ULA1_RAT
ID ULA1_RAT Reviewed; 534 AA.
AC Q9Z1A5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=NEDD8-activating enzyme E1 regulatory subunit;
DE AltName: Full=Amyloid beta precursor protein-binding protein 1, 59 kDa;
DE Short=APP-BP1;
DE AltName: Full=Amyloid protein-binding protein 1;
GN Name=Nae1; Synonyms=Appbp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Chow N., Mobley W.C., Dreger U.C., Coopersmith R., Neve R.L.;
RT "Localization of the amyloid protein precursor binding protein, APP-BP1, in
RT the developing central nervous system.";
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=8626687; DOI=10.1074/jbc.271.19.11339;
RA Chow N., Korenberg J.R., Chen X.-N., Neve R.L.;
RT "APP-BP1, a novel protein that binds to the carboxyl-terminal region of the
RT amyloid precursor protein.";
RL J. Biol. Chem. 271:11339-11346(1996).
RN [3]
RP FUNCTION, INTERACTION WITH APP, AND SUBCELLULAR LOCATION.
RX PubMed=14557245; DOI=10.1083/jcb.200304003;
RA Chen Y., Liu W., McPhie D.L., Hassinger L., Neve R.L.;
RT "APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased
RT in Alzheimer's disease brain.";
RL J. Cell Biol. 163:27-33(2003).
CC -!- FUNCTION: Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1
CC activates NEDD8 by first adenylating its C-terminal glycine residue
CC with ATP, thereafter linking this residue to the side chain of the
CC catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1
CC finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary
CC for cell cycle progression through the S-M checkpoint. Overexpression
CC of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.
CC {ECO:0000269|PubMed:14557245}.
CC -!- ACTIVITY REGULATION: Binding of TP53BP2 to the regulatory subunit NAE1
CC decreases neddylation activity. {ECO:0000250}.
CC -!- PATHWAY: Protein modification; protein neddylation.
CC -!- SUBUNIT: Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and
CC UBE2M. Binds APP and TP53BP2.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14557245}.
CC Note=Colocalizes with APP in lipid rafts.
CC -!- TISSUE SPECIFICITY: Expressed throughout the brain. In hippocampus,
CC strongly expressed in granule cells and in the pyramidal cell layer.
CC Strongly expressed in the piriform cortex. In the cerebellum, expressed
CC only in Purkinje cells. {ECO:0000269|PubMed:8626687}.
CC -!- PTM: Ubiquitinated by TRIP12, leading to its degradation by the
CC proteasome. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. ULA1
CC subfamily. {ECO:0000305}.
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DR EMBL; U90829; AAD09247.1; -; mRNA.
DR AlphaFoldDB; Q9Z1A5; -.
DR SMR; Q9Z1A5; -.
DR STRING; 10116.ENSRNOP00000045593; -.
DR iPTMnet; Q9Z1A5; -.
DR PhosphoSitePlus; Q9Z1A5; -.
DR jPOST; Q9Z1A5; -.
DR PaxDb; Q9Z1A5; -.
DR PRIDE; Q9Z1A5; -.
DR UCSC; RGD:619945; rat.
DR RGD; 619945; Nae1.
DR eggNOG; KOG2016; Eukaryota.
DR InParanoid; Q9Z1A5; -.
DR PhylomeDB; Q9Z1A5; -.
DR Reactome; R-RNO-8951664; Neddylation.
DR UniPathway; UPA00885; -.
DR PRO; PR:Q9Z1A5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0019781; F:NEDD8 activating enzyme activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central.
DR GO; GO:0045116; P:protein neddylation; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISO:RGD.
DR InterPro; IPR030667; APP-BP1.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00899; ThiF; 1.
DR PIRSF; PIRSF039099; APP-BP1; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; Cell cycle; Cell membrane; Membrane;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13564"
FT CHAIN 2..534
FT /note="NEDD8-activating enzyme E1 regulatory subunit"
FT /id="PRO_0000194954"
FT REGION 331..344
FT /note="Interaction with UBA3"
FT /evidence="ECO:0000250"
FT SITE 211
FT /note="Interaction with UBA3"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q13564"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13564"
FT MOD_RES 341
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VBW6"
SQ SEQUENCE 534 AA; 60383 MW; 5A759E170D7A99B2 CRC64;
MAQQGKILKE QKYDRQLRLW GDHGQEALES AHVCLINATA TGTEILKNLV LPGIGSFTII
DGNQVSGEDV GNNFFLQKCS IGKNRAQAAM EFLQELNSDV SGSFVEESPE NLLDNDPSFF
CRFTIVVATQ LLESTLLRLA DVLWNSQIPL LICRTYGLVG YMRIIIKEHP VIESHPDNAL
EDLRLDKPFP ELREHFQSYD LDHMEKKDHS HTPWIVIIAK YLAQWYSETN GRIPKSYKEK
EDFRELIRQG ILKNENGAPE DEENFEEAIK NVNTALNTTQ IPSSIEDIFN DDRCINITKQ
TPSFWILARA LKEFVAKEGQ GNLPVRGTIP DMIADSNKYI KLQNVYREKA KKDAAAVGNH
VAKLLQSCGQ APESISEKEL KLLCSNSAFL RVVRCRSLAE EYGLHTVNKD EIISSMDNPD
NEIVLYLMLR AVDRFHKQHG RYPGVSNYQV EEDIGKLKSC LTGFLQEYGL SVMVKDDYVH
EFCRYGAAEP HTVAAFLGGA AAQEVIKIIT KQFVIFNNTY IYSGMSQTSA TFQL
