Q9Y5A7 (NUB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NEDD8 ultimate buster 1

Alternative name(s):
Negative regulator of ubiquitin-like proteins 1
Renal carcinoma antigen NY-REN-18

Gene names

Name:	NUB1
Synonyms:	NYREN18

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	615 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Specific down-regulator of the NEDD8 conjugation system. Recruits NEDD8, UBD, and their conjugates to the proteasome for degradation. Isoform 1 promotes the degradation of NEDD8 more efficiently than isoform 2. Ref.10
Subunit structure	Directly interacts with NEDD8 and PSMD4/S5a, a member of the regulatory subunit of the 26S proteasome. Isoform 1 binds to NEDD8 more efficiently than isoform 2. Interacts with AIPL1. The interaction with UBD via UBA domains facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates UBD degradation and that of its conjugates. Ref.2 Ref.7 Ref.8 Ref.9 Ref.10
Subcellular location	Nucleus. Note: Predominantly nuclear. Ref.2
Tissue specificity	Widely expressed with lowest expression in the pancreas for isoform 1 and in leukocytes, liver, prostate and skeletal muscle for isoform 2.
Induction	By TNF, IFNG/IFN-gamma and IFNB1/IFN-beta. Ref.2 Ref.10
Sequence similarities	Contains 3 UBA domains.
Sequence caution	The sequence AAD42865.1 differs from that shown. Reason: Frameshift at positions 365 and 393.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.10. Source: UniProtKB protein ubiquitination Inferred from mutant phenotype Ref.10. Source: UniProtKB response to interferon-gamma Inferred from expression pattern Ref.10. Source: UniProtKB response to tumor necrosis factor Inferred from expression pattern Ref.10. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y5A7-1)

Also known as: NUB1L;

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.

Isoform 2 (identifier: Q9Y5A7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     452-465: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 615

615

NEDD8 ultimate buster 1

PRO_0000210992

Regions

Domain

374 – 413

40

UBA 1

Domain

424 – 470

47

UBA 2

Domain

489 – 529

41

UBA 3

Region

427 – 474

48

NEDD8-binding 1

Region

550 – 598

49

NEDD8-binding 2

Coiled coil

36 – 70

35

Potential

Coiled coil

152 – 203

52

Potential

Motif

414 – 431

18

Nuclear localization signal Probable

Natural variations

Alternative sequence

452 – 465

14

Missing in isoform 2.

VSP_008335

Natural variant

13

1

Q → R.
Corresponds to variant rs2302131 [ dbSNP | Ensembl ].

VAR_057369

Experimental info

Mutagenesis

448

1

A → V: No effect on NEDD8-binding. Ref.3

Mutagenesis

453

1

L → A: Partial inhibition of NEDD8-binding. Ref.3

Mutagenesis

464

1

L → A: Partial inhibition of NEDD8-binding. Ref.3

Mutagenesis

468

1

L → A: Partial inhibition of NEDD8-binding. Ref.3

Mutagenesis

587

1

L → A: Suppression of NEDD8-binding; when associated with A-464; A-468 and A-591. Suppression of NEDD8-buster function; when associated with A-591. Ref.3

Mutagenesis

591

1

L → A: Suppression of NEDD8-binding; when associated with A-464; A-468 and A-587. Suppression of NEDD8-buster function; when associated with A-587. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

615

Helix Strand Turn

Details...

