Q8IYM9 (TRI22_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase TRIM22
EC=6.3.2.-

Alternative name(s):
50 kDa-stimulated trans-acting factor
RING finger protein 94
Staf-50
Tripartite motif-containing protein 22

Gene names

Name:	TRIM22
Synonyms:	RNF94, STAF50

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

General annotation (Comments)

Function	Interferon-induced antiviral protein involved in cell innate immunity. The antiviral activity could in part be mediated by TRIM22-dependent ubiquitination of viral proteins. Plays a role in restricting the replication of HIV-1, encephalomyocarditis virus (EMCV) and hepatitis B virus (HBV). Acts as a transcriptional repressor of HBV core promoter. May have E3 ubiquitin-protein ligase activity. Ref.5 Ref.6 Ref.9 Ref.10
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with HIV-1 Gag polyprotein; this interaction seems to reduce gag production or virus budding. Interacts with EMCV protease 3C; this interaction leads to viral protease ubiquitination. Ref.6 Ref.10
Subcellular location	Cytoplasm. Nucleus. Nucleus speckle. Nucleus › Cajal body. Note: Localizes predominanltly into the nucleus, found in cytoplasm to some extent. Forms distinct nuclear bodies that undergo dynamic changes during cell cycle progression. Nuclear bodies start to form in the early G0/G1 phase but become speckle-like in the S-phase and completely dispersed in mitosis. 35% of TRIM22 nuclear bodies overlap or are found adjacent to Cajal bodies. Ref.3 Ref.5 Ref.7 Ref.8
Tissue specificity	Strongly expressed in peripheral blood leukocytes, spleen, thymus, and ovary. Expressed at basal levels in other tissues. Ref.1
Induction	By interferons alpha and beta. Up-regulated by p53/TP53. Dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells and T47D cells. Ref.1 Ref.4 Ref.6 Ref.7
Domain	The C-terminal SPRY domain is required for the transcriptional suppressor activity, probably by mediating correct nuclear localization. Residues 491-494 are essential for nuclear localization and nuclear bodies formation. The RING domain is essential for antiviral activity and for TRIM22 nuclear bodies (NB) formation but is not necessary for nuclear localization.
Post-translational modification	Auto-ubiquitinated.
Sequence similarities	Belongs to the TRIM/RBCC family. Contains 1 B box-type zinc finger. Contains 1 B30.2/SPRY domain. Contains 1 RING-type zinc finger.
Sequence caution	The sequence CAA57684.1 differs from that shown. Reason: Frameshift at position 439.

Ontologies

Keywords
Biological process	Antiviral defense Host-virus interaction Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase Repressor
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW immune response Traceable author statement Ref.1. Source: ProtInc protein trimerization Inferred from direct assay PubMed 17156811. Source: UniProtKB protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-UniPathway response to virus Traceable author statement Ref.1. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Cajal body Inferred from electronic annotation. Source: UniProtKB-SubCell Golgi apparatus Inferred from direct assay. Source: HPA nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 17156811. Source: UniProtKB
Molecular_function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc transcription corepressor activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IYM9-1)

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.

Note: No experimental confirmation available.

