Q99PP7 (TRI33_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase TRIM33
EC=6.3.2.-

Alternative name(s):
Ectodermin homolog
Transcription intermediary factor 1-gamma
Short name=TIF1-gamma
Tripartite motif-containing protein 33

Gene names

Name:	Trim33
Synonyms:	Kiaa1113

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1142 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway By similarity. May act as a transcriptional repressor By similarity. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade By similarity. Plays a role in the control of cell proliferation By similarity. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor. Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade) By similarity. Ref.5
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homooligomer and heterooligomer with TRIM24 and TRIM28 family members By similarity. Interacts with SMAD4 in unstimulated cells By similarity. Found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta By similarity. Interacts with SMAD2 and SMAD3 By similarity. Interacts with SMAD4 under basal and induced conditions and, upon TGF-beta signaling, with activated SMAD2. Forms a ternary complex with SMAD4 and SMAD2 upon TGF-beta signaling By similarity.
Subcellular location	Nucleus. Note: In discrete nuclear dots resembling nuclear bodies. Ref.4 Ref.5
Tissue specificity	Ubiquitous with high level in testis.
Developmental stage	Expressed in round hematopoietic cells in yolk sac blood islands at 8.5 dpc. Expressed uniformly at 10.5 dpc. Expressed in the brain, spinal cord, neuroepithelium and in spinal ganglia at 12.5 dpc. Expressed in brain, spinal cord, developing epithelia of the lung, stomach, intestine, outer region of the developing kidney, liver, brown fat tissue, skeletal muscle, developing craniofacial region, thymus, cochlear and pharyngeal epithelia and olfactory and respiratory epithelia at 16.5 dpc. Ref.4 Ref.5
Post-translational modification	Sumoylated with SUMO1. Ref.6
Sequence similarities	Belongs to the TRIM/RBCC family. Contains 2 B box-type zinc fingers. Contains 1 bromo domain. Contains 1 PHD-type zinc finger. Contains 1 RING-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Bromodomain Coiled coil Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase Repressor
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB protein ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW regulation of transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.4. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW R-SMAD binding Inferred from sequence or structural similarity. Source: BHF-UCL co-SMAD binding Inferred from sequence or structural similarity. Source: BHF-UCL ligase activity Inferred from electronic annotation. Source: UniProtKB-KW 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 Alpha (identifier: Q99PP7-1)

