O76041 (NEBL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nebulette

Alternative name(s):
Actin-binding Z-disk protein

Gene names

Name:	NEBL
Synonyms:	LNEBL

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	1014 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to actin and plays an important role in the assembly of the Z-disk. Isoform 2 might play a role in the assembly of focal adhesion. Ref.3
Subunit structure	Isoform 2 interacts with ZYX (Zyxin). Ref.3
Subcellular location	Isoform 2: Cytoplasm Ref.3.
Tissue specificity	Abundantly expressed in cardiac muscle, but not in skeletal or smooth muscle. Localized to Z-lines in cardiac cells and to dense bodies in nonmuscle cells. Isoform 2 is expressed in non-muscle cells such as in fibroblasts.
Sequence similarities	Contains 23 nebulin repeats. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH3 domain
Ligand	Actin-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle thin filament assembly Inferred from mutant phenotype PubMed 11822876PubMed 18823973. Source: UniProtKB
Cellular_component	Z disc Inferred from direct assay Ref.2PubMed 20951326. Source: UniProtKB stress fiber Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	actin filament binding Inferred from direct assay Ref.2. Source: UniProtKB structural constituent of muscle Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O76041-1)

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: O76041-2)

Also known as: LIM-nebulette; LNEBL;

The sequence of this isoform differs from the canonical sequence as follows:
     1-664: Missing.
     665-782: TPVSMTPEIE...VKEAQNHISM → MNPQCARCGK...LKRTQEQISN
     840-920: Missing.

Note: Expressed in non-muscle cells. May be transcribed from an upstream promoter active in non-muscle cells.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1014

1014

Nebulette

PRO_0000096774

Regions

Repeat

29 – 63

35

Nebulin 1

Repeat

64 – 99

36

Nebulin 2

Repeat

100 – 136

37

Nebulin 3

Repeat

137 – 172

36

Nebulin 4

Repeat

173 – 205

33

Nebulin 5

Repeat

206 – 241

36

Nebulin 6

Repeat

242 – 278

37

Nebulin 7

Repeat

279 – 313

35

Nebulin 8

Repeat

314 – 348

35

Nebulin 9

Repeat

349 – 385

37

Nebulin 10

Repeat

386 – 422

37

Nebulin 11

Repeat

423 – 459

37

Nebulin 12

Repeat

460 – 496

37

Nebulin 13

Repeat

497 – 533

37

Nebulin 14

Repeat

534 – 569

36

Nebulin 15

Repeat

570 – 599

30

Nebulin 16

Repeat

600 – 635

36

Nebulin 17

Repeat

636 – 666

31

Nebulin 18

Repeat

667 – 693

27

Nebulin 19

Repeat

694 – 728

35

Nebulin 20

Repeat

729 – 759

31

Nebulin 21

Repeat

760 – 794

35

Nebulin 22

Repeat

795 – 830

36

Nebulin 23

Domain

954 – 1014

61

SH3

Region

836 – 953

118

Linker

Natural variations

Alternative sequence

1 – 664

664

Missing in isoform 2.

VSP_043816

Alternative sequence

665 – 782

118

TPVSM…NHISM → MNPQCARCGKVVYPTEKVNC LDKYWHKGCFHCEVCKMALN MNNYKGYEKKPYCNAHYPKQ SFTTVADTPENLRLKQQSEL QSQVKYKRDFEESKGRGFSI VTDTPELQRLKRTQEQISN in isoform 2.

VSP_043817

Alternative sequence

840 – 920

81

Missing in isoform 2.

VSP_043818

Natural variant

187

1

Q → H. Ref.9

VAR_010289

Natural variant

219

1

A → D.
Corresponds to variant rs2296610 [ dbSNP | Ensembl ].

VAR_021887

Natural variant

351

1

M → V. Ref.9
Corresponds to variant rs4025981 [ dbSNP | Ensembl ].

VAR_010290

Natural variant

378

1

D → H.
Corresponds to variant rs41277370 [ dbSNP | Ensembl ].

VAR_051229

Natural variant

654

1

N → K Higher frequency of homozygotes in a cohort of non-familial cardiomyopathy Japanese patients as compared to healthy controls. Ref.9
Corresponds to variant rs4748728 [ dbSNP | Ensembl ].

