P63272 (SPT4H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription elongation factor SPT4
Short name=hSPT4

Alternative name(s):
DRB sensitivity-inducing factor 14 kDa subunit
Short name=DSIF p14
DRB sensitivity-inducing factor small subunit
Short name=DSIF small subunit

Gene names

Name:	SUPT4H1
Synonyms:	SPT4H, SUPT4H

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

General annotation (Comments)

Function	Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21
Subunit structure	Interacts with SUPT5H to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of WHSC2/NELFA, COBRA1/NELFB, TH1L/NELFD and RDBP/NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with HRMT1L2/PRMT1, HTATSF1/TATSF1, RNGTT/CAP1A, SKB1/PRMT5, SUPT6H, and can interact with PIN1. Ref.8 Ref.10 Ref.13 Ref.16 Ref.17 Ref.19
Subcellular location	Nucleus Ref.2.
Tissue specificity	Widely expressed. Ref.1 Ref.2
Sequence similarities	Belongs to the SPT4 family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Activator Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	chromatin remodeling Traceable author statement. Source: ProtInc negative regulation of transcription elongation, DNA-dependent Inferred from direct assay Ref.8Ref.7. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.8Ref.7. Source: UniProtKB positive regulation of transcription elongation, DNA-dependent Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of viral transcription Traceable author statement. Source: Reactome transcription elongation from RNA polymerase II promoter Inferred from direct assay Ref.8Ref.7. Source: UniProtKB viral reproduction Traceable author statement. Source: Reactome
Cellular component	nucleoplasm Traceable author statement. Source: Reactome
Molecular function	protein heterodimerization activity Inferred from physical interaction Ref.8. Source: UniProtKB sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SUPT5H	O00267	3	EBI-727250,EBI-710464

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 117

117

Transcription elongation factor SPT4

PRO_0000210325

Regions

Zinc finger

16 – 36

21

C4-type Potential

Region

1 – 40

40

Interaction with SUPT5H

Experimental info

Sequence conflict

95 – 117

23

QGIVR…TAIKT → HAKDSRSNVNKYEPRESSEG HDTCLASLFHSLRHSNSLFA L in BAC85230. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

117

Helix Strand Turn

Details...

