Reviewed, UniProtKB/Swiss-Prot O15164 (TIF1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Transcription intermediary factor 1-alpha
      Short name=TIF1-alpha
Alternative name(s):
    Tripartite motif-containing protein 24
    RING finger protein 82

Gene names

Name:	TRIM24
Synonyms:	RNF82, TIF1, TIF1A

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	1050 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Interacts selectively in vitro with the AF2-activating domain of the estrogen receptors. Association with DNA-bound estrogen receptors requires the presence of estradiol.
Subunit structure	Interacts with CBX1 and CBX3 By similarity. Interacts with NR3C2.
Subcellular location	Nucleus Potential.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.8 Ref.9
Involvement in disease	A chromosomal aberration involving TIF1 is a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Translocation t(7;10)(q32;q11) with RET. The translocation generates the TIF1/RET (PTC6) oncogene.
Sequence similarities	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
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Bromodomain Coiled coil Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription from RNA polymerase II promoter Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW SUMO binding Inferred from physical interaction. Source: UniProtKB receptor binding Ref.1 Traceable author statement. Source: ProtInc transcription coactivator activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform Long (identifier: O15164-1)

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 Short (identifier: O15164-2)

The sequence of this isoform differs from the canonical sequence as follows:
     477-510: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1050

1050

Transcription intermediary factor 1-alpha

PRO_0000056390

Regions

Domain

932 – 987

56

Bromo

Zinc finger

56 – 82

27

RING-type

Zinc finger

158 – 211

54

B box-type 1

Zinc finger

218 – 259

42

B box-type 2

Zinc finger

826 – 873

48

PHD-type

Region

754 – 779

26

Nuclear receptor binding site (NRBS)

Coiled coil

289 – 359

71

Potential

Motif

891 – 907

17

Nuclear localization signal Potential

Compositional bias

9 – 15

7

Poly-Ala

Compositional bias

344 – 347

4

Poly-Gln

Sites

Site

476 – 477

2

Breakpoint for translocation to form TIF1-RET oncogene

Amino acid modifications

Modified residue

660

1

Phosphoserine Ref.9

Modified residue

667

1

Phosphoserine Ref.9

Modified residue

768

1

Phosphoserine Ref.8 Ref.9

Modified residue

808

1

Phosphoserine Ref.9

Modified residue

811

1

Phosphoserine Ref.7 Ref.9

Modified residue

1019

1

Phosphoserine Ref.9

Modified residue

1025

1

Phosphoserine Ref.9

Modified residue

1028

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

477 – 510

34

Missing in isoform Short.

VSP_005772

Natural variant

320

1

I → T in an ovarian serous carcinoma sample; somatic mutation. Ref.11

VAR_042382

Natural variant

403

1

T → N in a lung squamous cell carcinoma sample; somatic mutation. Ref.11

VAR_042383

Natural variant

762

1

S → N Ref.11

VAR_042384

Natural variant

796

1

N → S: dbSNP rs35356723.

VAR_052148

Natural variant

1009

1

R → S Ref.11

VAR_042385

Experimental info

Sequence conflict

14 – 20

7

AASAAAS → RLGCAP in AAB63585. Ref.1

Sequence conflict

24 – 28

5

SAAPS → RGG in AAB63585. Ref.1

Sequence conflict

109 – 114

6

GSPVSG → ARRSA in AAB63585. Ref.1

Sequence conflict

350

1

A → T in AAB63585. Ref.1

Sequence conflict

600

1

D → N in AAB63585. Ref.1

Sequence conflict

608

1

M → I in AAB63585. Ref.1

Sequence conflict

967

1

A → R in AAB63585. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1050

Helix Strand Turn

Details...

