Q9Y2M5 (KLH20_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kelch-like protein 20

Alternative name(s):
Kelch-like ECT2-interacting protein
Kelch-like protein X

Gene names

Name:	KLHL20
Synonyms:	KLEIP

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

General annotation (Comments)

Function	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis. Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. Ref.6 Ref.7 Ref.8
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Component of the BCR(KLHL20) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL20 and RBX1. Interacts with DAPK1. Interacts with F-actin. Interacts with IFN-gamma (IFNG). Ref.1 Ref.6 Ref.8
Subcellular location	Cytoplasm › perinuclear region. Nucleus. Note: Localizes in the perinuclear region in normal conditions. Following IFN-alpha or IFN-gamma treatment, it is relocalized and sequestrated to the PML nuclear bodies, preventing DAPK1 ubiquitination. Ref.8
Sequence similarities	Contains 1 BACK (BTB/Kelch associated) domain. Contains 1 BTB (POZ) domain. Contains 6 Kelch repeats.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Kelch repeat Repeat
Ligand	Actin-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytoskeleton organization Traceable author statement PubMed 10888605. Source: ProtInc negative regulation of apoptotic process Inferred from mutant phenotype Ref.8. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.8. Source: UniProtKB response to interferon-alpha Traceable author statement Ref.8. Source: UniProtKB
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from direct assay Ref.8. Source: UniProtKB Golgi apparatus Inferred from direct assay. Source: HPA PML body Inferred from direct assay Ref.8. Source: UniProtKB actin cytoskeleton Traceable author statement PubMed 10888605. Source: ProtInc cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	interferon-gamma binding Inferred from direct assay Ref.8. Source: UniProtKB ubiquitin-protein ligase activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PML	P29590	4	EBI-714379,EBI-295890

