Q9Y4X5 (ARI1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase ARIH1
EC=6.3.2.-

Alternative name(s):
H7-AP2
HHARI
Monocyte protein 6
Short name=MOP-6
Protein ariadne-1 homolog
Short name=ARI-1
UbcH7-binding protein
UbcM4-interacting protein
Ubiquitin-conjugating enzyme E2-binding protein 1

Gene names

Name:	ARIH1
Synonyms:	ARI, MOP6, UBCH7BP
ORF Names:	HUSSY-27

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

General annotation (Comments)

Function	E3 ubiquitin-protein ligase, which catalyzes polyubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. May play a role in protein translation by mediating polyubiquitination of EIF4E2, leading to its subsequent degradation. Ref.13 Ref.15 Ref.16
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with UBE2L3. Ref.12 Ref.15
Subcellular location	Cytoplasm. Note: Mainly cytoplasmic. Ref.12
Tissue specificity	Widely expressed. Ref.1
Domain	The RING-type 2 zinc finger is atypical: it only binds 1 zinc ion instead of 2 and uses a different hydrophobic network compared to classical RING-types. Ref.16
Miscellaneous	Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain (Ref.15).
Sequence similarities	Belongs to the RBR family. Ariadne subfamily. Contains 1 IBR-type zinc finger. Contains 2 RING-type zinc fingers.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ubiquitin-dependent protein catabolic process Traceable author statement Ref.1. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay Ref.12. Source: UniProtKB ubiquitin ligase complex Traceable author statement Ref.1. Source: UniProtKB
Molecular function	ubiquitin protein ligase binding Inferred from physical interaction Ref.12Ref.15. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.13Ref.16Ref.15. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 557

557

E3 ubiquitin-protein ligase ARIH1

PRO_0000055752

Regions

Zinc finger

186 – 236

51

RING-type 1; atypical

Zinc finger

256 – 317

62

IBR-type

Zinc finger

344 – 375

32

RING-type 2

Region

186 – 254

69

Interaction with UBE2L3

Coiled coil

433 – 449

17

Potential

Compositional bias

10 – 38

29

Asp/Glu-rich (acidic)

Compositional bias

51 – 92

42

Gly-rich

Sites

Metal binding

344

1

Zinc

Metal binding

347

1

Zinc

Metal binding

362

1

Zinc

Metal binding

367

1

Zinc

Experimental info

Mutagenesis

187 – 188

2

QI → HV: No loss of interaction with UBE2L3. Ref.12

Mutagenesis

188

1

I → A: Loss of interaction with UBE2L3. Ref.12

Mutagenesis

208

1

C → A or H: Loss of interaction with UBE2L3. Ref.12

Mutagenesis

258

1

Y → A: No loss of interaction with UBE2L3. Ref.12

Mutagenesis

347

1

C → A: Impairs zinc-binding and folding. Abolishes E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

351

1

I → A: Disrupts the hydrophobic network. Abolishes E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

357

1

C → A or S: Does not affect zinc binding and folding. Abolishes ability to transfer ubiquitin and E3 ubiquitin-protein ligase activity. Ref.15 Ref.16

Mutagenesis

359

1

H → A: Does not affect zinc binding, folding. Does not impair E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

367

1

C → A: Impairs zinc-binding and folding. Abolishes E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

371

1

F → A: Disrupts the hydrophobic network. Abolishes E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

372

1

C → A: Impairs E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

373

1

W → A: Abolishes E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

379

1

W → A: Does not affect E3 ubiquitin-protein ligase activity. Ref.16

Mutagenesis

386

1

W → A: Does not affect E3 ubiquitin-protein ligase activity. Ref.16

Sequence conflict

122

1

E → D in AAD28088. Ref.3

Sequence conflict

227

1

Q → H in CAB45870. Ref.1

Sequence conflict

237

1

D → N in CAA10274. Ref.8

Sequence conflict

303

1

F → S in CAA08817. Ref.9

Sequence conflict

309 – 316

8

ENWHDPVK → AIGMILFQ in CAA08817. Ref.9

Sequence conflict

322

1

K → T in CAA08817. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

557

Helix Strand Turn

Details...

