Q9GZZ9 (UBA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-like modifier-activating enzyme 5
Short name=Ubiquitin-activating enzyme 5

Alternative name(s):
ThiFP1
UFM1-activating enzyme
Ubiquitin-activating enzyme E1 domain-containing protein 1

Gene names

Name:	UBA5
Synonyms:	UBE1DC1

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	404 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E1-like enzyme which activates UFM1 and SUMO2. Ref.1 Ref.8 Ref.13
Subcellular location	Cytoplasm. Nucleus. Note: Localizes mainly in cytoplasm, while it mainly localizes to the nucleus in presence of SUMO2. Ref.8
Tissue specificity	Widely expressed. Ref.2
Sequence similarities	Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein ufmylation Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	aggresome Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay. Source: LIFEdb intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW UFM1 activating enzyme activity Inferred from direct assay Ref.1. Source: UniProtKB cofactor binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAP	O95166	2	EBI-747805,EBI-712001
GABARAPL1	Q9H0R8	2	EBI-747805,EBI-746969
GABARAPL2	P60520	9	EBI-747805,EBI-720116
MAP1LC3B	Q9GZQ8	2	EBI-747805,EBI-373144
MAP1LC3C	Q9BXW4	2	EBI-747805,EBI-2603996

Alternative products

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

Isoform 1 (identifier: Q9GZZ9-1)

Also known as: UBE1DC1A;

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: Q9GZZ9-2)

Also known as: UBE1DC1B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 404

404

Ubiquitin-like modifier-activating enzyme 5

PRO_0000194970

Sites

Active site

250

1

Glycyl thioester intermediate Ref.1 Ref.13

Metal binding

226

1

Zinc

Metal binding

229

1

Zinc

Metal binding

303

1

Zinc

Metal binding

308

1

Zinc

Binding site

83

1

ATP; via amide nitrogen

Binding site

104

1

ATP

Binding site

127

1

ATP

Binding site

150

1

ATP

Binding site

184

1

ATP

Amino acid modifications

Modified residue

45

1

Phosphoserine Ref.10

Modified residue

358

1

Phosphoserine Ref.11

Natural variations

Alternative sequence

1 – 56

56

Missing in isoform 2.

VSP_038528

Experimental info

Mutagenesis

250

1

C → S: Forms a stable intermediate complex. Ref.1

Sequence conflict

403

1

N → S in BAB55199. Ref.4

Secondary structure

1

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404

Helix Strand Turn

Details...

