UniProt functional annotation for P35613



	UniProt functional annotation for P35613

UniProt code: P35613.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: [Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857). {ECO:0000250|UniProtKB:P18572, ECO:0000269|PubMed:21620857, ECO:0000269|PubMed:25957687}.

Function: [Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11943775, PubMed:11688976). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:12553375, PubMed:11992541, PubMed:15833850). {ECO:0000269|PubMed:11688976, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:12553375, ECO:0000269|PubMed:15833850, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:19837976, ECO:0000269|PubMed:21778275, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:28666119}.

Function: [Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2. {ECO:0000269|PubMed:22080952}.

Function: [Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866). {ECO:0000269|PubMed:22080952, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866}.

Function: [Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus- associated PPIA/CYPA. {ECO:0000269|PubMed:15688292}.

Function: [Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:11353871}.

Function: [Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), it is not required for SARS-CoV-2 infection. {ECO:0000269|PubMed:33432067, ECO:0000303|PubMed:32307653}.

Function: [Isoform 2]: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269|PubMed:20147391}.

Function: [Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells. {ECO:0000269|PubMed:29739904}.

Subunit: [Isoform 1]: Homooligomer (PubMed:19768682). Interacts with NXNL1 (PubMed:25957687). Interacts with SLC2A1 and SLC16A1/GLUT1 (By similarity). {ECO:0000250|UniProtKB:P17790, ECO:0000269|PubMed:19768682, ECO:0000269|PubMed:25957687}.

Subunit: [Isoform 2]: Homooligomer (PubMed:18430721). Forms heterooligomers with isoform 3 (PubMed:21536654). Interacts with VEGFA and KDR/VEGFR2 (PubMed:25825981). Interacts with PPIA/CYPA (PubMed:11353871, PubMed:11943775, PubMed:15688292, PubMed:21245143). Interacts with PPIL2; regulates BSG transport to the cell membrane (PubMed:15946952). Interacts with SLC16A1/GLUT1 (PubMed:17127621). Interacts with SLC16A12 (PubMed:21778275). Interacts with SLC16A11 (PubMed:28666119). Interacts with AJAP1 (PubMed:17267690). Interacts with SLC1A3, ATP1B2, MAG and L1CAM (By similarity). {ECO:0000250|UniProtKB:P18572, ECO:0000250|UniProtKB:P26453, ECO:0000269|PubMed:11353871, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15688292, ECO:0000269|PubMed:15946952, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:17267690, ECO:0000269|PubMed:18430721, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21536654, ECO:0000269|PubMed:21778275, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:28666119}.

Subunit: [Isoform 3]: Forms heterooligomers with isoform 2. {ECO:0000269|PubMed:21536654}.

Subunit: [Isoform 1]: (Microbial infection) Interacts with P.falciparum (isolate 3D7) RH5/PfRH5; the interaction is required for the invasion of the host erythrocytes by the parasite at the merozoite stage. {ECO:0000269|PubMed:22080952}.

Subunit: [Isoform 2]: (Microbial infection) Interacts with P.falciparum (isolates 3D7 or 7G8) RH5/PfRH5; the interaction is required for the invasion of the host erythrocytes by the parasite at the merozoite stage. {ECO:0000269|PubMed:22080952, ECO:0000269|PubMed:24297912, ECO:0000269|PubMed:25132548, ECO:0000269|PubMed:26195724}.

Subunit: [Isoform 2]: (Microbial infection) Does not interact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein, even if previous works were based on a putative interaction. {ECO:0000269|PubMed:33432067, ECO:0000303|PubMed:32307653}.

Subcellular location: Melanosome {ECO:0000269|PubMed:17081065}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269|PubMed:17081065}.

Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:25957687}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P26453}. Photoreceptor inner segment {ECO:0000250|UniProtKB:P18572}. Cell projection, cilium, photoreceptor outer segment {ECO:0000250|UniProtKB:P18572}.

Subcellular location: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:15688292, ECO:0000269|PubMed:15946952, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:21536654, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866, ECO:0000269|PubMed:29739904}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P26453}. Endosome {ECO:0000269|PubMed:29739904}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:15688292}; Single- pass type I membrane protein {ECO:0000250|UniProtKB:P26453}. Basolateral cell membrane {ECO:0000269|PubMed:17267690}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P26453}.

Subcellular location: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:21536654}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P26453}.

Subcellular location: [Isoform 4]: Cell membrane {ECO:0000269|PubMed:21536654}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:P26453}.