Beta strand

76 – 78

3

Beta strand

82 – 88

7

Beta strand

96 – 108

13

Helix

109 – 119

11

Beta strand

128 – 131

4

Helix

142 – 145

4

Beta strand

149 – 156

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (NUB1L) [UniParc]. Last modified September 26, 2003. Version 2. Checksum: D70FD6B21F4CD42E	FASTA	615	70,538
	10 20 30 40 50 60 MAQKKYLQAK LTQFLREDRI QLWKPPYTDE NKKVGLALKD LAKQYSDRLE CCENEVEKVI 70 80 90 100 110 120 EEIRCKAIER GTGNDNYRTT GIATIEVFLP PRLKKDRKNL LETRLHITGR ELRSKIAETF 130 140 150 160 170 180 GLQENYIKIV INKKQLQLGK TLEEQGVAHN VKAMVLELKQ SEEDARKNFQ LEEEEQNEAK 190 200 210 220 230 240 LKEKQIQRTK RGLEILAKRA AETVVDPEMT PYLDIANQTG RSIRIPPSER KALMLAMGYH 250 260 270 280 290 300 EKGRAFLKRK EYGIALPCLL DADKYFCECC RELLDTVDNY AVLQLDIVWC YFRLEQLECL 310 320 330 340 350 360 DDAEKKLNLA QKCFKNCYGE NHQRLVHIKG NCGKEKVLFL RLYLLQGIRN YHSGNDVEAY 370 380 390 400 410 420 EYLNKARQLF KELYIDPSKV DNLLQLGFTA QEARLGLRAC DGNVDHAATH ITNRREELAQ 430 440 450 460 470 480 IRKEEKEKKR RRLENIRFLK GMGYSTHAAQ QVLHAASGNL DEALKILLSN PQMWWLNDSN 490 500 510 520 530 540 PETDNRQESP SQENIDRLVY MGFDALVAEA ALRVFRGNVQ LAAQTLAHNG GSLPPELPLS 550 560 570 580 590 600 PEDSLSPPAT SPSDSAGTSS ASTDEDMETE AVNEILEDIP EHEEDYLDST LEDEEIIIAE 610 YLSYVENRKS ATKKN
	Isoform 2 [UniParc]. Checksum: 05F92632C2FCB547	FASTA	601	69,119
	10 20 30 40 50 60 MAQKKYLQAK LTQFLREDRI QLWKPPYTDE NKKVGLALKD LAKQYSDRLE CCENEVEKVI 70 80 90 100 110 120 EEIRCKAIER GTGNDNYRTT GIATIEVFLP PRLKKDRKNL LETRLHITGR ELRSKIAETF 130 140 150 160 170 180 GLQENYIKIV INKKQLQLGK TLEEQGVAHN VKAMVLELKQ SEEDARKNFQ LEEEEQNEAK 190 200 210 220 230 240 LKEKQIQRTK RGLEILAKRA AETVVDPEMT PYLDIANQTG RSIRIPPSER KALMLAMGYH 250 260 270 280 290 300 EKGRAFLKRK EYGIALPCLL DADKYFCECC RELLDTVDNY AVLQLDIVWC YFRLEQLECL 310 320 330 340 350 360 DDAEKKLNLA QKCFKNCYGE NHQRLVHIKG NCGKEKVLFL RLYLLQGIRN YHSGNDVEAY 370 380 390 400 410 420 EYLNKARQLF KELYIDPSKV DNLLQLGFTA QEARLGLRAC DGNVDHAATH ITNRREELAQ 430 440 450 460 470 480 IRKEEKEKKR RRLENIRFLK GMGYSTHAAQ QILLSNPQMW WLNDSNPETD NRQESPSQEN 490 500 510 520 530 540 IDRLVYMGFD ALVAEAALRV FRGNVQLAAQ TLAHNGGSLP PELPLSPEDS LSPPATSPSD 550 560 570 580 590 600 SAGTSSASTD EDMETEAVNE ILEDIPEHEE DYLDSTLEDE EIIIAEYLSY VENRKSATKK N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[2]	"NUB1, a NEDD8-interacting protein, is induced by interferon and down-regulates the NEDD8 expression." Kito K., Yeh E.T.H., Kamitani T. J. Biol. Chem. 276:20603-20609(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH NEDD8, SUBCELLULAR LOCATION, INDUCTION BY INTERFERONS. Tissue: Heart.
[3]	"Regulation of the NEDD8 conjugation system by a splicing variant, NUB1L." Tanaka T., Kawashima H., Yeh E.T.H., Kamitani T. J. Biol. Chem. 278:32905-32913(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CHARACTERIZATION, MUTAGENESIS OF ALA-448; LEU-453; LEU-464; LEU-468; LEU-587 AND LEU-591. Tissue: Testis.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[6]	Rump A., Rosenthal A., Drescher B., Weber J., Schattevoy R., Korenberg J. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-365.
[7]	"Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1." Kamitani T., Kito K., Fukuda-Kamitani T., Yeh E.T.H. J. Biol. Chem. 276:46655-46660(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PSMD4.
[8]	"The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1." Akey D.T., Zhu X., Dyer M., Li A., Sorensen A., Blackshaw S., Fukuda-Kamitani T., Daiger S.P., Craft C.M., Kamitani T., Sohocki M.M. Hum. Mol. Genet. 11:2723-2733(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AIPL1. Tissue: Retina.
[9]	"NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein FAT10 and accelerates its degradation." Hipp M.S., Raasi S., Groettrup M., Schmidtke G. J. Biol. Chem. 279:16503-16510(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBD.
[10]	"The UBA domains of NUB1L are required for binding but not for accelerated degradation of the ubiquitin-like modifier FAT10." Schmidtke G., Kalveram B., Weber E., Bochtler P., Lukasiak S., Hipp M.S., Groettrup M. J. Biol. Chem. 281:20045-20054(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH UBD AND PROTEASOME, INDUCTION BY TNF AND IFNG.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Solution structure of N-terminal ubiquitin-like domain of human NEDD8 ultimate buster-1." RIKEN structural genomics initiative (RSGI) Submitted (JAN-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 75-161.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF155099 mRNA. Translation: AAD42865.1. Frameshift.
AF300717 mRNA. Translation: AAK21001.1.
AF459743 mRNA. Translation: AAO14547.1.
AY129295 mRNA. Translation: AAN01355.1.
AC005486 Genomic DNA. Translation: AAS02030.1.
BC046354 mRNA. Translation: AAH46354.1.
AF108083 Genomic DNA. Translation: AAC82474.2.

