PACS1

Protein-coding gene in the species Homo sapiens
PACS1
Identifiers
AliasesPACS1, MRD17, phosphofurin acidic cluster sorting protein 1, SHMS
External IDsOMIM: 607492; MGI: 1277113; HomoloGene: 9970; GeneCards: PACS1; OMA:PACS1 - orthologs
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for PACS1
Genomic location for PACS1
Band11q13.1-q13.2Start66,070,272 bp[1]
End66,244,744 bp[1]
Gene location (Mouse)
Chromosome 19 (mouse)
Chr.Chromosome 19 (mouse)[2]
Chromosome 19 (mouse)
Genomic location for PACS1
Genomic location for PACS1
Band19|19 AStart5,183,186 bp[2]
End5,323,147 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • minor salivary glands

  • granulocyte

  • stromal cell of endometrium

  • apex of heart

  • cerebellar hemisphere

  • right hemisphere of cerebellum

  • right lung

  • right coronary artery

  • popliteal artery

  • tibial arteries
Top expressed in
  • granulocyte

  • seminiferous tubule

  • internal carotid artery

  • external carotid artery

  • genital tubercle

  • spermatid

  • tail of embryo

  • lacrimal gland

  • zygote

  • spermatocyte
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
  • protein binding
  • transmembrane transporter binding
Cellular component
  • cytosol
  • Golgi apparatus
  • COPI-coated vesicle
Biological process
  • mitigation of host defenses by virus
  • viral process
  • protein localization to plasma membrane
  • protein localization to Golgi apparatus
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

55690

107975

Ensembl

ENSG00000175115

ENSMUSG00000024855

UniProt

Q6VY07

Q8K212

RefSeq (mRNA)

NM_018026
NM_178178

NM_153129
NM_001362451

RefSeq (protein)

NP_060496
NP_060496.2

NP_694769
NP_001349380
NP_001390495
NP_001390496
NP_001390497

NP_001390498

Location (UCSC)Chr 11: 66.07 – 66.24 MbChr 19: 5.18 – 5.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Phosphofurin acidic cluster sorting protein 1, also known as PACS-1, is a protein that in humans is encoded by the PACS1 gene.[5][6][7]

Function

The PACS-1 protein has a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance.[7][8]

Interactions

PACS1 has been shown to interact with Furin.[8]

Clinical significance

A de novo mutation c.607C>T in the PACS1 gene has been shown to result in a syndromic phenotype (colloquially called PACS1 Syndrome) that is characterized by global developmental delay, intellectual disability, and specific facial features.[9][10]

Prevalence and diagnosis

The first two cases were identified in early 2011 by doctors in the Netherlands.[9] As of late 2014, there were 20 cases identified worldwide.[11]

Diagnosis is typically done using full genome or exome sequencing.[12] There are likely several more cases that will eventually be reported as knowledge of the mutation spreads and testing becomes more accessible.

Observed and reported traits

Individuals with the mutation have been reported to have similar facial features, such as:

  • Widely spaced eyes and low-set ears
  • Down-slanting eye corners and mild uni-brow
  • Highly arched eyebrows and long eyelashes
  • Rounded “button” nose with a flat bridge
  • Wide mouth with down-turned corners
  • Thin upper lip and widely spaced teeth

Other common traits reported by care givers of affected individuals are:

Prognosis and treatment

In combination, these traits affect walking, talking, feeding, and learning skills. No impact on life expectancy has been found. As with many developmental disabilities, there is no "cure".

