Gram domain containing 1b

GRAM domain containing 1B, also known as GRAMD1B, Aster-B and KIAA1201, is a protein that is encoded by the GRAMD1B gene.[5][6] It contains a transmembrane region and two domains of known function; the GRAM domain and a VASt domain. It is predicted to localize in the nucleus, supported by several nuclear transport signals and nuclearly associated motifs. This highly conserved gene is found in a variety of vertebrates and invertebrates, however is not found in bacteria or fungi.[7]

GRAMD1B
Identifiers
AliasesGRAMD1B, GRAM domain containing 1B, LINC01059
External IDsMGI: 1925037 HomoloGene: 18223 GeneCards: GRAMD1B
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q24.1Start123,358,428 bp[1]
End123,627,774 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

57476

235283

Ensembl

ENSG00000023171

ENSMUSG00000040111

UniProt

Q3KR37

Q80TI0

RefSeq (mRNA)

NM_001286563
NM_001286564
NM_020716
NM_001330396

RefSeq (protein)
Location (UCSC)Chr 11: 123.36 – 123.63 MbChr 9: 40.29 – 40.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

GRAMD1B, also known as KIAA1201, is located in the human genome at 11q24.1.[8] It is located on the + strand and is flanked by a variety of other genes. It spans 269,347 bases.[5]

GRAMD1B and surrounding genes

mRNA

The most verified isoform, isoform 1, contains 21 exons. There are four validated isoform variants of human GRAMD1B.[5] These consist of truncated 5’ and 3’ regions, resulting in the loss of an exon.

Isoform mRNA length (bp) Exons Protein length (aa) Status
1 7927 21 745 Validated
2 7906 20 738 Validated
3 7636 20 698 Validated
4 7561 20 694 Validated

Protein

GRAMD1B contains several domains, motifs and signals.

GRAMD1B protein structure

Domains

There are two confirmed domains within GRAMD1B. The protein gets its name from the GRAM domain, located approximately 100 amino acids from the start codon. The GRAM domain is commonly found in myotubularin family phosphatases and predominantly involved in membrane coupled processes.[9] GRAMD1B also contains the VASt (VAD1 Analog of StAR-related lipid transfer) domain. The VASt domain is predominantly associated with lipid binding domains, such as GRAM. It is most likely to function in binding large hydrophobic ligands and may be specific for sterol.[10]

Composition Features

There are two negative charge clusters, located from amino acids 232-267 and 348-377.[11] The first cluster is not highly conserved, nor is it located in a motif or domain. The second cluster is located directly before the VASt domain and is conserved.

There are three repeat sequence regions, all fairly conserved in orthologs.[11]

Repeat # Sets of Repeats Length (aa) Location Similarity Score
1 3 18 Within first 100 amino acids 83.44
2 2 21 GRAM domain 77.22
3 2 22 VASt domain 67.94

Molecular weight and isoelectric point are conserved in orthologs.

Region Amino Acids[5] Isoelectric point[12] Molecular Weight (kdal)[13]
Human GRAMD1B 745 pH of 6.02 86.5
GRAM domain 94 pH of 8.27 11.3
VASt domain 144 pH of 9.41 17.3
Transmembrane region 21 pH of 5.18 2.3

Structure

The mature protein contains two nuclear localization signals, pat4 and pat7.[14] There are four dileucine motifs, three located within or close to the GRAM domain.[14] A leucine zipper pattern extends through a majority the transmembrane region.[14] A SUMOylation site is located directly after the VASt domain.[15] The proteins secondary structure consists of alpha-helices, beta-strands and coils.[16] Beta-strands are mainly located within the two domains, while the alpha-helixes are concentrated near the transmembrane region. Three disulfide bonds are predicted throughout the protein.[17]

Predicted alpha-helix structure of GRAMD1B transmembrane region.[18]
Predicted 3D structure of GRAMD1B,[16]

Subcellular location

GRAMD1B is predicted to localize in the nucleus and contains a transmembrane domain, most likely placing it in the membrane of the nucleus.[11]

Expression

GRAMD1B is expressed in a variety of tissues. It is most highly expressed in the gonadal tissue, adrenal gland, brain and placenta.[19] It has raised expression rates in adrenal tumors, lung tumors. Developmentally, it is most highly expressed during infancy. The EST profile is supported with experimental data from multiple sources[20]

GRAMD1B expression in a variety of tissues.[19]
[19] Tissue expression of GRAMD1B

Homology

Orthologs

The ortholog space for GRAMD1B spans a large portion of evolutionary time. GRAMD1B can be found in mammals, bird, fish and invertebrates. It is not present in bacteria, archaea or fungi.[7]

Genus species Common Name Accession Number Date of Divergence (MYA)[21] Identity[7]
Homo sapiens Human NP_001273492.1 0 100.00%
Aotus nancymaae Nancy Ma's Night Monkey XP_012325676.1 3.2 99.00%
Papio anubis Olive Baboon XP_017804515.1 29.44 97.00%
Castor canadensis Beaver XP_020037170.1 90 98.00%
Octodon degus Dengu XP_004636450.1 90 97.00%
Pantholops hodgsonii Tibetan Antelope XP_005958036.1 96 99.00%
Bos mutus Domestic Yak XP_005896826.1 96 98.00%
Tursiops truncatus Dolphin XP_019797543 96 83.00%
Elephantulus edwardii Cape Elephant Shrew XP_006895663.1 105 98.00%
Gallus gallus Chicken XP_015153638.1 312 93.00%
Calypte anna Anna's Humming Bird XP_008490701.1 312 91.00%
Pygoscelis adeliae Adelie Penguin XP_009331694.1 312 91.00%
Coturnix japonica Japanese Quail XP_015739426.1 312 90.00%
Anolis carolinensis Carolina Anole XP_008111963.1 312 87.00%
Danio rerio Zebra Fish XP_009303888.1 435 73.00%
Callorhinchus milii Australian Ghost Shark XP_007894251.1 473 77.00%
Branchiostoma belcheri Lancelet XP_019624725.1 684 40.00%
Octopus bimaculoides California Two-Spot Octopus XP_014769036.1 797 40.00%
Lingula anatina Brachiopod XP_013415578 797 38.00%
Zootermopsis nevadensis Termite KDR17240.1 797 37.00%
Trachymyrmex cornetzi Ant XP_018362289.1 797 34.00%

Paralogs

There are four paralogs of GRAMD1B.[7] The most closely related is GRAMD1A while the most distant ortholog is GRAMD2A/GRAMD2.