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 609	609	Kelch-like protein 20		PRO_0000119123
Regions
	Domain	68 – 135	68	BTB
	Domain	170 – 272	103	BACK
	Repeat	319 – 365	47	Kelch 1
	Repeat	367 – 413	47	Kelch 2
	Repeat	414 – 460	47	Kelch 3
	Repeat	462 – 507	46	Kelch 4
	Repeat	509 – 554	46	Kelch 5
	Repeat	556 – 601	46	Kelch 6
Experimental info
	Mutagenesis	109	1	V → A: Abolishes interaction with CUL3; when associated with A-111; A-113; A-146; A-148 and A-150. Ref.8
	Mutagenesis	111	1	I → A: Abolishes interaction with CUL3; when associated with A-109; A-113; A-146; A-148 and A-150. Ref.8
	Mutagenesis	113	1	D → A: Abolishes interaction with CUL3; when associated with A-109; A-111; A-146; A-148 and A-150. Ref.8
	Mutagenesis	146	1	C → A: Abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-148 and A-150. Ref.8
	Mutagenesis	148	1	L → A: Abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-150. Ref.8
	Mutagenesis	150	1	L → A: Abolishes interaction with CUL3; when associated with A-109; A-111; A-113; A-146 and A-148. Ref.8
	Sequence conflict	171	1	L → Q in BAG50912. Ref.3
	Sequence conflict	321	1	F → S in BAG50912. Ref.3
	Sequence conflict	334	1	S → N in BAG50912. Ref.3
	Sequence conflict	396	1	V → M in BAG50912. Ref.3
	Sequence conflict	593	1	G → W in BAA77027. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y2M5 [UniParc]. Last modified September 1, 2009. Version 4. Checksum: FA05E3FE8341B422	FASTA	609	67,955
	10 20 30 40 50 60 MEGKPMRRCT NIRPGETGMD VTSRCTLGDP NKLPEGVPQP ARMPYISDKH PRQTLEVINL 70 80 90 100 110 120 LRKHRELCDV VLVVGAKKIY AHRVILSACS PYFRAMFTGE LAESRQTEVV IRDIDERAME 130 140 150 160 170 180 LLIDFAYTSQ ITVEEGNVQT LLPAACLLQL AEIQEACCEF LKRQLDPSNC LGIRAFADTH 190 200 210 220 230 240 SCRELLRIAD KFTQHNFQEV MESEEFMLLP ANQLIDIISS DELNVRSEEQ VFNAVMAWVK 250 260 270 280 290 300 YSIQERRPQL PQVLQHVRLP LLSPKFLVGT VGSDPLIKSD EECRDLVDEA KNYLLLPQER 310 320 330 340 350 360 PLMQGPRTRP RKPIRCGEVL FAVGGWCSGD AISSVERYDP QTNEWRMVAS MSKRRCGVGV 370 380 390 400 410 420 SVLDDLLYAV GGHDGSSYLN SVERYDPKTN QWSSDVAPTS TCRTSVGVAV LGGFLYAVGG 430 440 450 460 470 480 QDGVSCLNIV ERYDPKENKW TRVASMSTRR LGVAVAVLGG FLYAVGGSDG TSPLNTVERY 490 500 510 520 530 540 NPQENRWHTI APMGTRRKHL GCAVYQDMIY AVGGRDDTTE LSSAERYNPR TNQWSPVVAM 550 560 570 580 590 600 TSRRSGVGLA VVNGQLMAVG GFDGTTYLKT IEVFDPDANT WRLYGGMNYR RLGGGVGVIK MTHCESHIW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel kelch-like protein, KLEIP, is involved in actin assembly at cell-cell contact sites of Madin-Darby canine kidney cells." Hara T., Ishida H., Raziuddin R., Dorkhom S., Kamijo K., Miki T. Mol. Biol. Cell 15:1172-1184(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ACTIN.
[2]	"Kelch motif containing protein." Yoshida K., Sugano S. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[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]. Tissue: Teratocarcinoma.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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].
[6]	"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases." Furukawa M., He Y.J., Borchers C., Xiong Y. Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3.
[7]	"The BTB-Kelch protein KLEIP controls endothelial migration and sprouting angiogenesis." Nacak T.G., Alajati A., Leptien K., Fulda C., Weber H., Miki T., Czepluch F.S., Waltenberger J., Wieland T., Augustin H.G., Kroll J. Circ. Res. 100:1155-1163(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses." Lee Y.R., Yuan W.C., Ho H.C., Chen C.H., Shih H.M., Chen R.H. EMBO J. 29:1748-1761(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH DAPK AND IFNG, MUTAGENESIS OF VAL-109; ILE-111; ASP-113; CYS-146; LEU-148 AND LEU-150.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ844466 mRNA. Translation: CAH59617.1. AB026190 mRNA. Translation: BAA77027.1. AK001430 mRNA. Translation: BAG50912.1. AL109921, BX248409 Genomic DNA. Translation: CAI20377.1. BX248409, AL109921 Genomic DNA. Translation: CAH73000.1. BC063418 mRNA. Translation: AAH63418.1.
IPI	IPI00032338.
RefSeq	NP_055273.2. NM_014458.3.
UniGene	Hs.495035.
3D structure databases
ProteinModelPortal	Q9Y2M5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2M5. 12 interactions.
MINT	MINT-6783961.
STRING	9606.ENSP00000209884.
PTM databases
PhosphoSite	Q9Y2M5.
Polymorphism databases
DMDM	257051084.
Proteomic databases
PaxDb	Q9Y2M5.
PRIDE	Q9Y2M5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000209884; ENSP00000209884; ENSG00000076321.
GeneID	27252.
KEGG	hsa:27252.
UCSC	uc001gjc.3. human.
Organism-specific databases
CTD	27252.
GeneCards	GC01P173684.
HGNC	HGNC:25056. KLHL20.
HPA	HPA025034.
neXtProt	NX_Q9Y2M5.
PharmGKB	PA134982126.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG236397.
HOGENOM	HOG000230814.
HOVERGEN	HBG014286.
InParanoid	Q9Y2M5.
KO	K10457.
OMA	PMSKRRC.
OrthoDB	EOG4N8R47.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	Q9Y2M5.
Bgee	Q9Y2M5.
CleanEx	HS_KLHL20.
Genevestigator	Q9Y2M5.
GermOnline	ENSG00000076321. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.80. 1 hit. 3.30.710.10. 1 hit.
InterPro	IPR011705. BACK. IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. IPR013069. BTB_POZ. IPR015916. Gal_Oxidase_b-propeller. IPR017096. Kelch-like_gigaxonin. IPR006652. Kelch_1. [Graphical view]
Pfam	PF07707. BACK. 1 hit. PF00651. BTB. 1 hit. PF01344. Kelch_1. 6 hits. [Graphical view]
PIRSF	PIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMART	SM00875. BACK. 1 hit. SM00225. BTB. 1 hit. SM00612. Kelch. 6 hits. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
PROSITE	PS50097. BTB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	27252.
NextBio	50186.

Entry information

Entry name

KLH20_HUMAN

Accession

Primary (citable) accession number: Q9Y2M5
Secondary accession number(s): B3KMA0 , Q5TZF2, Q5ZF45, Q9H457

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	September 1, 2009
Last modified:	May 29, 2013
This is version 105 of the entry and version 4 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.