P36406 (TRI23_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase TRIM23
EC=6.3.2.-

Alternative name(s):
ADP-ribosylation factor domain-containing protein 1
GTP-binding protein ARD-1
RING finger protein 46
Tripartite motif-containing protein 23

Gene names

Name:	TRIM23
Synonyms:	ARD1, ARFD1, RNF46

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

General annotation (Comments)

Function	Acts as an E3 ubiquitin-protein ligase. In the presence of the human cytomegalovirus (HCMV) protein UL144, participates in 'Lys-63'-linked auto-ubiquitination of TRAF6 resulting in the virally controlled activation of NF-kappa-B at early time of infection. The C-terminus can act as an allosteric activator of the cholera toxin catalytic subunit. Ref.6
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with PSCD1. Interacts with human cytomegalovirus protein UL144; this interaction might causes auto-ubiquitination of TRAF6, leading to NF-kappaB activation. Ref.5 Ref.7
Subcellular location	Endomembrane system. Golgi apparatus membrane. Lysosome membrane. Note: Membrane-associated with the Golgi complex and lysosomal structures. Ref.4
Domain	The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.
Sequence similarities	In the C-terminal section; belongs to the small GTPase superfamily. Arf family. Contains 1 B box-type zinc finger. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Golgi apparatus Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	GTP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi membrane Inferred from direct assay Ref.4. Source: HGNC lysosomal membrane Inferred from direct assay Ref.4. Source: HGNC nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	GDP binding Inferred from direct assay PubMed 8700863. Source: HGNC GTP binding Inferred from direct assay PubMed 8700863. Source: HGNC GTPase activity Inferred from direct assay PubMed 8700863. Source: HGNC enzyme activator activity Traceable author statement Ref.1. Source: ProtInc ubiquitin-protein ligase activity Inferred from direct assay Ref.6. Source: HGNC zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-740098,EBI-740098
GEM	P55040	3	EBI-740098,EBI-744104
Hoxa1	P09022	2	EBI-740098,EBI-3957603	From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: P36406-1)

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 Beta (identifier: P36406-2)

The sequence of this isoform differs from the canonical sequence as follows:
     551-574: GMGLYEGLDWLSRQLVAAGVLDVA → VFQIICDQYTGKEVVTEKG

Isoform Gamma (identifier: P36406-3)