Paralog Sequence Length Sequence Identity[7] Date of Divergence (MYA)[21]
GRAMD1A 724 aa 46.60% 421.0
GRAMD1C 662 aa 37.90% 934.7
GRAMD2B/GRAMD3 491 aa 18.50% 1625.6
GRAMD2A 353 aa 16.70% 1724.2

Phylogeny

GRAMD2 diverged earliest in history while the most recent split is GRAMD1A. The GRAMD1B gene’s rate of divergence significantly faster than Fibrinogen but is not as high as Cytochrome C.

Phylogeny of GRAMD1B

Function

Currently, the function of GRAMD1B has not been characterized.

Protein interactions

Several different proteins have been experimentally confirmed or predicted to interact with GRAMD1B.[22][23]

Protein Interaction identified via[22][23] Function Location
COPA Experimental Binds dilysine motifs. Required for budding from the Golgi and retrograde Golgi to ER transport systolic
SPICE1 Data Mining Spindle and centriole associated. Regulates centriole duplication, proper bipolar spindle formation and chromosome congregation in mitosis nuclear
GTPBP8 Data Mining GTP binding protein unconfirmed
Ywhae Co-sedimentation Adapter protein associated with regulating nuclear transport to the cytoplasm nuclear

Clinical significance

A study tagging SNPs from chronic lymphocytic leukemia found GRAMD1B to be the second strongest risk allele region.[24] This association is supported through a number of studies[25][26] The aberrant tri-methylation of histone H3 lysine 27 induces inflammation and has been shown to increase GRAMD1B levels in colon tumors.[27]

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References
  1. GRCh38: Ensembl release 89: ENSG00000023171 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000040111 - 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. "Entrez Gene: GRAM domain containing 1B". Retrieved 2017-02-19.
  6. "UniProtKB - Q3KR37 (ASTRB_HUMAN)". Retrieved March 6, 2020.
  7. "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2 May 2017.
  8. "GRAMD1B Gene - GeneCards | GRM1B Protein | GRM1B Antibody". GeneCards Human Gene. Retrieved 2 May 2017.
  9. "GRAM Protein Domain".
  10. "PROSITE". prosite.expasy.org. Retrieved 2 May 2017.
  11. "PSORT II Prediction". PSORT. Retrieved 2 May 2017.
  12. Toldo L. "Isoelectric Point Service". Archived from the original on 2008-10-26.
  13. "AASTATS: Statistics Based on Amino Acid Abundance, including weight and specific volume".
  14. "SAPS: Statistical Analysis of PS".
  15. "SUMOplot".
  16. "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2 May 2017.
  17. "DiANNA". clavius.bc.edu. Retrieved 2 May 2017.
  18. Remmert M. "Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2 May 2017.
  19. "EST Profile - Hs.144725". www.ncbi.nlm.nih.gov. Schuler Group. Retrieved 2 May 2017.
  20. "GDS1085 / 5768". www.ncbi.nlm.nih.gov. Retrieved 2 May 2017.
  21. "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2 May 2017.
  22. "STRING: functional protein association networks". string-db.org. Retrieved 2 May 2017.
  23. Lab, Mike Tyers. "GRAMD1B (UNQ3032/PRO9834) Result Summary | BioGRID". thebiogrid.org. Retrieved 2 May 2017.
  24. "OMIM Entry: 612559 - Leukemia, chronic lymphocytic, susceptibility to, 5". Online Mendelian Inheritance in Man (OMIM). Retrieved 2 May 2017.
  25. Lan Q, Au WY, Chanock S, Tse J, Wong KF, Shen M, Siu LP, Yuenger J, Yeager M, Hosgood HD, Purdue MP, Liang R, Rothman N (December 2010). "Genetic susceptibility for chronic lymphocytic leukemia among Chinese in Hong Kong". European Journal of Haematology. 85 (6): 492–5. doi:10.1111/j.1600-0609.2010.01518.x. PMC 2980583. PMID 20731705.
  26. Slager SL, Goldin LR, Strom SS, Lanasa MC, Spector LG, Rassenti L, Leis JF, Camp NJ, Kay NE, Vachon CM, Glenn M, Weinberg JB, Rabe KG, Cunningham JM, Achenbach SJ, Hanson CA, Marti GE, Call TG, Caporaso NE, Cerhan JR (April 2010). "Genetic susceptibility variants for chronic lymphocytic leukemia". Cancer Epidemiology, Biomarkers & Prevention. 19 (4): 1098–102. doi:10.1158/1055-9965.EPI-09-1217. PMC 2852480. PMID 20332261.
  27. Takeshima H, Ikegami D, Wakabayashi M, Niwa T, Kim YJ, Ushijima T (December 2012). "Induction of aberrant trimethylation of histone H3 lysine 27 by inflammation in mouse colonic epithelial cells". Carcinogenesis. 33 (12): 2384–90. doi:10.1093/carcin/bgs294. PMID 22976929.
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