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

Summary

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

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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).
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.
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.
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.

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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	Compare labs

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 EBI GWAS CatalogPubMed

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

WI-17588 (e-PCR)
- UniSTS:37167

RH48161 (e-PCR)
- UniSTS:46964

BCD1539 (e-PCR)
- UniSTS:36054

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)

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]
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
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
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
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]