Q8IWT6 (LRC8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat-containing protein 8A

Gene names

Name:	LRRC8A
Synonyms:	KIAA1437, LRRC8
ORF Names:	UNQ221/PRO247

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

General annotation (Comments)

Function	Involved in B-cell development. Required for the pro-B cell to pre-B cell transition By similarity. Ref.1
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Expressed in brain, kidney, ovary, lung, liver, heart, and fetal brain and liver. Found at high levels in bone marrow; lower levels are detected in peripheral blood cells. Expressed on T-cells as well as on B-lineage cells. Ref.1 Ref.2
Involvement in disease	Agammaglobulinemia 5 (AGM5) [MIM:613506]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. Note: The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving LRRC8 has been found in a patient with congenital agammaglobulinemia. Translocation t(9;20)(q33.2;q12). The translocation truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of the seventh LRR domains. Ref.1
Sequence similarities	Contains 17 LRR (leucine-rich) repeats.
Sequence caution	The sequence AAQ88653.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA92675.1 differs from that shown. Reason: Erroneous initiation. The sequence BAC11161.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Membrane
Coding sequence diversity	Chromosomal rearrangement
Domain	Leucine-rich repeat Repeat Transmembrane Transmembrane helix
PTM	Acetylation Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	pre-B cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 810	810	Leucine-rich repeat-containing protein 8A		PRO_0000084499
Regions
	Transmembrane	26 – 45	20	Helical; Potential
	Transmembrane	124 – 146	23	Helical; Potential
	Transmembrane	263 – 285	23	Helical; Potential
	Transmembrane	320 – 342	23	Helical; Potential
	Repeat	373 – 401	29	LRR 1
	Repeat	402 – 424	23	LRR 2
	Repeat	425 – 447	23	LRR 3
	Repeat	448 – 470	23	LRR 4
	Repeat	471 – 494	24	LRR 5
	Repeat	495 – 518	24	LRR 6
	Repeat	519 – 545	27	LRR 7
	Repeat	546 – 568	23	LRR 8
	Repeat	569 – 592	24	LRR 9
	Repeat	593 – 615	23	LRR 10
	Repeat	616 – 640	25	LRR 11
	Repeat	641 – 663	23	LRR 12
	Repeat	664 – 686	23	LRR 13
	Repeat	687 – 706	20	LRR 14
	Repeat	707 – 732	26	LRR 15
	Repeat	733 – 755	23	LRR 16
	Repeat	756 – 777	22	LRR 17
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.5
	Modified residue	217	1	Phosphoserine Ref.9 Ref.10
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	191	1	N-linked (GlcNAc...) Potential
	Glycosylation	526	1	N-linked (GlcNAc...) Potential
	Glycosylation	554	1	N-linked (GlcNAc...) Potential
	Glycosylation	592	1	N-linked (GlcNAc...) Potential
	Glycosylation	660	1	N-linked (GlcNAc...) Potential
	Glycosylation	696	1	N-linked (GlcNAc...) Potential
	Glycosylation	755	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	323	1	S → P in BAC11161. Ref.7
	Sequence conflict	744	1	Q → R in BAC11161. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q8IWT6 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: E0C5E6EBEE8275E8	FASTA	810	94,199
	10 20 30 40 50 60 MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD KMICLPCKWV 70 80 90 100 110 120 TKDSCNDSFR GWAAPGPEPT YPNSTILPTP DTGPTGIKYD LDRHQYNYVD AVCYENRLHW 130 140 150 160 170 180 FAKYFPYLVL LHTLIFLACS NFWFKFPRTS SKLEHFVSIL LKCFDSPWTT RALSETVVEE 190 200 210 220 230 240 SDPKPAFSKM NGSMDKKSST VSEDVEATVP MLQRTKSRIE QGIVDRSETG VLDKKEGEQA 250 260 270 280 290 300 KALFEKVKKF RTHVEEGDIV YRLYMRQTII KVIKFILIIC YTVYYVHNIK FDVDCTVDIE 310 320 330 340 350 360 SLTGYRTYRC AHPLATLFKI LASFYISLVI FYGLICMYTL WWMLRRSLKK YSFESIREES 370 380 390 400 410 420 SYSDIPDVKN DFAFMLHLID QYDPLYSKRF AVFLSEVSEN KLRQLNLNNE WTLDKLRQRL 430 440 450 460 470 480 TKNAQDKLEL HLFMLSGIPD TVFDLVELEV LKLELIPDVT IPPSIAQLTG LKELWLYHTA 490 500 510 520 530 540 AKIEAPALAF LRENLRALHI KFTDIKEIPL WIYSLKTLEE LHLTGNLSAE NNRYIVIDGL 550 560 570 580 590 600 RELKRLKVLR LKSNLSKLPQ VVTDVGVHLQ KLSINNEGTK LIVLNSLKKM ANLTELELIR 610 620 630 640 650 660 CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH IAYIPIQIGN 670 680 690 700 710 720 LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTFL PADIGLLQNL QNLAITANRI 730 740 750 760 770 780 ETLPPELFQC RKLRALHLGN NVLQSLPSRV GELTNLTQIE LRGNRLECLP VELGECPLLK 790 800 810 RSGLVVEEDL FNTLPPEVKE RLWRADKEQA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans." Sawada A., Takihara Y., Kim J.Y., Matsuda-Hashii Y., Tokimasa S., Fujisaki H., Kubota K., Endo H., Onodera T., Ohta H., Ozono K., Hara J. J. Clin. Invest. 112:1707-1713(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION, INVOLVEMENT IN AGM5.
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [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]. Tissue: Pancreas.
[5]	Bienvenut W.V., Pchelintsev N., Adams P.D. Submitted (OCT-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-8; 483-492; 534-541 AND 735-749, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: Lung fibroblast.
[6]	"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] OF 239-810.
[7]	"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] OF 259-810.
[8]	"LRRC8 extracellular domain is composed of 17 leucine-rich repeats." Smits G., Kajava A.V. Mol. Immunol. 41:561-562(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS LEUCINE-RICH REPEATS.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

