P51668 (UB2D1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-conjugating enzyme E2 D1
EC=6.3.2.19

Alternative name(s):
Stimulator of Fe transport
Short name=SFT
UBC4/5 homolog
UbcH5
Ubiquitin carrier protein D1
Ubiquitin-conjugating enzyme E2(17)KB 1
Ubiquitin-conjugating enzyme E2-17 kDa 1
Ubiquitin-protein ligase D1

Gene names

Name:	UBE2D1
Synonyms:	SFT, UBC5A, UBCH5, UBCH5A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	147 AA.
Sequence status	Complete.
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 catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. Ubiquitinates STUB1-associated HSP90AB1 in vitro. Lacks inherent specificity for any particular lysine residue of ubiquitin. Essential for viral activation of IRF3. Mediates polyubiquitination of CYP3A4. Ref.12 Ref.14 Ref.15 Ref.16 Ref.17
Catalytic activity	ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with RNF11. Ref.10 Ref.11
Subcellular location	Cytoplasm Ref.13.
Tissue specificity	Ubiquitous. Up-regulated in livers of iron-overloaded patients with hereditary hemochromatosis. Ref.2 Ref.8
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.
Caution	Ref.8 cloned and sequenced SFT which consisted of UBE2D1 last coding exon along with intronic sequences on the 5'-end of this exon. A function in iron transport has been described.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	BMP signaling pathway Traceable author statement. Source: Reactome anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome mitotic cell cycle spindle assembly checkpoint Traceable author statement. Source: Reactome negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome protein K48-linked ubiquitination Inferred from direct assay Ref.17. Source: UniProtKB transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct ubiquitin-protein ligase activity Inferred from direct assay Ref.14Ref.17. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RNF11	Q9Y3C5	4	EBI-743540,EBI-396669
RNF126	Q9BV68	3	EBI-743540,EBI-357322
TRAF6	Q9Y4K3	2	EBI-743540,EBI-359276
XIAP	P98170	2	EBI-743540,EBI-517127
ZNRF1	Q8ND25	4	EBI-743540,EBI-2129250

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 147

147

Ubiquitin-conjugating enzyme E2 D1

PRO_0000082460

Sites

Active site

85

1

Glycyl thioester intermediate By similarity

Secondary structure

1

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147

Helix Strand Turn

Details...