IPI

IPI00157365.
IPI00377271.

RefSeq

NP_001230280.1. NM_001243351.1.
NP_057202.3. NM_016118.4.

UniGene

Hs.647082.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WJU	NMR	-	A	75-161	[»]

ProteinModelPortal

Q9Y5A7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y5A7. 1 interaction.

STRING

9606.ENSP00000398644.

PTM databases

PhosphoSite

Q9Y5A7.

Polymorphism databases

DMDM

37154888.

Proteomic databases

PaxDb

Q9Y5A7.

PRIDE

Q9Y5A7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355851; ENSP00000348110; ENSG00000013374.
ENST00000566856; ENSP00000457628; ENSG00000013374.

GeneID

51667.

KEGG

hsa:51667.

UCSC

uc003wjw.3. human.
uc003wjx.3. human.

Organism-specific databases

CTD

51667.

GeneCards

GC07P151038.

H-InvDB

HIX0019486.

HGNC

HGNC:17623. NUB1.

HPA

HPA021220.
HPA050722.

MIM

607981. gene.

neXtProt

NX_Q9Y5A7.

PharmGKB

PA147357533.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG302480.

HOGENOM

HOG000113882.

HOVERGEN

HBG045600.

InParanoid

Q9Y5A7.

OMA

MWWLNDS.

PhylomeDB

Q9Y5A7.

Gene expression databases

ArrayExpress

Q9Y5A7.

Bgee

Q9Y5A7.

CleanEx

HS_NUB1.

Genevestigator

Q9Y5A7.

GermOnline

ENSG00000013374. Homo sapiens.

Family and domain databases

InterPro

IPR009060. UBA-like.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF00627. UBA. 2 hits.
[Graphical view]

SMART

SM00165. UBA. 3 hits.
[Graphical view]

SUPFAM

SSF46934. UBA_like. 3 hits.

PROSITE

PS50030. UBA. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NUB1. human.

EvolutionaryTrace

Q9Y5A7.

GenomeRNAi

51667.

NextBio

55660.

SOURCE

Search...

Entry information

Entry name

NUB1_HUMAN

Accession

Primary (citable) accession number: Q9Y5A7
Secondary accession number(s): O95422 , Q75MR9, Q8IX22, Q9BXR2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	September 26, 2003
Last modified:	May 29, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.