id: P08195
gene_symbol: SLC3A2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'SLC3A2 (also known as 4F2hc, CD98 heavy chain) encodes the essential heavy chain subunit of heteromeric amino acid transporters (HATs). It functions as a type II transmembrane glycoprotein that forms disulfide-linked heterodimers with various SLC7 family light chain transporters (SLC7A5/LAT1, SLC7A6/y+LAT2, SLC7A7/y+LAT1, SLC7A8/LAT2, SLC7A10/Asc-1, SLC7A11/xCT). SLC3A2 acts as a chaperone essential for the trafficking, plasma membrane localization, and stability of these light chain partners, which provide the actual catalytic transport activity. The SLC3A2/SLC7A5 (LAT1) complex mediates Na+-independent transport of large neutral amino acids (leucine, phenylalanine, tryptophan, tyrosine) and is critical for mTORC1 activation. The SLC3A2/SLC7A11 (xCT) complex functions as the cystine/glutamate antiporter system xc-, important for glutathione synthesis and protection against ferroptosis. SLC3A2 also modulates integrin signaling independently of its transport functions. High-resolution cryo-EM structures have elucidated the molecular architecture of these complexes.

  '
existing_annotations:
- term:
    id: GO:1903801
    label: L-leucine import across plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'SLC3A2 partners with LAT1 (SLC7A5) and LAT2 (SLC7A8) to form heterodimeric amino acid transporters that mediate leucine import. This is a core function well-supported by phylogenetic analysis and experimental evidence from multiple studies (PMID:9751058, PMID:10574970, PMID:11557028, PMID:30867591).

      '
    action: ACCEPT
    reason: 'L-leucine import is a well-established core function of SLC3A2-containing heterodimeric transporters. The IBA annotation is consistent with extensive experimental evidence.

      '
    supported_by:
    - reference_id: PMID:9751058
      supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
    - reference_id: file:human/SLC3A2/SLC3A2-deep-research-falcon.md
      supporting_text: 'model: Edison Scientific Literature'
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Phenylalanine is a well-established substrate for the LAT1-4F2hc and LAT2-4F2hc complexes. Multiple experimental studies confirm phenylalanine transport activity.

      '
    action: ACCEPT
    reason: 'Phenylalanine transport is a core function of SLC3A2-containing HAT complexes, supported by phylogenetic and experimental evidence.

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'SLC3A2 localizes to both apical and basolateral plasma membranes in polarized epithelial cells. Basolateral localization is well-documented for kidney and intestinal epithelia where it partners with LAT2.

      '
    action: ACCEPT
    reason: 'Basolateral localization is supported by phylogenetic inference and consistent with experimental data from polarized epithelial cells (PMID:31791063).

      '
    supported_by:
    - reference_id: PMID:31791063
      supporting_text: 'Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.'
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'SLC3A2 is found at the apical membrane of syncytiotrophoblasts and other polarized cells. Apical localization depends on the light chain partner.

      '
    action: ACCEPT
    reason: 'Apical localization is well-documented in multiple cell types and tissues.

      '
    supported_by:
    - reference_id: PMID:31791063
      supporting_text: 'Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.'
- term:
    id: GO:1904273
    label: L-alanine import across plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'L-alanine transport is mediated by the LAT2-4F2hc complex. LAT2 has broader specificity for small and large neutral amino acids compared to LAT1.

      '
    action: ACCEPT
    reason: 'L-alanine import is established function of the SLC3A2/LAT2 complex based on experimental evidence (PMID:10391915).

      '
    supported_by:
    - reference_id: PMID:10391915
      supporting_text: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
- term:
    id: GO:0001618
    label: virus receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'SLC3A2/CD98 has been demonstrated to act as a receptor for Plasmodium vivax entry into immature red blood cells (PMID:34294905) and facilitates hepatitis C virus entry (PMID:30341327). This represents a secondary function exploited by pathogens.

      '
    action: KEEP_AS_NON_CORE
    reason: 'While virus/pathogen receptor activity is experimentally validated, it represents exploitation of SLC3A2 by pathogens rather than a core physiological function.

      '
    supported_by:
    - reference_id: PMID:34294905
      supporting_text: 2021 Jul 22. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells.
    - reference_id: PMID:30341327
      supporting_text: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
- term:
    id: GO:0005765
    label: lysosomal membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'SLC3A2 is recruited to lysosomes by LAPTM4B where the LAT1-4F2hc complex promotes leucine uptake into lysosomes, facilitating mTORC1 activation (PMID:25998567).

      '
    action: ACCEPT
    reason: 'Lysosomal localization is experimentally verified and functionally important for mTORC1 signaling.

      '
    supported_by:
    - reference_id: PMID:25998567
      supporting_text: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Plasma membrane localization is the primary site of SLC3A2 function where it forms heterodimeric transporters. Extensively validated by experimental studies and structural biology.

      '
    action: ACCEPT
    reason: 'Core localization supported by cryo-EM structures and numerous functional studies.

      '
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
- term:
    id: GO:0005975
    label: carbohydrate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'This annotation is based on the glycoside hydrolase domain annotation in InterPro. However, SLC3A2 does NOT function as a glycoside hydrolase - it functions as an amino acid transporter chaperone. The alpha-amylase-like fold is structural but not catalytically active. This is an erroneous electronic annotation.

      '
    action: REMOVE
    reason: 'SLC3A2 does not participate in carbohydrate metabolism. While it contains an alpha-amylase-like domain fold, this domain has been repurposed for structural roles in membrane association and heterodimer formation, not carbohydrate hydrolysis. Recent structural studies (PMID:30867591, PMID:33298890) confirm this domain mediates protein-protein interactions, not enzymatic activity.

