Reviewed, UniProtKB/Swiss-Prot Q53G59 (KLH12_HUMAN)

Names and origin

Protein names

Recommended name:
    Kelch-like protein 12
Alternative name(s):
    CUL3-interacting protein 1

Gene names

Name:	KLHL12
Synonyms:	C3IP1

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

General annotation (Comments)

Function	Serves as a substrate-specific adapter for the CUL3-based ubiquitin-protein E3 ligase complex. Negatively regulates the Wnt signaling pathway via the targeted ubiquitination and subsequent proteolysis of DVL3. Ref.6
Subunit structure	Component of an ubiquitin-protein E3 ligase complex which includes at least CUL3 and KLHL12. This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A. Ref.6
Tissue specificity	Highly expressed in testis and at lower levels in the submandibular salivary gland. Ref.5
Domain	The BTB domain is required for interaction with CUL3.
Sequence similarities	Contains 1 BTB (POZ) domain. Contains 6 Kelch repeats.

Ontologies

Keywords
Biological process	Ubl conjugation pathway Wnt signaling pathway
Coding sequence diversity	Polymorphism
Domain	Kelch repeat Repeat
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATXN1	P54253	1	EBI-740929,EBI-930964
PEF1	Q9UBV8	1	EBI-740929,EBI-724639

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 568

568

Kelch-like protein 12

PRO_0000234349

Regions

Domain

33 – 100

68

BTB

Repeat

282 – 329

48

Kelch 1

Repeat

331 – 379

49

Kelch 2

Repeat

380 – 426

47

Kelch 3

Repeat

427 – 473

47

Kelch 4

Repeat

475 – 520

46

Kelch 5

Repeat

522 – 567

46

Kelch 6

Region

405 – 568

164

Interaction with DVL3

Amino acid modifications

Modified residue

31

1

Phosphothreonine Ref.7

Modified residue

36

1

Phosphothreonine Ref.7

Natural variations

Natural variant

72

1

P → L: dbSNP rs12569087.

VAR_050049

Experimental info

Sequence conflict

122

1

C → R in BAD96792. Ref.3

Sequence conflict

197 – 198

2

FE → LG in BAD96792. Ref.3

Sequence conflict

394

1

T → A in BAD96792. Ref.3

Secondary structure

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568

Helix Strand Turn

Details...

Beta strand

281 – 286

6

Turn

291 – 293

3

Beta strand

299 – 303

5

Turn

304 – 307

4

Beta strand

308 – 311

4

Beta strand

323 – 327

5

Beta strand

330 – 334

5

Beta strand

346 – 350

5

Beta strand

360 – 362

3

Beta strand

373 – 377

5

Beta strand

380 – 384

5

Beta strand

395 – 400

6

Turn

401 – 404

4

Beta strand

405 – 411

7

Beta strand

420 – 424

5

Beta strand

427 – 431

5

Beta strand

443 – 446

4

Turn

448 – 450

3

Beta strand

453 – 456

4

Beta strand

467 – 471

5

Beta strand

474 – 478

5

Beta strand

483 – 486

4

Beta strand

490 – 494

5

Turn

495 – 498

4

Beta strand

499 – 503

5

Beta strand

514 – 518

5

Beta strand

521 – 525

5

Beta strand

530 – 541

12

Turn

542 – 545

4

Beta strand

546 – 559

14

Beta strand

561 – 566

6

Sequences

	Sequence		Length	Mass (Da)
	Q53G59-1 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: 4EB1BC33B6351B5D	FASTA	568	63,277
	10 20 30 40 50 60 MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA 70 80 90 100 110 120 MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ 130 140 150 160 170 180 ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE 190 200 210 220 230 240 KLIKCDEIQV DSEEPVFEAV INWVKHAKKE REESLPNLLQ YVRMPLLTPR YITDVIDAEP 250 260 270 280 290 300 FIRCSLQCRD LVDEAKKFHL RPELRSQMQG PRTRARLGAN EVLLVVGGFG SQQSPIDVVE 310 320 330 340 350 360 KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY 370 380 390 400 410 420 SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG 430 440 450 460 470 480 LVVASGVIYC LGGYDGLNIL NSVEKYDPHT GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG 490 500 510 520 530 540 FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY 550 560 DPIIDSWEVV TSMGTQRCDA GVCVLREK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a novel kelch-like protein, C3IP1." Du M., Zu Z., Liou J.-Y., Chu K.-Y., Sansores Garcia L., Yeh E., Wu K.K. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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: Teratocarcinoma and Thyroid.
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: Kidney adenocarcinoma.
[5]	"Identification of specific autoantigens in Sjoegren's syndrome by SEREX." Uchida K., Akita Y., Matsuo K., Fujiwara S., Nakagawa A., Kazaoka Y., Hachiya H., Naganawa Y., Oh-Iwa I., Ohura K., Saga S., Kawai T., Matsumoto Y., Shimozato K., Kozaki K. Immunology 116:53-63(2005) [PubMed: 16108817] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"The KLHL12-cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation." Angers S., Thorpe C.J., Biechele T.L., Goldenberg S.J., Zheng N., Maccoss M.J., Moon R.T. Nat. Cell Biol. 8:348-357(2006) [PubMed: 16547521] [Abstract] Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CUL3 AND DVL3.
[7]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-31 AND THR-36, MASS SPECTROMETRY.

Cross-references

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Sequence databases

EMBLGenBankDDBJ

AF190900 mRNA. Translation: AAG17175.1.
AK027656 mRNA. Translation: BAB55271.1.
AK223072 mRNA. Translation: BAD96792.1.
BC003183 mRNA. Translation: AAH03183.1.
BC004175 mRNA. Translation: AAH04175.1.

RefSeq

NP_067646.1.

UniGene

Hs.282878

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VPJ	X-ray	1.85	A	268-567	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q53G59. 17 interactions.

PTM databases

PhosphoSite

Q53G59.

Proteomic databases

PRIDE

Q53G59.

Genome annotation databases

Ensembl

ENSG00000117153. Homo sapiens. [Contig view]

GeneID

59349.

KEGG

hsa:59349.

Organism-specific databases

GeneCards

GC01M201126.

H-InvDB

HIX0001481.

HGNC

HGNC:19360. KLHL12.

PharmGKB

PA134952416.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q53G59.

HOVERGEN

Q53G59.

Gene expression databases

CleanEx

HS_KLHL12.

GermOnline

ENSG00000117153. Homo sapiens.

Family and domain databases

InterPro

IPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR006651. Kelch.
IPR017096. Kelch-like_gigaxonin.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
IPR013089. Kelch_related.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.
G3DSA:2.120.10.80. Kelch-typ_b-propeller. 1 hit.

PANTHER

PTHR23230. Kelch_related. 1 hit.

Pfam

PF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]

PIRSF

PIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.

PRINTS

PR00501. KELCHREPEAT.

SMART

SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]

PROSITE

PS50097. BTB. 1 hit.
[Graphical view]