YIF1A explained

Protein YIF1A is a Yip1 domain family proteins that in humans is encoded by the YIF1A gene.^{[1] [2] [3] [4]}

Gene

YIF1A (Yip1 interacting factor homolog A) is also known as YIF1, YIF1P, FinGER7, and 54TM.^[5] It has 4,591 base pairs with 8 exons, and it is located on the minus strand of chromosome 11, at 11q13.2, in humans.^[6]

Promoters

There are four predicted promoter for YIIF1A.^[7] The predicted promoter region with highest confidence is GXP_50494 and has 1252 base pairs long; it extends past the first exon of YIF1A. This promoter is located on the minus strand of chromosome 11.

Transcription factors

The promoter of YIF1A transcript variant 1 contains numerous transcription factor binding sites.^[8] Transcription factors predicted to bind to the promoter region include the following.

• Acute myeloid leukemia 1 protein, RUNX1 (runt-related transcription factor 1)
• Zinc finger protein 263, ZKSCAN12 (zinc finger protein with KRAB and SCAN domains 12)
• E2F transcription factor 1
• EGR1, early growth response 1
• GATA-binding factor 1
• Transcription factor CP2-like 1 (LBP-9)
• X-box binding protein RFX1
• Estrogen response elements (ER alpha), IR3 sites
• Lactotransferrin and deltalactoferrin, growth-inhibiting protein 12
• TGFB-inducible early growth response protein 1 (KLF10)

Expression

The expression of YIF1A is highest in the duodenum and liver. It is also expressed at moderate levels in tissues including the colon, ovary, pancreases, spleen, and esophagus, and expressed at lower levels in a variety of other tissues.^{[9] [10] [11]} NCBI GeoProfile data provide the tissue expression graph for YIF1A in humans; it also indicates that YIF1A is expressed at moderately to moderately low across all other tissues.^[12]

mRNA

YIF1A has isoforms 1 and 2, with exons 8 and 7 respectively.^[6] The two transcripts undergo alternate splicing and are translated into proteins with 293 and 241 amino acids, respectively.^{[13] [14]}

RNA-binding proteins

The 5' untranslated region has predicted sites for binding by RBXM, EIF4B, and FUS. The 3' untranslated region has predicted sites for binding by ELAVL1, which is AU rich elements and regulate mRNA stability.^[15]

Protein

The longest protein isoform of YIF1A is 293 amino acids in length. It has an observed molecular weight of approximately 32.0 kDa with a predicted isoelectric point of approximately 8.98.^{[14] [16] [17]}

Composition

YIF1 is a very normal protein in terms of the amino acid quantities it contains. The composition of each amino acid residue is similar to its average relative composition among human proteins. There are no charge clusters, runs, or patterns. There is a repetitive structure for protein YIF1A at [201- 204 and 288- 291 ] TFHL.^[16]

Domain and motifs

YIF1A has a conserved domain, pfam03878 (AA 57 →287).^[6] Within the domain, there are 5 transmembrane domains, 3 non-cytosolic domains, and 3 cytosolic domains. It has been hypothesized that there is a possible role in transport between the endoplasmic reticulum and Golgi.^[5]

Structure

The structure of YIF1A consist of approximately 59% alpha-helices, with TM helix and disordered regions making up the rest of the structure; no beta- strand was predicted.^[18]

Localization

YIF1A's predicted location is in the endoplasmic reticulum, with intracellular N-terminus and an extracellular C-terminus.^{[19] [20]}

Post-translational modifications

YIF1A undergoes methionine cleavage and N-terminal acetylation, which is one of the most common post translation modifications of eukaryotic proteins.^[21] It also phosphorylated by unspecified kinases at several sites.^[22] Three glycation site is predicted in lysine residue(lys 104,161, and 211).^[23] YIF1A undergoes O-ß-GlcNAc modification at 5 sites, 1 of them being Yin-Yang sites.^[24]

Interacting protein

Based on fluorescence microscopy, validated two hybrid, and anti tag coimmunoprecipitation, the protein that is most likely to interact with YIF1A are GPR37, SEC23IP, REEP2, and YIPF5. Studies suggest that interaction between VAPB and YIF1A control membrane delivery into dendrites.^[25] It also participates in ER unfolded protein response (UPR) by inducing ERN1/IRE1.^[26] Additionally, the YIF1A protein interacts with the M protein of SARS-Cov-2.^[27]

Homology

YIF1A has a single Paralog called YIF1B, which is located on human chromosome 19.^[5] YIF1A has 238 identified orthologs.^[28] The ortholog contains vertebrates such as mammals, amphibians, and reptiles. It also has invertebrates species such as Insecta, Anthozoa, and Ascidiacea. No ortholog was found in protists, bacteria, or archaea.

