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UniProtKB - Q13564 (ULA1_HUMAN)

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Protein

NEDD8-activating enzyme E1 regulatory subunit

Gene

NAE1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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

  • NEDD8 activating enzyme activity Source: InterPro
  • protein heterodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • mitotic DNA replication checkpoint Source: UniProtKB
  • neuron apoptotic process Source: UniProtKB
  • protein neddylation Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • regulation of neuron apoptotic process Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywordsi

Biological processApoptosis, Cell cycle, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-8951664. Neddylation.
SIGNORiQ13564.
UniPathwayiUPA00885.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:621. NAE1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

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.

PTM databases

iPTMnetiQ13564.
PhosphoSitePlusiQ13564.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000159593.
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 heterodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi114402. 40 interactors.
IntActiQ13564. 7 interactors.
MINTiMINT-1429663.
STRINGi9606.ENSP00000290810.

Chemistry databases

BindingDBiQ13564.

Structurei

Secondary structure

1534
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 12Combined sources10
Helixi14 – 30Combined sources17
Beta strandi32 – 36Combined sources5
Helixi40 – 50Combined sources11
Turni51 – 53Combined sources3
Beta strandi55 – 60Combined sources6
Helixi67 – 72Combined sources6
Helixi78 – 80Combined sources3
Helixi85 – 94Combined sources10
Beta strandi104 – 107Combined sources4
Helixi109 – 114Combined sources6
Helixi117 – 122Combined sources6
Beta strandi124 – 130Combined sources7
Helixi133 – 145Combined sources13
Beta strandi150 – 156Combined sources7
Beta strandi159 – 165Combined sources7
Beta strandi169 – 172Combined sources4
Beta strandi185 – 187Combined sources3
Helixi190 – 197Combined sources8
Beta strandi201 – 204Combined sources4
Helixi209 – 211Combined sources3
Helixi214 – 225Combined sources12
Turni226 – 229Combined sources4
Helixi236 – 249Combined sources14
Beta strandi257 – 259Combined sources3
Helixi262 – 275Combined sources14
Helixi283 – 289Combined sources7
Helixi292 – 295Combined sources4
Beta strandi299 – 301Combined sources3
Helixi303 – 316Combined sources14
Turni317 – 321Combined sources5
Helixi336 – 366Combined sources31
Turni367 – 369Combined sources3
Beta strandi372 – 375Combined sources4
Helixi377 – 385Combined sources9
Helixi387 – 389Combined sources3
Beta strandi391 – 393Combined sources3
Helixi398 – 402Combined sources5
Turni404 – 406Combined sources3
Helixi409 – 415Combined sources7
Helixi423 – 439Combined sources17
Turni447 – 449Combined sources3
Helixi450 – 467Combined sources18
Helixi476 – 484Combined sources9
Turni485 – 487Combined sources3
Helixi491 – 510Combined sources20
Beta strandi520 – 523Combined sources4
Turni524 – 527Combined sources4
Beta strandi528 – 531Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
3GZNX-ray3.00A/C1-534[»]
ProteinModelPortaliQ13564.
SMRiQ13564.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13564.

Family & Domainsi

Region

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

Sequence similaritiesi

Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.Curated

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.
PANTHERiPTHR10953:SF177. PTHR10953:SF177. 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

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

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
3GZNX-ray3.00A/C1-534[»]
ProteinModelPortaliQ13564.
SMRiQ13564.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114402. 40 interactors.
IntActiQ13564. 7 interactors.
MINTiMINT-1429663.
STRINGi9606.ENSP00000290810.

Chemistry databases

BindingDBiQ13564.
ChEMBLiCHEMBL2016431.
DrugBankiDB00171. Adenosine triphosphate.

PTM databases

iPTMnetiQ13564.
PhosphoSitePlusiQ13564.

Polymorphism and mutation databases

BioMutaiNAE1.
DMDMi50400302.

Proteomic databases

EPDiQ13564.
MaxQBiQ13564.
PaxDbiQ13564.
PeptideAtlasiQ13564.
PRIDEiQ13564.

Protocols and materials databases

DNASUi8883.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi8883.
DisGeNETi8883.
GeneCardsiNAE1.
HGNCiHGNC:621. NAE1.
HPAiHPA041178.
HPA042041.
MIMi603385. gene.
neXtProtiNX_Q13564.
OpenTargetsiENSG00000159593.
PharmGKBiPA162396730.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00885.
ReactomeiR-HSA-8951664. Neddylation.
SIGNORiQ13564.

Miscellaneous databases

ChiTaRSiNAE1. human.
EvolutionaryTraceiQ13564.
GeneWikiiAPPBP1.
GenomeRNAii8883.
PROiPR:Q13564.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159593.
CleanExiHS_NAE1.
ExpressionAtlasiQ13564. baseline and differential.
GenevisibleiQ13564. HS.

Family and domain databases

InterProiView protein in InterPro
IPR030667. APP-BP1.
IPR000594. ThiF_NAD_FAD-bd.
PANTHERiPTHR10953:SF177. PTHR10953:SF177. 1 hit.
PfamiView protein in Pfam
PF00899. ThiF. 1 hit.
PIRSFiPIRSF039099. APP-BP1. 1 hit.
SUPFAMiSSF69572. SSF69572. 1 hit.
ProtoNetiSearch...

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: June 7, 2017
This is version 162 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

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.