CLIP4

Short description: Protein

CLIP4 protein predicted tertiary structure. Taken from PhyreRisk.[1]

Generic protein structure example

CAP-Gly Domain Containing Linker Protein Family Member 4 is a protein that in humans is encoded by the CLIP4 gene.[2] In terms of conserved domains, the CLIP4 gene contains primarily ankyrin repeats and the eponymous CAP-Gly domains.[2] The structure of the CLIP4 protein is largely made up of coil, with alpha helices dominating the rest of the protein.[3] CLIP4 mRNA expression occurs largely in the adrenal cortex and atrioventricular node.[4] The literature encompassing CLIP4's conserved domains and paralogs points toward microtubule regulation as a possible function of CLIP4.

## Contents

* 1 Gene
* 2 Transcript
* 2.1 Transcript variants
* 3 Protein
* 3.1 Protein isoforms
* 4 Expression
* 5 Regulation
* 5.1 Gene
* 5.1.1 Common transcription factor binding sites
* 5.2 Transcriptional
* 5.3 Protein
* 6 Function
* 7 Interacting Proteins
* 8 Clinical significance
* 8.1 Importance in various cancers
* 8.2 Importance in other diseases
* 9 Homology
* 9.1 CLIP4 orthologs
* 10 References

## Gene

The human CLIP4 gene, also known as Restin-Like Protein 2 (RSNL2),[5] is located on the plus strand of the short (p) arm of chromosome 2 at region 2, band 3[5] from base pair 29,096,676 to base pair 29,189,643. CLIP4 is 92,968 base pairs in length and consists of 23 exons.[5]

## Transcript

### Transcript variants

Transcript  | mRNA size (nucleotides)

|

CLIP4 transcript variant 1[6] | 4299
CLIP4 transcript variant 2[7] | 4295
CLIP4 transcript variant 3[8] | 2353

## Protein

The human CLIP4 protein is 705 amino acids in length and is composed of two main types of conserved domains: Two CAP-Gly domains and numerous ankyrin repeats.[5] The secondary structure of CLIP4 consists largely of random coil, with alpha helices as the second-most abundant structure and beta sheets as the third-most abundant structure.[3]

The isoelectronic point of the unprocessed CLIP4 protein is slightly basic (8.62 pI), meaning there is a slight excess of basic amino acids compared to acidic amino acids.[9] The molecular weight is about 65 kD.[9] The most abundant amino acid in CLIP4 is Serine, which makes up 10.7% of the protein.[10] Aligned matching blocks of separated, tandem, and periodic repeats are found between positions 340-345 and 542-547, as well as 447-547 and 564-568.[10] The unusual 9-figure periodic element of a singular Lysine followed by eight other amino acids occurs five times within the protein when compared to the swp23s.q dataset.[10] Another unusual phenomenon is a 7-figure periodic element of a negatively charged amino acid followed by six other hydrophobic amino acids, which occurs six times within the protein when compared to the swp23s.q dataset.[10] There are two instances of Serine spacing and two instances of Phenylalanine spacing that comprise unusually large distances when compared to the swp23s.q dataset.[10]

### Protein isoforms

Isoform  | Protein size (amino acids)

|

CLIP4 isoform 1[11] | 705
CLIP4 isoform 2[12] | 599

## Expression

CLIP4 RNA expression is consistently measured to a high degree in the thyroid.[2] Additionally, high degrees of transcription occur in the adrenal cortex and atrioventricular node.[4] The Human Protein Atlas points toward high RNA expression values in the muscle tissues, as well as some in the skin, endocrine tissues, and proximal digestive tract.[13] Greatest protein expression values appeared in the muscle tissues as well, in addition to some in the lung, gastrointestinal tract, liver & gallbladder, and bone marrow & lymphoid tissues.[13]

CLIP4 protein expression seems to be highly expressed during Ada3 deficiency.[14] There also exists a higher trend towards higher CLIP4 expression in the absence of U28.[14]

## Regulation

### Gene

#### Common transcription factor binding sites

These transcription factors were chosen and organized based on proximity to the promoter and matrix similarity.[15]

