LRRIQ3
Identifiers
AliasesLRRIQ3, LRRC44, leucine-rich repeats and IQ motif containing 3, leucine rich repeats and IQ motif containing 3
External IDsOMIM: 617957 MGI: 1921685 HomoloGene: 23668 GeneCards: LRRIQ3
Orthologs
SpeciesHumanMouse
Entrez

127255

74435

Ensembl

ENSG00000162620

ENSMUSG00000028182

UniProt

A6PVS8
H0Y5F9

Q14DL3

RefSeq (mRNA)

NM_001105659
NM_145258
NM_001322315

NM_028938

RefSeq (protein)

NP_001099129
NP_001309244

NP_083214

Location (UCSC)Chr 1: 74.03 – 74.2 MbChr 3: 154.8 – 154.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

LRRIQ3 (Leucine-rich repeats and IQ motif containing 3), which is also known as LRRC44, is a protein that in humans is encoded by the LRRIQ3 gene.[5] It is predominantly expressed in the testes, and is linked to a number of diseases.[6]

Gene

Locus

LRRIQ3 is found on the minus strand of the end of the short arm of human chromosome 1 at 1p31.1.[7]

Overall Structure

There are a total of 7 exons in the putative sequence of LRRIQ3.[7]

mRNA

Expression

LRRIQ3 is expressed as 2 primary isoforms, which produce proteins of length 624 amino acids and 464 amino acids respectively.[7] It is expressed at low levels in human and brown rat tissues,[8][9] with highest expression levels in testes tissue. There are relatively high expression levels in T cells, the epididymis, the kidney, and a number of glands.[10]

Protein

General Characteristics and Compositional Features

Human protein LRRIQ3 Isoform 1 consists of 624 amino acids, and has a molecular weight of 73.7 kDa. The isoelectric point of LRRIQ3 is 9.73, which suggests that LRRIQ3 is basic at normal physiological pH (~7.4).[11] Additionally, there is strong evidence that human LRRIQ3 localizes to the plasma membrane from antibody staining.[12] LRRIQ3 is rich in lysine residues, with a total of 82 lysines. It is also slightly low on glycines.[13]

Domains and Motifs

In total, there are 4 conserved domains within LRRIQ3: 3 leucine-rich repeats and 1 IQ calmodulin-binding motif.[13] Leucine-rich repeats are typically involved in protein-protein interactions, and form a characteristic α/β horseshoe fold.[14][15] An IQ motif provides a binding site for calmodulin (CaM) or CaM-like proteins.[16]

Secondary and Tertiary Structure

LRRIQ3 is predicted to be mostly alpha-helical in structure, including a long alpha-helical C-terminal domain. It is also predicted to function as a monomer.[17][18][19][20]

The best model generated by I-TASSER[21] for LRRIQ3. The 3 leucine-rich repeats are shown in red, salmon, and magenta respectively. The IQ calmodulin-binding domain is shown in green.

Post-translational Modifications

LRRIQ3 is predicted to undergo many post-translational modifications. These include O-GlcNAcylation, SUMOylation, ubiquitination, and phosphorylation.[22][23] LRRIQ3 is predicted to have 4 well conserved SUMOylation sites and 1 well conserved ubiquitination site.[22] A representation of these post-translational modifications is shown in the figure below.

A representation of the domains, motif, and post-translational modification sites of LRRIQ3, generated using DOG 2.0.[24]

Protein Interactions

There is evidence that LRRIQ3 interacts with a number of proteins from two-hybrid assays and affinity chromatography. The proteins LRRIQ3 interact with include LYN, NCK2, GNB4, and ABL1.[25][26] These proteins are associated with cell signalling, cytoskeletal reorganization, and cell differentiation, as well as others.[27][28][29][30]

Homology and evolution

Paralogs and Orthologs

No paralogs exists for LRRIQ3 in humans.[6] However, there are a number of orthologs, as reported by BLAST, some of which are listed below.[31] The number of years since divergence from the human protein, listed in "million of years ago (MYA)" below, were calculated using TimeTree.[32]