      '
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
- term:
    id: GO:0006865
    label: amino acid transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Amino acid transport is the primary function of SLC3A2 when complexed with SLC7 family light chains. This is a core function.

      '
    action: ACCEPT
    reason: 'Core function well-established by extensive experimental evidence.

      '
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Duplicate of IBA annotation above. Phenylalanine transport is a well-established substrate for LAT1 and LAT2 complexes with SLC3A2.

      '
    action: ACCEPT
    reason: 'Core function - phenylalanine is a well-characterized substrate.

      '
- term:
    id: GO:0015827
    label: tryptophan transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Tryptophan is a substrate for LAT1-4F2hc and LAT2-4F2hc complexes. Experimentally verified in multiple studies.

      '
    action: ACCEPT
    reason: 'Core function supported by experimental evidence (PMID:10574970, PMID:11557028, PMID:11564694).

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Generic membrane annotation. SLC3A2 is a type II transmembrane protein - more specific annotations (plasma membrane, lysosomal membrane) are also present.

      '
    action: ACCEPT
    reason: 'Valid but general annotation. More specific CC annotations are preferable.

      '
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Duplicate of IBA annotation. Valid localization for SLC3A2 in polarized epithelial cells.

      '
    action: ACCEPT
    reason: 'Well-supported localization.

      '
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Duplicate of IBA annotation. Valid localization.

      '
    action: ACCEPT
    reason: 'Well-supported localization in polarized cells.

      '
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'SLC3A2 was identified in melanosome proteomics studies. This likely reflects amino acid transporter activity in these specialized organelles.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Melanosome localization is based on proteomics data but not a core localization.

      '
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Heterodimerization with SLC7 family members is THE core molecular function of SLC3A2. It forms obligate disulfide-linked heterodimers with light chains.

      '
    action: ACCEPT
    reason: 'Core molecular function. SLC3A2 forms heterodimers with at least 6 different SLC7 family members (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10, SLC7A11).

      '
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
    - reference_id: PMID:34880232
      supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc().
- term:
    id: GO:0070161
    label: anchoring junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'SLC3A2 localizes to cell-cell adhesion sites and interacts with integrins. This relates to its integrin signaling modulation function.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Junction localization is secondary to its transport function.

      '
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20374249
  review:
    summary: 'This annotation is based on interaction with E. coli EspZ effector protein. Represents pathogen exploitation of SLC3A2.

      '
    action: MARK_AS_OVER_ANNOTATED
    reason: 'Generic protein binding annotation - more specific MF terms exist for the relevant interactions (heterodimerization with SLC7 proteins).

      '
    supported_by:
    - reference_id: PMID:20374249
      supporting_text: The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28298427
  review:
    summary: 'Interaction with GPR37. Represents a GPCR interaction study.

      '
    action: MARK_AS_OVER_ANNOTATED
    reason: 'Generic protein binding - should be replaced with more specific term if functional significance is established.

      '
    supported_by:
    - reference_id: PMID:28298427
      supporting_text: Systematic protein-protein interaction mapping for clinically relevant human GPCRs.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30867591
  review:
    summary: 'Structural study demonstrating interaction with SLC7A5/LAT1.

      '
    action: MODIFY
    reason: 'This is heterodimerization with SLC7A5 - should use GO:0046982 protein heterodimerization activity, which is also present.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34880232
  review:
    summary: 'Structural study of xCT/SLC7A11 interaction with SLC3A2.

      '
    action: MODIFY
    reason: 'This is heterodimerization - more specific term exists.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:34880232
      supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc().
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: 'OpenCell high-throughput study detecting LAT1 interaction.

      '
    action: MARK_AS_OVER_ANNOTATED
    reason: 'Generic protein binding from HT study - heterodimerization terms are more informative.

      '
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40355756
  review:
    summary: 'SLC transporter interactome study.

      '
    action: MARK_AS_OVER_ANNOTATED
    reason: 'Generic protein binding - specific interactions should use more specific terms.

      '
    supported_by:
    - reference_id: PMID:40355756
      supporting_text: 2025 May 12. The solute carrier superfamily interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9878049
  review:
    summary: 'Early study establishing y+LAT interaction with 4F2hc.

      '
    action: MODIFY
    reason: 'This demonstrates heterodimerization with SLC7A7.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:9878049
      supporting_text: Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Leucine transport is a core function of SLC3A2-containing complexes, especially LAT1-4F2hc. Critical for mTORC1 signaling.

      '
    action: ACCEPT
    reason: 'Well-established core function.

      '
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Crystal structure of the SLC3A2 ectodomain (PMID:17724034) shows it can form homodimers, though heterodimer formation with SLC7 proteins is its primary functional form.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Homodimerization has been structurally observed but heterodimerization with SLC7 light chains is the functional form.

      '
    supported_by:
    - reference_id: PMID:17724034
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Neuronal localization transferred from mouse ortholog. SLC3A2/LAT1 is expressed in neurons and at the blood-brain barrier.

      '
    action: ACCEPT
    reason: 'Neuronal expression is well-documented for amino acid transport functions.

      '
- term:
    id: GO:0044225
    label: apical pole of neuron
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Specific neuronal localization from ortholog transfer.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Valid but cell-type specific localization.

      '
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: 'Synaptic localization likely reflects amino acid transporter function at synapses. Asc-1/CD98hc transports D-serine and glycine, key NMDAR co-agonists.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Synaptic localization is relevant for neuromodulator transport.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: 'HPA immunofluorescence data confirming plasma membrane localization.

      '
    action: ACCEPT
    reason: 'Core localization validated by immunofluorescence.

      '
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: NAS
  original_reference_id: PMID:10734121
  review:
    summary: 'Small neutral amino acid transporter asc-2/SLC7A10 association with 4F2hc for amino acid import.

      '
    action: ACCEPT
    reason: 'Amino acid import is a core function of SLC3A2-containing transporters.