The following table provides a sample of the ortholog of YIF1A.

!Genus and species!Accession Number!Date of Divergence (MYA)^[29] !Sequence Length(AA)!Sequence Identity^[30]

Homo sapiens (Human)	NP_065203	0	293	100
Aotus nancymaae (Ma's night monkey)	XP_012318344	43	317	94
Mus musculus (Mouse)	NP_080829	90	293	93
Sus scrofa (Wild Boar)	XP_013849519	96	311	92
Delphinapterus leucas (White whale)	XP_022447094	96	306	91
Phascolarctos cinereus (Koala)	XP_020823757	159	293	88
Ornithorhynchus anatinus(Platypus)	XP_028915982	177	293	88
Chelonia mydas(Green turtle)	XP_007056281	312	240	78
Chrysemys picta bellii(Painted turtle)	XP_005305497	312	293	73
Microcaecilia unicolor(Amph.)	XP_029470520	352	306	72
Rhinatrema bivittatum(Two-lined caecilian)	XP_029470520	352	307	71
Latimeria chalumnae (Gombessa)	XP_014345204	413	296	71
Salmo trutta (Brown trou)	XP_029585843	435	309	70
Echeneis naucrates (live sharksucker)	XP_029368074	435	308	66
Danio rerio (Zebrafish)	NP_956225	435	307	65
Maylandia zebra (zebra mbuna)	XP_004545672	435	308	63
Saccharomyces cerevisiae S288C (Baker's yeast)	NP_014136	1017	314	33
Physcomitrium patens (moss)	XP_024362517	1275	282	30

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Gisler SM, Stagljar I, Traebert M, Bacic D, Biber J, Murer H . Interaction of the type IIa Na/Pi cotransporter with PDZ proteins . The Journal of Biological Chemistry . 276 . 12 . 9206–13 . March 2001 . 11099500 . 10.1074/jbc.M008745200 . free .
• Calero M, Winand NJ, Collins RN . Identification of the novel proteins Yip4p and Yip5p as Rab GTPase interacting factors . FEBS Letters . 515 . 1–3 . 89–98 . March 2002 . 11943201 . 10.1016/S0014-5793(02)02442-0 . 34319925 . free .
• Breuza L, Halbeisen R, Jenö P, Otte S, Barlowe C, Hong W, Hauri HP . Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46 . The Journal of Biological Chemistry . 279 . 45 . 47242–53 . November 2004 . 15308636 . 10.1074/jbc.M406644200 . free .
• Jin C, Zhang Y, Zhu H, Ahmed K, Fu C, Yao X . Human Yip1A specifies the localization of Yif1 to the Golgi apparatus . Biochemical and Biophysical Research Communications . 334 . 1 . 16–22 . August 2005 . 15990086 . 10.1016/j.bbrc.2005.06.051 .