Orthologs to Human LRRIQ3 Protein (NP_001099129.1)
Genus and Species Common Name Divergence from Human Lineage (MYA) Accession Number Sequence length (aa) Sequence Identity to Human Protein Sequence Similarity to Human Protein
Gorilla gorilla gorilla Gorilla 9.06 XP_004026030.1 624 97% 98%
Macaca mulatta Rhesus monkey 29.44 XP_001097148.2 623 93% 95%
Ursus maritimus Polar bear 96 XP_008689049.1 625 76% 87%
Felis catus Domestic cat 96 XP_003990274.1 625 74% 86%
Camelus ferus Bactrian camel 96 XP_006178380.1 618 73% 84%
Oryctolagus cuniculus European rabbit 90 XP_002715603.1 622 71% 83%
Bison bison bison American bison 96 XP_010847739.1 625 70% 82%
Trichechus manatus latirostris Manatee 105 XP_004369192.1 623 70% 82%
Loxodonta africana African elephant 105 XP_003411181.1 625 68% 80%
Condylura cristata Star-nosed mole 96 XP_004679575.1 627 67% 80%
Eptesicus fuscus Big brown bat 96 XP_008137759.1 621 66% 80%
Myotis davidii Vesper bat 96 XP_006775977.1 618 65% 79%
Rattus norvegicus Norway rat 90 NP_001019478.1 633 62% 77%
Mus Musculus House mouse 90 NP_083214.2 633 63% 76%
Sorex araneus Common shrew 96 XP_004603704.1 612 55% 73%
Chrysemys picta bellii Painted turtle 312 XP_005285573.1 624 40% 56%
Pogona vitticeps Bearded dragon 312 XP_020650341.1 651 35% 54%
Apteryx australis mantelli Brown kiwi 312 XP_013800580.1 664 35% 54%
Struthio camelus australis Southern Ostrich 312 XP_009685099.1 628 34% 51%

