Q99942 (RNF5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RNF5
EC=6.3.2.-

Alternative name(s):
Protein G16
RING finger protein 5
Ram1 homolog
Short name=HsRma1

Gene names

Name:	RNF5
Synonyms:	G16, NG2, RMA1

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

General annotation (Comments)

Function	Has E2-dependent E3 ubiquitin-protein ligase activity. May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4. Mediates ubiquitination of PXN/paxillin and Salmonella type III secreted protein sopA. May be involved in regulation of cell motility and localization of PXN/paxillin. Mediates the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N. Mediates the 'Lys-48'-linked polyubiquitination of TMEM173 at 'Lys-150' leading to its proteasomal degradation; the ubiquitination occurrs in mitochondria after viral transfection and regulates antiviral responses. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with PXN. Interacts with Salmonella typhimurium sopA. Interacts with JKAMP. Interacts with TMEM173; the interaction of endogenous proteins is dependent on viral infection. Ref.9 Ref.11 Ref.12
Subcellular location	Membrane; Multi-pass membrane protein. Mitochondrion membrane. Endoplasmic reticulum membrane. Note: Predominantly located in the plasma membrane, with some localization occurring within cytoplasmic organelles. Ref.9 Ref.11
Tissue specificity	Widely expressed. Ref.1
Sequence similarities	Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane Mitochondrion
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ER-associated misfolded protein catabolic process Inferred from mutant phenotype Ref.12. Source: UniProtKB protein K48-linked ubiquitination Inferred from direct assay Ref.11. Source: UniProtKB protein K63-linked ubiquitination Inferred from direct assay Ref.12. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.12. Source: UniProtKB zinc ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CFTR	P13569	3	EBI-348482,EBI-349854
PXN	P49023	6	EBI-348482,EBI-702209
UBE2D2	P62837	3	EBI-348482,EBI-347677
UBE2D3	P61077	3	EBI-348482,EBI-348268

