Q9Y5Y0 (FLVC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 76.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Feline leukemia virus subgroup C receptor-related protein 1 Short name=Feline leukemia virus subgroup C receptor Short name=hFLVCR | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 555 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Heme transporter that exports cytoplasmic heme. It can also export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. Heme export depends on the presence of HPX and may be required to protect developing erythroid cells from heme toxicity. Heme export also provides protection from heme or ferrous iron toxicities in liver and brain. Causes susceptibility to FeLV-C in vitro. Ref.1 Ref.7 Ref.10 |
| Subunit structure | Interacts with HPX. Ref.10 |
| Subcellular location | Cell membrane; Multi-pass membrane protein By similarity. |
| Tissue specificity | Found all hematopoietic tissues including peripheral blood lymphocytes. Some expression is found in pancreas and kidney. Ref.1 |
| Developmental stage | Down-regulated in haemopoietic progenitor cells undergoing differentiation and hemoglobinization. Abundant in fetal liver. Ref.7 |
| Involvement in disease | Defects in FLVCR1 are the cause of posterior column ataxia with retinitis pigmentosa (PCARP) [MIM:609033]. A neurodegenerative syndrome beginning in infancy with areflexia and retinitis pigmentosa. Nyctalopia (night blindness) and peripheral visual field loss are usually evident during late childhood or teenage years, with subsequent progressive constriction of the visual fields and loss of central retinal function over time. A sensory ataxia caused by degeneration of the posterior columns of the spinal cord results in a loss of proprioceptive sensation that is clinically evident in the second decade of life and gradually progresses. Scoliosis, camptodactyly, achalasia, gastrointestinal dysmotility, and a sensory peripheral neuropathy are variable features of the disease. Affected individuals have no clinical or radiological evidence of cerebral or cerebellar involvement. Note=Defective neuronal heme transmembrane export due to FLVCR1 mutations may abrogate the neuroprotective effects of neuroglobin and initiate an apoptotic cascade that results in the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior spinal cord. Ref.11 Ref.12 |
| Sequence similarities | Belongs to the major facilitator superfamily. Feline leukemia virus subgroup C receptor (TC 2.A.1.28.1) family. [View classification] |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transport |
| Cellular component | Cell membrane Membrane |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation Neurodegeneration Retinitis pigmentosa |
| Domain | Transmembrane Transmembrane helix |
| Molecular function | Receptor |
| PTM | Acetylation Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular iron ion homeostasisTraceable author statement. Source: Reactome heme exportInferred from mutant phenotype Ref.7. Source: UniProtKB transmembrane transportTraceable author statement. Source: Reactome |
| Cellular component | integral to plasma membrane Traceable author statement. Source: ProtInc |
| Molecular function | heme transporter activity Inferred from direct assay Ref.10. Source: UniProtKB protein bindingInferred from physical interaction Ref.10. Source: UniProtKB receptor activityInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 555 | 554 | Feline leukemia virus subgroup C receptor-related protein 1 | PRO_0000084844 | |||||
Regions | |||||||||
| Transmembrane | 108 – 128 | 21 | Helical; Potential | ||||||
| Transmembrane | 148 – 168 | 21 | Helical; Potential | ||||||
| Transmembrane | 175 – 195 | 21 | Helical; Potential | ||||||
| Transmembrane | 200 – 220 | 21 | Helical; Potential | ||||||
| Transmembrane | 241 – 261 | 21 | Helical; Potential | ||||||
| Transmembrane | 276 – 296 | 21 | Helical; Potential | ||||||
| Transmembrane | 332 – 352 | 21 | Helical; Potential | ||||||
| Transmembrane | 373 – 393 | 21 | Helical; Potential | ||||||
| Transmembrane | 402 – 422 | 21 | Helical; Potential | ||||||
| Transmembrane | 425 – 445 | 21 | Helical; Potential | ||||||
| Transmembrane | 460 – 480 | 21 | Helical; Potential | ||||||
| Transmembrane | 491 – 511 | 21 | Helical; Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine Ref.8 | ||||||
| Modified residue | 56 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 536 | 1 | Phosphoserine Ref.8 | ||||||
Natural variations | |||||||||
| Natural variant | 52 | 1 | A → P. Ref.4 Corresponds to variant rs11120047 [ dbSNP | Ensembl ]. | VAR_050297 | |||||
| Natural variant | 121 | 1 | N → D in PCARP. Ref.11 | VAR_065158 | |||||