Helix

902 – 916

15

Helix

919 – 924

6

Helix

935 – 938

4

Helix

945 – 953

9

Beta strand

954 – 956

3

Helix

962 – 979

18

Helix

985 – 1004

20

Beta strand

1005 – 1007

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified January 24, 2001. Version 3. Checksum: D341E8022AACC67E	FASTA	1,050	116,831
	10 20 30 40 50 60 MEVAVEKAVA AAAAASAAAS GGPSAAPSGE NEAESRQGPD SERGGEAARL NLLDTCAVCH 70 80 90 100 110 120 QNIQSRAPKL LPCLHSFCQR CLPAPQRYLM LPAPMLGSAE TPPPVPAPGS PVSGSSPFAT 130 140 150 160 170 180 QVGVIRCPVC SQECAERHII DNFFVKDTTE VPSSTVEKSN QVCTSCEDNA EANGFCVECV 190 200 210 220 230 240 EWLCKTCIRA HQRVKFTKDH TVRQKEEVSP EAVGVTSQRP VFCPFHKKEQ LKLYCETCDK 250 260 270 280 290 300 LTCRDCQLLE HKEHRYQFIE EAFQNQKVII DTLITKLMEK TKYIKFTGNQ IQNRIIEVNQ 310 320 330 340 350 360 NQKQVEQDIK VAIFTLMVEI NKKGKALLHQ LESLAKDHRM KLMQQQQEVA GLSKQLEHVM 370 380 390 400 410 420 HFSKWAVSSG SSTALLYSKR LITYRLRHLL RARCDASPVT NNTIQFHCDP SFWAQNIINL 430 440 450 460 470 480 GSLVIEDKES QPQMPKQNPV VEQNSQPPSG LSSNQLSKFP TQISLAQLRL QHMQQQVMAQ 490 500 510 520 530 540 RQQVQRRPAP VGLPNPRMQG PIQQPSISHQ QPPPRLINFQ NHSPKPNGPV LPPHPQQLRY 550 560 570 580 590 600 PPNQNIPRQA IKPNPLQMAF LAQQAIKQWQ ISSGQGTPST TNSTSSTPSS PTITSAAGYD 610 620 630 640 650 660 GKAFGSPMID LSSPVGGSYN LPSLPDIDCS STIMLDNIVR KDTNIDHGQP RPPSNRTVQS 670 680 690 700 710 720 PNSSVPSPGL AGPVTMTSVH PPIRSPSASS VGSRGSSGSS SKPAGADSTH KVPVVMLEPI 730 740 750 760 770 780 RIKQENSGPP ENYDFPVVIV KQESDEESRP QNANYPRSIL TSLLLNSSQS STSEETVLRS 790 800 810 820 830 840 DAPDSTGDQP GLHQDNSSNG KSEWLDPSQK SPLHVGETRK EDDPNEDWCA VCQNGGELLC 850 860 870 880 890 900 CEKCPKVFHL SCHVPTLTNF PSGEWICTFC RDLSKPEVEY DCDAPSHNSE KKKTEGLVKL 910 920 930 940 950 960 TPIDKRKCER LLLFLYCHEM SLAFQDPVPL TVPDYYKIIK NPMDLSTIKK RLQEDYSMYS 970 980 990 1000 1010 1020 KPEDFVADFR LIFQNCAEFN EPDSEVANAG IKLENYFEEL LKNLYPEKRF PKPEFRNESE 1030 1040 1050 DNKFSDDSDD DFVQPRKKRL KSIEERQLLK
	Isoform Short. Checksum: 4621C94EB3A74AE2	FASTA	1,016	113,018
	10 20 30 40 50 60 MEVAVEKAVA AAAAASAAAS GGPSAAPSGE NEAESRQGPD SERGGEAARL NLLDTCAVCH 70 80 90 100 110 120 QNIQSRAPKL LPCLHSFCQR CLPAPQRYLM LPAPMLGSAE TPPPVPAPGS PVSGSSPFAT 130 140 150 160 170 180 QVGVIRCPVC SQECAERHII DNFFVKDTTE VPSSTVEKSN QVCTSCEDNA EANGFCVECV 190 200 210 220 230 240 EWLCKTCIRA HQRVKFTKDH TVRQKEEVSP EAVGVTSQRP VFCPFHKKEQ LKLYCETCDK 250 260 270 280 290 300 LTCRDCQLLE HKEHRYQFIE EAFQNQKVII DTLITKLMEK TKYIKFTGNQ IQNRIIEVNQ 310 320 330 340 350 360 NQKQVEQDIK VAIFTLMVEI NKKGKALLHQ LESLAKDHRM KLMQQQQEVA GLSKQLEHVM 370 380 390 400 410 420 HFSKWAVSSG SSTALLYSKR LITYRLRHLL RARCDASPVT NNTIQFHCDP SFWAQNIINL 430 440 450 460 470 480 GSLVIEDKES QPQMPKQNPV VEQNSQPPSG LSSNQLSKFP TQISLAQLRL QHMQQQQPPP 490 500 510 520 530 540 RLINFQNHSP KPNGPVLPPH PQQLRYPPNQ NIPRQAIKPN PLQMAFLAQQ AIKQWQISSG 550 560 570 580 590 600 QGTPSTTNST SSTPSSPTIT SAAGYDGKAF GSPMIDLSSP VGGSYNLPSL PDIDCSSTIM 610 620 630 640 650 660 LDNIVRKDTN IDHGQPRPPS NRTVQSPNSS VPSPGLAGPV TMTSVHPPIR SPSASSVGSR 670 680 690 700 710 720 GSSGSSSKPA GADSTHKVPV VMLEPIRIKQ ENSGPPENYD FPVVIVKQES DEESRPQNAN 730 740 750 760 770 780 YPRSILTSLL LNSSQSSTSE ETVLRSDAPD STGDQPGLHQ DNSSNGKSEW LDPSQKSPLH 790 800 810 820 830 840 VGETRKEDDP NEDWCAVCQN GGELLCCEKC PKVFHLSCHV PTLTNFPSGE WICTFCRDLS 850 860 870 880 890 900 KPEVEYDCDA PSHNSEKKKT EGLVKLTPID KRKCERLLLF LYCHEMSLAF QDPVPLTVPD 910 920 930 940 950 960 YYKIIKNPMD LSTIKKRLQE DYSMYSKPED FVADFRLIFQ NCAEFNEPDS EVANAGIKLE 970 980 990 1000 1010 NYFEELLKNL YPEKRFPKPE FRNESEDNKF SDDSDDDFVQ PRKKRLKSIE ERQLLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1." Thenot S., Henriquet C., Rochefort H., Cavailles V. J. Biol. Chem. 272:12062-12068(1997) [PubMed: 9115274] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Mammary cancer.
[2]	"TIF1gamma, a novel member of the transcriptional intermediary factor 1 family." Venturini L., You J., Stadler M., Galien R., Lallemand V., Koken M.H.M., Mattei M.-G., Ganser A., Chambon P., Losson R., De The H. Oncogene 18:1209-1217(1999) [PubMed: 10022127] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	Cavailles V. Submitted (JAN-1999) to UniProtKB Cited for: PROTEIN SEQUENCE OF 477-510 (ISOFORM LONG). Tissue: Mammary cancer.
[5]	"Crucial role of the H11-H12 loop in stabilizing the active conformation of the human mineralocorticoid receptor." Hellal-Levy C., Fagart J., Souque A., Wurtz J.-M., Moras D., Rafestin-Oblin M.-E. Mol. Endocrinol. 14:1210-1221(2000) [PubMed: 10935545] [Abstract] Cited for: INTERACTION WITH NR3C2.
[6]	"The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas." Klugbauer S., Rabes H.M. Oncogene 18:4388-4393(1999) [PubMed: 10439047] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH RET. Tissue: Thyroid.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-811, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-768, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-660; SER-667; SER-768; SER-808; SER-811; SER-1019; SER-1025 AND SER-1028, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-320; ASN-403; ASN-762 AND SER-1009.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF009353 mRNA. Translation: AAB63585.1.
AF119042 mRNA. Translation: AAD17258.1.
BC028689 mRNA. Translation: AAH28689.2.