VAR_010291

Natural variant

728

1

T → A. Ref.9

VAR_010292

Experimental info

Sequence conflict

53 – 60

8

RYKEEFKK → VIKKSLKS in AAF24858. Ref.2

Sequence conflict

75

1

N → T in AAF24858. Ref.2

Sequence conflict

129 – 138

10

KHDAAKGFSD → NMMLPRILS in AAF24858. Ref.2

Sequence conflict

439 – 445

7

RASEMAS → QPLKWQG in AAF24858. Ref.2

Sequence conflict

706 – 726

21

RAKEN…QLGRA → PKETRKTSACLLQSSAGES in AAF24858. Ref.2

Sequence conflict

732

1

T → I in AAF24858. Ref.2

Sequence conflict

740

1

K → E in AAF24858. Ref.2

Sequence conflict

743

1

E → G in AAF24858. Ref.2

Sequence conflict

902 – 904

3

EIY → RDL in AAF24858. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

1014

Helix Strand Turn

Details...

Beta strand

959 – 963

5

Beta strand

980 – 986

7

Beta strand

988 – 996

9

Turn

997 – 1000

4

Beta strand

1001 – 1006

6

Helix

1007 – 1009

3

Beta strand

1010 – 1012

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 81712E38BC6AC9E1	FASTA	1,014	116,453
	10 20 30 40 50 60 MRVPVFEDIK DETEEEKIGE EENEEDQVFY KPVIEDLSME LARKCTELIS DIRYKEEFKK 70 80 90 100 110 120 SKDKCTFVTD SPMLNHVKNI GAFISEAKYK GTIKADLSNS LYKRMPATID SVFAGEVTQL 130 140 150 160 170 180 QSEVAYKQKH DAAKGFSDYA HMKEPPEVKH AMEVNKHQSN ISYRKDVQDT HTYSAELDRP 190 200 210 220 230 240 DIKMATQISK IISNAEYKKG QGIMNKEPAV IGRPDFEHAV EASKLSSQIK YKEKFDNEMK 250 260 270 280 290 300 DKKHHYNPLE SASFRQNQLA ATLASNVKYK KDIQNMHDPV SDLPNLLFLD HVLKASKMLS 310 320 330 340 350 360 GREYKKLFEE NKGMYHFDAD AVEHLHHKGN AVLQSQVKYK EEYEKNKGKP MLEFVETPSY 370 380 390 400 410 420 QASKEAQKMQ SEKVYKEDFE KEIKGRSSLD LDKTPEFLHV KYITNLLREK EYKKDLENEI 430 440 450 460 470 480 KGKGMELNSE VLDIQRAKRA SEMASEKEYK KDLESIIKGK GMQAGTDTLE MQHAKKAAEI 490 500 510 520 530 540 ASEKDYKRDL ETEIKGKGMQ VSTDTLDVQR AKKASEMASQ KQYKKDLENE IKGKGMQVSM 550 560 570 580 590 600 DIPDILRAKR TSEIYSQRKY KDEAEKMLSN YSTIADTPEI QRIKTTQQNI SAVFYKKEVG 610 620 630 640 650 660 AGTAVKDSPE IERVKKNQQN ISSVKYKEEI KHATAISDPP ELKRVKENQK NISNLQYKEQ 670 680 690 700 710 720 NYKATPVSMT PEIERVRRNQ EQLSAVKYKG ELQRGTAISD PPELKRAKEN QKNISNVYYR 730 740 750 760 770 780 GQLGRATTLS VTPEMERVKK NQENISSVKY TQDHKQMKGR PSLILDTPAM RHVKEAQNHI 790 800 810 820 830 840 SMVKYHEDFE KTKGRGFTPV VDDPVTERVR KNTQVVSDAA YKGVHPHIVE MDRRPGIIVD 850 860 870 880 890 900 LKVWRTDPGS IFDLDPLEDN IQSRSLHMLS EKASHYRRHW SRSHSSSTFG TGLGDDRSEI 910 920 930 940 950 960 SEIYPSFSCC SEVTRPSDEG APVLPGAYQQ SHSQGYGYMH QTSVSSMRSM QHSPNLRTYR 970 980 990 1000 1010 AMYDYSAQDE DEVSFRDGDY IVNVQPIDDG WMYGTVQRTG RTGMLPANYI EFVN
	Isoform 2 (LIM-nebulette) (LNEBL) [UniParc]. Checksum: E3A31825D585FAA1	FASTA	270	31,196
	10 20 30 40 50 60 MNPQCARCGK VVYPTEKVNC LDKYWHKGCF HCEVCKMALN MNNYKGYEKK PYCNAHYPKQ 70 80 90 100 110 120 SFTTVADTPE NLRLKQQSEL QSQVKYKRDF EESKGRGFSI VTDTPELQRL KRTQEQISNV 130 140 150 160 170 180 KYHEDFEKTK GRGFTPVVDD PVTERVRKNT QVVSDAAYKG VHPHIVEMDR RPGIIVAPVL 190 200 210 220 230 240 PGAYQQSHSQ GYGYMHQTSV SSMRSMQHSP NLRTYRAMYD YSAQDEDEVS FRDGDYIVNV 250 260 270 QPIDDGWMYG TVQRTGRTGM LPANYIEFVN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of nebulette and nebulin and emerging concepts of their roles for vertebrate Z-discs." Millevoi S., Trombitas K., Kolmerer B., Kostin S., Schaper J., Pelin K., Granzier H., Labeit S. J. Mol. Biol. 282:111-123(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart muscle.
[2]	"Functional dissection of nebulette demonstrates actin binding of nebulin-like repeats and Z-line targeting of SH3 and linker domains." Moncman C.L., Wang K. Cell Motil. Cytoskeleton 44:1-22(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Heart.
[3]	"Zyxin interacts with the SH3 domains of the cytoskeletal proteins LIM-nebulette and Lasp-1." Li B., Zhuang L., Trueb B. J. Biol. Chem. 279:20401-20410(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH ZYX, SUBCELLULAR LOCATION (ISOFORM 2). Tissue: Placenta.
[4]	"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.
[5]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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] (ISOFORMS 1 AND 2).
[9]	"Characterization of the human nebulette gene: a polymorphism in an actin-binding motif is associated with nonfamilial idiopathic dilated cardiomyopathy." Arimura T., Nakamura T., Hiroi S., Satoh M., Takahashi M., Ohbuchi N., Ueda K., Nouchi T., Yamaguchi N., Akai J., Matsumori A., Sasayama S., Kimura A. Hum. Genet. 107:440-451(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HIS-187; VAL-351; LYS-654 AND ALA-728.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y16241 mRNA. Translation: CAA76130.1.
Y17673 mRNA. Translation: CAA76810.1.
AF047368 mRNA. Translation: AAF24858.1.
AJ580772 mRNA. Translation: CAE45323.1.
AK295186 mRNA. Translation: BAG58190.1.
EF445000 Genomic DNA. Translation: ACA06022.1.
EF445000 Genomic DNA. Translation: ACA06023.1.
EF445000 Genomic DNA. Translation: ACA06024.1.
EF445000 Genomic DNA. Translation: ACA06026.1.
AL359175, AL157398, AL731547 Genomic DNA. Translation: CAH71371.1.
AL731547, AL157398, AL359175 Genomic DNA. Translation: CAI15775.1.
AL157398, AL359175, AL731547 Genomic DNA. Translation: CAI41189.1.
AL157398 Genomic DNA. Translation: CAC19642.1.
AL158160 Genomic DNA. No translation available.
CH471072 Genomic DNA. Translation: EAW86175.1.
BC110453 mRNA. Translation: AAI10454.1.
BC126132 mRNA. Translation: AAI26133.1.
BC126134 mRNA. Translation: AAI26135.1.

IPI

IPI00872370.

RefSeq

NP_001166955.1. NM_001173484.1.
NP_006384.1. NM_006393.2.
NP_998734.1. NM_213569.2.

UniGene

Hs.5025.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F14	X-ray	1.20	A	955-1014	[»]

ProteinModelPortal

O76041.

ModBase

Search...

Protein-protein interaction databases

IntAct

O76041. 2 interactions.

STRING

9606.ENSP00000366326.

PTM databases

PhosphoSite

O76041.

Proteomic databases

PaxDb

O76041.

PRIDE

O76041.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377122; ENSP00000366326; ENSG00000078114.
ENST00000417816; ENSP00000393896; ENSG00000078114.

GeneID

10529.

KEGG

hsa:10529.

UCSC

uc001iqi.3. human.

Organism-specific databases

CTD

10529.

GeneCards

GC10M021110.

HGNC

HGNC:16932. NEBL.

HPA

HPA013994.
HPA013995.

MIM

605491. gene.

neXtProt

NX_O76041.

PharmGKB

PA134981177.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG249897.

HOGENOM

HOG000048710.

HOVERGEN

HBG006459.

OMA

TVANSTH.

OrthoDB

EOG4JWVCQ.

PhylomeDB

O76041.

Gene expression databases

ArrayExpress

O76041.

Bgee

O76041.

CleanEx

HS_NEBL.

Genevestigator

O76041.

GermOnline

ENSG00000078114. Homo sapiens.

Family and domain databases

InterPro

IPR000900. Nebulin_35r-motif.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00880. Nebulin. 14 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00452. SH3DOMAIN.

SMART

SM00227. NEBU. 23 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS51216. NEBULIN. 23 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

NEBL. human.

GenomeRNAi

10529.

NextBio

39946.

SOURCE

Search...

Entry information

Entry name

NEBL_HUMAN

Accession

Primary (citable) accession number: O76041
Secondary accession number(s): B0YJ45 , Q2TBD0, Q70I54, Q9UIC4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 108 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.