Isoform 2 (identifier: Q8IYM9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     174-177: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 498	498	E3 ubiquitin-protein ligase TRIM22		PRO_0000056232
Regions
	Domain	283 – 498	216	B30.2/SPRY
	Zinc finger	15 – 60	46	RING-type
	Zinc finger	92 – 133	42	B box-type
	Coiled coil	132 – 248	117	Potential
	Motif	257 – 275	19	Nuclear localization signal Potential
Natural variations
	Alternative sequence	174 – 177	4	Missing in isoform 2.		VSP_012060
	Natural variant	155	1	D → N. Ref.2 Corresponds to variant rs7935564 [ dbSNP | Ensembl ].		VAR_052134
	Natural variant	232	1	T → A. Corresponds to variant rs2291843 [ dbSNP | Ensembl ].		VAR_052135
	Natural variant	242	1	R → T. Ref.1 Corresponds to variant rs1063303 [ dbSNP | Ensembl ].		VAR_052136
	Natural variant	321	1	R → K. Corresponds to variant rs12364019 [ dbSNP | Ensembl ].		VAR_052137
Experimental info
	Mutagenesis	15	1	C → A: Loss of E3 ubiquitin-protein ligase activity, reduces auto-ubiquitination and not affect nuclear bodies formation. Loss of antiviral activity; when associated with A-18. Ref.5 Ref.6 Ref.8
	Mutagenesis	18	1	C → A: Loss of antiviral activity and not affect nuclear bodies formation; when associated with A-15. Ref.6 Ref.8
	Mutagenesis	493 – 494	2	VC → AA: Reduces formation of regular nuclear bodies.
	Sequence conflict	464	1	A → R in CAA57684. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: AFADB968DE76F7DD	FASTA	498	56,947
	10 20 30 40 50 60 MDFSVKVDIE KEVTCPICLE LLTEPLSLDC GHSFCQACIT AKIKESVIIS RGESSCPVCQ 70 80 90 100 110 120 TRFQPGNLRP NRHLANIVER VKEVKMSPQE GQKRDVCEHH GKKLQIFCKE DGKVICWVCE 130 140 150 160 170 180 LSQEHQGHQT FRINEVVKEC QEKLQVALQR LIKEDQEAEK LEDDIRQERT AWKNYIQIER 190 200 210 220 230 240 QKILKGFNEM RVILDNEEQR ELQKLEEGEV NVLDNLAAAT DQLVQQRQDA STLISDLQRR 250 260 270 280 290 300 LRGSSVEMLQ DVIDVMKRSE SWTLKKPKSV SKKLKSVFRV PDLSGMLQVL KELTDVQYYW 310 320 330 340 350 360 VDVMLNPGSA TSNVAISVDQ RQVKTVRTCT FKNSNPCDFS AFGVFGCQYF SSGKYYWEVD 370 380 390 400 410 420 VSGKIAWILG VHSKISSLNK RKSSGFAFDP SVNYSKVYSR YRPQYGYWVI GLQNTCEYNA 430 440 450 460 470 480 FEDSSSSDPK VLTLFMAVPP CRIGVFLDYE AGIVSFFNVT NHGALIYKFS GCRFSRPAYP 490 YFNPWNCLVP MTVCPPSS
	Isoform 2 [UniParc]. Checksum: 22A7DA4B4B697621	FASTA	494	56,429
	10 20 30 40 50 60 MDFSVKVDIE KEVTCPICLE LLTEPLSLDC GHSFCQACIT AKIKESVIIS RGESSCPVCQ 70 80 90 100 110 120 TRFQPGNLRP NRHLANIVER VKEVKMSPQE GQKRDVCEHH GKKLQIFCKE DGKVICWVCE 130 140 150 160 170 180 LSQEHQGHQT FRINEVVKEC QEKLQVALQR LIKEDQEAEK LEDDIRQERT AWKIERQKIL 190 200 210 220 230 240 KGFNEMRVIL DNEEQRELQK LEEGEVNVLD NLAAATDQLV QQRQDASTLI SDLQRRLRGS 250 260 270 280 290 300 SVEMLQDVID VMKRSESWTL KKPKSVSKKL KSVFRVPDLS GMLQVLKELT DVQYYWVDVM 310 320 330 340 350 360 LNPGSATSNV AISVDQRQVK TVRTCTFKNS NPCDFSAFGV FGCQYFSSGK YYWEVDVSGK 370 380 390 400 410 420 IAWILGVHSK ISSLNKRKSS GFAFDPSVNY SKVYSRYRPQ YGYWVIGLQN TCEYNAFEDS 430 440 450 460 470 480 SSSDPKVLTL FMAVPPCRIG VFLDYEAGIV SFFNVTNHGA LIYKFSGCRF SRPAYPYFNP 490 WNCLVPMTVC PPSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression." Tissot C., Mechti N. J. Biol. Chem. 270:14891-14898(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION, TISSUE SPECIFICITY, VARIANT THR-242.
[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] (ISOFORM 1), VARIANT ASN-155. Tissue: Lung and Testis.
[3]	"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: SUBCELLULAR LOCATION.
[4]	"Staf50 is a novel p53 target gene conferring reduced clonogenic growth of leukemic U-937 cells." Obad S., Brunnstrom H., Vallon-Christersson J., Borg A., Drott K., Gullberg U. Oncogene 23:4050-4059(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[5]	"Identification of TRIM22 as a RING finger E3 ubiquitin ligase." Duan Z., Gao B., Xu W., Xiong S. Biochem. Biophys. Res. Commun. 374:502-506(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOUBIQUITINATION, MUTAGENESIS OF CYS-15.