IPI

IPI00005184.
IPI00184317.

RefSeq

NP_056989.2.

UniGene

Hs.490287

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2YYN	X-ray	2.50	A/B/C/D	891-1012	[»]

ModBase

Search...

PTM databases

PhosphoSite

O15164.

Proteomic databases

PRIDE

O15164.

Genome annotation databases

Ensembl

ENSG00000122779. Homo sapiens. [Contig view]

GeneID

8805.

Organism-specific databases

GeneCards

GC07P137795.

H-InvDB

HIX0007122.

HGNC

HGNC:11812. TRIM24.

MIM

188550. phenotype.
603406. gene.

Orphanet

146. Thyroid carcinoma, papillary or follicular.

PharmGKB

PA36519.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O15164.

HOVERGEN

O15164.

OMA

O15164. GPYNLPS.

Gene expression databases

ArrayExpress

O15164.

Bgee

O15164.

CleanEx

HS_TRIM24.

GermOnline

ENSG00000122779. Homo sapiens.

Family and domain databases

InterPro

IPR003649. Bbox_C.
IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR019786. Zinc_finger_PHD-type_CS.
IPR000315. Znf_B-box.
IPR018957. Znf_C3HC4_RING-type.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:1.20.920.10. Bromodomain. 1 hit.

Pfam

PF00439. Bromodomain. 1 hit.
PF00628. PHD. 1 hit.
PF00643. zf-B_box. 2 hits.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

PRINTS

PR00503. BROMODOMAIN.

SMART

SM00502. BBC. 1 hit.
SM00336. BBOX. 2 hits.
SM00297. BROMO. 1 hit.
SM00249. PHD. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS00633. BROMODOMAIN_1. 1 hit.
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 Resources

NextBio

33028.

SOURCE

Search...

Entry information

Entry name

TIF1A_HUMAN

Accession

Primary (citable) accession number: O15164
Secondary accession number(s): O95854

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 24, 2001
Last modified:	June 16, 2009
This is version 100 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)