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: Q99PP7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1056-1072: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1142	1142	E3 ubiquitin-protein ligase TRIM33		PRO_0000056396
Regions
	Domain	989 – 1061	73	Bromo
	Zinc finger	141 – 201	61	RING-type
	Zinc finger	228 – 275	48	B box-type 1
	Zinc finger	287 – 328	42	B box-type 2
	Zinc finger	902 – 949	48	PHD-type
	Region	1 – 163	163	Necessary for E3 ubiquitin-protein ligase activity and repression of SMAD4 signaling and transcriptional repression By similarity
	Region	315 – 417	103	Necessary for oligomerization By similarity
	Coiled coil	315 – 417	103	Potential
	Compositional bias	13 – 18	6	Poly-Gly
	Compositional bias	20 – 122	103	Ala-rich
	Compositional bias	524 – 636	113	Gln-rich
	Compositional bias	708 – 785	78	Ser-rich
Amino acid modifications
	Modified residue	778	1	N6-acetyllysine By similarity
	Modified residue	784	1	N6-acetyllysine By similarity
	Modified residue	877	1	Phosphoserine By similarity
	Modified residue	968	1	N6-acetyllysine By similarity
	Modified residue	1117	1	Phosphothreonine By similarity
	Modified residue	1120	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1056 – 1072	17	Missing in isoform Beta.		VSP_012068
Experimental info
	Sequence conflict	949 – 952	4	IGKP → HASA Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified December 7, 2004. Version 2. Checksum: D43699AE75F0893F	FASTA	1,142	123,843
	10 20 30 40 50 60 MAENKGGGEA ESGGGGSGSA PVTAGAAGPT AQEAEPPLAA VLVEEEEEEG GRAGAEGGAA 70 80 90 100 110 120 GPDDGGVAAA SSSSAPAASV PAASVGSAVP GGAASTPAPA AAPAPAPAPA PAPAPAPAPA 130 140 150 160 170 180 PAPGSSSGPP LGPPASLLDT CAVCQQSLQS RREAEPKLLP CLHSFCLRCL PEPERQLSVP 190 200 210 220 230 240 IPGGSNGDVQ QVGVIRCPVC RQECRQIDLV DNYFVKDTSE APSSSDEKSE QVCTSCEDNA 250 260 270 280 290 300 SAVGFCVECG EWLCKTCIEA HQRVKFTKDH LIRKKEDVSE SVGTSGQRPV FCPVHKQEQL 310 320 330 340 350 360 KLFCETCDRL TCRDCQLLEH KEHRYQFLEE AFQNQKGAIE NLLAKLLEKK NYVHFAATQV 370 380 390 400 410 420 QNRIKEVNET NKRVEQEIKV AIFTLINEIN KKGKSLLQQL ENVTKERQMK LLQQQNDITG 430 440 450 460 470 480 LSRQVKHVMN FTNWAIASGS STALLYSKRL ITFQLRHILK ARCDPVPAAN GAIRFHCDPT 490 500 510 520 530 540 FWAKNVVNLG NLVIESKPAP GYTPNVVVGQ VPPGTNHISK TPGQINLAQL RLQHMQQQVY 550 560 570 580 590 600 AQKHQQLQQM RLQQPPAPIP TTTATTQQHP RQAAPQMLQQ QPPRLISVQT MQRGNMNCGA 610 620 630 640 650 660 FQAHQMRLAQ NAARIPGIPR HSAPQYSMMQ PHLQRQHSNP GHAGPFPVVS AHNPINPTSP 670 680 690 700 710 720 TTATMANANR GPTSPSVTAI ELIPSVTNPE NLPSLPDIPP IQLEDAGSSS LDNLLSRYIS 730 740 750 760 770 780 GSHLPPQPTS TMNPSPGPSA LSPGSSGLSN SHTPVRPPST SSTGSRGSCG SSGRTAEKSA 790 800 810 820 830 840 HSFKSDQVKV KQEPGTEEEI CSFSGAVKQE KTEDGRRSAC MLSSPESSLT PPLSTNLHLE 850 860 870 880 890 900 SELDTLTGLE NHVKTEPTDI SESCKQSGLS NLVNGKSPIR NLMHRSARIG GDGNSKDDDP 910 920 930 940 950 960 NEDWCAVCQN GGDLLCCEKC PKVFHLTCHV PTLLSFPSGD WICTFCRDIG KPEVEYDCDN 970 980 990 1000 1010 1020 MQHSKKGKTA QGLSPVDQRK CERLLLYLYC HELSIEFQEP VPVSIPNYYK IIKKPMDLST 1030 1040 1050 1060 1070 1080 VKKKLQKKHS QHYQIPDDFV ADVRLIFKNC ERFNEMMKVV QVYADTQEIN LKGDSEVAKA 1090 1100 1110 1120 1130 1140 GKAVALYFED KLSEIYSDRT FTPLPEFEQD EDDGEVTEDS DEDFIQPRRK RLKSDERPVH IK
	Isoform Beta [UniParc]. Checksum: E19A5D1F2973E83D	FASTA	1,125	121,850
	10 20 30 40 50 60 MAENKGGGEA ESGGGGSGSA PVTAGAAGPT AQEAEPPLAA VLVEEEEEEG GRAGAEGGAA 70 80 90 100 110 120 GPDDGGVAAA SSSSAPAASV PAASVGSAVP GGAASTPAPA AAPAPAPAPA PAPAPAPAPA 130 140 150 160 170 180 PAPGSSSGPP LGPPASLLDT CAVCQQSLQS RREAEPKLLP CLHSFCLRCL PEPERQLSVP 190 200 210 220 230 240 IPGGSNGDVQ QVGVIRCPVC RQECRQIDLV DNYFVKDTSE APSSSDEKSE QVCTSCEDNA 250 260 270 280 290 300 SAVGFCVECG EWLCKTCIEA HQRVKFTKDH LIRKKEDVSE SVGTSGQRPV FCPVHKQEQL 310 320 330 340 350 360 KLFCETCDRL TCRDCQLLEH KEHRYQFLEE AFQNQKGAIE NLLAKLLEKK NYVHFAATQV 370 380 390 400 410 420 QNRIKEVNET NKRVEQEIKV AIFTLINEIN KKGKSLLQQL ENVTKERQMK LLQQQNDITG 430 440 450 460 470 480 LSRQVKHVMN FTNWAIASGS STALLYSKRL ITFQLRHILK ARCDPVPAAN GAIRFHCDPT 490 500 510 520 530 540 FWAKNVVNLG NLVIESKPAP GYTPNVVVGQ VPPGTNHISK TPGQINLAQL RLQHMQQQVY 550 560 570 580 590 600 AQKHQQLQQM RLQQPPAPIP TTTATTQQHP RQAAPQMLQQ QPPRLISVQT MQRGNMNCGA 610 620 630 640 650 660 FQAHQMRLAQ NAARIPGIPR HSAPQYSMMQ PHLQRQHSNP GHAGPFPVVS AHNPINPTSP 