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

    Gene ID: 55681, updated on 14-Nov-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
    mouse all
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    Genomic context

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    See SCYL2 in Genome Data Viewer
    Location:
    12q23.1
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (100267177..100341715)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (100228403..100303144)
    RS_2024_09 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 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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    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
    		not available

    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)

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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