Tissue specificity: [Isoform 1]: Retina-specific (PubMed:25957687). Expressed in retinal cone photoreceptors (at protein level) (PubMed:25957687). {ECO:0000269|PubMed:25957687}.

Tissue specificity: [Isoform 2]: Expressed in erythrocytes (at protein level) (PubMed:26195724, PubMed:28409866). Highly expressed in melanoma cell lines (at protein level) (PubMed:11992541). Highly expressed in the heart, kidney, skeletal muscle and testis (PubMed:21536654). {ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:21536654, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866}.

Tissue specificity: [Isoform 3]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus. {ECO:0000269|PubMed:21536654}.

Tissue specificity: [Isoform 4]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus. {ECO:0000269|PubMed:21536654}.

Ptm: [Isoform 2]: N-glycosylated. {ECO:0000269|PubMed:21536654}.

Ptm: [Isoform 3]: N-glycosylated. {ECO:0000269|PubMed:21536654}.

Ptm: [Isoform 4]: N-glycosylated. {ECO:0000269|PubMed:21536654}.

Biotechnology: [Isoform 2]: Potential candidate for the development of parasite blood stage vaccines. In vitro and in vivo, neutralizing antibodies are capable of inhibiting merozoite invasion of host erythrocytes. {ECO:0000269|PubMed:26195724}.

Miscellaneous: [Isoform 3]: Produced by alternative promoter usage. {ECO:0000269|PubMed:21536654}.

Miscellaneous: [Isoform 4]: Produced by alternative promoter usage. {ECO:0000269|PubMed:21536654}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		[Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857). {ECO:0000250\|UniProtKB:P18572, ECO:0000269\|PubMed:21620857, ECO:0000269\|PubMed:25957687}.



Function:		[Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11943775, PubMed:11688976). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:12553375, PubMed:11992541, PubMed:15833850). {ECO:0000269\|PubMed:11688976, ECO:0000269\|PubMed:11943775, ECO:0000269\|PubMed:11992541, ECO:0000269\|PubMed:12553375, ECO:0000269\|PubMed:15833850, ECO:0000269\|PubMed:17127621, ECO:0000269\|PubMed:19837976, ECO:0000269\|PubMed:21778275, ECO:0000269\|PubMed:25825981, ECO:0000269\|PubMed:28666119}.



Function:		[Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2. {ECO:0000269\|PubMed:22080952}.



Function:		[Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866). {ECO:0000269\|PubMed:22080952, ECO:0000269\|PubMed:26195724, ECO:0000269\|PubMed:28409866}.



Function:		[Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus- associated PPIA/CYPA. {ECO:0000269\|PubMed:15688292}.



Function:		[Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269\|PubMed:11353871}.



Function:		[Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), it is not required for SARS-CoV-2 infection. {ECO:0000269\|PubMed:33432067, ECO:0000303\|PubMed:32307653}.



Function:		[Isoform 2]: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269\|PubMed:20147391}.



Function:		[Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells. {ECO:0000269\|PubMed:29739904}.