Helix

3 – 5

3

Beta strand

8 – 10

3

Beta strand

13 – 16

4

Turn

17 – 19

3

Beta strand

21 – 24

4

Helix

25 – 30

6

Turn

34 – 36

3

Helix

37 – 40

4

Helix

46 – 52

7

Beta strand

53 – 55

3

Beta strand

60 – 64

5

Helix

66 – 68

3

Helix

70 – 74

5

Beta strand

85 – 89

5

Helix

98 – 103

6

Sequences

	Sequence		Length	Mass (Da)
	P63272 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: 09EDF007501D0F03	FASTA	117	13,193
	10 20 30 40 50 60 MALETVPKDL RHLRACLLCS LVKTIDQFEY DGCDNCDAYL QMKGNREMVY DCTSSSFDGI 70 80 90 100 110 IAMMSPEDSW VSKWQRVSNF KPGVYAVSVT GRLPQGIVRE LKSRGVAYKS RDTAIKT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the human and mouse homologues (SUPT4H and Supt4h) of the yeast SPT4 gene." Chiang P.-W., Wang S.-Q., Smithivas P., Song W.-J., Crombez E., Akhtar A., Im R., Greenfield J., Ramamoorthy S., van Keuren M.L., Blackburn C.C., Tsai C.-H., Kurnit D.M. Genomics 34:368-375(1996) [PubMed: 8786137] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Identification and analysis of a functional human homolog of the SPT4 gene of Saccharomyces cerevisiae." Hartzog G.A., Basrai M.A., Ricupero-Hovasse S.L., Hieter P., Winston F. Mol. Cell. Biol. 16:2848-2856(1996) [PubMed: 8649394] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Dermoid cancer and Testis.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: Placenta.
[7]	"Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro." Wada T., Takagi T., Yamaguchi Y., Watanabe D., Handa H. EMBO J. 17:7395-7403(1998) [PubMed: 9857195] [Abstract] Cited for: FUNCTION.
[8]	"DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs." Wada T., Takagi T., Yamaguchi Y., Ferdous A., Imai T., Hirose S., Sugimoto S., Yano K., Hartzog G.A., Winston F., Buratowski S., Handa H. Genes Dev. 12:343-356(1998) [PubMed: 9450929] [Abstract] Cited for: FUNCTION, INTERACTION WITH SUPT5H.
[9]	"NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation." Yamaguchi Y., Takagi T., Wada T., Yano K., Furuya A., Sugimoto S., Hasegawa J., Handa H. Cell 97:41-51(1999) [PubMed: 10199401] [Abstract] Cited for: FUNCTION.
[10]	"Structure and function of the human transcription elongation factor DSIF." Yamaguchi Y., Wada T., Watanabe D., Takagi T., Hasegawa J., Handa H. J. Biol. Chem. 274:8085-8092(1999) [PubMed: 10075709] [Abstract] Cited for: FUNCTION, INTERACTION WITH SUPT5H.
[11]	"Tat-SF1 protein associates with RAP30 and human SPT5 proteins." Kim J.B., Yamaguchi Y., Wada T., Handa H., Sharp P.A. Mol. Cell. Biol. 19:5960-5968(1999) [PubMed: 10454543] [Abstract] Cited for: FUNCTION.
[12]	"FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH." Wada T., Orphanides G., Hasegawa J., Kim D.-K., Shima D., Yamaguchi Y., Fukuda A., Hisatake K., Oh S., Reinberg D., Handa H. Mol. Cell 5:1067-1072(2000) [PubMed: 10912001] [Abstract] Cited for: FUNCTION.
[13]	"Domains in the SPT5 protein that modulate its transcriptional regulatory properties." Ivanov D., Kwak Y.T., Guo J., Gaynor R.B. Mol. Cell. Biol. 20:2970-2983(2000) [PubMed: 10757782] [Abstract] Cited for: INTERACTION WITH SUPT5H.
[14]	"DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation." Ping Y.-H., Rana T.M. J. Biol. Chem. 276:12951-12958(2001) [PubMed: 11112772] [Abstract] Cited for: FUNCTION.
[15]	"A highly purified RNA polymerase II elongation control system." Renner D.B., Yamaguchi Y., Wada T., Handa H., Price D.H. J. Biol. Chem. 276:42601-42609(2001) [PubMed: 11553615] [Abstract] Cited for: FUNCTION.
[16]	"Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex." Kim D.-K., Inukai N., Yamada T., Furuya A., Sato H., Yamaguchi Y., Wada T., Handa H. Genes Cells 8:371-378(2003) [PubMed: 12653964] [Abstract] Cited for: FUNCTION, INTERACTION WITH SUPT5H.
[17]	"Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties." Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B., Gehrig P., Gaynor R.B. Mol. Cell 11:1055-1066(2003) [PubMed: 12718890] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH SUPT5H.
[18]	"Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila." Jennings B.H., Shah S., Yamaguchi Y., Seki M., Phillips R.G., Handa H., Ish-Horowicz D. Curr. Biol. 14:1680-1684(2004) [PubMed: 15380072] [Abstract] Cited for: FUNCTION.
[19]	"Human Spt6 stimulates transcription elongation by RNA polymerase II in vitro." Endoh M., Zhu W., Hasegawa J., Watanabe H., Kim D.-K., Aida M., Inukai N., Narita T., Yamada T., Furuya A., Sato H., Yamaguchi Y., Mandal S.S., Reinberg D., Wada T., Handa H. Mol. Cell. Biol. 24:3324-3336(2004) [PubMed: 15060154] [Abstract] Cited for: INTERACTION WITH SUPT5H.
[20]	"Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II." Mandal S.S., Chu C., Wada T., Handa H., Shatkin A.J., Reinberg D. Proc. Natl. Acad. Sci. U.S.A. 101:7572-7577(2004) [PubMed: 15136722] [Abstract] Cited for: FUNCTION.
[21]	"A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS." Palangat M., Renner D.B., Price D.H., Landick R. Proc. Natl. Acad. Sci. U.S.A. 102:15036-15041(2005) [PubMed: 16214896] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U38818 mRNA. Translation: AAB18674.1.
U38817 mRNA. Translation: AAB18675.1.
U43923 mRNA. Translation: AAB07814.1.
AK129758 mRNA. Translation: BAC85230.1.
AK311986 mRNA. Translation: BAG34925.1.
CR407663 mRNA. Translation: CAG28591.1.
CH471109 Genomic DNA. Translation: EAW94464.1.
CH471109 Genomic DNA. Translation: EAW94466.1.
BC002802 mRNA. Translation: AAH02802.1.

IPI

IPI00002895.

RefSeq

NP_003159.1. NM_003168.1.

UniGene

Hs.439481.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3H7H	X-ray	1.55	A	2-117	[»]

ProteinModelPortal

P63272.

SMR

P63272. Positions 2-117.

ModBase

Search...

Protein-protein interaction databases

IntAct

P63272. 2 interactions.

MINT

MINT-1382313.

STRING

P63272.

Polymorphism databases

DMDM

54039624.

Proteomic databases

PeptideAtlas

P63272.

PRIDE

P63272.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225504; ENSP00000225504; ENSG00000213246.

GeneID

6827.

KEGG

hsa:6827.

UCSC

uc002iwe.1. human.

Organism-specific databases

CTD

6827.

GeneCards

GC17M056422.

H-InvDB

HIX0014028.
HIX0014029.

HGNC

HGNC:11467. SUPT4H1.

MIM

603555. gene.

neXtProt

NX_P63272.

PharmGKB

PA36253.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000018559.

HOGENOM

HBG623003.

HOVERGEN

HBG055988.

InParanoid

P63272.

OMA

SWVAKWQ.

OrthoDB

EOG4P2Q3R.

PhylomeDB

P63272.

Enzyme and pathway databases

Reactome

REACT_1788. Transcription.
REACT_1892. Elongation arrest and recovery.
REACT_6185. HIV Infection.
REACT_71. Gene Expression.
REACT_769. Pausing and recovery of elongation.

Gene expression databases

ArrayExpress

P63272.

Bgee

P63272.

CleanEx

HS_SUPT4H1.

Genevestigator

P63272.

GermOnline

ENSG00000108375. Homo sapiens.

Family and domain databases

InterPro

IPR009287. Spt4.
IPR016046. Spt4-like.
IPR022800. Spt4/RpoE2_Znf.
[Graphical view]

KO

K15171.

PANTHER

PTHR12882. Spt4. 1 hit.

Pfam

PF06093. Spt4. 1 hit.
[Graphical view]

PIRSF

PIRSF025023. Spt4. 1 hit.

ProtoNet

Search...

Other

NextBio

26657.

SOURCE

Search...

Entry information

Entry name

SPT4H_HUMAN

Accession

Primary (citable) accession number: P63272
Secondary accession number(s): B2R4X8 , D3DTZ4, Q16550, Q62387, Q6ZP89

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	January 25, 2012
This is version 73 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.