      '
    supported_by:
    - reference_id: PMID:10734121
      supporting_text: Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids.
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:10903140
  review:
    summary: 'Demonstrates arginine efflux in exchange with glutamine via y+LAT2/4F2hc.

      '
    action: ACCEPT
    reason: 'Core function - amino acid exchange across plasma membrane.

      '
    supported_by:
    - reference_id: PMID:10903140
      supporting_text: The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine.
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:11417227
  review:
    summary: 'Key paper identifying xCT/SLC7A11 as the partner of 4F2hc for system xc- activity (cystine/glutamate antiporter). Cystine import is critical.

      '
    action: ACCEPT
    reason: 'Core function - cystine import is essential for glutathione synthesis.

      '
    supported_by:
    - reference_id: PMID:11417227
      supporting_text: Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-.
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:30867591
  review:
    summary: 'Cryo-EM structure of LAT1-4F2hc complex with functional characterization.

      '
    action: ACCEPT
    reason: 'Core function supported by structural and functional studies.

      '
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:33758168
  review:
    summary: 'Mechanism of substrate transport and inhibition of LAT1-4F2hc.

      '
    action: ACCEPT
    reason: 'Core function with mechanistic detail.

      '
    supported_by:
    - reference_id: PMID:33758168
      supporting_text: Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.
- term:
    id: GO:0089718
    label: amino acid import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9878049
  review:
    summary: 'Early characterization of y+L-type transport by 4F2hc heterodimers.

      '
    action: ACCEPT
    reason: 'Foundational paper establishing amino acid transport function.

      '
    supported_by:
    - reference_id: PMID:9878049
      supporting_text: Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.
- term:
    id: GO:0150104
    label: transport across blood-brain barrier
  evidence_type: NAS
  original_reference_id: PMID:27912058
  review:
    summary: 'LAT1-4F2hc at the blood-brain barrier transports essential amino acids. Impaired transport is linked to autism spectrum disorder.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Tissue-specific function reflecting amino acid transport at BBB.

      '
    supported_by:
    - reference_id: PMID:27912058
      supporting_text: Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:33298890
  review:
    summary: 'Cryo-EM structure of LAT2-4F2hc complex demonstrating heterodimer architecture.

      '
    action: ACCEPT
    reason: 'Core molecular function directly demonstrated by structural biology.

      '
    supported_by:
    - reference_id: PMID:33298890
      supporting_text: Structural insight into the substrate recognition and transport mechanism of the human LAT2-4F2hc complex.
- term:
    id: GO:0140272
    label: exogenous protein binding
  evidence_type: IDA
  original_reference_id: PMID:30341327
  review:
    summary: 'Binding to hepatitis C virus envelope proteins facilitating viral entry.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Pathogen exploitation of SLC3A2 - not a core function.

      '
    supported_by:
    - reference_id: PMID:30341327
      supporting_text: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
- term:
    id: GO:0140272
    label: exogenous protein binding
  evidence_type: IDA
  original_reference_id: PMID:34294905
  review:
    summary: 'CD98hc serves as a receptor for Plasmodium vivax entry into reticulocytes.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Pathogen receptor function - exploited by malaria parasite.

      '
    supported_by:
    - reference_id: PMID:34294905
      supporting_text: 2021 Jul 22. Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33298890
  review:
    summary: 'Interaction with SLC7A8/LAT2 demonstrated structurally.

      '
    action: MODIFY
    reason: 'Heterodimerization - more specific term available.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:33298890
      supporting_text: Structural insight into the substrate recognition and transport mechanism of the human LAT2-4F2hc complex.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:11311135
  review:
    summary: 'Study showing domain requirements for 4F2hc association with LAT1, LAT2, y+LAT2.

      '
    action: ACCEPT
    reason: 'Well-established core localization.

      '
    supported_by:
    - reference_id: PMID:11311135
      supporting_text: Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'LAT1 characterization showing plasma membrane localization.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:12225859
  review:
    summary: 'System L amino acid transporter in T24 bladder carcinoma cells.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
    supported_by:
    - reference_id: PMID:12225859
      supporting_text: Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.
- term:
    id: GO:0015818
    label: isoleucine transport
  evidence_type: IDA
  original_reference_id: PMID:11311135
  review:
    summary: 'Isoleucine is transported by LAT1-4F2hc and LAT2-4F2hc complexes.

      '
    action: ACCEPT
    reason: 'Core function - isoleucine is a branched-chain amino acid substrate.

      '
    supported_by:
    - reference_id: PMID:11311135
      supporting_text: Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains.
- term:
    id: GO:0015818
    label: isoleucine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'LAT1 characterization showing isoleucine transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:10574970
  review:
    summary: 'LAT2 characterization showing leucine transport.

      '
    action: ACCEPT
    reason: 'Core function - leucine is essential for mTORC1 signaling.

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'LAT1 characterization in tumor cells.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:11564694
  review:
    summary: 'System L transporter characterization.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11564694
      supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:12225859
  review:
    summary: 'T24 bladder carcinoma cell characterization.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:12225859
      supporting_text: Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:15769744
  review:
    summary: 'S-nitroso-L-cysteine transport via LAT1/LAT2.

      '
    action: ACCEPT
    reason: 'Core function with additional substrate discovery.

      '
    supported_by:
    - reference_id: PMID:15769744
      supporting_text: '2005 Mar 15. Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols.'
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IDA
  original_reference_id: PMID:9751058
  review:
    summary: 'Foundational paper establishing 4F2hc permease heterodimer transport.

      '
    action: ACCEPT
    reason: 'Core function - seminal paper.