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 180	180	E3 ubiquitin-protein ligase RNF5		PRO_0000240393
Regions
	Transmembrane	118 – 138	21	Helical; Potential
	Transmembrane	160 – 180	21	Helical; Potential
	Zinc finger	27 – 68	42	RING-type
Experimental info
	Mutagenesis	42	1	C → S: Loss of E3 ubiquitin-protein ligase activity. Ref.2
	Sequence conflict	22	1	G → S in CAB51286. Ref.3
	Sequence conflict	60	1	E → D in CAB51286. Ref.3
	Sequence conflict	117	1	T → A in CAB51286. Ref.3
	Sequence conflict	148	1	T → A in CAB51286. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q99942 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: E5AFA4DE6DE85942	FASTA	180	19,881
	10 20 30 40 50 60 MAAAEEEDGG PEGPNRERGG AGATFECNIC LETAREAVVS VCGHLYCWPC LHQWLETRPE 70 80 90 100 110 120 RQECPVCKAG ISREKVVPLY GRGSQKPQDP RLKTPPRPQG QRPAPESRGG FQPFGDTGGF 130 140 150 160 170 180 HFSFGVGAFP FGFFTTVFNA HEPFRRGTGV DLGQGHPASS WQDSLFLFLA IFFFFWLLSI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans." Kyushiki H., Kuga Y., Suzuki M., Takahashi E., Horie M. Cytogenet. Cell Genet. 79:114-117(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Rma1, a novel type of RING finger protein conserved from Arabidopsis to human, is a membrane-bound ubiquitin ligase." Matsuda N., Suzuki T., Tanaka K., Nakano A. J. Cell Sci. 114:1949-1957(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, MUTAGENESIS OF CYS-42.
[3]	"Characterisation of a novel gene, G16, in the class III region of the human major histocompatibility complex." Khanna A., Campbell R.D. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"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].
[6]	"Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse." Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L. Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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.
[9]	"RNF5, a RING finger protein that regulates cell motility by targeting paxillin ubiquitination and altered localization." Didier C., Broday L., Bhoumik A., Israeli S., Takahashi S., Nakayama K., Thomas S.M., Turner C.E., Henderson S., Sabe H., Ronai Z. Mol. Cell. Biol. 23:5331-5345(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PXN.
[10]	"Recognition and ubiquitination of Salmonella type III effector SopA by a ubiquitin E3 ligase, HsRMA1." Zhang Y., Higashide W., Dai S., Sherman D.M., Zhou D. J. Biol. Chem. 280:38682-38688(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA." Zhong B., Zhang L., Lei C., Li Y., Mao A.P., Yang Y., Wang Y.Y., Zhang X.L., Shu H.B. Immunity 30:397-407(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF TMEM173, INTERACTION WITH TMEM173, SUBCELLULAR LOCATION.
[12]	"Regulation of endoplasmic reticulum-associated degradation by RNF5-dependent ubiquitination of JNK-associated membrane protein (JAMP)." Tcherpakov M., Delaunay A., Toth J., Kadoya T., Petroski M.D., Ronai Z.A. J. Biol. Chem. 284:12099-12109(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN UBIQUITINATION OF JKAMP, INTERACTION WITH JKAMP.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB056869 mRNA. Translation: BAB39359.1. AJ243936 mRNA. Translation: CAB51286.1. AK311859 mRNA. Translation: BAG34800.1. BT007105 mRNA. Translation: AAP35769.1. U89336 Genomic DNA. Translation: AAB47492.1. AL845464 Genomic DNA. Translation: CAI41808.1. AL662884 Genomic DNA. Translation: CAI18351.1. AL662830 Genomic DNA. Translation: CAI17532.1. BX284686 Genomic DNA. Translation: CAM26222.1. BX927239 Genomic DNA. Translation: CAQ06594.1. CR812478 Genomic DNA. Translation: CAQ10698.1. CR933878 Genomic DNA. Translation: CAQ09623.1. BC004155 mRNA. Translation: AAH04155.1. BC111392 mRNA. Translation: AAI11393.1. BC119741 mRNA. Translation: AAI19742.1. BC119742 mRNA. Translation: AAI19743.1. BC127651 mRNA. Translation: AAI27652.1. BC127652 mRNA. Translation: AAI27653.1. BC148255 mRNA. Translation: AAI48256.1.
IPI	IPI00012608.
RefSeq	NP_008844.1. NM_006913.3.
UniGene	Hs.731774.
3D structure databases
ProteinModelPortal	Q99942.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29268N.
IntAct	Q99942. 21 interactions.
MINT	MINT-1032027.
STRING	9606.ENSP00000364235.
PTM databases
PhosphoSite	Q99942.
Polymorphism databases
DMDM	74762702.
Proteomic databases
PaxDb	Q99942.
PRIDE	Q99942.
Protocols and materials databases
DNASU	6048.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375094; ENSP00000364235; ENSG00000204308. ENST00000413786; ENSP00000387879; ENSG00000225452. ENST00000432616; ENSP00000413131; ENSG00000183574. ENST00000445885; ENSP00000401172; ENSG00000227277. ENST00000449794; ENSP00000415784; ENSG00000223767. ENST00000453473; ENSP00000415127; ENSG00000228907. ENST00000456167; ENSP00000388795; ENSG00000228405.
GeneID	6048.
KEGG	hsa:6048.
UCSC	uc003oaj.4. human.
Organism-specific databases
CTD	6048.
GeneCards	GC06P032146.
H-InvDB	HIX0034363.
HGNC	HGNC:10068. RNF5.
HPA	CAB034107.
MIM	602677. gene.
neXtProt	NX_Q99942.
PharmGKB	PA34442.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300581.
HOGENOM	HOG000238304.
HOVERGEN	HBG054495.
InParanoid	Q99942.
KO	K10666.
OMA	FQSFGDT.
OrthoDB	EOG469QVX.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q99942.
Bgee	Q99942.
CleanEx	HS_RNF5.
Genevestigator	Q99942.
GermOnline	ENSG00000204308. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6048.
NextBio	23565.
SOURCE	Search...

Entry information

Entry name

RNF5_HUMAN

Accession

Primary (citable) accession number: Q99942
Secondary accession number(s): A2BFI6 , B2R4K3, Q0VDB7, Q9UMQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 27, 2006
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 122 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.