Turn

345 – 347

3

Beta strand

359 – 361

3

Helix

366 – 368

3

Beta strand

372 – 375

4

Helix

380 – 383

4

Beta strand

385 – 389

5

Sequences

	Sequence		Length	Mass (Da)
	Q9Y4X5 [UniParc]. Last modified May 10, 2002. Version 2. Checksum: DFFF8965DAB41DC8	FASTA	557	64,118
	10 20 30 40 50 60 MDSDEGYNYE FDEDEECSEE DSGAEEEEDE DDDEPDDDTL DLGEVELVEP GLGVGGERDG 70 80 90 100 110 120 LLCGETGGGG GSALGPGGGG GGGGGGGGGG PGHEQEEDYR YEVLTAEQIL QHMVECIREV 130 140 150 160 170 180 NEVIQNPATI TRILLSHFNW DKEKLMERYF DGNLEKLFAE CHVINPSKKS RTRQMNTRSS 190 200 210 220 230 240 AQDMPCQICY LNYPNSYFTG LECGHKFCMQ CWSEYLTTKI MEEGMGQTIS CPAHGCDILV 250 260 270 280 290 300 DDNTVMRLIT DSKVKLKYQH LITNSFVECN RLLKWCPAPD CHHVVKVQYP DAKPVRCKCG 310 320 330 340 350 360 RQFCFNCGEN WHDPVKCKWL KKWIKKCDDD SETSNWIAAN TKECPKCHVT IEKDGGCNHM 370 380 390 400 410 420 VCRNQNCKAE FCWVCLGPWE PHGSAWYNCN RYNEDDAKAA RDAQERSRAA LQRYLFYCNR 430 440 450 460 470 480 YMNHMQSLRF EHKLYAQVKQ KMEEMQQHNM SWIEVQFLKK AVDVLCQCRA TLMYTYVFAF 490 500 510 520 530 540 YLKKNNQSII FENNQADLEN ATEVLSGYLE RDISQDSLQD IKQKVQDKYR YCESRRRVLL 550 QHVHEGYEKD LWEYIED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1." Moynihan T.P., Ardley H.C., Nuber U., Rose S.A., Jones P.F., Markham A.F., Scheffner M., Robinson P.A. J. Biol. Chem. 274:30963-30968(1999) [PubMed: 10521492] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	Ardley H.C. Submitted (MAY-2002) to UniProtKB Cited for: SEQUENCE REVISION TO 227.
[3]	"Human ariadne homolog." Trockenbacher A., Marksteiner R., Schneider R. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[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: Brain.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [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: Brain.
[8]	"Ariadne-1: a vital Drosophila gene is required in development and defines a new conserved family of ring-finger proteins." Aguilera M., Oliveros M., Martinez-Padron M., Barbas J.A., Ferrus A. Genetics 155:1231-1244(2000) [PubMed: 10880484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 95-557.
[9]	"Characterization of 16 novel human genes showing high similarity to yeast sequences." Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N., Zimbello R., Lanfranchi G., Valle G. Yeast 18:69-80(2001) [PubMed: 11124703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 298-557. Tissue: Brain.
[10]	"Molecular and biological characterization of a new ring finger protein, MOP-6 which is highly expressed in activated human monocytes." Fujii Y., Takayama K., Ukai Y., Yoshimoto M. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 377-557. Tissue: Monocyte.
[11]	"Characterisation of the human and mouse orthologues of the Drosophila ariadne gene." Tan N.G., Ardley H.C., Rose S.A., Leek J.P., Markham A.F., Robinson P.A. Cytogenet. Cell Genet. 90:242-245(2000) [PubMed: 11124525] [Abstract] Cited for: IDENTIFICATION.
[12]	"Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7." Ardley H.C., Tan N.G.S., Rose S.A., Markham A.F., Robinson P.A. J. Biol. Chem. 276:19640-19647(2001) [PubMed: 11278816] [Abstract] Cited for: INTERACTION WITH UBE2L3, MUTAGENESIS OF 187-GLN-ILE-188; ILE-188; CYS-208 AND TYR-258, SUBCELLULAR LOCATION.
[13]	"Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP." Tan N.G., Ardley H.C., Scott G.B., Rose S.A., Markham A.F., Robinson P.A. FEBS Lett. 554:501-504(2003) [PubMed: 14623119] [Abstract] Cited for: FUNCTION.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids." Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E. Nature 474:105-108(2011) [PubMed: 21532592] [Abstract] Cited for: FUNCTION, REACTION MECHANISM, INTERACTION WITH UBE2L3, MUTAGENESIS OF CYS-357.
[16]	"Structure of the C-terminal RING finger from a RING-IBR-RING/TRIAD motif reveals a novel zinc-binding domain distinct from a RING." Capili A.D., Edghill E.L., Wu K., Borden K.L. J. Mol. Biol. 340:1117-1129(2004) [PubMed: 15236971] [Abstract] Cited for: STRUCTURE BY NMR OF 336-394 IN COMPLEX WITH ZINC, DOMAIN RING-TYPE 2 ZINC FINGER, FUNCTION, MUTAGENESIS OF CYS-347; ILE-351; CYS-357; HIS-359; CYS-367; PHE-371; CYS-372; TRP-373; TRP-379 AND TRP-386.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ243190 mRNA. Translation: CAB45870.1.
AF072832 mRNA. Translation: AAD28088.1.
AK312715 mRNA. Translation: BAG35590.1.
AC079322 Genomic DNA. No translation available.
AC100827 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77907.1.
BC051877 mRNA. Translation: AAH51877.1.
AJ130976 mRNA. Translation: CAA10274.1.
AJ009771 mRNA. Translation: CAA08817.1.
AB014774 mRNA. Translation: BAB19786.1.