Transcription Factor | Detailed Matrix Info | Anchor Base | Matrix Similarity | Sequence

|
|
|
|

NOLF  | Early B-cell factor 1

| 17
| 0.98  | taagagTCCCcagggcagaaaca

PAX2  | Zebrafish PAX2 paired domain protein

| 18  | 0.8  | aagagtccccagggcagAAACaa

AP2F  | Transcription factor AP-2, alpha

| 16  | 0.98  | ctgcCCTGgggactc

AP2F  | Transcription factor AP-2, beta

| 16  | 0.899  | gagTCCCcagggcag

SORY  | SRY (sex-determining region Y) box 9, dimeric binding sites

| 35  | 0.768  | aAACAaaatccagtgagggagag

HNF6  | CUT-homeodomain transcription factor Onecut-2

| 32  | 0.827  | aaacaaAATCcagtgag

PAX5  | B-cell-specific activator protein

| 40  | 0.815  | acaaaaTCCAgtgagggagagatgcaggg

ZF16  | PR/SET domain 15

| 36  | 0.852  | aaatccagtgaGGGA

SORY  | HMGI(Y) high-mobility-group protein I (Y), architectural transcription factor organizing the framework of a nuclear protein-DNA transcriptional complex

| 78  | 0.945  | tggaAATTttctaccttaggagc

NFAT  | Nuclear factor of activated T-cells 5

| 83  | 0.955  | ttttGGAAattttctacct

NFAT  | Nuclear factor of activated T-cells 5

| 83  | 0.871  | aggtAGAAaatttccaaaa

CEBP  | CCAAT/enhancer binding protein (C/EBP), epsilon

| 89  | 0.975  | agccttttGGAAatt

CAAT  | Cellular and viral CCAAT box

| 110  | 0.91  | gcagCCATttaatct

CAAT  | Avian C-type LTR CCAAT box

| 165  | 0.875  | cccaCCAAgcagtgg

CEBP  | CCAAT/enhancer binding protein (C/EBP), gamma

| 650  | 0.866  | ctaaTTGCtcaacgt

CEBP  | CCAAT/enhancer binding protein alpha

| 651  | 0.971  | cacgttgaGCAAtta

VTBP  | Mammalian C-type LTR TATA box

| 680  | 0.903  | tgctgTAAAaggcctaa

TF2B  | Transcription factor II B (TFIIB) recognition element

| 983  | 1  | ccgCGCC

TF2B  | Transcription factor II B (TFIIB) recognition element

| 1157  | 1  | ccgCGCC

TF2B  | Transcription factor II B (TFIIB) recognition element

| 1228  | 1  | ccgCGCC

### Transcriptional

The human CLIP4 mRNA sequence has 12 stem-loop structures in its 5' UTR and 13 stem-loop structures in its 3' UTR. Of those secondary structures, there are 12 conserved stem-loop secondary structures in the 5'UTR as well as 1 conserved stem-loop secondary structure in the 3' UTR.[16]

### Protein

The human CLIP4 protein is localized within the cellular nuclear membrane.[17] CLIP4 does not have a signal peptide due to its intracellular localization.[18] It also does not have N-linked glycosylation sites for that same reason.[19] CLIP4 is not cleaved.[20] However, numerous O-linked glycosylation sites are present.[21] A high density of phosphorylation sites are present in the 400-599 amino acid positions on the CLIP4 protein, although many are also present throughout the rest of the protein.[22]

## Function

CAP-Gly domains are often associated with microtubule regulation.[23] In addition, ankyrin repeats are known to mediate protein-protein interactions.[24] Furthermore, CLIP1, a paralog of CLIP4 in humans, is known to bind to microtubules and regulate the microtubule cytoskeleton.[25] The CLIP4 protein is also predicted to interact with various microtubule-associated proteins.[26] As a result, it is likely that the CLIP4 protein, although uncharacterized, is associated with microtubule regulation.

## Interacting Proteins

The CLIP4 protein is predicted to interact with many proteins associated with microtubules; namely, MAPRE1, MAPRE2, and MAPRE3. It is also predicted to interact with CKAP5 and DCTN1, a cytoskeleton-associated protein and dynactin-associated protein respectively.[26]

## Clinical significance

### Importance in various cancers

CLIP4 activity is correlated with the spread of renal cell carcinomas (RCCs) within the host and could therefore be a potential biomarker for RCC metastasis in cancer patients.[27] Additionally, measurement of promotor methylation levels of CLIP4 using a Global Methylation DNA Index reveals that higher methylation of CLIP4 is associated with an increase in severity of gastritis to possibly gastric cancer.[28] This indicates that CLIP4 could be used for early detection of gastric cancer.[29] A similar finding was also documented for prostate cancer, in which CLIP4 was found to be hypermethylated in patients with prostate cancer.[30]

### Importance in other diseases

The presence of CLIP4 was found to be highly increased in samples with predicted severe fibrosis as a result of Chronic Hepatitis C virus (HCV).[31] Additionally, the presence of CLIP4 as a novel self-antigen in Systemic Lupus Arythematosus points to it having a potential role in the disease mechanism.[32]