Clinical significance

LRRIQ3 is linked to a number of cancers. RNA-seq experiments have shown that LRRIQ3 is severely down-regulated (Log2-fold changes between -3.4 and -4.2) in a number of disease states, including pancreatic cancer, colorectal cancer, and breast cancer.[33][34][35]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000162620 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028182 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "LRRIQ3 Gene - GeneCards".
  6. 1 2 "AceView entry on LRRIQ3".
  7. 1 2 3 "LRRIQ3 leucine rich repeats and IQ motif containing 3 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-04-30.
  8. ↑ "Lrriq3 protein abundance in PaxDb". pax-db.org. Retrieved 2018-04-30.
  9. ↑ "LRRIQ3 protein abundance in PaxDb". pax-db.org. Retrieved 2018-04-30.
  10. ↑ "GDS3834 / 3169". www.ncbi.nlm.nih.gov. Retrieved 2018-05-06.
  11. ↑ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2018-04-30.
  12. ↑ "Cell atlas - LRRIQ3 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2018-04-30.
  13. 1 2 EMBL-EBI. "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-04-30.
  14. ↑ Kobe B, Deisenhofer J (October 1994). "The leucine-rich repeat: a versatile binding motif". Trends Biochem. Sci. 19 (10): 415–21. doi:10.1016/0968-0004(94)90090-6. ISSN 0968-0004. PMID 7817399.
  15. ↑ Enkhbayar P, Kamiya M, Osaki M, Matsumoto T, Matsushima N (February 2004). "Structural principles of leucine-rich repeat (LRR) proteins". Proteins. 54 (3): 394–403. doi:10.1002/prot.10605. ISSN 1097-0134. PMID 14747988. S2CID 19951452.
  16. ↑ Rhoads AR, Friedberg F (April 1997). "Sequence motifs for calmodulin recognition". FASEB J. 11 (5): 331–40. doi:10.1096/fasebj.11.5.9141499. ISSN 0892-6638. PMID 9141499. S2CID 1877645.
  17. ↑ Rost B (2001). "Review: protein secondary structure prediction continues to rise". J. Struct. Biol. 134 (2–3): 204–18. CiteSeerX 10.1.1.8.8169. doi:10.1006/jsbi.2001.4336. ISSN 1047-8477. PMID 11551180.
  18. ↑ Ouali M, King RD (June 2000). "Cascaded multiple classifiers for secondary structure prediction". Protein Sci. 9 (6): 1162–76. doi:10.1110/ps.9.6.1162. ISSN 0961-8368. PMC 2144653. PMID 10892809.
  19. ↑ Cuff JA, Barton GJ (August 2000). "Application of multiple sequence alignment profiles to improve protein secondary structure prediction". Proteins. 40 (3): 502–11. doi:10.1002/1097-0134(20000815)40:3<502::AID-PROT170>3.0.CO;2-Q. ISSN 0887-3585. PMID 10861942. S2CID 855816.
  20. ↑ Jones DT (September 1999). "Protein secondary structure prediction based on position-specific scoring matrices". J. Mol. Biol. 292 (2): 195–202. doi:10.1006/jmbi.1999.3091. ISSN 0022-2836. PMID 10493868. S2CID 15506630.
  21. ↑ Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (January 2015). "The I-TASSER Suite: protein structure and function prediction". Nat. Methods. 12 (1): 7–8. doi:10.1038/nmeth.3213. ISSN 1548-7091. PMC 4428668. PMID 25549265.
  22. 1 2 Pagni M, Ioannidis V, Cerutti L, Zahn-Zabal M, Jongeneel CV, Falquet L (July 2004). "MyHits: a new interactive resource for protein annotation and domain identification". Nucleic Acids Res. 32 (Web Server issue): W332–5. doi:10.1093/nar/gkh479. ISSN 0305-1048. PMC 441617. PMID 15215405.
  23. ↑ de Castro E, Sigrist CJ, Gattiker A, Bulliard V, Langendijk-Genevaux PS, Gasteiger E, Bairoch A, Hulo N (July 2006). "ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins". Nucleic Acids Res. 34 (Web Server issue): W362–5. doi:10.1093/nar/gkl124. ISSN 1362-4962. PMC 1538847. PMID 16845026.
  24. ↑ Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X (February 2009). "DOG 1.0: illustrator of protein domain structures". Cell Res. 19 (2): 271–3. doi:10.1038/cr.2009.6. ISSN 1001-0602. PMID 19153597.
  25. ↑ "Results - mentha: the interactome browser". mentha.uniroma2.it. Retrieved 2018-04-30.
  26. ↑ "LRRIQ3 - Leucine-rich repeat and IQ domain-containing protein 3 - Homo sapiens (Human) - LRRIQ3 gene & protein". www.uniprot.org. Retrieved 2018-04-30.
  27. ↑ Harder KW, Parsons LM, Armes J, Evans N, Kountouri N, Clark R, Quilici C, Grail D, Hodgson GS, Dunn AR, Hibbs ML (October 2001). "Gain- and loss-of-function Lyn mutant mice define a critical inhibitory role for Lyn in the myeloid lineage". Immunity. 15 (4): 603–15. doi:10.1016/s1074-7613(01)00208-4. ISSN 1074-7613. PMID 11672542.
  28. ↑ Downes GB, Gautam N (December 1999). "The G protein subunit gene families". Genomics. 62 (3): 544–52. doi:10.1006/geno.1999.5992. ISSN 0888-7543. PMID 10644457.
  29. ↑ Tu Y, Li F, Wu C (December 1998). "Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways". Mol. Biol. Cell. 9 (12): 3367–82. doi:10.1091/mbc.9.12.3367. ISSN 1059-1524. PMC 25640. PMID 9843575.
  30. ↑ Era T (July 2002). "Bcr-Abl is a "molecular switch" for the decision for growth and differentiation in hematopoietic stem cells". Int. J. Hematol. 76 (1): 35–43. doi:10.1007/BF02982716. PMID 12138893. S2CID 10269867.
  31. ↑ Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (October 1990). "Basic local alignment search tool". J. Mol. Biol. 215 (3): 403–10. doi:10.1016/S0022-2836(05)80360-2. ISSN 0022-2836. PMID 2231712. S2CID 14441902.
  32. ↑ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2018-05-06.
  33. ↑ "Tissue expression of LRRIQ3 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2018-05-06.
  34. ↑ github.com/gxa/atlas/graphs/contributors, EMBL-EBI Expression Atlas development team. "Search results < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-04-30. {{cite web}}: |last= has generic name (help)
  35. ↑ github.com/gxa/atlas/graphs/contributors, EMBL-EBI Expression Atlas development team. "Experiment < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-05-06. {{cite web}}: |last= has generic name (help)
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