The sequence of this isoform differs from the canonical sequence as follows:
     541-574: WYIQGCDARSGMGLYEGLDWLSRQLVAAGVLDVA → CFSDNM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 574	574	E3 ubiquitin-protein ligase TRIM23		PRO_0000207483
Regions
	Zinc finger	31 – 76	46	RING-type; degenerate
	Zinc finger	122 – 168	47	B box-type; degenerate
	Nucleotide binding	411 – 418	8	GTP By similarity
	Nucleotide binding	454 – 458	5	GTP By similarity
	Nucleotide binding	513 – 516	4	GTP By similarity
	Region	390 – 574	185	ARF-like
	Coiled coil	352 – 379	28	Potential
Natural variations
	Alternative sequence	541 – 574	34	WYIQG…VLDVA → CFSDNM in isoform Gamma.		VSP_000297
	Alternative sequence	551 – 574	24	GMGLY…VLDVA → VFQIICDQYTGKEVVTEKG in isoform Beta.		VSP_000296
	Natural variant	480	1	D → N. Corresponds to variant rs34046496 [ dbSNP | Ensembl ].		VAR_048320
Experimental info
	Mutagenesis	34	1	C → A: Loss of E3 ubiquitin-protein ligase activity. Ref.6
	Mutagenesis	53	1	H → A: Loss of E3 ubiquitin-protein ligase activity. Ref.6
	Mutagenesis	418	1	T → N: Maintains GTPase activity. Increases interaction with PSCD1. Ref.5
	Mutagenesis	458	1	K → I: Suppresses GTPase activity. Decreases interaction with PSCD1. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified June 1, 1994. Version 1. Checksum: CB85923B29BF0320	FASTA	574	64,067
	10 20 30 40 50 60 MATLVVNKLG AGVDSGRQGS RGTAVVKVLE CGVCEDVFSL QGDKVPRLLL CGHTVCHDCL 70 80 90 100 110 120 TRLPLHGRAI RCPFDRQVTD LGDSGVWGLK KNFALLELLE RLQNGPIGQY GAAEESIGIS 130 140 150 160 170 180 GESIIRCDED EAHLASVYCT VCATHLCSEC SQVTHSTKTL AKHRRVPLAD KPHEKTMCSQ 190 200 210 220 230 240 HQVHAIEFVC LEEGCQTSPL MCCVCKEYGK HQGHKHSVLE PEANQIRASI LDMAHCIRTF 250 260 270 280 290 300 TEEISDYSRK LVGIVQHIEG GEQIVEDGIG MAHTEHVPGT AENARSCIRA YFYDLHETLC 310 320 330 340 350 360 RQEEMALSVV DAHVREKLIW LRQQQEDMTI LLSEVSAACL HCEKTLQQDD CRVVLAKQEI 370 380 390 400 410 420 TRLLETLQKQ QQQFTEVADH IQLDASIPVT FTKDNRVHIG PKMEIRVVTL GLDGAGKTTI 430 440 450 460 470 480 LFKLKQDEFM QPIPTIGFNV ETVEYKNLKF TIWDVGGKHK LRPLWKHYYL NTQAVVFVVD 490 500 510 520 530 540 SSHRDRISEA HSELAKLLTE KELRDALLLI FANKQDVAGA LSVEEITELL SLHKLCCGRS 550 560 570 WYIQGCDARS GMGLYEGLDW LSRQLVAAGV LDVA
	Isoform Beta [UniParc]. Checksum: 21399953A4224B7A	FASTA	569	63,690
	10 20 30 40 50 60 MATLVVNKLG AGVDSGRQGS RGTAVVKVLE CGVCEDVFSL QGDKVPRLLL CGHTVCHDCL 70 80 90 100 110 120 TRLPLHGRAI RCPFDRQVTD LGDSGVWGLK KNFALLELLE RLQNGPIGQY GAAEESIGIS 130 140 150 160 170 180 GESIIRCDED EAHLASVYCT VCATHLCSEC SQVTHSTKTL AKHRRVPLAD KPHEKTMCSQ 190 200 210 220 230 240 HQVHAIEFVC LEEGCQTSPL MCCVCKEYGK HQGHKHSVLE PEANQIRASI LDMAHCIRTF 250 260 270 280 290 300 TEEISDYSRK LVGIVQHIEG GEQIVEDGIG MAHTEHVPGT AENARSCIRA YFYDLHETLC 310 320 330 340 350 360 RQEEMALSVV DAHVREKLIW LRQQQEDMTI LLSEVSAACL HCEKTLQQDD CRVVLAKQEI 370 380 390 400 410 420 TRLLETLQKQ QQQFTEVADH IQLDASIPVT FTKDNRVHIG PKMEIRVVTL GLDGAGKTTI 430 440 450 460 470 480 LFKLKQDEFM QPIPTIGFNV ETVEYKNLKF TIWDVGGKHK LRPLWKHYYL NTQAVVFVVD 490 500 510 520 530 540 SSHRDRISEA HSELAKLLTE KELRDALLLI FANKQDVAGA LSVEEITELL SLHKLCCGRS 550 560 WYIQGCDARS VFQIICDQYT GKEVVTEKG
	Isoform Gamma [UniParc]. Checksum: D21D92EED6E967A2	FASTA	546	61,068
	10 20 30 40 50 60 MATLVVNKLG AGVDSGRQGS RGTAVVKVLE CGVCEDVFSL QGDKVPRLLL CGHTVCHDCL 70 80 90 100 110 120 TRLPLHGRAI RCPFDRQVTD LGDSGVWGLK KNFALLELLE RLQNGPIGQY GAAEESIGIS 130 140 150 160 170 180 GESIIRCDED EAHLASVYCT VCATHLCSEC SQVTHSTKTL AKHRRVPLAD KPHEKTMCSQ 190 200 210 220 230 240 HQVHAIEFVC LEEGCQTSPL MCCVCKEYGK HQGHKHSVLE PEANQIRASI LDMAHCIRTF 250 260 270 280 290 300 TEEISDYSRK LVGIVQHIEG GEQIVEDGIG MAHTEHVPGT AENARSCIRA YFYDLHETLC 310 320 330 340 350 360 RQEEMALSVV DAHVREKLIW LRQQQEDMTI LLSEVSAACL HCEKTLQQDD CRVVLAKQEI 370 380 390 400 410 420 TRLLETLQKQ QQQFTEVADH IQLDASIPVT FTKDNRVHIG PKMEIRVVTL GLDGAGKTTI 430 440 450 460 470 480 LFKLKQDEFM QPIPTIGFNV ETVEYKNLKF TIWDVGGKHK LRPLWKHYYL NTQAVVFVVD 490 500 510 520 530 540 SSHRDRISEA HSELAKLLTE KELRDALLLI FANKQDVAGA LSVEEITELL SLHKLCCGRS CFSDNM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain." Mishima K., Tsuchiya M., Nightingale M.S., Moss J., Vaughan M. J. Biol. Chem. 268:8801-8807(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[2]	"The tripartite motif family identifies cell compartments." Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L., Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S., Pelicci P.G., Ballabio A. EMBO J. 20:2140-2151(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA).
