O95198 (KLHL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kelch-like protein 2

Alternative name(s):
Actin-binding protein Mayven

Gene names

Name:

KLHL2

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

General annotation (Comments)

Function	Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation By similarity. Plays a role in the reorganization of the actin cytoskeleton. Promotes growth of cell projections in oligodendrocyte precursors. Ref.6
Subunit structure	Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Interacts with NPTXR and CUL3 By similarity. Binds actin. Interacts with KLHL12. Interacts (via N-terminus) with FYN (via SH3 domain). Ref.1 Ref.5 Ref.6
Subcellular location	Cytoplasm › cytoskeleton. Cell projection › ruffle. Cell projection By similarity. Cell projection › lamellipodium By similarity. Cytoplasm › cytosol. Note: A proportion colocalizes with the actin cytoskeleton. When over-expressed, colocalizes with NPTXR in perinuclear aggresomes By similarity. Ref.1 Ref.6
Tissue specificity	Ubiquitous. Detected throughout the brain. Ref.1
Sequence similarities	Contains 1 BTB (POZ) domain. Contains 6 Kelch repeats.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Domain	Kelch repeat Repeat
Ligand	Actin-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from sequence or structural similarity. Source: UniProtKB actin cytoskeleton Inferred from direct assay Ref.1. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	actin binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O95198-1)

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: O95198-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: METPPLPPA → MVWLEARPQILFV

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 593

593

Kelch-like protein 2

PRO_0000119101

Regions

Domain

56 – 123

68

BTB

Repeat

308 – 353

46

Kelch 1

Repeat

354 – 400

47

Kelch 2

Repeat

402 – 447

46

Kelch 3

Repeat

449 – 496

48

Kelch 4

Repeat

497 – 543

47

Kelch 5

Repeat

545 – 591

47

Kelch 6

Natural variations

Alternative sequence

1 – 9

9

METPPLPPA → MVWLEARPQILFV in isoform 2.

VSP_042837

Experimental info

Sequence conflict

273

1

D → N in AAC67502. Ref.1

Sequence conflict

342

1

R → G in AAH36468. Ref.4

Sequence conflict

457

1

G → V in AAH22503. Ref.4

Sequence conflict

462

1

C → Y in AAC67502. Ref.1

Sequence conflict

592

1

P → R in AAH22503. Ref.4

Secondary structure

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593

Helix Strand Turn

Details...

