O95600 (KLF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Krueppel-like factor 8

Alternative name(s):
Basic krueppel-like factor 3
Zinc finger protein 741

Gene names

Name:	KLF8
Synonyms:	BKLF3, ZNF741

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	359 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor and activator. Binds to CACCC-boxes promoter elements. Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G1 phase as a downstream target of focal adhesion kinase (FAK). Ref.8 Ref.9 Ref.10
Subunit structure	Interacts with corepressor CtBP2. Interacts with PIAS1, PIAS2, AND PIAS4; the interaction with each ligase sumoylates KLF8. Ref.8 Ref.10
Subcellular location	Nucleus Ref.10.
Tissue specificity	Ubiquitous. Ref.8
Post-translational modification	Sumoylation at Lys-67 represses transcriptional activity and reduces cell cycle progression into the G1 phase. Has no effect on subcellular location. Ref.10
Sequence similarities	Belongs to the Sp1 C2H2-type zinc-finger protein family. Contains 3 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Repressor
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of transcription, DNA-templated Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-templated Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95600-1)

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 2 (identifier: O95600-3)

The sequence of this isoform differs from the canonical sequence as follows:
     254-359: PAAMAQMQGE...SLHRRRHDTM → REAL

Isoform 3 (identifier: O95600-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MVDMDKLINNLEVQLNSEGGSMQVFKQ → MSLPEDGMSSGHFRSPQLVTWS
     254-359: PAAMAQMQGE...SLHRRRHDTM → REAL

Isoform 4 (identifier: O95600-5)