[3]	"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] (ISOFORM ALPHA). Tissue: Brain.
[4]	"Localization of ADP-ribosylation factor domain protein 1 (ARD1) in lysosomes and Golgi apparatus." Vitale N., Horiba K., Ferrans V.J., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 95:8613-8618(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[5]	"Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1)." Vitale N., Pacheco-Rodriguez G., Ferrans V.J., Riemenschneider W., Moss J., Vaughan M. J. Biol. Chem. 275:21331-21339(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PSCD1, MUTAGENESIS OF THR-418 AND LYS-458.
[6]	"E3 ubiquitin ligase activity of the trifunctional ARD1 (ADP-ribosylation factor domain protein 1)." Vichi A., Payne D.M., Pacheco-Rodriguez G., Moss J., Vaughan M. Proc. Natl. Acad. Sci. U.S.A. 102:1945-1950(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-34 AND HIS-53.
[7]	"Identification of TRIM23 as a cofactor involved in the regulation of NF-kappaB by human cytomegalovirus." Poole E., Groves I., MacDonald A., Pang Y., Alcami A., Sinclair J. J. Virol. 83:3581-3590(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL144.
[8]	"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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L04510 mRNA. Translation: AAA35940.1. AF230397 mRNA. Translation: AAG50176.1. AF230398 mRNA. Translation: AAG50177.1. AF230399 mRNA. Translation: AAG50178.1. BC022510 mRNA. Translation: AAH22510.1.
IPI	IPI00003328. IPI00018593. IPI00220244.
PIR	A46054.
RefSeq	NP_001647.1. NM_001656.3. NP_150230.1. NM_033227.2. NP_150231.1. NM_033228.2.
UniGene	Hs.792.
3D structure databases
ProteinModelPortal	P36406.
ModBase	Search...
Protein-protein interaction databases
IntAct	P36406. 40 interactions.
MINT	MINT-1442172.
STRING	9606.ENSP00000231524.
PTM databases
PhosphoSite	P36406.
Polymorphism databases
DMDM	543839.
Proteomic databases
PaxDb	P36406.
PRIDE	P36406.
Protocols and materials databases
DNASU	373.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000231524; ENSP00000231524; ENSG00000113595. ENST00000274327; ENSP00000274327; ENSG00000113595. ENST00000381018; ENSP00000370406; ENSG00000113595.
GeneID	373.
KEGG	hsa:373.
UCSC	uc003jtw.3. human. uc003jtx.3. human. uc003jty.3. human.
Organism-specific databases
CTD	373.
GeneCards	GC05M064885.
HGNC	HGNC:660. TRIM23.
HPA	HPA039605.
MIM	601747. gene.
neXtProt	NX_P36406.
PharmGKB	PA24943.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1100.
HOGENOM	HOG000008208.
HOVERGEN	HBG000551.
InParanoid	P36406.
KO	K07963.
OMA	RAVRCPF.
OrthoDB	EOG4001HX.
PhylomeDB	P36406.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	P36406.
Bgee	P36406.
CleanEx	HS_TRIM23.
Genevestigator	P36406.
GermOnline	ENSG00000113595. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR003649. Bbox_C. IPR027417. P-loop_NTPase. IPR005225. Small_GTP-bd_dom. IPR024156. Small_GTPase_ARF. IPR006689. Small_GTPase_ARF/SAR. IPR000315. Znf_B-box. IPR007087. Znf_C2H2. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Pfam	PF00025. Arf. 1 hit. PF00643. zf-B_box. 1 hit. [Graphical view]
PRINTS	PR00328. SAR1GTPBP.
SMART	SM00177. ARF. 1 hit. SM00502. BBC. 1 hit. SM00336. BBOX. 2 hits. SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF52540. SSF52540. 1 hit.
TIGRFAMs	TIGR00231. small_GTP. 1 hit.
PROSITE	PS51417. ARF. 1 hit. PS50119. ZF_BBOX. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	373.
NextBio	1557.
SOURCE	Search...

Entry information

Entry name

TRI23_HUMAN

Accession

Primary (citable) accession number: P36406
Secondary accession number(s): Q9BZY4, Q9BZY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 29, 2013
This is version 130 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.