Subunit:		[Isoform 1]: Homooligomer (PubMed:19768682). Interacts with NXNL1 (PubMed:25957687). Interacts with SLC2A1 and SLC16A1/GLUT1 (By similarity). {ECO:0000250\|UniProtKB:P17790, ECO:0000269\|PubMed:19768682, ECO:0000269\|PubMed:25957687}.
Subunit:		[Isoform 2]: Homooligomer (PubMed:18430721). Forms heterooligomers with isoform 3 (PubMed:21536654). Interacts with VEGFA and KDR/VEGFR2 (PubMed:25825981). Interacts with PPIA/CYPA (PubMed:11353871, PubMed:11943775, PubMed:15688292, PubMed:21245143). Interacts with PPIL2; regulates BSG transport to the cell membrane (PubMed:15946952). Interacts with SLC16A1/GLUT1 (PubMed:17127621). Interacts with SLC16A12 (PubMed:21778275). Interacts with SLC16A11 (PubMed:28666119). Interacts with AJAP1 (PubMed:17267690). Interacts with SLC1A3, ATP1B2, MAG and L1CAM (By similarity). {ECO:0000250\|UniProtKB:P18572, ECO:0000250\|UniProtKB:P26453, ECO:0000269\|PubMed:11353871, ECO:0000269\|PubMed:11943775, ECO:0000269\|PubMed:15688292, ECO:0000269\|PubMed:15946952, ECO:0000269\|PubMed:17127621, ECO:0000269\|PubMed:17267690, ECO:0000269\|PubMed:18430721, ECO:0000269\|PubMed:21245143, ECO:0000269\|PubMed:21536654, ECO:0000269\|PubMed:21778275, ECO:0000269\|PubMed:25825981, ECO:0000269\|PubMed:28666119}.
Subunit:		[Isoform 3]: Forms heterooligomers with isoform 2. {ECO:0000269\|PubMed:21536654}.
Subunit:		[Isoform 1]: (Microbial infection) Interacts with P.falciparum (isolate 3D7) RH5/PfRH5; the interaction is required for the invasion of the host erythrocytes by the parasite at the merozoite stage. {ECO:0000269\|PubMed:22080952}.
Subunit:		[Isoform 2]: (Microbial infection) Interacts with P.falciparum (isolates 3D7 or 7G8) RH5/PfRH5; the interaction is required for the invasion of the host erythrocytes by the parasite at the merozoite stage. {ECO:0000269\|PubMed:22080952, ECO:0000269\|PubMed:24297912, ECO:0000269\|PubMed:25132548, ECO:0000269\|PubMed:26195724}.
Subunit:		[Isoform 2]: (Microbial infection) Does not interact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein, even if previous works were based on a putative interaction. {ECO:0000269\|PubMed:33432067, ECO:0000303\|PubMed:32307653}.
Subcellular location:		Melanosome {ECO:0000269\|PubMed:17081065}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269\|PubMed:17081065}.
Subcellular location:		[Isoform 1]: Cell membrane {ECO:0000269\|PubMed:25957687}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}. Photoreceptor inner segment {ECO:0000250\|UniProtKB:P18572}. Cell projection, cilium, photoreceptor outer segment {ECO:0000250\|UniProtKB:P18572}.
Subcellular location:		[Isoform 2]: Cell membrane {ECO:0000269\|PubMed:11992541, ECO:0000269\|PubMed:15688292, ECO:0000269\|PubMed:15946952, ECO:0000269\|PubMed:17127621, ECO:0000269\|PubMed:21536654, ECO:0000269\|PubMed:25825981, ECO:0000269\|PubMed:26195724, ECO:0000269\|PubMed:28409866, ECO:0000269\|PubMed:29739904}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}. Endosome {ECO:0000269\|PubMed:29739904}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:15688292}; Single- pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}. Basolateral cell membrane {ECO:0000269\|PubMed:17267690}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}.
Subcellular location:		[Isoform 3]: Cell membrane {ECO:0000269\|PubMed:21536654}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}.
Subcellular location:		[Isoform 4]: Cell membrane {ECO:0000269\|PubMed:21536654}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:P26453}.
Tissue specificity:		[Isoform 1]: Retina-specific (PubMed:25957687). Expressed in retinal cone photoreceptors (at protein level) (PubMed:25957687). {ECO:0000269\|PubMed:25957687}.
Tissue specificity:		[Isoform 2]: Expressed in erythrocytes (at protein level) (PubMed:26195724, PubMed:28409866). Highly expressed in melanoma cell lines (at protein level) (PubMed:11992541). Highly expressed in the heart, kidney, skeletal muscle and testis (PubMed:21536654). {ECO:0000269\|PubMed:11992541, ECO:0000269\|PubMed:21536654, ECO:0000269\|PubMed:26195724, ECO:0000269\|PubMed:28409866}.
Tissue specificity:		[Isoform 3]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus. {ECO:0000269\|PubMed:21536654}.
Tissue specificity:		[Isoform 4]: Highly expressed in the bone marrow, fetal liver, lung, testis and thymus. {ECO:0000269\|PubMed:21536654}.
Ptm:		[Isoform 2]: N-glycosylated. {ECO:0000269\|PubMed:21536654}.
Ptm:		[Isoform 3]: N-glycosylated. {ECO:0000269\|PubMed:21536654}.
Ptm:		[Isoform 4]: N-glycosylated. {ECO:0000269\|PubMed:21536654}.
Biotechnology:		[Isoform 2]: Potential candidate for the development of parasite blood stage vaccines. In vitro and in vivo, neutralizing antibodies are capable of inhibiting merozoite invasion of host erythrocytes. {ECO:0000269\|PubMed:26195724}.
Miscellaneous:		[Isoform 3]: Produced by alternative promoter usage. {ECO:0000269\|PubMed:21536654}.
Miscellaneous:		[Isoform 4]: Produced by alternative promoter usage. {ECO:0000269\|PubMed:21536654}.