      '
    supported_by:
    - reference_id: PMID:9751058
      supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
- term:
    id: GO:0015821
    label: methionine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'LAT1 transports methionine, which is important for methylation reactions.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IDA
  original_reference_id: PMID:10574970
  review:
    summary: 'LAT2 phenylalanine transport characterization.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'LAT1 phenylalanine transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IDA
  original_reference_id: PMID:11564694
  review:
    summary: 'System L transporter phenylalanine transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11564694
      supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IDA
  original_reference_id: PMID:9751058
  review:
    summary: 'Foundational study on 4F2hc heterodimer transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:9751058
      supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
- term:
    id: GO:0015824
    label: proline transport
  evidence_type: IDA
  original_reference_id: PMID:10574970
  review:
    summary: 'Proline transport by LAT2-4F2hc.

      '
    action: ACCEPT
    reason: 'LAT2 has broader substrate specificity including proline.

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
- term:
    id: GO:0015827
    label: tryptophan transport
  evidence_type: IDA
  original_reference_id: PMID:10574970
  review:
    summary: 'Tryptophan transport by LAT2.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:10574970
      supporting_text: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine.
- term:
    id: GO:0015827
    label: tryptophan transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'Tryptophan transport by LAT1.

      '
    action: ACCEPT
    reason: 'Core function - large neutral aromatic amino acid.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015827
    label: tryptophan transport
  evidence_type: IDA
  original_reference_id: PMID:11564694
  review:
    summary: 'System L tryptophan transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11564694
      supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
- term:
    id: GO:0015828
    label: tyrosine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'Tyrosine transport by LAT1.

      '
    action: ACCEPT
    reason: 'Core function - aromatic amino acid.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0015828
    label: tyrosine transport
  evidence_type: IDA
  original_reference_id: PMID:11564694
  review:
    summary: 'System L tyrosine transport.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11564694
      supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
- term:
    id: GO:0015829
    label: valine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'Valine transport by LAT1.

      '
    action: ACCEPT
    reason: 'Core function - branched-chain amino acid.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:0070327
    label: thyroid hormone transport
  evidence_type: IDA
  original_reference_id: PMID:11564694
  review:
    summary: 'LAT1 and LAT2 transport thyroid hormones (T3, T4) which structurally resemble tyrosine.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Valid function but secondary to amino acid transport - thyroid hormones are structurally similar to tyrosine.

      '
    supported_by:
    - reference_id: PMID:11564694
      supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter.
- term:
    id: GO:1902024
    label: L-histidine transport
  evidence_type: IDA
  original_reference_id: PMID:11557028
  review:
    summary: 'Histidine transport by LAT1.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:11557028
      supporting_text: 'Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.'
- term:
    id: GO:1902024
    label: L-histidine transport
  evidence_type: IDA
  original_reference_id: PMID:9751058
  review:
    summary: 'Histidine transport by 4F2hc heterodimers.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:9751058
      supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30341327
  review:
    summary: 'Interaction with HCV E2 envelope protein.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Pathogen interaction - exogenous protein binding term more appropriate.

      '
    supported_by:
    - reference_id: PMID:30341327
      supporting_text: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
- term:
    id: GO:0015820
    label: L-leucine transport
  evidence_type: IMP
  original_reference_id: PMID:30341327
  review:
    summary: 'Leucine transport enhanced during HCV infection promoting mTORC1 signaling.

      '
    action: ACCEPT
    reason: 'Core function demonstrated by mutant phenotype.

      '
    supported_by:
    - reference_id: PMID:30341327
      supporting_text: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
- term:
    id: GO:0046718
    label: symbiont entry into host cell
  evidence_type: IMP
  original_reference_id: PMID:30341327
  review:
    summary: 'SLC3A2 facilitates HCV entry into host cells.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Pathogen exploitation function - not a normal physiological role.

      '
    supported_by:
    - reference_id: PMID:30341327
      supporting_text: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:28112518
  review:
    summary: 'Mass spectrometry quantitation in retinal pigment epithelial cells.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
    supported_by:
    - reference_id: PMID:28112518
      supporting_text: Epub 2017 Feb 14. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.
- term:
    id: GO:0015180
    label: L-alanine transmembrane transporter activity
  evidence_type: IGI
  original_reference_id: PMID:10391915
  review:
    summary: 'LAT2-4F2hc complex transports alanine - shown by co-expression with SLC7A8.

      '
    action: ACCEPT
    reason: 'Core molecular function demonstrated by genetic interaction.

      '
    supported_by:
    - reference_id: PMID:10391915
      supporting_text: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
- term:
    id: GO:0015190
    label: L-leucine transmembrane transporter activity
  evidence_type: IGI
  original_reference_id: PMID:10391915
  review:
    summary: 'LAT2-4F2hc leucine transporter activity.

      '
    action: ACCEPT
    reason: 'Core molecular function.

      '
    supported_by:
    - reference_id: PMID:10391915
      supporting_text: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
- term:
    id: GO:1903801
    label: L-leucine import across plasma membrane
  evidence_type: IGI
  original_reference_id: PMID:10391915
  review:
    summary: 'Leucine import by LAT2-4F2hc.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:10391915
      supporting_text: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
- term:
    id: GO:1904273
    label: L-alanine import across plasma membrane
  evidence_type: IGI
  original_reference_id: PMID:10391915
  review:
    summary: 'Alanine import by LAT2-4F2hc.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:10391915
      supporting_text: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
- term:
    id: GO:0009925
    label: basal plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Basal membrane localization inferred from sequence similarity.

      '
    action: ACCEPT
    reason: 'Valid localization consistent with basolateral distribution.

      '
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:31791063
  review:
    summary: 'Direct experimental evidence for basolateral localization in RPE cells.

      '
    action: ACCEPT
    reason: 'Core localization validated experimentally.

      '
    supported_by:
    - reference_id: PMID:31791063
      supporting_text: 'Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.'
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Apical localization from sequence similarity.