[6]	"The interferon response inhibits HIV particle production by induction of TRIM22." Barr S.D., Smiley J.R., Bushman F.D. PLoS Pathog. 4:E1000007-E1000007(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, INTERACTION WITH HIV-1 GAG POLYPROTEIN, MUTAGENESIS OF CYS-15 AND CYS-18.
[7]	"Dynamic localization of tripartite motif-containing 22 in nuclear and nucleolar bodies." Sivaramakrishnan G., Sun Y., Tan S.K., Lin V.C. Exp. Cell Res. 315:1521-1532(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INDUCTION.
[8]	"B30.2/SPRY domain in tripartite motif-containing 22 is essential for the formation of distinct nuclear bodies." Sivaramakrishnan G., Sun Y., Rajmohan R., Lin V.C. FEBS Lett. 583:2093-2099(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-15; CYS-18 AND 493-VAL-CYS-494.
[9]	"Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain." Gao B., Duan Z., Xu W., Xiong S. Hepatology 50:424-433(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus." Eldin P., Papon L., Oteiza A., Brocchi E., Lawson T.G., Mechti N. J. Gen. Virol. 90:536-545(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EMCV PROTEASE 3C.
[11]	"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	X82200 mRNA. Translation: CAA57684.1. Frameshift. BC022281 mRNA. Translation: AAH22281.1. BC035582 mRNA. Translation: AAH35582.1.
IPI	IPI00477398. IPI00477812.
PIR	A57041.
RefSeq	NP_001186502.1. NM_001199573.1. NP_006065.2. NM_006074.4.
UniGene	Hs.501778. Hs.684559. Hs.733231.
3D structure databases
ProteinModelPortal	Q8IYM9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IYM9. 9 interactions.
MINT	MINT-2868217.
STRING	9606.ENSP00000369299.
PTM databases
PhosphoSite	Q8IYM9.
Polymorphism databases
DMDM	47606181.
Proteomic databases
PaxDb	Q8IYM9.
PRIDE	Q8IYM9.
Protocols and materials databases
DNASU	10346.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379965; ENSP00000369299; ENSG00000132274.
GeneID	10346.
KEGG	hsa:10346.
UCSC	uc001mbr.3. human. uc009yes.3. human.
Organism-specific databases
CTD	10346.
GeneCards	GC11P005667.
HGNC	HGNC:16379. TRIM22.
HPA	HPA003307. HPA003575.
MIM	606559. gene.
neXtProt	NX_Q8IYM9.
PharmGKB	PA38129.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG258942.
HOGENOM	HOG000234134.
HOVERGEN	HBG001357.
InParanoid	Q8IYM9.
KO	K11999.
OMA	HQTFRIN.
OrthoDB	EOG4229JJ.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q8IYM9.
Bgee	Q8IYM9.
CleanEx	HS_TRIM22.
Genevestigator	Q8IYM9.
GermOnline	ENSG00000132274. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit. 4.10.45.10. 1 hit.
InterPro	IPR001870. B30.2/SPRY. IPR003879. Butyrophylin. IPR008985. ConA-like_lec_gl_sf. IPR003877. SPRY_rcpt. IPR000315. Znf_B-box. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Pfam	PF00622. SPRY. 1 hit. PF00643. zf-B_box. 1 hit. [Graphical view]
PRINTS	PR01407. BUTYPHLNCDUF.
SMART	SM00336. BBOX. 1 hit. SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 1 hit.
PROSITE	PS50188. B302_SPRY. 1 hit. PS50119. ZF_BBOX. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TRIM22. human.
GenomeRNAi	10346.
NextBio	39235.
SOURCE	Search...

Entry information

Entry name

TRI22_HUMAN

Accession

Primary (citable) accession number: Q8IYM9
Secondary accession number(s): Q05CQ0, Q15521

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 24, 2004
Last sequence update:	March 1, 2003
Last modified:	May 29, 2013
This is version 109 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.