670 680 690 700 710 720 TTATMANANR GPTSPSVTAI ELIPSVTNPE NLPSLPDIPP IQLEDAGSSS LDNLLSRYIS 730 740 750 760 770 780 GSHLPPQPTS TMNPSPGPSA LSPGSSGLSN SHTPVRPPST SSTGSRGSCG SSGRTAEKSA 790 800 810 820 830 840 HSFKSDQVKV KQEPGTEEEI CSFSGAVKQE KTEDGRRSAC MLSSPESSLT PPLSTNLHLE 850 860 870 880 890 900 SELDTLTGLE NHVKTEPTDI SESCKQSGLS NLVNGKSPIR NLMHRSARIG GDGNSKDDDP 910 920 930 940 950 960 NEDWCAVCQN GGDLLCCEKC PKVFHLTCHV PTLLSFPSGD WICTFCRDIG KPEVEYDCDN 970 980 990 1000 1010 1020 MQHSKKGKTA QGLSPVDQRK CERLLLYLYC HELSIEFQEP VPVSIPNYYK IIKKPMDLST 1030 1040 1050 1060 1070 1080 VKKKLQKKHS QHYQIPDDFV ADVRLIFKNC ERFNEGDSEV AKAGKAVALY FEDKLSEIYS 1090 1100 1110 1120 DRTFTPLPEF EQDEDDGEVT EDSDEDFIQP RRKRLKSDER PVHIK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, genomic structure, and expression analysis of the mouse transcriptional intermediary factor 1 gamma gene." Yan K.P., Dolle P., Mark M., Lerouge T., Wendling O., Chambon P., Losson R. Gene 334:3-13(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-1142 (ISOFORM BETA). Tissue: Embryonic tail.
[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: NUCLEOTIDE SEQUENCE [MRNA] OF 949-1142 (ISOFORM ALPHA).
[4]	"The zebrafish moonshine gene encodes transcriptional intermediary factor 1 gamma, an essential regulator of hematopoiesis." Ransom D.G., Bahary N., Niss K., Traver D., Burns C., Trede N.S., Paffett-Lugassy N., Saganic W.J., Lim C.A., Hersey C., Zhou Y., Barut B.A., Lin S., Kingsley P.D., Palis J., Orkin S.H., Zon L.I. PLoS Biol. 2:1188-1196(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
[5]	"Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway." He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J. Cell 125:929-941(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[6]	"In vivo localization and identification of SUMOylated proteins in the brain of His6-HA-SUMO1 knock-in mice." Tirard M., Hsiao H.H., Nikolov M., Urlaub H., Melchior F., Brose N. Proc. Natl. Acad. Sci. U.S.A. 109:21122-21127(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION WITH SUMO1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY458590 mRNA. Translation: AAS10352.1. AK129293 mRNA. Translation: BAC98103.1. AF220138 mRNA. Translation: AAG53511.1.
IPI	IPI00409904. IPI00480381.
RefSeq	NP_001073299.1. NM_001079830.1. NP_444400.2. NM_053170.2.
UniGene	Mm.195036.
3D structure databases
ProteinModelPortal	Q99PP7.
SMR	Q99PP7. Positions 286-330, 898-1101.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59674N.
IntAct	Q99PP7. 2 interactions.
MINT	MINT-1867560.
PTM databases
PhosphoSite	Q99PP7.
Proteomic databases
PaxDb	Q99PP7.
PRIDE	Q99PP7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	94093.
KEGG	mmu:94093.
Organism-specific databases
CTD	51592.
MGI	MGI:2137357. Trim33.
Rouge	Search...
Phylogenomic databases
eggNOG	COG5076.
HOGENOM	HOG000252971.
HOVERGEN	HBG054599.
InParanoid	Q99PP7.
KO	K08883.
OrthoDB	EOG4SN1N0.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q99PP7.
Bgee	Q99PP7.
CleanEx	MM_TRIM33.
Genevestigator	Q99PP7.
GermOnline	ENSMUSG00000033014. Mus musculus.
Family and domain databases
Gene3D	1.20.920.10. 1 hit. 3.30.40.10. 2 hits. 4.10.45.10. 1 hit.
InterPro	IPR003649. Bbox_C. IPR001487. Bromodomain. IPR019786. Zinc_finger_PHD-type_CS. IPR000315. Znf_B-box. IPR011011. Znf_FYVE_PHD. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Pfam	PF00439. Bromodomain. 1 hit. PF00628. PHD. 1 hit. PF00643. zf-B_box. 2 hits. PF13639. zf-RING_2. 1 hit. [Graphical view]
PRINTS	PR00503. BROMODOMAIN.
SMART	SM00502. BBC. 1 hit. SM00336. BBOX. 2 hits. SM00297. BROMO. 1 hit. SM00249. PHD. 2 hits. SM00184. RING. 2 hits. [Graphical view]
SUPFAM	SSF47370. Bromodomain. 1 hit. SSF57903. FYVE_PHD_ZnF. 1 hit.
PROSITE	PS50014. BROMODOMAIN_2. 1 hit. PS50119. ZF_BBOX. 2 hits. PS01359. ZF_PHD_1. 1 hit. PS50016. ZF_PHD_2. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	352085.
SOURCE	Search...

Entry information

Entry name

TRI33_MOUSE

Accession

Primary (citable) accession number: Q99PP7
Secondary accession number(s): Q6SI71, Q6ZPX5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 7, 2004
Last sequence update:	December 7, 2004
Last modified:	May 29, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program