      '
    action: ACCEPT
    reason: 'Valid localization.

      '
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:31791063
  review:
    summary: 'Direct evidence for apical localization in RPE cells.

      '
    action: ACCEPT
    reason: 'Core localization validated experimentally.

      '
    supported_by:
    - reference_id: PMID:31791063
      supporting_text: 'Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.'
- term:
    id: GO:0015173
    label: aromatic amino acid transmembrane transporter activity
  evidence_type: IGI
  original_reference_id: PMID:15589117
  review:
    summary: 'LAT1-4F2hc aromatic amino acid transporter activity demonstrated.

      '
    action: ACCEPT
    reason: 'Core molecular function - LAT1 preferentially transports large neutral aromatics.

      '
    supported_by:
    - reference_id: PMID:15589117
      supporting_text: Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport.
- term:
    id: GO:0015823
    label: phenylalanine transport
  evidence_type: IGI
  original_reference_id: PMID:15589117
  review:
    summary: 'Phenylalanine transport by LAT1-4F2hc.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:15589117
      supporting_text: Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport.
- term:
    id: GO:0015175
    label: neutral L-amino acid transmembrane transporter activity
  evidence_type: IGI
  original_reference_id: PMID:17197568
  review:
    summary: 'Neutral amino acid transporter activity demonstrated for SLC3A2-containing complexes.

      '
    action: ACCEPT
    reason: 'Core molecular function.

      '
    supported_by:
    - reference_id: PMID:17197568
      supporting_text: Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells.
- term:
    id: GO:1903801
    label: L-leucine import across plasma membrane
  evidence_type: IGI
  original_reference_id: PMID:17197568
  review:
    summary: 'Leucine import function.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:17197568
      supporting_text: Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:23137377
  review:
    summary: 'Quantitative proteomics in cerebral microvascular endothelial cells.

      '
    action: ACCEPT
    reason: 'Core localization at blood-brain barrier.

      '
    supported_by:
    - reference_id: PMID:23137377
      supporting_text: Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood-brain barrier model.
- term:
    id: GO:1990184
    label: amino acid transport complex
  evidence_type: IDA
  original_reference_id: PMID:30867591
  review:
    summary: 'Cryo-EM structure directly demonstrating SLC3A2 as part of heteromeric amino acid transporter complex.

      '
    action: ACCEPT
    reason: 'Core function - SLC3A2 is an obligate component of HAT complexes.

      '
    supported_by:
    - reference_id: PMID:30867591
      supporting_text: Mar 13. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  review:
    summary: 'High-throughput study identifying E-cadherin interactome. SLC3A2 localized to cell-cell junctions.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Secondary function related to cell adhesion role.

      '
    supported_by:
    - reference_id: PMID:25468996
      supporting_text: E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25998567
  review:
    summary: 'Interaction with LAPTM4B for lysosomal recruitment.

      '
    action: ACCEPT
    reason: 'Functionally important interaction for mTORC1 activation.

      '
    supported_by:
    - reference_id: PMID:25998567
      supporting_text: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:25998567
  review:
    summary: 'Plasma membrane and lysosomal localization study.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
    supported_by:
    - reference_id: PMID:25998567
      supporting_text: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12270127
  review:
    summary: 'Interaction with CT120/TLCD3A.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Minor interaction - function unclear.

      '
    supported_by:
    - reference_id: PMID:12270127
      supporting_text: Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:12270127
  review:
    summary: 'Plasma membrane localization.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
    supported_by:
    - reference_id: PMID:12270127
      supporting_text: Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IDA
  original_reference_id: PMID:25063885
  review:
    summary: 'Cell surface localization detected - relevant for pathogen binding.

      '
    action: ACCEPT
    reason: 'Valid localization term.

      '
    supported_by:
    - reference_id: PMID:25063885
      supporting_text: 2014 Jul 24. KSHV attachment and entry are dependent on αVβ3 integrin localized to specific cell surface microdomains and do not correlate with the presence of heparan sulfate.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: HDA
  original_reference_id: PMID:19581412
  review:
    summary: 'Proteomics study on cell surface proteins.

      '
    action: ACCEPT
    reason: 'Valid localization.

      '
    supported_by:
    - reference_id: PMID:19581412
      supporting_text: Jul 6. Quantitative proteomics identifies a Dab2/integrin module regulating cell migration.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: 'Detected in prostatic exosomes by proteomics.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Secondary localization - exosomal presence common for membrane proteins.

      '
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: 'NK cell membrane proteome.

      '
    action: ACCEPT
    reason: 'Valid general localization.

      '
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: Defining the membrane proteome of NK cells.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  review:
    summary: 'High-throughput mRNA interactome study detected SLC3A2. This is likely non-specific or secondary.

      '
    action: MARK_AS_OVER_ANNOTATED
    reason: 'SLC3A2 is a membrane transporter chaperone with no known RNA-related function. High-throughput RNA binding studies can capture non-specific associations. No structural or functional evidence supports RNA binding.

      '
    supported_by:
    - reference_id: PMID:22658674
      supporting_text: May 31. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19199708
  review:
    summary: 'Parotid gland exosome proteomics.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Secondary localization.

      '
    supported_by:
    - reference_id: PMID:19199708
      supporting_text: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  review:
    summary: 'Urinary exosome proteomics.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Secondary localization.

      '
    supported_by:
    - reference_id: PMID:19056867
      supporting_text: 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes.
- term:
    id: GO:0003725
    label: double-stranded RNA binding
  evidence_type: IDA
  original_reference_id: PMID:21266579
  review:
    summary: 'Study on raftlin involvement in poly(I:C)-mediated TLR3 activation found SLC3A2 in nucleocapture complex. This appears to be a specialized immunological context.