The sequence of this isoform differs from the canonical sequence as follows:
     216-299: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 359	359	Krueppel-like factor 8		PRO_0000047176
Regions
	Zinc finger	274 – 298	25	C2H2-type 1
	Zinc finger	304 – 328	25	C2H2-type 2
	Zinc finger	334 – 356	23	C2H2-type 3
Amino acid modifications
	Cross-link	67		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.10
Natural variations
	Alternative sequence	1 – 27	27	MVDMD…QVFKQ → MSLPEDGMSSGHFRSPQLVT WS in isoform 3.		VSP_047480
	Alternative sequence	216 – 299	84	Missing in isoform 4.		VSP_047481
	Alternative sequence	254 – 359	106	PAAMA…RHDTM → REAL in isoform 2 and isoform 3.		VSP_045460
Experimental info
	Mutagenesis	67	1	K → R: Abolishes sumoylation. No change in nuclear location. Increases transcriptional activity and cell cycle progression. Abolishes sumoylation; when associated with R-217. Ref.10
	Mutagenesis	217	1	K → R: No change in sumoylation. Abolishes sumoylation; when associated with R-67. Ref.10
	Sequence conflict	167	1	S → I in BAG58895. Ref.3
	Sequence conflict	263	1	E → G in AAC99849. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2001. Version 2. Checksum: F8FDCC1FD477C04F	FASTA	359	39,314
	10 20 30 40 50 60 MVDMDKLINN LEVQLNSEGG SMQVFKQVTA SVRNRDPPEI EYRSNMTSPT LLDANPMENP 70 80 90 100 110 120 ALFNDIKIEP PEELLASDFS LPQVEPVDLS FHKPKAPLQP ASMLQAPIRP PKPQSSPQTL 130 140 150 160 170 180 VVSTSTSDMS TSANIPTVLT PGSVLTSSQS TGSQQILHVI HTIPSVSLPN KMGGLKTIPV 190 200 210 220 230 240 VVQSLPMVYT TLPADGGPAA ITVPLIGGDG KNAGSVKVDP TSMSPLEIPS DSEESTIESG 250 260 270 280 290 300 SSALQSLQGL QQEPAAMAQM QGEESLDLKR RRIHQCDFAG CSKVYTKSSH LKAHRRIHTG 310 320 330 340 350 EKPYKCTWDG CSWKFARSDE LTRHFRKHTG IKPFRCTDCN RSFSRSDHLS LHRRRHDTM
	Isoform 2 [UniParc]. Checksum: 86CF13DBD7494270	FASTA	257	27,242
	10 20 30 40 50 60 MVDMDKLINN LEVQLNSEGG SMQVFKQVTA SVRNRDPPEI EYRSNMTSPT LLDANPMENP 70 80 90 100 110 120 ALFNDIKIEP PEELLASDFS LPQVEPVDLS FHKPKAPLQP ASMLQAPIRP PKPQSSPQTL 130 140 150 160 170 180 VVSTSTSDMS TSANIPTVLT PGSVLTSSQS TGSQQILHVI HTIPSVSLPN KMGGLKTIPV 190 200 210 220 230 240 VVQSLPMVYT TLPADGGPAA ITVPLIGGDG KNAGSVKVDP TSMSPLEIPS DSEESTIESG 250 SSALQSLQGL QQEREAL
	Isoform 3 [UniParc]. Checksum: 0B68B09E33AC87A8	FASTA	252	26,623
	10 20 30 40 50 60 MSLPEDGMSS GHFRSPQLVT WSVTASVRNR DPPEIEYRSN MTSPTLLDAN PMENPALFND 70 80 90 100 110 120 IKIEPPEELL ASDFSLPQVE PVDLSFHKPK APLQPASMLQ APIRPPKPQS SPQTLVVSTS 130 140 150 160 170 180 TSDMSTSANI PTVLTPGSVL TSSQSTGSQQ ILHVIHTIPS VSLPNKMGGL KTIPVVVQSL 190 200 210 220 230 240 PMVYTTLPAD GGPAAITVPL IGGDGKNAGS VKVDPTSMSP LEIPSDSEES TIESGSSALQ 250 SLQGLQQERE AL
	Isoform 4 [UniParc]. Checksum: 7CB5F2431F0E06D0	FASTA	275	30,050
	10 20 30 40 50 60 MVDMDKLINN LEVQLNSEGG SMQVFKQVTA SVRNRDPPEI EYRSNMTSPT LLDANPMENP 70 80 90 100 110 120 ALFNDIKIEP PEELLASDFS LPQVEPVDLS FHKPKAPLQP ASMLQAPIRP PKPQSSPQTL 130 140 150 160 170 180 VVSTSTSDMS TSANIPTVLT PGSVLTSSQS TGSQQILHVI HTIPSVSLPN KMGGLKTIPV 190 200 210 220 230 240 VVQSLPMVYT TLPADGGPAA ITVPLIGGDG KNAGSGEKPY KCTWDGCSWK FARSDELTRH 250 260 270 FRKHTGIKPF RCTDCNRSFS RSDHLSLHRR RHDTM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Gorski J.L., MacDonald M., Vananthwerp M., Burright E.N., Bialecki M. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Shaking the family tree: Identification of novel and biologically active alternatively spliced isoforms across the KLF family of transcription factors." Camacho-Vanegas O., Till J., Miranda-Lorenzo I., Ozturk B., Camacho S.C., Martignetti J.A. FASEB J. 27:432-436(2013) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), ALTERNATIVE SPLICING.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Thalamus.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[6]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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). Tissue: Brain.
[8]	"Human Kruppel-like factor 8: a CACCC-box binding protein that associates with CtBP and represses transcription." van Vliet J., Turner J., Crossley M. Nucleic Acids Res. 28:1955-1962(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
[9]	"Identification of transcription factor KLF8 as a downstream target of focal adhesion kinase in its regulation of cyclin D1 and cell cycle progression." Zhao J., Bian Z.C., Yee K., Chen B.P., Chien S., Guan J.L. Mol. Cell 11:1503-1515(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle regulation." Wei H., Wang X., Gan B., Urvalek A.M., Melkoumian Z.K., Guan J.-L., Zhao J. J. Biol. Chem. 281:16664-16671(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-67, INTERACTION WITH PIAS1; PIAS2 AND PIAS4, FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-67 AND LYS-217.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U28282 mRNA. Translation: AAC99849.1. HF546207 mRNA. Translation: CCO02793.1. HF546208 mRNA. Translation: CCO02794.1. HF546209 mRNA. Translation: CCO02795.1. AK296156 mRNA. Translation: BAG58895.1. AB209004 mRNA. Translation: BAD92241.1. Sequence problems. BX641066 mRNA. Translation: CAE46033.1. Sequence problems. BX322609, AL050309 Genomic DNA. Translation: CAI41397.1. AL050309, BX322609 Genomic DNA. Translation: CAI42343.1. BC105130 mRNA. Translation: AAI05131.1. BC112109 mRNA. Translation: AAI12110.1.
CCDS	CCDS14373.1. [O95600-1] CCDS55428.1. [O95600-3]
RefSeq	NP_001152768.1. NM_001159296.1. [O95600-3] NP_009181.2. NM_007250.4. [O95600-1] XP_005262034.1. XM_005261977.1. [O95600-1] XP_005262035.1. XM_005261978.1. [O95600-1] XP_005262036.1. XM_005261979.1. [O95600-1] XP_006724638.1. XM_006724575.1. [O95600-3]
UniGene	Hs.646614.
3D structure databases
ProteinModelPortal	O95600.
SMR	O95600. Positions 274-356.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	116435. 9 interactions.
IntAct	O95600. 1 interaction.
MINT	MINT-7969747.
STRING	9606.ENSP00000417303.
PTM databases
PhosphoSite	O95600.
Proteomic databases
PaxDb	O95600.
PRIDE	O95600.
Protocols and materials databases
DNASU	11279.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374928; ENSP00000364063; ENSG00000102349. [O95600-3] ENST00000468660; ENSP00000417303; ENSG00000102349. [O95600-1]
GeneID	11279.
KEGG	hsa:11279.
UCSC	uc004dur.3. human. [O95600-1] uc011mop.2. human.
Organism-specific databases
CTD	11279.
GeneCards	GC0XP056275.
HGNC	HGNC:6351. KLF8.
MIM	300286. gene.
neXtProt	NX_O95600.
PharmGKB	PA30141.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5048.
HOVERGEN	HBG003941.
InParanoid	O95600.
KO	K09205.
OMA	PVQIRDP.
OrthoDB	EOG7Z69CW.
PhylomeDB	O95600.
TreeFam	TF350556.
Gene expression databases
ArrayExpress	O95600.
Bgee	O95600.
CleanEx	HS_KLF8.
Genevestigator	O95600.
Family and domain databases
Gene3D	3.30.160.60. 3 hits.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
SMART	SM00355. ZnF_C2H2. 3 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 3 hits. PS50157. ZINC_FINGER_C2H2_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
GeneWiki	KLF8.
GenomeRNAi	11279.
NextBio	42937.
PRO	O95600.
SOURCE	Search...

Entry information

Entry name

KLF8_HUMAN

Accession

Primary (citable) accession number: O95600
Secondary accession number(s): B4DJN3 , E7EQQ8, L0R3U8, L0R4U2, Q2M246, Q59GV5, Q5HYQ5, Q5JXP7, Q6MZJ7, Q9UGC4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 2, 2001
Last sequence update:	November 2, 2001
Last modified:	July 9, 2014
This is version 121 of the entry and version 2 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.