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SCYL2 SCY1 like pseudokinase 2 [ Homo sapiens (human) ]

Gene ID: 55681, updated on 5-Mar-2024

Summary

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Official Symbol
SCYL2provided by HGNC
Official Full Name
SCY1 like pseudokinase 2provided by HGNC
Primary source
HGNC:HGNC:19286
See related
Ensembl:ENSG00000136021 MIM:616365; AllianceGenome:HGNC:19286
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AMC4; AMCNACC; CVAK104
Summary
The protein encoded by this gene associates with clathrin-coated complexes at the plasma membrane and with endocytic coated vesicles. The encoded protein phosphorylates the beta2 subunit of the plasma membrane adapter complex AP2 and interacts with clathrin, showing involvement in clathrin-dependent pathways between the trans-Golgi network and the endosomal system. In addition, this protein has a role in the Wnt signaling pathway by targeting frizzled 5 (Fzd5) for lysosomal degradation. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]
Expression
Ubiquitous expression in colon (RPKM 12.7), esophagus (RPKM 10.5) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
12q23.1
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (100267177..100341715)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (100228403..100303144)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (100660955..100735493)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4764 Neighboring gene Sharpr-MPRA regulatory region 7946 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6854 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:100595701-100596388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:100596389-100597074 Neighboring gene microRNA 1827 Neighboring gene actin related protein 6 Neighboring gene DEP domain containing 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6856 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4765 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4766 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6857 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6858 Neighboring gene MPRA-validated peak1911 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:100688535-100689176 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:100689177-100689817 Neighboring gene Sharpr-MPRA regulatory region 7724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6859 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:100724514-100724735 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:100750302-100750802 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:100750803-100751303 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr12:100766477-100767226 Neighboring gene solute carrier family 17 member 8 Neighboring gene small nucleolar RNA U13 Neighboring gene MPRA-validated peak1912 silencer Neighboring gene nuclear receptor subfamily 1 group H member 4 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_22518 Neighboring gene MPRA-validated peak1913 silencer

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans. Seidahmed MZ, et al. Hum Genet, 2020 Apr. PMID 31960134
  2. CVAK104 is a novel regulator of clathrin-mediated SNARE sorting. Borner GH, et al. Traffic, 2007 Jul. PMID 17587408, Free PMC Article
  3. Clathrin-dependent association of CVAK104 with endosomes and the trans-Golgi network. Düwel M, et al. Mol Biol Cell, 2006 Oct. PMID 16914521, Free PMC Article
  4. CVAK104 is a novel poly-L-lysine-stimulated kinase that targets the beta2-subunit of AP2. Conner SD, et al. J Biol Chem, 2005 Jun 3. PMID 15809293
  5. Spinal cord repair: future directions. Fawcett JW. Paraplegia, 1992 Feb. PMID 1589293

See all (90) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. results suggest that severe neurogenic arthrogryposis with brain malformation is the human phenotypic consequence of SCYL2 loss of function mutations.
    Title: Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans.
  2. results suggest that SCYL2 serves as a regulatory factor for Vpu, reducing the extent of Vpu phosphorylation and consequently enhancing BST2-mediated viral restriction.
    Title: Interferon-induced SCYL2 limits release of HIV-1 by triggering PP2A-mediated dephosphorylation of the viral protein Vpu.
  3. Studies identify CVAK104 as a novel binding partner of Dishevelled (Dvl) and that CVAK104 also interacts with Fzd5.
    Title: A coated vesicle-associated kinase of 104 kDa (CVAK104) induces lysosomal degradation of frizzled 5 (Fzd5).
  4. CVAK104 is an evolutionarily conserved protein involved in SNARE sorting that is essential for normal embryonic development
    Title: CVAK104 is a novel regulator of clathrin-mediated SNARE sorting.
  5. Together, our data suggest a function for CVAK104 in clathrin-dependent pathways between the trans-Golgi network and the endosomal system.
    Title: Clathrin-dependent association of CVAK104 with endosomes and the trans-Golgi network.
  6. CVAK104 binds ATP and functions in vitro as a poly-L-lysine-stimulated kinase that is capable of autophosphorylation and phosphorylating the beta2-adaptin subunit of AP2.
    Title: CVAK104 is a novel poly-L-lysine-stimulated kinase that targets the beta2-subunit of AP2.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum
MedGen: C5231494 OMIM: 618766 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of SCY1-like 2 (SCYL2) by siRNA enhances HIV-1 release in transfected HeLa cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Nef nef Genome-wide shRNA screening identifies SCYL2, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells PubMed
Vpu vpu IFN-alpha and IFN-beta increases SCYL2 expression and the increase induces PP2A-mediated dephosphorylation of Vpu, suggesting that SCYL2 affects Vpu function through a phosphorylation-dependent mechanism PubMed
vpu Both the kinase-like domain (residues 1-375) and the clathrin-binding domain (residues 697-929) of SCYL2 are required for its anti-Vpu activity PubMed
vpu SCYL2 inhibits Vpu-induced BST2 and CD4 reduction at the cell surface by suppressing the phosphorylation of Vpu at positions Ser-52 and Ser-56 PubMed
vpu In vitro protein-protein interaction analysis identifies a Vpu-binding host protein SCYL2, which inhibits the particle release of Vpu-positive HIV-1, but not Vpu-deficient HIV-1 PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ10074, KIAA1360