      '
    action: KEEP_AS_NON_CORE
    reason: 'This is a specialized immune function in TLR3 signaling, not a core function of SLC3A2. The dsRNA binding may be indirect through complex formation.

      '
    supported_by:
    - reference_id: PMID:21266579
      supporting_text: 2011 Jan 25. Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
- term:
    id: GO:0043330
    label: response to exogenous dsRNA
  evidence_type: IMP
  original_reference_id: PMID:21266579
  review:
    summary: 'Involvement in TLR3 response to poly(I:C).

      '
    action: KEEP_AS_NON_CORE
    reason: 'Specialized immune function, not core transporter role.

      '
    supported_by:
    - reference_id: PMID:21266579
      supporting_text: 2011 Jan 25. Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  review:
    summary: 'B-cell exosome proteomics.

      '
    action: KEEP_AS_NON_CORE
    reason: 'Secondary localization.

      '
    supported_by:
    - reference_id: PMID:20458337
      supporting_text: 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-352191
  review:
    summary: 'Reactome annotation for SLC7A8-mediated uptake with SLC3A2.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-352232
  review:
    summary: 'Reactome annotation for SLC7A5:SLC3A2 transport.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-375131
  review:
    summary: 'Basigin binding to CD98 complex at plasma membrane.

      '
    action: ACCEPT
    reason: 'Valid localization.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-376200
  review:
    summary: 'SLC7A10-mediated uptake with SLC3A2.

      '
    action: ACCEPT
    reason: 'Core localization for Asc-1/4F2hc complex.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-378513
  review:
    summary: 'SLC7A11-mediated cystine/glutamate exchange - system xc-.

      '
    action: ACCEPT
    reason: 'Core localization for xCT/4F2hc (system xc-).

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-379415
  review:
    summary: 'SLC7A7:SLC3A2 arginine/leucine exchange.

      '
    action: ACCEPT
    reason: 'Core localization for y+LAT1/4F2hc.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-379426
  review:
    summary: 'SLC7A6 (y+LAT2) with SLC3A2.

      '
    action: ACCEPT
    reason: 'Core localization.

      '
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5660910
  review:
    summary: 'Defective SLC7A7 pathway annotation.

      '
    action: ACCEPT
    reason: 'Valid localization context.

      '
- term:
    id: GO:1903801
    label: L-leucine import across plasma membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Leucine import inferred from sequence similarity.

      '
    action: ACCEPT
    reason: 'Core function consistent with experimental evidence.

      '
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10506149
  review:
    summary: 'Cloning of b(0,+)-like transporter (SLC7A9 homolog) associating with 4F2hc.

      '
    action: MODIFY
    reason: 'This is heterodimerization with SLC7 family member.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:10506149
      supporting_text: Cloning and expression of a b(0,+)-like amino acid transporter functioning as a heterodimer with 4F2hc instead of rBAT.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10631289
  review:
    summary: 'Cloning of asc-1 (SLC7A10) interacting with 4F2hc.

      '
    action: MODIFY
    reason: 'This is heterodimerization with SLC7A10.

      '
    proposed_replacement_terms:
    - id: GO:0046982
      label: protein heterodimerization activity
    supported_by:
    - reference_id: PMID:10631289
      supporting_text: Cloning and functional characterization of a Na(+)-independent, broad-specific neutral amino acid transporter from mammalian intestine.
- term:
    id: GO:0015827
    label: tryptophan transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Tryptophan transport from sequence similarity.

      '
    action: ACCEPT
    reason: 'Core function consistent with experimental evidence.

      '
- term:
    id: GO:0006816
    label: calcium ion transport
  evidence_type: NAS
  original_reference_id: PMID:3036867
  review:
    summary: 'This annotation references the original cloning paper from 1987. Early speculation about calcium transport was not confirmed. SLC3A2 functions as an amino acid transporter chaperone, not a calcium transporter.

      '
    action: REMOVE
    reason: 'No evidence supports calcium transport function for SLC3A2. This appears to be a legacy annotation from early characterization before the amino acid transport function was established. Modern structural and functional studies confirm amino acid transport exclusively.

      '
    supported_by:
    - reference_id: PMID:3036867
      supporting_text: Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.
- term:
    id: GO:0006865
    label: amino acid transport
  evidence_type: TAS
  original_reference_id: PMID:10673541
  review:
    summary: 'Review on heterodimeric amino acid transporters in placenta.

      '
    action: ACCEPT
    reason: 'Core function.

      '
    supported_by:
    - reference_id: PMID:10673541
      supporting_text: 'Heterodimeric amino acid transporters: expression of heavy but not light chains of CD98 correlates with induction of amino acid transport systems in human placental trophoblast.'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:3476959
  review:
    summary: 'Original cloning paper establishing membrane localization.

      '
    action: ACCEPT
    reason: 'Valid core localization from foundational paper.

      '
    supported_by:
    - reference_id: PMID:3476959
      supporting_text: 'Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth.'
- term:
    id: GO:0015327
    label: cystine:glutamate antiporter activity
  evidence_type: IDA
  original_reference_id: PMID:11417227
  review:
    summary: 'SLC3A2/4F2hc partners with xCT/SLC7A11 to form system xc-, the cystine/glutamate antiporter. The complex mediates Na+-independent exchange of extracellular cystine for intracellular glutamate (PMID:11417227, PMID:34880232). This is a core molecular function of the SLC3A2-xCT complex.

      '
    action: NEW
    reason: 'This core molecular function term was not present in existing GOA annotations but is well-supported by multiple experimental studies including the original characterization (PMID:11417227) and recent cryo-EM structures (PMID:34880232). System xc- activity is essential for cysteine homeostasis and ferroptosis regulation.