In order to improve quality of life and enhance life skills of affected individuals, care givers have found a number of tools and strategies. It is important to note that all of these may not be applicable to a particular individual, and reported effectiveness has varied. It is recommended to consult with a physician prior to initiating any form of treatment.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175115 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024855 – 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. ^ Stove V, Naessens E, Stove C, Swigut T, Plum J, Verhasselt B (Oct 2003). "Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development". Blood. 102 (8): 2925–32. doi:10.1182/blood-2003-03-0833. PMID 12855553.
  6. ^ Hinners I, Wendler F, Fei H, Thomas L, Thomas G, Tooze SA (Dec 2003). "AP-1 recruitment to VAMP4 is modulated by phosphorylation-dependent binding of PACS-1". EMBO Reports. 4 (12): 1182–9. doi:10.1038/sj.embor.7400018. PMC 1326413. PMID 14608369.
  7. ^ a b "Entrez Gene: PACS1 phosphofurin acidic cluster sorting protein 1".
  8. ^ a b Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID 9695949. S2CID 15027198.
  9. ^ a b Schuurs-Hoeijmakers JH, Oh EC, Vissers LE, Swinkels ME, Gilissen C, Willemsen MA, Holvoet M, Steehouwer M, Veltman JA, de Vries BB, van Bokhoven H, de Brouwer AP, Katsanis N, Devriendt K, Brunner HG (2012). "Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome". Am. J. Hum. Genet. 91 (6): 1122–7. doi:10.1016/j.ajhg.2012.10.013. PMC 3516611. PMID 23159249.
  10. ^ Online Mendelian Inheritance in Man (OMIM): 615009
  11. ^ "Domain Details Page".[permanent dead link]
  12. ^ Callaway E (2012). "Gene hunt is on for mental disability". Nature. 484 (7394): 302–3. Bibcode:2012Natur.484..302C. doi:10.1038/484302a. PMID 22517145.
  13. ^ "Treatment". pacs1.info. Archived from the original on 2016-03-04. Retrieved 2015-07-30.

Further reading

  • Geyer M, Fackler OT, Peterlin BM (Jul 2001). "Structure--function relationships in HIV-1 Nef". EMBO Reports. 2 (7): 580–5. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
  • Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E (Feb 2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm". Current Protein & Peptide Science. 5 (1): 1–8. doi:10.2174/1389203043486955. PMID 14965316.
  • Joseph AM, Kumar M, Mitra D (Jan 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
  • Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID 9695949. S2CID 15027198.
  • Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (Oct 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
  • Piguet V, Wan L, Borel C, Mangasarian A, Demaurex N, Thomas G, Trono D (Mar 2000). "HIV-1 Nef protein binds to the cellular protein PACS-1 to downregulate class I major histocompatibility complexes". Nature Cell Biology. 2 (3): 163–7. doi:10.1038/35004038. PMC 1475706. PMID 10707087.
  • Crump CM, Xiang Y, Thomas L, Gu F, Austin C, Tooze SA, Thomas G (May 2001). "PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic". The EMBO Journal. 20 (9): 2191–201. doi:10.1093/emboj/20.9.2191. PMC 125242. PMID 11331585.
  • Williams M, Roeth JF, Kasper MR, Fleis RI, Przybycin CG, Collins KL (Dec 2002). "Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking". Journal of Virology. 76 (23): 12173–84. doi:10.1128/JVI.76.23.12173-12184.2002. PMC 136906. PMID 12414957.
  • Blagoveshchenskaya AD, Thomas L, Feliciangeli SF, Hung CH, Thomas G (Dec 2002). "HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway". Cell. 111 (6): 853–66. doi:10.1016/S0092-8674(02)01162-5. PMID 12526811. S2CID 14835284.
  • Scott GK, Gu F, Crump CM, Thomas L, Wan L, Xiang Y, Thomas G (Dec 2003). "The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic". The EMBO Journal. 22 (23): 6234–44. doi:10.1093/emboj/cdg596. PMC 291837. PMID 14633983.
  • Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
  • Köttgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Höpker K, Simmen KC, Tschucke CC, Sandford R, Kim E, Thomas G, Walz G (Feb 2005). "Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation". The EMBO Journal. 24 (4): 705–16. doi:10.1038/sj.emboj.7600566. PMC 549624. PMID 15692563.


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