P61087 (UBE2K_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-conjugating enzyme E2 K
EC=6.3.2.19

Alternative name(s):
Huntingtin-interacting protein 2
Short name=HIP-2
Ubiquitin carrier protein
Ubiquitin-conjugating enzyme E2-25 kDa
Short name=Ubiquitin-conjugating enzyme E2(25K)
Short name=Ubiquitin-conjugating enzyme E2-25K
Ubiquitin-protein ligase

Gene names

Name:	Ube2k
Synonyms:	Hip2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	200 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. Involved in stabilization of CASP12 during ER stress-mediated beta-amyloid neurotoxicity probably by inhibiting proteasome activity; in vitro ubiquitinates CASP12. Ref.4
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with RNF138/NARF. Interacts with BRCA1 By similarity.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed in the brain, with highest levels found in the mitral cells of the olfactory bulb, the pyramidal cell layer of the hippocampus and the Purkinje cells of the cerebellar cortex. Ref.1
Developmental stage	Expressed at all stages of brain development and increases significantly between postnatal days 7 and 14. Ref.1
Post-translational modification	Sumoylation at Lys-14 impairs catalytic activity By similarity.
Disruption phenotype	Neurons are resistant to beta-amyloid neurotoxicity. Significantly lower CASP12 expression in brain. Ref.4
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family. Contains 1 UBA domain.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
PTM	Acetylation Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein K48-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.4. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin protein ligase binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-ubiquitin ligase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 200	199	Ubiquitin-conjugating enzyme E2 K		PRO_0000082444
Regions
	Domain	160 – 200	41	UBA
Sites
	Active site	92	1	Glycyl thioester intermediate By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	14	1	N6-acetyllysine By similarity
	Cross-link	14		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Experimental info
	Sequence conflict	163	1	T → P in BAA24927. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P61087 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E40668099ED25828	FASTA	200	22,407
	10 20 30 40 50 60 MANIAVQRIK REFKEVLKSE ETSKNQIKVD LVDENFTELR GEIAGPPDTP YEGGRYQLEI 70 80 90 100 110 120 KIPETYPFNP PKVRFITKIW HPNISSVTGA ICLDILKDQW AAAMTLRTVL LSLQALLAAA 130 140 150 160 170 180 EPDDPQDAVV ANQYKQNPEM FKQTARLWAH VYAGAPVSSP EYTKKIENLC AMGFDRNAVI 190 200 VALSSKSWDV ETATELLLSN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Localization of huntingtin-interacting protein-2 (Hip-2) mRNA in the developing mouse brain." Tanno Y., Mori T., Yokoya S., Kanazawa K., Honma Y., Nikaido T., Takeda J., Tojo M., Yamamoto T., Wanaka A. J. Chem. Neuroanat. 17:99-107(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Brain.
[2]	"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: Bone and Mammary tumor.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 85-200. Strain: C57BL/6J. Tissue: Testis.
[4]	"E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Abeta neurotoxicity." Song S., Lee H., Kam T.I., Tai M.L., Lee J.Y., Noh J.Y., Shim S.M., Seo S.J., Kong Y.Y., Nakagawa T., Chung C.W., Choi D.Y., Oubrahim H., Jung Y.K. J. Cell Biol. 182:675-684(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF CASP12, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB011081 mRNA. Translation: BAA24927.1. BC002013 mRNA. Translation: AAH02013.1. BC085311 mRNA. Translation: AAH85311.1. AK006316 mRNA. Translation: BAB24523.1.
IPI	IPI00322440.
RefSeq	NP_058066.2. NM_016786.3.
UniGene	Mm.319512. Mm.441014.
3D structure databases
ProteinModelPortal	P61087.
ModBase	Search...
PTM databases
PhosphoSite	P61087.
2D gel databases
REPRODUCTION-2DPAGE	P61087.
Proteomic databases
PaxDb	P61087.
PRIDE	P61087.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000142407; ENSMUSP00000122471; ENSMUSG00000029203.
GeneID	53323.
KEGG	mmu:53323.
Organism-specific databases
CTD	3093.
MGI	MGI:1858216. Ube2k.
Phylogenomic databases
eggNOG	COG5078.
HOVERGEN	HBG063308.
InParanoid	P61087.
KO	K04649.
OMA	MAVSRIK.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	P61087.
Bgee	P61087.
Genevestigator	P61087.
GermOnline	ENSMUSG00000029203. Mus musculus.
Family and domain databases
Gene3D	3.10.110.10. 1 hit.
InterPro	IPR009060. UBA-like. IPR000449. UBA/transl_elong_EF1B_N. IPR015940. UBA/transl_elong_EF1B_N_euk. IPR000608. UBQ-conjugat_E2. IPR023313. UBQ-conjugating_AS. IPR016135. UBQ-conjugating_enzyme/RWD. [Graphical view]
Pfam	PF00627. UBA. 1 hit. PF00179. UQ_con. 1 hit. [Graphical view]
SMART	SM00165. UBA. 1 hit. [Graphical view]
SUPFAM	SSF46934. UBA_like. 1 hit. SSF54495. UBQ-conjugat/RWD-like. 1 hit.
PROSITE	PS50030. UBA. 1 hit. PS00183. UBIQUITIN_CONJUGAT_1. 1 hit. PS50127. UBIQUITIN_CONJUGAT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UBE2K. mouse.
NextBio	310133.
SOURCE	Search...

Entry information

Entry name

UBE2K_MOUSE

Accession

Primary (citable) accession number: P61087
Secondary accession number(s): O54806 , P27924, Q16721, Q9CVV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program