## Homology

### CLIP4 orthologs

These orthologs were chosen and organized based on estimated date of divergence from the human protein as well as the global sequence identity.[33]

Binomial Nomenclature  | Common Name  | Taxonomic Group  | Estimated DoD from Human (MYA)  | Accession Number  | Sequence Length (AA)  | Global Sequence Identity to Human Protein (%)  | Global Sequence Similarity to Human Protein (%)

|
|
|
|
|
|
|

Homo sapiens (Hsa)  | Human  | Primate  | 0  | AAP97312  | 601  | 100  | 100
Aotus nancymaae (Ana)  | Ma's night monkey  | Primate  | 43.2  | XP_012330895  | 704  | 83.5  | 83.7
Sorex araneus (Sar)  | Common shrew  | Eulipotyphla  | 96  | XP_004620056  | 707  | 74  | 78.5
Antrostomus carolinensis (Aca)  | Chuck-will's-widow  | Aves  | 312  | XP_028942997  | 702  | 66.5  | 75.4
Gekko japonicus (Gja)  | Schlegel's Japanese gecko  | Reptilia  | 312  | XP_015270366  | 702  | 63.8  | 73.1
Rhinatrema bivittatum (Rbi)  | Two-lined caecilian  | Amphibians  | 351.8  | XP_029448862  | 707  | 59.5  | 70.5
Callorhinchus milii (Cmi)  | Elephant shark  | Chondrichthyes  | 473  | XP_007895016  | 715  | 52.5  | 65.6
Branchiostoma floridae (Bfl)  | Florida lancelet  | Leptocardii  | 684  | XP_002606824  | 481  | 40.4  | 52.8
Saccoglossus kowalevskii (Sko)  | Acorn worm  | Enteropneusta  | 684  | XP_006822686  | 648  | 35.7  | 47.5
Ixodes scapularis (Isc)  | Black-legged tick  | Arachnid  | 797  | XP_029831090  | 527  | 38.9  | 53
Limulus polyphemus (Lpo)  | Atlantic horseshoe crab  | Arachnid  | 797  | XP_013786376  | 462  | 38  | 51.6
Lottia gigantea (Lgi)  | Owl limpet  | Gastropods  | 797  | XP_009046843  | 669  | 36.3  | 49.3
Mizuhopecten yessoensis (Mye)  | Yesso scallop  | Bivalvia  | 797  | XP_021359747  | 633  | 35.4  | 47.2
Parasteatoda tepidariorum (Pte)  | Common house spider  | Arachnid  | 797  | XP_015914966  | 616  | 34.7  | 47.6
Aplysia californica (Aca)  | California sea hare  | Gastropods  | 797  | XP_012945346  | 653  | 33.7  | 45.7
Crassostrea virginica (Cvi)  | Eastern oyster  | Bivalvia  | 797  | XP_022315879  | 646  | 32.7  | 45.1
Tetranychus urticae (Tur)  | Two-spotted spider mite  | Arachnid  | 797  | XP_015790536  | 652  | 31.9  | 43.5
Centruroides sculpturatus (Csc)  | Bark scorpion  | Arachnid  | 797  | XP_023229484  | 605  | 30.6  | 43.4
Penaeus vannamei (Pva)  | Pacific white shrimp  | Malacostracans  | 797  | XP_027206746  | 681  | 22.9  | 34
Monosiga brevicollis (Mbr)  | Choanoflagellate  | Choanoflagellatea  | 1023  | XP_001748580  | 576  | 25.3  | 40.8