Beta strand

307 – 312

6

Beta strand

315 – 319

5

Beta strand

323 – 327

5

Turn

328 – 331

4

Beta strand

332 – 336

5

Beta strand

347 – 351

5

Beta strand

354 – 359

6

Beta strand

363 – 366

4

Beta strand

370 – 374

5

Turn

375 – 378

4

Beta strand

379 – 383

5

Beta strand

394 – 398

5

Beta strand

401 – 408

8

Beta strand

413 – 421

9

Turn

422 – 425

4

Beta strand

426 – 430

5

Beta strand

441 – 445

5

Beta strand

448 – 452

5

Turn

457 – 460

4

Beta strand

466 – 470

5

Turn

471 – 474

4

Beta strand

475 – 479

5

Beta strand

490 – 494

5

Beta strand

497 – 501

5

Beta strand

504 – 509

6

Beta strand

513 – 517

5

Turn

518 – 521

4

Beta strand

522 – 526

5

Beta strand

537 – 541

5

Beta strand

544 – 548

5

Beta strand

553 – 556

4

Beta strand

560 – 563

4

Turn

565 – 567

3

Beta strand

570 – 572

3

Beta strand

585 – 590

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2004. Version 2. Checksum: 397AE02E69E56A18	FASTA	593	65,975
	10 20 30 40 50 60 METPPLPPAC TKQGHQKPLD SKDDNTEKHC PVTVNPWHMK KAFKVMNELR SQNLLCDVTI 70 80 90 100 110 120 VAEDMEISAH RVVLAACSPY FHAMFTGEMS ESRAKRVRIK EVDGWTLRML IDYVYTAEIQ 130 140 150 160 170 180 VTEENVQVLL PAAGLLQLQD VKKTCCEFLE SQLHPVNCLG IRAFADMHAC TDLLNKANTY 190 200 210 220 230 240 AEQHFADVVL SEEFLNLGIE QVCSLISSDK LTISSEEKVF EAVIAWVNHD KDVRQEFMAR 250 260 270 280 290 300 LMEHVRLPLL PREYLVQRVE EEALVKNSSA CKDYLIEAMK YHLLPTEQRI LMKSVRTRLR 310 320 330 340 350 360 TPMNLPKLMV VVGGQAPKAI RSVECYDFKE ERWHQVAELP SRRCRAGMVY MAGLVFAVGG 370 380 390 400 410 420 FNGSLRVRTV DSYDPVKDQW TSVANMRDRR STLGAAVLNG LLYAVGGFDG STGLSSVEAY 430 440 450 460 470 480 NIKSNEWFHV APMNTRRSSV GVGVVGGLLY AVGGYDGASR QCLSTVECYN ATTNEWTYIA 490 500 510 520 530 540 EMSTRRSGAG VGVLNNLLYA VGGHDGPLVR KSVEVYDPTT NAWRQVADMN MCRRNAGVCA 550 560 570 580 590 VNGLLYVVGG DDGSCNLASV EYYNPTTDKW TVVSSCMSTG RSYAGVTVID KPL
	Isoform 2 [UniParc]. Checksum: AFF604F55F423755	FASTA	597	66,624
	10 20 30 40 50 60 MVWLEARPQI LFVCTKQGHQ KPLDSKDDNT EKHCPVTVNP WHMKKAFKVM NELRSQNLLC 70 80 90 100 110 120 DVTIVAEDME ISAHRVVLAA CSPYFHAMFT GEMSESRAKR VRIKEVDGWT LRMLIDYVYT 130 140 150 160 170 180 AEIQVTEENV QVLLPAAGLL QLQDVKKTCC EFLESQLHPV NCLGIRAFAD MHACTDLLNK 190 200 210 220 230 240 ANTYAEQHFA DVVLSEEFLN LGIEQVCSLI SSDKLTISSE EKVFEAVIAW VNHDKDVRQE 250 260 270 280 290 300 FMARLMEHVR LPLLPREYLV QRVEEEALVK NSSACKDYLI EAMKYHLLPT EQRILMKSVR 310 320 330 340 350 360 TRLRTPMNLP KLMVVVGGQA PKAIRSVECY DFKEERWHQV AELPSRRCRA GMVYMAGLVF 370 380 390 400 410 420 AVGGFNGSLR VRTVDSYDPV KDQWTSVANM RDRRSTLGAA VLNGLLYAVG GFDGSTGLSS 430 440 450 460 470 480 VEAYNIKSNE WFHVAPMNTR RSSVGVGVVG GLLYAVGGYD GASRQCLSTV ECYNATTNEW 490 500 510 520 530 540 TYIAEMSTRR SGAGVGVLNN LLYAVGGHDG PLVRKSVEVY DPTTNAWRQV ADMNMCRRNA 550 560 570 580 590 GVCAVNGLLY VVGGDDGSCN LASVEYYNPT TDKWTVVSSC MSTGRSYAGV TVIDKPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain." Soltysik-Espanola M.B., Rogers R.A., Jiang S., Kim T.A., Gaedigk R., White R.A., Avraham H., Avraham S. Mol. Biol. Cell 10:2361-2375(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain cortex.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hypothalamus.
[5]	"hDKIR, a human homologue of the Drosophila kelch protein, involved in a ring-like structure." Mai A., Jung S.K., Yonehara S. Exp. Cell Res. 300:72-83(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KLHL12.
[6]	"Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven." Jiang S., Avraham H.K., Park S.Y., Kim T.A., Bu X., Seng S., Avraham S. J. Neurochem. 92:1191-1203(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FYN.
[7]	"Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases." Canning P., Cooper C.D., Krojer T., Murray J.W., Pike A.C., Chaikuad A., Keates T., Thangaratnarajah C., Hojzan V., Marsden B.D., Gileadi O., Knapp S., von Delft F., Bullock A.N. J. Biol. Chem. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 294-591.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF059569 mRNA. Translation: AAC67502.1.
AK294103 mRNA. Translation: BAG57438.1.
AC012504 Genomic DNA. No translation available.
AC055120 Genomic DNA. No translation available.
AC107059 Genomic DNA. No translation available.
BC022503 mRNA. Translation: AAH22503.1.
BC036468 mRNA. Translation: AAH36468.1.

IPI

IPI00296591.
IPI00936343.

RefSeq

NP_001154993.1. NM_001161521.1.
NP_001154994.1. NM_001161522.1.
NP_009177.3. NM_007246.3.

UniGene

Hs.388668.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XN4	X-ray	1.99	A/B	294-591	[»]

ProteinModelPortal

O95198.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95198. 3 interactions.

MINT

MINT-1463156.

STRING

9606.ENSP00000226725.

PTM databases

PhosphoSite

O95198.

Proteomic databases

PaxDb

O95198.

PRIDE

O95198.

Protocols and materials databases

DNASU

11275.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000226725; ENSP00000226725; ENSG00000109466.
ENST00000514860; ENSP00000424198; ENSG00000109466.

GeneID

11275.

KEGG

hsa:11275.

UCSC

uc003irb.3. human.

Organism-specific databases

CTD

11275.

GeneCards

GC04P166128.

H-InvDB

HIX0004470.
HIX0022043.

HGNC

HGNC:6353. KLHL2.

HPA

HPA051637.

MIM

605774. gene.

neXtProt

NX_O95198.

PharmGKB

PA30143.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149197.

HOGENOM

HOG000230814.

HOVERGEN

HBG014286.

InParanoid

O95198.

KO

K10443.

OMA

EQHFADV.

OrthoDB

EOG4T1HM8.

Gene expression databases

ArrayExpress

O95198.

Bgee

O95198.

CleanEx

HS_KLHL2.

Genevestigator

O95198.

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

EvolutionaryTrace

O95198.

GenomeRNAi

11275.

NextBio

42917.

SOURCE

Search...

Entry information

Entry name

KLHL2_HUMAN

Accession

Primary (citable) accession number: O95198
Secondary accession number(s): A6NCM7 , B4DFH7, Q8N484, Q8TBH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	September 27, 2004
Last modified:	May 1, 2013
This is version 103 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.