| Natural variant | 192 | 1 | C → R in PCARP. Ref.11 | VAR_065159 | |||||
| Natural variant | 241 | 1 | A → T in PCARP. Ref.11 | VAR_065160 | |||||
| Natural variant | 493 | 1 | G → R in PCARP. Ref.12 | VAR_065161 | |||||
| Natural variant | 544 | 1 | T → M. Ref.4 Corresponds to variant rs3207090 [ dbSNP | Ensembl ]. | VAR_050298 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A putative cell surface receptor for anemia-inducing feline leukemia virus subgroup C is a member of a transporter superfamily." Tailor C.S., Willett B.J., Kabat D. J. Virol. 73:6500-6505(1999) [PubMed: 10400745] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CHARACTERIZATION OF FELV-C RECEPTOR FUNCTION. Tissue: Lymphocyte. |
| [2] | NHLBI resequencing and genotyping service (RS&G) Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PRO-52 AND MET-544. Tissue: Duodenum. |
| [5] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 277-555. |
| [6] | "Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus." Lipovich L., Hughes A.L., King M.-C., Abkowitz J.L., Quigley J.G. Gene 286:203-213(2002) [PubMed: 11943475] [Abstract] Cited for: GENE STRUCTURE. |
| [7] | "Identification of a human heme exporter that is essential for erythropoiesis." Quigley J.G., Yang Z., Worthington M.T., Phillips J.D., Sabo K.M., Sabath D.E., Berg C.L., Sassa S., Wood B.L., Abkowitz J.L. Cell 118:757-766(2004) [PubMed: 15369674] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE. |
| [8] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-536, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [9] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [10] | "Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin." Yang Z., Philips J.D., Doty R.T., Giraudi P., Ostrow J.D., Tiribelli C., Smith A., Abkowitz J.L. J. Biol. Chem. 285:28874-28882(2010) [PubMed: 20610401] [Abstract] Cited for: FUNCTION, INTERACTION WITH HPX. |
| [11] | "Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa." Rajadhyaksha A.M., Elemento O., Puffenberger E.G., Schierberl K.C., Xiang J.Z., Putorti M.L., Berciano J., Poulin C., Brais B., Michaelides M., Weleber R.G., Higgins J.J. Am. J. Hum. Genet. 87:643-654(2010) [PubMed: 21070897] [Abstract] Cited for: VARIANTS PCARP ASP-121; ARG-192 AND THR-241. |
| [12] | "Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1." Ishiura H., Fukuda Y., Mitsui J., Nakahara Y., Ahsan B., Takahashi Y., Ichikawa Y., Goto J., Sakai T., Tsuji S. Neurogenetics 12:117-121(2011) [PubMed: 21267618] [Abstract] Cited for: VARIANT PCARP ARG-493. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF118637 mRNA. Translation: AAD45243.1. DQ496107 Genomic DNA. Translation: ABF47096.1. CH471100 Genomic DNA. Translation: EAW93374.1. BC048312 mRNA. Translation: AAH48312.1. AK001419 mRNA. Translation: BAA91679.1. |
| IPI | IPI00022344. |
| RefSeq | NP_054772.1. NM_014053.3. |
| UniGene | Hs.592816. Hs.7055. |
3D structure databases | |
| ProteinModelPortal | Q9Y5Y0. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q9Y5Y0. |
Protein family/group databases | |
| TCDB | 2.A.1.28.1. major facilitator superfamily (MFS). |
PTM databases | |
| PhosphoSite | Q9Y5Y0. |
Polymorphism databases | |
| DMDM | 46396053. |
Proteomic databases | |
| PRIDE | Q9Y5Y0. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000366971; ENSP00000355938; ENSG00000162769. |
| GeneID | 28982. |
| KEGG | hsa:28982. |
| UCSC | uc001hjt.1. human. |
Organism-specific databases | |
| CTD | 28982. |
| GeneCards | GC01P213031. |
| H-InvDB | HIX0001579. |
| HGNC | HGNC:24682. FLVCR1. |
| MIM | 609033. phenotype. 609144. gene. |
| neXtProt | NX_Q9Y5Y0. |
| Orphanet | 88628. Posterior column ataxia - retinitis pigmentosa. |
| GenAtlas | Search... |
Phylogenomic databases | |
| GeneTree | ENSGT00530000062892. |
| HOGENOM | HBG314332. |
| HOVERGEN | HBG051631. |
| InParanoid | Q9Y5Y0. |
| OMA | AWIKCGS. |
| OrthoDB | EOG4HT8RV. |
| PhylomeDB | Q9Y5Y0. |
Enzyme and pathway databases | |
| Reactome | REACT_15518. Transmembrane transport of small molecules. |
Gene expression databases | |
| ArrayExpress | Q9Y5Y0. |
| Bgee | Q9Y5Y0. |
| CleanEx | HS_FLVCR1. |
| Genevestigator | Q9Y5Y0. |
| GermOnline | ENSG00000162769. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. [Graphical view] |
| KO | K08220. |
| Pfam | PF07690. MFS_1. 1 hit. [Graphical view] |
| SUPFAM | SSF103473. MFS_gen_substrate_transporter. 1 hit. |
| PROSITE | PS50850. MFS. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 51873. |
| SOURCE | Search... |
Entry information
| Entry name | FLVC1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9Y5Y0 Secondary accession number(s): Q1HE16, Q86XY9, Q9NVR9 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with