Helix

70 – 73

4

Beta strand

75 – 79

5

Helix

83 – 95

13

Beta strand

98 – 103

6

Helix

120 – 122

3

Helix

127 – 138

12

Beta strand

142 – 147

6

Helix

154 – 166

13

Beta strand

167 – 170

4

Beta strand

176 – 180

5

Helix

185 – 198

14

Beta strand

202 – 207

6

Beta strand

211 – 219

9

Turn

221 – 223

3

Beta strand

229 – 231

3

Helix

247 – 274

28

Beta strand

281 – 286

6

Turn

287 – 290

4

Helix

306 – 317

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (UBE1DC1A) [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 02F0F64FEAA1E880	FASTA	404	44,863
	10 20 30 40 50 60 MAESVERLQQ RVQELERELA QERSLQVPRS GDGGGGRVRI EKMSSEVVDS NPYSRLMALK 70 80 90 100 110 120 RMGIVSDYEK IRTFAVAIVG VGGVGSVTAE MLTRCGIGKL LLFDYDKVEL ANMNRLFFQP 130 140 150 160 170 180 HQAGLSKVQA AEHTLRNINP DVLFEVHNYN ITTVENFQHF MDRISNGGLE EGKPVDLVLS 190 200 210 220 230 240 CVDNFEARMT INTACNELGQ TWMESGVSEN AVSGHIQLII PGESACFACA PPLVVAANID 250 260 270 280 290 300 EKTLKREGVC AASLPTTMGV VAGILVQNVL KFLLNFGTVS FYLGYNAMQD FFPTMSMKPN 310 320 330 340 350 360 PQCDDRNCRK QQEEYKKKVA ALPKQEVIQE EEEIIHEDNE WGIELVSEVS EEELKNFSGP 370 380 390 400 VPDLPEGITV AYTIPKKQED SVTELTVEDS GESLEDLMAK MKNM
	Isoform 2 (UBE1DC1B) [UniParc]. Checksum: 127B3CB48EB035B1	FASTA	348	38,537
	10 20 30 40 50 60 MALKRMGIVS DYEKIRTFAV AIVGVGGVGS VTAEMLTRCG IGKLLLFDYD KVELANMNRL 70 80 90 100 110 120 FFQPHQAGLS KVQAAEHTLR NINPDVLFEV HNYNITTVEN FQHFMDRISN GGLEEGKPVD 130 140 150 160 170 180 LVLSCVDNFE ARMTINTACN ELGQTWMESG VSENAVSGHI QLIIPGESAC FACAPPLVVA 190 200 210 220 230 240 ANIDEKTLKR EGVCAASLPT TMGVVAGILV QNVLKFLLNF GTVSFYLGYN AMQDFFPTMS 250 260 270 280 290 300 MKPNPQCDDR NCRKQQEEYK KKVAALPKQE VIQEEEEIIH EDNEWGIELV SEVSEEELKN 310 320 330 340 FSGPVPDLPE GITVAYTIPK KQEDSVTELT VEDSGESLED LMAKMKNM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier." Komatsu M., Chiba T., Tatsumi K., Iemura S., Tanida I., Okazaki N., Ueno T., Kominami E., Natsume T., Tanaka K. EMBO J. 23:1977-1986(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF CYS-250.
[2]	"Isolation and characterization of ubiquitin-activating enzyme E1-domain containing 1, UBE1DC1." Dou T., Gu S., Liu J., Chen F., Zeng L., Guo L., Xie Y., Mao Y. Mol. Biol. Rep. 32:265-271(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon and Teratocarcinoma.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Lung.
[8]	"UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins." Zheng M., Gu X., Zheng D., Yang Z., Li F., Zhao J., Xie Y., Ji C., Mao Y. J. Cell. Biochem. 104:2324-2334(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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].
[13]	"Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme." Bacik J.P., Walker J.R., Ali M., Schimmer A.D., Dhe-Paganon S. J. Biol. Chem. 285:20273-20280(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 57-329 IN COMPLEX WITH ATP AND ZINC, FUNCTION, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB154406 mRNA. Translation: BAD15375.1.
AY253672 mRNA. Translation: AAP79600.1.
AL136757 mRNA. Translation: CAB66691.1.
AK026904 mRNA. Translation: BAB15587.1.
AK027563 mRNA. Translation: BAB55199.1.
AC020632 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79192.1.
CH471052 Genomic DNA. Translation: EAW79189.1.
CH471052 Genomic DNA. Translation: EAW79191.1.
BC009737 mRNA. Translation: AAH09737.1.

IPI

IPI00015736.
IPI00383579.

RefSeq

NP_079094.1. NM_024818.3.
NP_938143.1. NM_198329.2.

UniGene

Hs.170737.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GUC	X-ray	2.25	A/B	57-329	[»]
3H8V	X-ray	2.00	A/B	57-329	[»]

ProteinModelPortal

Q9GZZ9.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9GZZ9. 35 interactions.

MINT

MINT-1475093.

STRING

9606.ENSP00000348565.

PTM databases

PhosphoSite

Q9GZZ9.

Polymorphism databases

DMDM

74733510.

Proteomic databases

PaxDb

Q9GZZ9.

PRIDE

Q9GZZ9.

Protocols and materials databases

DNASU

79876.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264991; ENSP00000264991; ENSG00000081307.
ENST00000356232; ENSP00000348565; ENSG00000081307.
ENST00000494238; ENSP00000418807; ENSG00000081307.

GeneID

79876.

KEGG

hsa:79876.

UCSC

uc003epa.4. human.

Organism-specific databases

CTD

79876.

GeneCards

GC03P132373.

HGNC

HGNC:23230. UBA5.

HPA

HPA017235.

MIM

610552. gene.

neXtProt

NX_Q9GZZ9.

PharmGKB

PA162407661.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0476.

HOGENOM

HOG000256352.

HOVERGEN

HBG056496.

InParanoid

Q9GZZ9.

KO

K12164.

OMA

ETHNYNI.

OrthoDB

EOG4T1HMP.

PhylomeDB

Q9GZZ9.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9GZZ9.

Bgee

Q9GZZ9.

CleanEx

HS_UBA5.

Genevestigator

Q9GZZ9.

GermOnline

ENSG00000081307. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

IPR006140. D-isomer_2_OHA_DH_NAD-bd.
IPR009036. Molybdenum_cofac_synth_MoeB.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]

Pfam

PF00899. ThiF. 1 hit.
[Graphical view]

SUPFAM

SSF69572. MoeB. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9GZZ9.

GenomeRNAi

79876.

NextBio

69659.

SOURCE

Search...

Entry information

Entry name

UBA5_HUMAN

Accession

Primary (citable) accession number: Q9GZZ9
Secondary accession number(s): A6NJL3, D3DNC8, Q96ST1

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 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.