IPI

IPI00294943.

RefSeq

NP_005735.2. NM_005744.3.

UniGene

Hs.268787.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WD2	NMR	-	A	336-394	[»]

ProteinModelPortal

Q9Y4X5.

SMR

Q9Y4X5. Positions 180-318, 336-394.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y4X5. 2 interactions.

STRING

Q9Y4X5.

Polymorphism databases

DMDM

20532376.

Proteomic databases

PeptideAtlas

Q9Y4X5.

PRIDE

Q9Y4X5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379887; ENSP00000369217; ENSG00000166233.

GeneID

25820.

KEGG

hsa:25820.

UCSC

uc002aut.2. human.

Organism-specific databases

CTD

25820.

GeneCards

GC15P072766.

H-InvDB

HIX0012409.
HIX0022573.

HGNC

HGNC:689. ARIH1.

HPA

HPA003295.

MIM

605624. gene.

neXtProt

NX_Q9Y4X5.

PharmGKB

PA24982.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04549.

GeneTree

ENSGT00600000084159.

HOGENOM

HBG315021.

HOVERGEN

HBG018737.

InParanoid

Q9Y4X5.

OMA

DEEDYRF.

OrthoDB

EOG4V437D.

PhylomeDB

Q9Y4X5.

Gene expression databases

ArrayExpress

Q9Y4X5.

Bgee

Q9Y4X5.

CleanEx

HS_ARIH1.

Genevestigator

Q9Y4X5.

GermOnline

ENSG00000166233. Homo sapiens.

Family and domain databases

InterPro

IPR002867. Znf_C6HC.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.

KO

K11968.

Pfam

PF01485. IBR. 2 hits.
[Graphical view]

SMART

SM00647. IBR. 2 hits.
SM00184. RING. 2 hits.
[Graphical view]

PROSITE

PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

47071.

SOURCE

Search...

Entry information

Entry name

ARI1_HUMAN

Accession

Primary (citable) accession number: Q9Y4X5
Secondary accession number(s): B2R6U3 , O76026, Q9H3T6, Q9UEN0, Q9UP39

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	May 10, 2002
Last modified:	January 25, 2012
This is version 108 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.