Helix

1 – 11

11

Turn

12 – 15

4

Beta strand

19 – 26

8

Beta strand

29 – 38

10

Turn

44 – 47

4

Beta strand

49 – 55

7

Turn

58 – 61

4

Beta strand

66 – 69

4

Helix

87 – 89

3

Turn

90 – 92

3

Helix

99 – 111

13

Helix

121 – 129

9

Helix

131 – 145

15

Sequences

	Sequence		Length	Mass (Da)
	P51668 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 2E96FD0179EE119D	FASTA	147	16,602
	10 20 30 40 50 60 MALKRIQKEL SDLQRDPPAH CSAGPVGDDL FHWQATIMGP PDSAYQGGVF FLTVHFPTDY 70 80 90 100 110 120 PFKPPKIAFT TKIYHPNINS NGSICLDILR SQWSPALTVS KVLLSICSLL CDPNPDDPLV 130 140 PDIAQIYKSD KEKYNRHARE WTQKYAM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53." Scheffner M., Huibregtse J.M., Howley P.M. Proc. Natl. Acad. Sci. U.S.A. 91:8797-8801(1994) [PubMed: 8090726] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis." Gehrke S.G., Riedel H.-D., Herrmann T., Hadaschik B., Bents K., Veltkamp C., Stremmel W. Blood 101:3288-3293(2003) [PubMed: 12480712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skeletal muscle.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [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 (JUL-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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Skin.
[8]	"Functional expression cloning and characterization of SFT, a stimulator of Fe transport." Gutierrez J.A., Yu J., Rivera S., Wessling-Resnick M. J. Cell Biol. 139:895-905(1997) [PubMed: 9362508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 134-147, TISSUE SPECIFICITY.
[9]	Erratum Gutierrez J.A., Yu J., Rivera S., Wessling-Resnick M. J. Cell Biol. 147:205-205(1999)
[10]	"Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses." Matsuzawa S., Reed J.C. Mol. Cell 7:915-926(2001) [PubMed: 11389839] [Abstract] Cited for: SUBUNIT OF A COMPLEX WITH SIAH1; CACYBP; SKP1; APC AND TBL1X.
[11]	"The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase." Subramaniam V., Li H., Wong M.J., Kitching R., Attisano L., Wrana J., Zubovits J., Burger A.M., Seth A.K. Br. J. Cancer 89:1538-1544(2003) [PubMed: 14562029] [Abstract] Cited for: INTERACTION WITH RNF11.
[12]	"Two different classes of E2 ubiquitin-conjugating enzymes are required for the mono-ubiquitination of proteins and elongation by polyubiquitin chains with a specific topology." Windheim M., Peggie M., Cohen P. Biochem. J. 409:723-729(2008) [PubMed: 18042044] [Abstract] Cited for: FUNCTION.
[13]	"The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide." Espinosa A., Oke V., Elfving A., Nyberg F., Covacu R., Wahren-Herlenius M. Exp. Cell Res. 314:3605-3613(2008) [PubMed: 18845142] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Members of the E2D (UbcH5) family mediate the ubiquitination of the conserved cysteine of Pex5p, the peroxisomal import receptor." Grou C.P., Carvalho A.F., Pinto M.P., Wiese S., Piechura H., Meyer H.E., Warscheid B., Sa-Miranda C., Azevedo J.E. J. Biol. Chem. 283:14190-14197(2008) [PubMed: 18359941] [Abstract] Cited for: FUNCTION.
[15]	"CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases." Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E., Correia M.A. Arch. Biochem. Biophys. 483:66-74(2009) [PubMed: 19103148] [Abstract] Cited for: FUNCTION.
[16]	"Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3." Zeng W., Xu M., Liu S., Sun L., Chen Z.J. Mol. Cell 36:315-325(2009) [PubMed: 19854139] [Abstract] Cited for: FUNCTION.
[17]	"The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines." David Y., Ziv T., Admon A., Navon A. J. Biol. Chem. 285:8595-8604(2010) [PubMed: 20061386] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X78140 mRNA. Translation: CAA55019.1.
AF257220 mRNA. Translation: AAM81086.1.
AJ272367 mRNA. Translation: CAC82177.1.
AK291901 mRNA. Translation: BAF84590.1.
AJ293565 Genomic DNA. Translation: CAC82097.1.
BT007041 mRNA. Translation: AAP35690.1.
AC016396 Genomic DNA. No translation available.
AC023170 Genomic DNA. No translation available.
CH471083 Genomic DNA. Translation: EAW54169.1.
BC005980 mRNA. Translation: AAH05980.1.
BC015997 mRNA. Translation: AAH15997.1.
AF020761 mRNA. No translation available.

IPI

IPI00019930.

PIR

I39202.

RefSeq

NP_003329.1. NM_003338.4.

UniGene

Hs.129683.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C4P	X-ray	2.35	A/B	1-147	[»]
2YHO	X-ray	2.10	B/D/F/H	1-147	[»]
3OJ4	X-ray	3.40	A/D	1-147	[»]
3PTF	X-ray	2.70	A/B	1-147	[»]

ProteinModelPortal

P51668.

SMR

P51668. Positions 1-147.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44088N.

IntAct

P51668. 83 interactions.

MINT

MINT-1433717.

STRING

P51668.

PTM databases

PhosphoSite

P51668.

Polymorphism databases

DMDM

1717848.

Proteomic databases

PRIDE

P51668.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373910; ENSP00000363019; ENSG00000072401.

GeneID

7321.

KEGG

hsa:7321.

UCSC

uc001jke.1. human.

Organism-specific databases

CTD

7321.

GeneCards

GC10P060094.

H-InvDB

HIX0008841.

HGNC

HGNC:12474. UBE2D1.

HPA

HPA003920.

MIM

602961. gene.

neXtProt

NX_P51668.

PharmGKB

PA37124.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19276.

GeneTree

ENSGT00590000082778.

HOGENOM

HBG756483.

HOVERGEN

HBG063308.

InParanoid

P51668.

OMA

QIATEWT.

OrthoDB

EOG4RR6JK.

PhylomeDB

P51668.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.
REACT_25177. RNF125 mediated ubiquitination of RIG-I, MDA5 and IPS-1.
REACT_6850. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
REACT_6900. Immune System.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.

Gene expression databases

ArrayExpress

P51668.

Bgee

P51668.

CleanEx

HS_UBE2D1.

Genevestigator

P51668.

GermOnline

ENSG00000072401. Homo sapiens.

Family and domain databases

InterPro

IPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]

Gene3D

G3DSA:3.10.110.10. UBQ-conjugat_E2. 1 hit.

KO

K06689.

Pfam

PF00179. UQ_con. 1 hit.
[Graphical view]

SUPFAM

SSF54495. UBQ-conjugat/RWD-like. 1 hit.

PROSITE

PS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

28626.

SOURCE

Search...

Entry information

Entry name

UB2D1_HUMAN

Accession

Primary (citable) accession number: P51668
Secondary accession number(s): A6NLF6, A8K786

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 112 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.