LRRC8Abase

LRRC8A mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY143166 mRNA. Translation: AAN18279.1. AB037858 mRNA. Translation: BAA92675.1. Different initiation. AL672142 Genomic DNA. Translation: CAI10839.1. BC051322 mRNA. Translation: AAH51322.1. AY358286 mRNA. Translation: AAQ88653.1. Different initiation. AK074723 mRNA. Translation: BAC11161.1. Different initiation.
IPI	IPI00002070.
RefSeq	NP_001120716.1. NM_001127244.1. NP_001120717.1. NM_001127245.1. NP_062540.2. NM_019594.3.
UniGene	Hs.643600.
3D structure databases
ProteinModelPortal	Q8IWT6.
ModBase	Search...
PTM databases
PhosphoSite	Q8IWT6.
Polymorphism databases
DMDM	37537912.
Proteomic databases
PaxDb	Q8IWT6.
PeptideAtlas	Q8IWT6.
PRIDE	Q8IWT6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259324; ENSP00000259324; ENSG00000136802. ENST00000372599; ENSP00000361680; ENSG00000136802. ENST00000372600; ENSP00000361682; ENSG00000136802.
GeneID	56262.
KEGG	hsa:56262.
UCSC	uc004bwl.4. human.
Organism-specific databases
CTD	56262.
GeneCards	GC09P131644.
HGNC	HGNC:19027. LRRC8A.
HPA	HPA016811.
MIM	608360. gene. 613506. phenotype.
neXtProt	NX_Q8IWT6.
Orphanet	33110. Autosomal agammaglobulinemia.
PharmGKB	PA134909315.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOGENOM	HOG000231806.
HOVERGEN	HBG052360.
InParanoid	Q8IWT6.
OMA	VDTQPAY.
OrthoDB	EOG45B1DW.
PhylomeDB	Q8IWT6.
Gene expression databases
ArrayExpress	Q8IWT6.
Bgee	Q8IWT6.
CleanEx	HS_LRRC8A.
Genevestigator	Q8IWT6.
GermOnline	ENSG00000136802. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR025875. Leu-rich_rpt_4. IPR003591. Leu-rich_rpt_typical-subtyp. IPR021040. LRR_protein-8_N. [Graphical view]
Pfam	PF12534. DUF3733. 2 hits. PF12799. LRR_4. 1 hit. [Graphical view]
SMART	SM00369. LRR_TYP. 2 hits. [Graphical view]
PROSITE	PS51450. LRR. 11 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	LRRC8A. human.
GenomeRNAi	56262.
NextBio	61921.
SOURCE	Search...

Entry information

Entry name

LRC8A_HUMAN

Accession

Primary (citable) accession number: Q8IWT6
Secondary accession number(s): Q6UXM2, Q8NCI0, Q9P2B1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 105 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.