      '
    supported_by:
    - reference_id: PMID:11417227
      supporting_text: Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-.
    - reference_id: PMID:34880232
      supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc().
- term:
    id: GO:0006749
    label: glutathione metabolic process
  evidence_type: IMP
  original_reference_id: PMID:34880232
  review:
    summary: 'The xCT-4F2hc (system xc-) complex provides cystine for glutathione biosynthesis. Cystine is reduced to cysteine intracellularly, and cysteine is the rate-limiting substrate for glutathione synthesis. Inhibition of system xc- depletes cellular glutathione leading to ferroptosis.

      '
    action: NEW
    reason: 'SLC3A2 involvement in glutathione metabolism is well-established through its partnership with xCT for cystine import. This biological process is directly downstream of the cystine:glutamate antiporter activity.

      '
    supported_by:
    - reference_id: PMID:34880232
      supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc().
- term:
    id: GO:0097707
    label: ferroptosis
  evidence_type: IMP
  original_reference_id: PMID:34880232
  review:
    summary: 'Inhibition of the xCT-4F2hc (system xc-) complex leads to cystine starvation, glutathione depletion, and ferroptotic cell death characterized by iron-dependent lipid peroxidation. System xc- is a major target for inducing ferroptosis in cancer therapy.

      '
    action: NEW
    reason: 'SLC3A2 plays a critical regulatory role in ferroptosis through its partnership with xCT. Genetic or pharmacological inhibition of system xc- triggers ferroptosis, establishing SLC3A2 as involved in this cell death process.

