi | 55 – 60 | Combined sources | 6 | |
Helixi | 67 – 72 | Combined sources | 6 | |
Helixi | 78 – 80 | Combined sources | 3 | |
Helixi | 85 – 94 | Combined sources | 10 | |
Beta strandi | 104 – 107 | Combined sources | 4 | |
Helixi | 109 – 114 | Combined sources | 6 | |
Helixi | 117 – 122 | Combined sources | 6 | |
Beta strandi | 124 – 130 | Combined sources | 7 | |
Helixi | 133 – 145 | Combined sources | 13 | |
Beta strandi | 150 – 156 | Combined sources | 7 | |
Beta strandi | 159 – 165 | Combined sources | 7 | |
Beta strandi | 169 – 172 | Combined sources | 4 | |
Beta strandi | 185 – 187 | Combined sources | 3 | |
Helixi | 190 – 197 | Combined sources | 8 | |
Beta strandi | 201 – 204 | Combined sources | 4 | |
Helixi | 209 – 211 | Combined sources | 3 | |
Helixi | 214 – 225 | Combined sources | 12 | |
Turni | 226 – 229 | Combined sources | 4 | |
Helixi | 236 – 249 | Combined sources | 14 | |
Beta strandi | 257 – 259 | Combined sources | 3 | |
Helixi | 262 – 275 | Combined sources | 14 | |
Helixi | 283 – 289 | Combined sources | 7 | |
Helixi | 292 – 295 | Combined sources | 4 | |
Beta strandi | 299 – 301 | Combined sources | 3 | |
Helixi | 303 – 316 | Combined sources | 14 | |
Turni | 317 – 321 | Combined sources | 5 | |
Helixi | 336 – 366 | Combined sources | 31 | |
Turni | 367 – 369 | Combined sources | 3 | |
Beta strandi | 372 – 375 | Combined sources | 4 | |
Helixi | 377 – 385 | Combined sources | 9 | |
Helixi | 387 – 389 | Combined sources | 3 | |
Beta strandi | 391 – 393 | Combined sources | 3 | |
Helixi | 398 – 402 | Combined sources | 5 | |
Turni | 404 – 406 | Combined sources | 3 | |
Helixi | 409 – 415 | Combined sources | 7 | |
Helixi | 423 – 439 | Combined sources | 17 | |
Turni | 447 – 449 | Combined sources | 3 | |
Helixi | 450 – 467 | Combined sources | 18 | |
Helixi | 476 – 484 | Combined sources | 9 | |
Turni | 485 – 487 | Combined sources | 3 | |
Helixi | 491 – 510 | Combined sources | 20 | |
Beta strandi | 520 – 523 | Combined sources | 4 | |
Turni | 524 – 527 | Combined sources | 4 | |
Beta strandi | 528 – 531 | Combined sources | 4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
3GZN | X-ray | 3.00 | A/C | 1-534 | [»] | |
ProteinModelPortali | Q13564. | |||||
SMRi | Q13564. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13564. |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 331 – 344 | Interaction with UBA3Add BLAST | 14 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2016. Eukaryota. COG0476. LUCA. |
GeneTreei | ENSGT00550000074901. |
HOGENOMi | HOG000216537. |
HOVERGENi | HBG079761. |
InParanoidi | Q13564. |
KOi | K04532. |
OMAi | NDDRCIN. |
OrthoDBi | EOG091G05WI. |
PhylomeDBi | Q13564. |
TreeFami | TF313972. |
Family and domain databases
InterProi | View protein in InterPro IPR030667. APP-BP1. IPR000594. ThiF_NAD_FAD-bd. IPR035985. Ubiquitin-activating_enz. |
PANTHERi | PTHR10953:SF29. PTHR10953:SF29. 1 hit. |
Pfami | View protein in Pfam PF00899. ThiF. 1 hit. |
PIRSFi | PIRSF039099. APP-BP1. 1 hit. |
SUPFAMi | SSF69572. SSF69572. 1 hit. |
s (4)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basket
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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 268 | A → V in BAG53511 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 285 | I → T in BAG53511 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052435 | 101 | S → F. Corresponds to variant dbSNP:rs363212Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054258 | 1 – 89 | Missing in isoform 3. CuratedAdd BLAST | 89 | |
Alternative sequenceiVSP_042895 | 1 – 17 | MAQLG…YDRQL → MDAQQTKTNEA in isoform 2. 1 PublicationAdd BLAST | 17 | |
Alternative sequenceiVSP_054259 | 53 | G → GNVG in isoform 4. 1 Publication | 1 |
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. |
CCDSi | CCDS10820.1. [Q13564-1] CCDS42171.1. [Q13564-2] CCDS42172.1. [Q13564-3] CCDS67050.1. [Q13564-4] |
RefSeqi | NP_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] |
UniGenei | Hs.460978. |
Genome annotation databases
Ensembli | ENST00000290810; ENSP00000290810; ENSG00000159593. [Q13564-1] ENST00000359087; ENSP00000351990; ENSG00000159593. [Q13564-4] ENST00000379463; ENSP00000368776; ENSG00000159593. [Q13564-2] ENST00000394074; ENSP00000377637; ENSG00000159593. [Q13564-3] |
GeneIDi | 8883. |
KEGGi | hsa:8883. |
UCSCi | uc002eqe.4. human. [Q13564-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | ULA1_HUMAN | |
Accessioni | Q13564Primary (citable) accession number: Q13564 Secondary accession number(s): A6NCK0 B3KUP9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | November 1, 1996 | |
Last modified: | March 28, 2018 | |
This is version 168 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |