Q9HBW1 (LRRC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat-containing protein 4

Alternative name(s):
Brain tumor-associated protein BAG
Nasopharyngeal carcinoma-associated gene 14 protein
Netrin-G2 ligand
Short name=NGL-2

Gene names

Name:	LRRC4
Synonyms:	BAG
ORF Names:	NAG14, UNQ554/PRO1111

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	653 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Synaptic adhesion protein. Regulates the formation of exitatory synapses through the recruitment of pre-and-postsynaptic proteins. Organize the lamina/pathway-specific differentiation of dendrites. Plays a important role for auditory synaptic responses. Involved in the suppression of glioma By similarity.
Subunit structure	Interacts with DLG4 By similarity. Interacts (via LRR repeats) with NTNG2. Forms a complex with DLG4 and with NMDA receptors.
Subcellular location	Membrane; Single-pass type I membrane protein. Cell junction › synapse › postsynaptic cell membrane By similarity. Note: LRRC4 and DLG4 are interdependent for synaptic localization By similarity.
Tissue specificity	Specifically expressed in brain. Ref.1
Domain	The last 4 C-terminal residues bind to the first 2 PDZ domains of DLG4 By similarity.
Post-translational modification	N-glycosylated By similarity.
Sequence similarities	Contains 1 Ig-like (immunoglobulin-like) domain. Contains 9 LRR (leucine-rich) repeats. Contains 1 LRRCT domain. Contains 1 LRRNT domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 38

38

Potential

Chain

39 – 653

615

Leucine-rich repeat-containing protein 4

PRO_0000014833

Regions

Topological domain

39 – 527

489

Extracellular Potential

Transmembrane

528 – 548

21

Helical; Potential

Topological domain

549 – 653

105

Cytoplasmic Potential

Domain

39 – 75

37

LRRNT

Repeat

76 – 97

22

LRR 1

Repeat

100 – 121

22

LRR 2

Repeat

124 – 145

22

LRR 3

Repeat

148 – 169

22

LRR 4

Repeat

172 – 194

23

LRR 5

Repeat

197 – 218

22

LRR 6

Repeat

219 – 240

22

LRR 7

Repeat

243 – 264

22

LRR 8

Repeat

267 – 288

22

LRR 9

Domain

300 – 352

53

LRRCT

Domain

353 – 442

90

Ig-like

Compositional bias

455 – 526

72

Thr-rich

Amino acid modifications

Glycosylation

277

1

N-linked (GlcNAc...) Potential

Glycosylation

322

1

N-linked (GlcNAc...) Potential

Glycosylation

363

1

N-linked (GlcNAc...) Potential

Glycosylation

388

1

N-linked (GlcNAc...) Potential

Glycosylation

410

1

N-linked (GlcNAc...) Potential

Glycosylation

434

1

N-linked (GlcNAc...) Potential

Glycosylation

440

1

N-linked (GlcNAc...) Potential

Glycosylation

447

1

N-linked (GlcNAc...) Potential

Glycosylation

450

1

N-linked (GlcNAc...) Potential

Disulfide bond

46 ↔ 52

Ref.8

Disulfide bond

50 ↔ 61

Ref.8

Disulfide bond

304 ↔ 329

Ref.8

Disulfide bond

306 ↔ 350

Ref.8

Disulfide bond

374 ↔ 424

Ref.8

Natural variations

Natural variant

579

1

T → A in a colorectal cancer sample; somatic mutation. Ref.9

VAR_035519

Experimental info

Sequence conflict

4

1

L → S in BAD18737. Ref.4

Sequence conflict

253 – 257

5

QVSLI → H in CAC82651. Ref.2

Sequence conflict

300

1

N → D in BAD18737. Ref.4

Sequence conflict

315

1

L → F in BAD18737. Ref.4

Secondary structure

1

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653

Helix Strand Turn

Details...