      '
    supported_by:
    - reference_id: PMID:34880232
      supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc().
- term:
    id: GO:0031929
    label: TOR signaling
  evidence_type: NAS
  review:
    summary: Added to align core_functions with existing annotations.
    action: NEW
    reason: Core function term not present in existing_annotations.
    supported_by:
    - reference_id: PMID:9751058
      supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family.
    - reference_id: PMID:25998567
      supporting_text: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.
core_functions:
- molecular_function:
    id: GO:0046982
    label: protein heterodimerization activity
  description: SLC3A2/4F2hc forms obligate disulfide-linked heterodimers with SLC7 family light chain transporters (LAT1/SLC7A5, LAT2/SLC7A8, y+LAT1/SLC7A7, y+LAT2/SLC7A6, Asc-1/SLC7A10, xCT/SLC7A11). The heavy chain provides trafficking, plasma membrane localization, and stability for the light chains which provide the catalytic transport activity. Cryo-EM structures have elucidated the heterodimer architecture (PMID:30867591, PMID:33298890, PMID:34880232).
  supported_by:
  - reference_id: PMID:30867591
    supporting_text: Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex resolved at 3.3A resolution
  - reference_id: PMID:34880232
    supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc resolved by cryo-EM
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005765
    label: lysosomal membrane
- molecular_function:
    id: GO:0015190
    label: L-leucine transmembrane transporter activity
  description: The LAT1-4F2hc (SLC7A5-SLC3A2) complex mediates Na+-independent transport of large neutral amino acids, particularly leucine, which is critical for mTORC1 activation and cell growth. LAT2-4F2hc (SLC7A8-SLC3A2) also transports leucine with broader substrate specificity. This function is essential for nutrient sensing and cell proliferation.
  supported_by:
  - reference_id: PMID:9751058
    supporting_text: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family established leucine as key substrate
  - reference_id: PMID:25998567
    supporting_text: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes for mTORC1 activation
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0005765
    label: lysosomal membrane
  directly_involved_in:
  - id: GO:0031929
    label: TOR signaling
- molecular_function:
    id: GO:0015327
    label: cystine:glutamate antiporter activity
  description: The xCT-4F2hc (SLC7A11-SLC3A2) complex functions as system xc-, a cystine/glutamate antiporter that imports cystine in exchange for glutamate. This activity is essential for maintaining intracellular cysteine levels required for glutathione synthesis. The system xc- transporter is a critical regulator of ferroptosis - inhibition leads to iron-dependent lipid peroxidation and cell death (PMID:34880232, PMID:11417227).
  supported_by:
  - reference_id: PMID:11417227
    supporting_text: Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-
  - reference_id: PMID:34880232
    supporting_text: Molecular basis for redox control by the human cystine/glutamate antiporter system xc structure and function
  locations:
  - id: GO:0005886
    label: plasma membrane
  directly_involved_in:
  - id: GO:0006749
    label: glutathione metabolic process
  - id: GO:0097707
    label: ferroptosis
- molecular_function:
    id: GO:0015173
    label: aromatic amino acid transmembrane transporter activity
  description: LAT1-4F2hc preferentially transports large neutral aromatic amino acids including phenylalanine, tyrosine, and tryptophan. This transport activity is Na+-independent and operates in exchange mode. LAT1 also transports thyroid hormones (T3, T4) which are structurally similar to tyrosine (PMID:11564694). LAT1 overexpression in tumors supports increased amino acid demand for cancer cell proliferation.
  supported_by:
  - reference_id: PMID:15589117
    supporting_text: LAT1-4F2hc aromatic amino acid transporter activity demonstrated with phenylalanine as substrate
  - reference_id: PMID:11564694
    supporting_text: Thyroid hormone transport by the heterodimeric human system L amino acid transporter
  locations:
  - id: GO:0005886
    label: plasma membrane
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:3036867
  title: Primary structure of the human 4F2 antigen heavy chain
  findings:
  - statement: Original cloning paper establishing SLC3A2 as a type II transmembrane glycoprotein
- id: PMID:3476959
  title: 'Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth.'
  findings:
  - statement: Foundational characterization of SLC3A2
- id: PMID:9751058
  title: Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family
  findings:
  - statement: Established that 4F2hc forms heterodimers with permease light chains for amino acid transport
- id: PMID:9878049
  title: Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98
  findings:
  - statement: Characterized y+L amino acid transport by 4F2hc heterodimers
- id: PMID:10391915
  title: Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
  findings:
  - statement: Discovery of LAT2/SLC7A8 as 4F2hc partner
- id: PMID:10574970
  title: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter
  findings:
  - statement: Characterization of LAT2-4F2hc in kidney and intestine
- id: PMID:10903140
  title: The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux
  findings:
  - statement: Established y+LAT2/4F2hc arginine/glutamine exchange
- id: PMID:11311135
  title: Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains
  findings:
  - statement: Domain mapping for light chain interactions
- id: PMID:11417227
  title: Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-.
  findings:
  - statement: Discovery of xCT/SLC7A11 as system xc- light chain partner of 4F2hc
  - statement: Cystine/glutamate antiporter activity established
- id: PMID:11557028
  title: Human L-type amino acid transporter 1 (LAT1) characterization
  findings:
  - statement: Comprehensive LAT1-4F2hc functional characterization in tumor cells
- id: PMID:11564694
  title: Thyroid hormone transport by the heterodimeric human system L amino acid transporter
  findings:
  - statement: Demonstrated T3/T4 transport by system L
- id: PMID:25998567
  title: LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes
  findings:
  - statement: Lysosomal recruitment and mTORC1 activation mechanism
- id: PMID:30341327
  title: Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral Propagation.
  findings:
  - statement: HCV exploits SLC3A2 for entry and mTORC1 activation
- id: PMID:30867591
  title: Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex
  findings:
  - statement: First cryo-EM structure of LAT1-4F2hc at 3.3A resolution
  - statement: Revealed heterodimer architecture and disulfide linkage
- id: PMID:33298890
  title: Structural insight into the substrate recognition and transport mechanism of the human LAT2-4F2hc complex.
  findings:
  - statement: Cryo-EM structure of LAT2-4F2hc with substrates
- id: PMID:33758168
  title: Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.
  findings:
  - statement: Transport mechanism and inhibitor binding details
- id: PMID:34294905
  title: Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells.
  findings:
  - statement: SLC3A2 serves as malaria parasite receptor
- id: PMID:34880232
  title: Molecular basis for redox control by the human cystine/glutamate antiporter system xc
  findings:
  - statement: Cryo-EM structure of xCT/SLC7A11-4F2hc complex
  - statement: Ferroptosis protection mechanism
- id: Reactome:R-HSA-378513
  title: SLC7A11-mediated exchange of extracellular cysteine and cytosolic glutamate
  findings:
  - statement: System xc- pathway annotation
- id: PMID:10506149
  title: Cloning and expression of a b(0,+)-like amino acid transporter functioning as a heterodimer with 4F2hc instead of rBAT. A new candidate gene for cystinuria.
  findings: []
- id: PMID:10631289
  title: Cloning and functional characterization of a Na(+)-independent, broad-specific neutral amino acid transporter from mammalian intestine.
  findings: []
- id: PMID:10673541
  title: 'Heterodimeric amino acid transporters: expression of heavy but not light chains of CD98 correlates with induction of amino acid transport systems in human placental trophoblast.'
  findings: []
- id: PMID:10734121
  title: Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids.
  findings: []
- id: PMID:12225859
  title: Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells.
  findings: []
- id: PMID:12270127
  title: Molecular cloning and characterization of CT120, a novel membrane-associated gene involved in amino acid transport and glutathione metabolism.
  findings: []
- id: PMID:15589117
  title: Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport.
  findings: []
- id: PMID:15769744
  title: 'Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols.'
  findings: []
- id: PMID:17197568
  title: Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells.
  findings: []
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
- id: PMID:19199708
  title: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
  findings: []
- id: PMID:19581412
  title: Quantitative proteomics identifies a Dab2/integrin module regulating cell migration.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:20374249
  title: The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling.
  findings: []
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
  findings: []
- id: PMID:21266579
  title: Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation.
  findings: []
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:23137377
  title: Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood-brain barrier model.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
  findings: []
- id: PMID:25063885
  title: "KSHV attachment and entry are dependent on αVβ3 integrin localized to specific cell surface microdomains and do not correlate with the presence of heparan sulfate."
  findings: []
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
  findings: []
- id: PMID:27912058
  title: Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.
  findings: []
- id: PMID:28112518
  title: LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.
  findings: []
- id: PMID:28298427
  title: Systematic protein-protein interaction mapping for clinically relevant human GPCRs.
  findings: []
- id: PMID:31791063
  title: 'Quantitative Protein Expression in the Human Retinal Pigment Epithelium: Comparison Between Apical and Basolateral Plasma Membranes With Emphasis on Transporters.'
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:40355756
  title: The solute carrier superfamily interactome.
  findings: []
- id: Reactome:R-HSA-352191
  title: SLC7A8-mediated uptake of neutral amino acids
  findings: []
- id: Reactome:R-HSA-352232
  title: SLC7A5:SLC3A2 transports neutral amino acids from extracellular region to cytosol
  findings: []
- id: Reactome:R-HSA-375131
  title: Basigin binds CD98 complex
  findings: []
- id: Reactome:R-HSA-376200
  title: SLC7A10-mediated uptake of small neutral amino acids
  findings: []
- id: Reactome:R-HSA-379415
  title: SLC7A7:SLC3A2 exchanges L-Arg for L-Leu, Na+ across the plasma membrane
  findings: []
- id: Reactome:R-HSA-379426
  title: SLC7A6 (y+LAT2)-mediated exchange of extracellular leucine for cytosolic arginine
  findings: []
- id: Reactome:R-HSA-5660910
  title: Defective SLC7A7 does not exchange L-Arg for L-Leu, Na+ across the plasma membrane
  findings: []
- id: file:human/SLC3A2/SLC3A2-deep-research-falcon.md
  title: Deep research report on SLC3A2
  findings: []
tags:
- ferroptosis