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables signaling receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in brain development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in clathrin-dependent endocytosis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in endosome to lysosome transport IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of negative regulation of canonical Wnt signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in pyramidal neuron development ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in receptor internalization IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in clathrin-coated vesicle IEA
Inferred from Electronic Annotation
more info
  
located_in endosome membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
SCY1-like protein 2
Names
SCY1-like 2
SCY1-like, kinase-like 2
coated vesicle-associated kinase of 104 kDa

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001317784.2 → NP_001304713.1  SCY1-like protein 2 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AB037781, BC011525, CN337316, DA234206
    Consensus CDS
    CCDS9076.1
    UniProtKB/Swiss-Prot
    A8KAB5, Q6P3W7, Q96EF4, Q96ST4, Q9H7V5, Q9NVH3, Q9P2I7
    Conserved Domains (2) summary
    cd14011
    Location:38 → 329
    PK_SCY1_like; Pseudokinase domain of Scy1-like proteins
    sd00044
    Location:373 → 403
    HEAT; HEAT repeat [structural motif]

  2. NM_001330253.2 → NP_001317182.1  SCY1-like protein 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate in-frame exon in its central coding region, compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is longer than isoform 1. Both variants 3 and 4 encode the same isoform (2).
    Source sequence(s)
    AB037781, AC026110, BC063798, CN337316, DB127407
    Consensus CDS
    CCDS81726.1
    UniProtKB/TrEMBL
    A0A0U1RQQ9

  3. NM_001330254.2 → NP_001317183.1  SCY1-like protein 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and contains an alternate in-frame exon in its central coding region, compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is longer than isoform 1. Both variants 3 and 4 encode the same isoform (2).
    Source sequence(s)
    AB037781, BC011525, DA234206
    Consensus CDS
    CCDS81726.1
    UniProtKB/TrEMBL
    A0A0U1RQQ9
    Related
    ENSP00000489123.1, ENST00000635101.1

  4. NM_001330256.2 → NP_001317185.1  SCY1-like protein 2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and contains two alternate exons compared to variant 1. This variant represents translation initiation at a downstream start codon compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream start codon to encode an isoform (3) that has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AB037781, AC026110, BC011525, DA234206, DB261340
    UniProtKB/Swiss-Prot
    Q6P3W7

  5. NM_017988.6 → NP_060458.3  SCY1-like protein 2 isoform 1

    See identical proteins and their annotated locations for NP_060458.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1. Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AB037781, AC026110, BC063798, CN337316, DB127407
    Consensus CDS
    CCDS9076.1
    UniProtKB/Swiss-Prot
    A8KAB5, Q6P3W7, Q96EF4, Q96ST4, Q9H7V5, Q9NVH3, Q9P2I7
    Related
    ENSP00000354061.2, ENST00000360820.7
    Conserved Domains (2) summary
    cd14011
    Location:38 → 329
    PK_SCY1_like; Pseudokinase domain of Scy1-like proteins
    sd00044
    Location:373 → 403
    HEAT; HEAT repeat [structural motif]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    100267177..100341715
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    100228403..100303144
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6P3W7.1 GenPept UniProtKB/Swiss-Prot:Q6P3W7

Gene LinkOut

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