## References

1. ↑ "PhyreRisk". http://phyrerisk.bc.ic.ac.uk/.
2. ↑ 2.0 2.1 2.2 "CLIP4 CAP-Gly domain containing linker protein family member 4 [Homo sapiens (human) \- Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/79745.
3. ↑ 3.0 3.1 "CFSSP: Chou & Fasman Secondary Structure Prediction Server". http://www.biogem.org/tool/chou-fasman/index.php.
4. ↑ 4.0 4.1 "BioGPS - your Gene Portal System". http://biogps.org/#goto=genereport&id=79745.
5. ↑ 5.0 5.1 5.2 5.3 "CLIP4 Gene - GeneCards | CLIP4 Protein | CLIP4 Antibody". https://www.genecards.org/cgi-bin/carddisp.pl?gene=CLIP4.
6. ↑ (in en-US) Homo sapiens CAP-Gly domain containing linker protein family member 4 (CLIP4), transcript variant 1, mRNA. 2020-04-25. http://www.ncbi.nlm.nih.gov/nuccore/NM_024692.6.
7. ↑ (in en-US) Homo sapiens CAP-Gly domain containing linker protein family member 4 (CLIP4), transcript variant 2, mRNA. 2020-04-25. http://www.ncbi.nlm.nih.gov/nuccore/NM_001287527.2.
8. ↑ (in en-US) Homo sapiens CAP-Gly domain containing linker protein family member 4 (CLIP4), transcript variant 3, mRNA. 2020-04-25. http://www.ncbi.nlm.nih.gov/nuccore/NM_001287528.1.
9. ↑ 9.0 9.1 "ExPASy - Compute pI/Mw tool". https://web.expasy.org/compute_pi/.
10. ↑ 10.0 10.1 10.2 10.3 10.4 "SAPS < Sequence Statistics < EMBL-EBI". https://www.ebi.ac.uk/Tools/seqstats/saps/.
11. ↑ "CAP-Gly domain-containing linker protein 4 isoform 1 [Homo sapiens \- Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/NP_001274456.1.
12. ↑ "CAP-Gly domain-containing linker protein 4 isoform 2 [Homo sapiens \- Protein - NCBI"]. https://www.ncbi.nlm.nih.gov/protein/NP_001274457.1.
13. ↑ 13.0 13.1 "CLIP4 protein expression summary - The Human Protein Atlas". https://www.proteinatlas.org/ENSG00000115295-CLIP4.
14. ↑ 14.0 14.1 "CLIP4 - GEO Profiles - NCBI". https://www.ncbi.nlm.nih.gov/geoprofiles/?term=CLIP4.
15. ↑ "Sequence Utilities". https://www.bioline.com/media/calculator/01_12.html.
16. ↑ "RNA secondary structure prediction". http://www.genebee.msu.su/services/rna2_reduced.html.
17. ↑ "PSORT II Prediction". https://psort.hgc.jp/form2.html.
18. ↑ "SignalP-5.0". http://www.cbs.dtu.dk/services/SignalP/.
19. ↑ "NetNGlyc 1.0 Server". http://www.cbs.dtu.dk/services/NetNGlyc/.
20. ↑ "ProP 1.0 Server". http://www.cbs.dtu.dk/services/ProP/.
21. ↑ "NetOGlyc 4.0 Server" (in en). http://www.cbs.dtu.dk/services/NetOGlyc/.
22. ↑ "NetPhos 3.1 Server". http://www.cbs.dtu.dk/services/NetPhos/.
23. ↑ "Structure-function relationship of CAP-Gly domains". Nature Structural & Molecular Biology 14 (10): 959–67. October 2007. doi:10.1038/nsmb1291. PMID 17828277. https://www.nature.com/articles/nsmb1291.
24. ↑ "Ankyrin repeat: a unique motif mediating protein-protein interactions". Biochemistry 45 (51): 15168–78. December 2006. doi:10.1021/bi062188q. PMID 17176038.
25. ↑ "UniProtKB - P30622 (CLIP1_HUMAN)". https://www.uniprot.org/uniprot/P30622.
26. ↑ 26.0 26.1 "CLIP4 protein (human) - STRING interaction network". https://string-db.org/cgi/network.pl?taskId=4usn7zuMc06t.
27. ↑ "CLIP4 - CAP-Gly domain-containing linker protein 4 - Homo sapiens (Human) - CLIP4 gene & protein". https://www.uniprot.org/uniprot/Q8N3C7.
28. ↑ "Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies". Oncotarget 8 (24): 38501–38516. June 2017. doi:10.18632/oncotarget.16258. PMID 28418867.
29. ↑ "Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies". Oncotarget 8 (24): 38501–38516. June 2017. doi:10.18632/oncotarget.16258. PMID 28418867.
30. ↑ "Discovery of novel hypermethylated genes in prostate cancer using genomic CpG island microarrays". PLOS ONE 4 (3): e4830. 2009-03-13. doi:10.1371/journal.pone.0004830. PMID 19283074. Bibcode: 2009PLoSO...4.4830K.
31. ↑ "Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection". Fibrogenesis & Tissue Repair 5 (Suppl 1): S11. 2012-06-06. doi:10.1186/1755-1536-5-S1-S11. PMID 23259646.
32. ↑ "Barbara Dema" (in en). Discovery Medicine. http://www.discoverymedicine.com/Barbara-Dema/2014/05/22/advances-in-mechanismsof-systemic-lupus-erythematosus/.
33. ↑ "Nucleotide BLAST: Search nucleotide databases using a nucleotide query". https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE_TYPE=BlastSearch.

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/CLIP4. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:CLIP4&oldid=284218"