Beta strand

50 – 52

3

Beta strand

54 – 56

3

Beta strand

58 – 60

3

Beta strand

78 – 81

4

Turn

92 – 97

6

Beta strand

103 – 105

3

Turn

116 – 121

6

Beta strand

127 – 129

3

Turn

140 – 142

3

Beta strand

143 – 145

3

Beta strand

151 – 153

3

Turn

164 – 169

6

Beta strand

175 – 177

3

Turn

189 – 194

6

Beta strand

200 – 202

3

Beta strand

222 – 224

3

Beta strand

231 – 233

3

Helix

235 – 238

4

Beta strand

246 – 248

3

Turn

259 – 264

6

Beta strand

270 – 272

3

Beta strand

294 – 296

3

Turn

306 – 308

3

Helix

309 – 318

10

Beta strand

328 – 332

5

Turn

333 – 337

5

Helix

345 – 347

3

Beta strand

362 – 365

4

Beta strand

370 – 372

3

Beta strand

380 – 385

6

Turn

387 – 389

3

Beta strand

390 – 393

4

Beta strand

399 – 403

5

Beta strand

405 – 407

3

Beta strand

409 – 413

5

Turn

416 – 418

3

Beta strand

420 – 427

8

Beta strand

432 – 440

9

Sequences

	Sequence		Length	Mass (Da)
	Q9HBW1 [UniParc]. Last modified October 1, 2001. Version 2. Checksum: 38159C81F6850E37	FASTA	653	72,717
	10 20 30 40 50 60 MKLLWQVTVH HHTWNAILLP FVYLTAQVWI LCAAIAAAAS AGPQNCPSVC SCSNQFSKVV 70 80 90 100 110 120 CTRRGLSEVP QGIPSNTRYL NLMENNIQMI QADTFRHLHH LEVLQLGRNS IRQIEVGAFN 130 140 150 160 170 180 GLASLNTLEL FDNWLTVIPS GAFEYLSKLR ELWLRNNPIE SIPSYAFNRV PSLMRLDLGE 190 200 210 220 230 240 LKKLEYISEG AFEGLFNLKY LNLGMCNIKD MPNLTPLVGL EELEMSGNHF PEIRPGSFHG 250 260 270 280 290 300 LSSLKKLWVM NSQVSLIERN AFDGLASLVE LNLAHNNLSS LPHDLFTPLR YLVELHLHHN 310 320 330 340 350 360 PWNCDCDILW LAWWLREYIP TNSTCCGRCH APMHMRGRYL VEVDQASFQC SAPFIMDAPR 370 380 390 400 410 420 DLNISEGRMA ELKCRTPPMS SVKWLLPNGT VLSHASRHPR ISVLNDGTLN FSHVLLSDTG 430 440 450 460 470 480 VYTCMVTNVA GNSNASAYLN VSTAELNTSN YSFFTTVTVE TTEISPEDTT RKYKPVPTTS 490 500 510 520 530 540 TGYQPAYTTS TTVLIQTTRV PKQVAVPATD TTDKMQTSLD EVMKTTKIII GCFVAVTLLA 550 560 570 580 590 600 AAMLIVFYKL RKRHQQRSTV TAARTVEIIQ VDEDIPAATS AAATAAPSGV SGEGAVVLPT 610 620 630 640 650 IHDHINYNTY KPAHGAHWTE NSLGNSLHPT VTTISEPYII QTHTKDKVQE TQI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression and functional characterization of LRRC4, a novel brain-specific member of the LRR superfamily." Zhang Q., Wang J., Fan S., Wang L., Cao L., Tang K., Peng C., Li Z., Li W., Gan K., Liu Z., Li X., Shen S., Li G. FEBS Lett. 579:3674-3682(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	Wang J. Thesis (2000), Zhongshan Medical University / Guangzhou, China Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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].
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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].
[7]	"Solution structure of the Ig-like domain of human leucine-rich repeat-containing protein 4." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 351-442.
[8]	"Structural basis for cell surface patterning through NetrinG-NGL interactions." Seiradake E., Coles C.H., Perestenko P.V., Harlos K., McIlhinney R.A., Aricescu A.R., Jones E.Y. EMBO J. 30:4479-4488(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-444 IN COMPLEX WITH NTNG2, DISULFIDE BONDS.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-579.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF196976 mRNA. Translation: AAG28019.2.
AJ297858 mRNA. Translation: CAC82651.1.
AY358307 mRNA. Translation: AAQ88674.1.
AK172751 mRNA. Translation: BAD18737.1.
AK314047 mRNA. Translation: BAG36756.1.
CH236947 Genomic DNA. Translation: EAL24316.1.
BC111561 mRNA. Translation: AAI11562.1.
BC111745 mRNA. Translation: AAI11746.1.

IPI

IPI00005516.

RefSeq

NP_071426.1. NM_022143.4.

UniGene

Hs.655003.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DL9	NMR	-	A	353-442	[»]
3ZYI	X-ray	2.60	A	1-444	[»]

ProteinModelPortal

Q9HBW1.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000249363.

Protein family/group databases

MEROPS

I43.001.

PTM databases

PhosphoSite

Q9HBW1.

Polymorphism databases

DMDM

51701696.

Proteomic databases

PaxDb

Q9HBW1.

PRIDE

Q9HBW1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000249363; ENSP00000249363; ENSG00000128594.

GeneID

64101.

KEGG

hsa:64101.

UCSC

uc003vmk.3. human.

Organism-specific databases

CTD

64101.

GeneCards

GC07M127667.

HGNC

HGNC:15586. LRRC4.

HPA

HPA051100.

MIM

610486. gene.

neXtProt

NX_Q9HBW1.

PharmGKB

PA30463.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000252924.

HOVERGEN

HBG052359.

InParanoid

Q9HBW1.

KO

K16351.

OMA

CGCEAVW.

OrthoDB

EOG4NGGM6.

PhylomeDB

Q9HBW1.

Gene expression databases

ArrayExpress

Q9HBW1.

Bgee

Q9HBW1.

CleanEx

HS_LRRC4.

Genevestigator

Q9HBW1.

GermOnline

ENSG00000128594. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR000483. Cys-rich_flank_reg_C.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003598. Ig_sub2.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRR-contain_N.
IPR026906. LRR_5.
IPR026882. Lrrc4.
[Graphical view]

PANTHER

PTHR24369:SF9. PTHR24369:SF9. 1 hit.

Pfam

PF07679. I-set. 1 hit.
PF13306. LRR_5. 1 hit.
[Graphical view]

SMART

SM00408. IGc2. 1 hit.
SM00369. LRR_TYP. 3 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
PS51450. LRR. 7 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HBW1.

GenomeRNAi

64101.

NextBio

65940.

SOURCE

Search...

Entry information

Entry name

LRRC4_HUMAN

Accession

Primary (citable) accession number: Q9HBW1
Secondary accession number(s): A4D0Y9 , Q14DU9, Q6ZMI8, Q96A85

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	October 1, 2001
Last modified:	May 1, 2013
This is version 111 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.