Notes and References

1. Vitale G, Alexandrov K, Ullrich O, Horiuchi H, Giner A, Dobson C, Baykova O, Gournier H, Stenmark H, Zerial M . 6 . The GDP/GTP cycle of Rab5 in the regulation of endocytotic membrane traffic . Cold Spring Harbor Symposia on Quantitative Biology . 60 . 211–20 . Jan 1997 . 8824393 . 10.1101/SQB.1995.060.01.024 .
2. Matern H, Yang X, Andrulis E, Sternglanz R, Trepte HH, Gallwitz D . A novel Golgi membrane protein is part of a GTPase-binding protein complex involved in vesicle targeting . The EMBO Journal . 19 . 17 . 4485–92 . September 2000 . 10970842 . 302084 . 10.1093/emboj/19.17.4485 .
3. Yoshida Y, Suzuki K, Yamamoto A, Sakai N, Bando M, Tanimoto K, Yamaguchi Y, Sakaguchi T, Akhter H, Fujii G, Yoshimura S, Ogata S, Sohda M, Misumi Y, Nakamura N . 6 . YIPF5 and YIF1A recycle between the ER and the Golgi apparatus and are involved in the maintenance of the Golgi structure . Experimental Cell Research . 314 . 19 . 3427–43 . November 2008 . 18718466 . 10.1016/j.yexcr.2008.07.023 .
4. Web site: Entrez Gene: YIF1A Yip1 interacting factor homolog A (S. cerevisiae).
5. Web site: YIF1A related genes - GeneCards Search Results. 2020-06-21. www.genecards.org.
6. Web site: YIF1A - Gene - NCBI. 2020-06-21. www.ncbi.nlm.nih.gov.
7. Web site: Genomatix: Genome Annotation and Browser: Query Input. 2020-07-30. www.genomatix.de.
8. Web site: Genomatix: MatInspector Input. 2020-08-03. www.genomatix.de.
9. Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, Asplund A, Sjöstedt E, Lundberg E, Szigyarto CA, Skogs M, Takanen JO, Berling H, Tegel H, Mulder J, Nilsson P, Schwenk JM, Lindskog C, Danielsson F, Mardinoglu A, Sivertsson A, von Feilitzen K, Forsberg M, Zwahlen M, Olsson I, Navani S, Huss M, Nielsen J, Ponten F, Uhlén M . 6 . Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics . Molecular & Cellular Proteomics . 13 . 2 . 397–406 . February 2014 . 24309898 . 3916642 . 10.1074/mcp.M113.035600 . free .
10. Duff MO, Olson S, Wei X, Garrett SC, Osman A, Bolisetty M, Plocik A, Celniker SE, Graveley BR . 6 . Genome-wide identification of zero nucleotide recursive splicing in Drosophila . Nature . 521 . 7552 . 376–9 . May 2015 . 25970244 . 4529404 . 10.1038/nature14475 . 2015Natur.521..376D .
11. Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, Parast MM, Murry CE, Laurent LC, Salzman J . 6 . Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development . Genome Biology . 16 . 126 . June 2015 . 1 . 26076956 . 4506483 . 10.1186/s13059-015-0690-5 . free .
12. Web site: GDS596 / 202418_at. 2020-08-02. www.ncbi.nlm.nih.gov.
13. Web site: protein YIF1A isoform 2 [Homo sapiens] - Protein - NCBI]. 2020-07-28. www.ncbi.nlm.nih.gov.
14. Web site: protein YIF1A isoform 1 [Homo sapiens] - Protein - NCBI]. 2020-07-28. www.ncbi.nlm.nih.gov.
15. Web site: RBPDB: The database of RNA-binding specificities. 2020-08-01. rbpdb.ccbr.utoronto.ca.
16. Web site: SAPS < Sequence Statistics < EMBL-EBI. 2020-07-28. www.ebi.ac.uk.
17. Web site: ExPASy - Compute pI/Mw tool. 2020-07-28. web.expasy.org.
18. Web site: NPS@ : GOR4 secondary structure prediction. 2020-07-28. npsa-prabi.ibcp.fr.
19. Web site: PredictProtein - Protein Sequence Analysis, Prediction of Structural and Functional Features. 2020-07-28. www.predictprotein.org.
20. Web site: Phobius. 2020-07-28. phobius.sbc.su.se.
21. Web site: TERMINUS - Welcome to terminus. 2020-07-28. terminus.unige.ch.
22. Web site: NetPhosK 1.0 Server. 2020-07-28. www.cbs.dtu.dk. 2021-07-09. https://web.archive.org/web/20210709183544/http://www.cbs.dtu.dk/services/NetPhosK/. dead.
23. Web site: NetGlycate 1.0 Server - prediction results. 2020-08-01. www.cbs.dtu.dk.
24. Web site: YinOYang 1.2 Server. 2020-07-28. www.cbs.dtu.dk.
25. Casper Hoogenraad . Kuijpers M, Yu KL, Teuling E, Akhmanova A, Jaarsma D, Hoogenraad CC . The ALS8 protein VAPB interacts with the ER-Golgi recycling protein YIF1A and regulates membrane delivery into dendrites . The EMBO Journal . 32 . 14 . 2056–72 . July 2013 . 23736259 . 3715857 . 10.1038/emboj.2013.131 .
26. Web site: YIF1A protein (human) - STRING interaction network. 2020-07-29. string-db.org.
27. Mahen. Robert. 2020-04-09. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. 2020-08-05. 10.1242/prelights.18355. 243418486 .
28. Web site: Nucleotide BLAST: Search nucleotide databases using a nucleotide query. 2020-08-03. blast.ncbi.nlm.nih.gov.
29. Web site: TimeTree :: The Timescale of Life. 2020-07-02. www.timetree.org.
30. Web site: Human BLAT Search. 2020-07-02. genome.ucsc.edu.