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UniProtKB - Q13564 (ULA1_HUMAN)

UniProt

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

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

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...

Keywords - Biological processi

Apoptosis, Cell cycle, Ubl conjugation pathway

Enzyme and pathway databases

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
  • cytosol Source: GO_Central
  • nucleus Source: GO_Central
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi331 – 3311D → A: Impairs the formation of the NEDD8-UBA3 thioester. 1 Publication

Organism-specific databases

PharmGKBiPA162396730.

Chemistry

ChEMBLiCHEMBL2016431.
DrugBankiDB00171. Adenosine triphosphate.

Polymorphism and mutation databases

BioMutaiNAE1.
DMDMi50400302.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 534533NEDD8-activating enzyme E1 regulatory subunitPRO_0000194951Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei6 – 61N6-acetyllysineCombined sources
Modified residuei341 – 3411N6-acetyllysineBy similarity

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.
PhosphoSiteiQ13564.

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei211 – 2111Interaction with UBA3

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114402. 40 interactions.
IntActiQ13564. 6 interactions.
MINTiMINT-1429663.
STRINGi9606.ENSP00000290810.

Chemistry

BindingDBiQ13564.

Structurei

Secondary structure

1
534
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 1210Combined sources
Helixi14 – 3017Combined sources
Beta strandi32 – 365Combined sources
Helixi40 – 5011Combined sources
Turni51 – 533Combined sources
Beta strandi55 – 606Combined sources
Helixi67 – 726Combined sources
Helixi78 – 803Combined sources
Helixi85 – 9410Combined sources
Beta strandi104 – 1074Combined sources
Helixi109 – 1146Combined sources
Helixi117 – 1226Combined sources
Beta strandi124 – 1307Combined sources
Helixi133 – 14513Combined sources
Beta strandi150 – 1567Combined sources
Beta strandi159 – 1657Combined sources
Beta strandi169 – 1724Combined sources
Beta strandi185 – 1873Combined sources
Helixi190 – 1978Combined sources
Beta strandi201 – 2044Combined sources
Helixi209 – 2113Combined sources
Helixi214 – 22512Combined sources
Turni226 – 2294Combined sources
Helixi236 – 24914Combined sources
Beta strandi257 – 2593Combined sources
Helixi262 – 27514Combined sources
Helixi283 – 2897Combined sources
Helixi292 – 2954Combined sources
Beta strandi299 – 3013Combined sources
Helixi303 – 31614Combined sources
Turni317 – 3215Combined sources
Helixi336 – 36631Combined sources
Turni367 – 3693Combined sources
Beta strandi372 – 3754Combined sources
Helixi377 – 3859Combined sources
Helixi387 – 3893Combined sources
Beta strandi391 – 3933Combined sources
Helixi398 – 4025Combined sources
Turni404 – 4063Combined sources
Helixi409 – 4157Combined sources
Helixi423 – 43917Combined sources
Turni447 – 4493Combined sources
Helixi450 – 46718Combined sources
Helixi476 – 4849Combined sources
Turni485 – 4873Combined sources
Helixi491 – 51020Combined sources
Beta strandi520 – 5234Combined sources
Turni524 – 5274Combined sources
Beta strandi528 – 5314Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 6-534.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13564.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni331 – 34414Interaction with UBA3Add
BLAST

Sequence similaritiesi

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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.720. 3 hits.
InterProiIPR030667. APP-BP1.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]
PfamiPF00899. ThiF. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti268 – 2681A → V in BAG53511 (PubMed:14702039).Curated
Sequence conflicti285 – 2851I → T in BAG53511 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti101 – 1011S → F.
Corresponds to variant rs363212 [ dbSNP | Ensembl ].		VAR_052435

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 8989Missing in isoform 3. CuratedVSP_054258Add
BLAST
Alternative sequencei1 – 1717MAQLG…YDRQL → MDAQQTKTNEA in isoform 2. 1 PublicationVSP_042895Add
BLAST
Alternative sequencei53 – 531G → GNVG in isoform 4. 1 PublicationVSP_054259

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
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. Positions 6-534.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114402. 40 interactions.
IntActiQ13564. 6 interactions.
MINTiMINT-1429663.
STRINGi9606.ENSP00000290810.

Chemistry

BindingDBiQ13564.
ChEMBLiCHEMBL2016431.
DrugBankiDB00171. Adenosine triphosphate.

PTM databases

iPTMnetiQ13564.
PhosphoSiteiQ13564.

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

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayiUPA00885.

Miscellaneous databases

ChiTaRSiNAE1. human.
EvolutionaryTraceiQ13564.
GeneWikiiAPPBP1.
GenomeRNAii8883.
PROiQ13564.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di3.40.50.720. 3 hits.
InterProiIPR030667. APP-BP1.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]
PfamiPF00899. ThiF. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: November 1, 1996
Last modified: September 7, 2016
This is version 156 of the entry and version 1 of the sequence. [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

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.

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.