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Protein

Feline leukemia virus subgroup C receptor-related protein 1

Gene

FLVCR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Isoform 1: 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 is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythtopoiesis, a process in which heme synthesis intensifies. Causes susceptibility to FeLV-C in vitro.4 Publications
Isoform 2: Heme transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.

GO - Molecular functioni

  • heme transporter activity Source: UniProtKB
  • transporter activity Source: ProtInc

GO - Biological processi

  • blood vessel development Source: Ensembl
  • cellular iron ion homeostasis Source: Reactome
  • embryonic digit morphogenesis Source: Ensembl
  • embryonic skeletal system morphogenesis Source: Ensembl
  • erythrocyte differentiation Source: MGI
  • erythrocyte maturation Source: UniProtKB-KW
  • head morphogenesis Source: Ensembl
  • heme export Source: UniProtKB
  • heme transport Source: MGI
  • in utero embryonic development Source: Ensembl
  • mitochondrial transport Source: MGI
  • multicellular organism development Source: ProtInc
  • multicellular organism growth Source: Ensembl
  • regulation of organ growth Source: Ensembl
  • spleen development Source: Ensembl
  • transmembrane transport Source: InterPro
  • transport Source: ProtInc

Keywordsi

Molecular functionReceptor
Biological processErythrocyte maturation, Transport

Enzyme and pathway databases

ReactomeiR-HSA-917937. Iron uptake and transport.

Protein family/group databases

TCDBi2.A.1.28.1. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Feline leukemia virus subgroup C receptor-related protein 1
Short name:
Feline leukemia virus subgroup C receptor
Short name:
hFLVCR
Gene namesi
Name:FLVCR1
Synonyms:FLVCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:24682. FLVCR1.

Subcellular locationi

Isoform 1 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 107CytoplasmicSequence analysisAdd BLAST107
Transmembranei108 – 128HelicalSequence analysisAdd BLAST21
Topological domaini129 – 147ExtracellularSequence analysisAdd BLAST19
Transmembranei148 – 168HelicalSequence analysisAdd BLAST21
Topological domaini169 – 174CytoplasmicSequence analysis6
Transmembranei175 – 195HelicalSequence analysisAdd BLAST21
Topological domaini196 – 199ExtracellularSequence analysis4
Transmembranei200 – 220HelicalSequence analysisAdd BLAST21
Topological domaini221 – 240CytoplasmicSequence analysisAdd BLAST20
Transmembranei241 – 261HelicalSequence analysisAdd BLAST21
Topological domaini262 – 275ExtracellularSequence analysisAdd BLAST14
Transmembranei276 – 296HelicalSequence analysisAdd BLAST21
Topological domaini297 – 331CytoplasmicSequence analysisAdd BLAST35
Transmembranei332 – 352HelicalSequence analysisAdd BLAST21
Topological domaini353 – 372ExtracellularSequence analysisAdd BLAST20
Transmembranei373 – 393HelicalSequence analysisAdd BLAST21
Topological domaini394 – 401CytoplasmicSequence analysis8
Transmembranei402 – 422HelicalSequence analysisAdd BLAST21
Topological domaini423 – 424ExtracellularSequence analysis2
Transmembranei425 – 445HelicalSequence analysisAdd BLAST21
Topological domaini446 – 459CytoplasmicSequence analysisAdd BLAST14
Transmembranei460 – 480HelicalSequence analysisAdd BLAST21
Topological domaini481 – 490ExtracellularSequence analysis10
Transmembranei491 – 511HelicalSequence analysisAdd BLAST21
Topological domaini512 – 555CytoplasmicSequence analysisAdd BLAST44

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • mitochondrial membrane Source: UniProtKB-SubCell
  • mitochondrion Source: MGI
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Cell membrane, Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Posterior column ataxia with retinitis pigmentosa (PCARP)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. 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.
Disease descriptionA 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.
See also OMIM:609033
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065158121N → D in PCARP. 1 PublicationCorresponds to variant dbSNP:rs267606820Ensembl.1
Natural variantiVAR_065159192C → R in PCARP; also found in a patient with sensory neuropathy and pain insensitivity. 2 PublicationsCorresponds to variant dbSNP:rs267606821Ensembl.1
Natural variantiVAR_065160241A → T in PCARP. 1 PublicationCorresponds to variant dbSNP:rs267606819Ensembl.1
Natural variantiVAR_065161493G → R in PCARP. 1 Publication1
Defects in FLVCR1 are a cause of a sensory neuropathy resulting in pain insensitivity. Patients have decreased sensing of pain, temperature and touch. Self-injury, ulcers and amputations are commonly observed in affected individuals.1 Publication

Keywords - Diseasei

Disease mutation, Neurodegeneration, Neuropathy, Retinitis pigmentosa

Organism-specific databases

DisGeNETi28982.
MalaCardsiFLVCR1.
MIMi609033. phenotype.
OpenTargetsiENSG00000162769.
Orphaneti88628. Posterior column ataxia - retinitis pigmentosa.
PharmGKBiPA162388695.

Polymorphism and mutation databases

BioMutaiFLVCR1.
DMDMi46396053.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000848441 – 555Feline leukemia virus subgroup C receptor-related protein 1Add BLAST555

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei56PhosphoserineCombined sources1
Glycosylationi265N-linked (GlcNAc...)Sequence analysis1
Glycosylationi273N-linked (GlcNAc...)Sequence analysis1
Modified residuei536PhosphoserineCombined sources1

Post-translational modificationi

N-Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9Y5Y0.
PaxDbiQ9Y5Y0.
PeptideAtlasiQ9Y5Y0.
PRIDEiQ9Y5Y0.

PTM databases

iPTMnetiQ9Y5Y0.
PhosphoSitePlusiQ9Y5Y0.

Expressioni

Tissue specificityi

Found all hematopoietic tissues including peripheral blood lymphocytes. Some expression is found in pancreas and kidney.1 Publication

Developmental stagei

Down-regulated in haemopoietic progenitor cells undergoing differentiation and hemoglobinization. Abundant in fetal liver.1 Publication

Gene expression databases

BgeeiENSG00000162769.
CleanExiHS_FLVCR1.
ExpressionAtlasiQ9Y5Y0. baseline and differential.
GenevisibleiQ9Y5Y0. HS.

Organism-specific databases

HPAiHPA046646.

Interactioni

Subunit structurei

Interacts with HPX.1 Publication

Protein-protein interaction databases

BioGridi118803. 19 interactors.
IntActiQ9Y5Y0. 2 interactors.
STRINGi9606.ENSP00000355938.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5Y0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2563. Eukaryota.
ENOG410XSTK. LUCA.
GeneTreeiENSGT00530000062892.
HOGENOMiHOG000019717.
HOVERGENiHBG051631.
InParanoidiQ9Y5Y0.
KOiK08220.
OMAiVIAFKEK.
OrthoDBiEOG090B06SF.
PhylomeDBiQ9Y5Y0.
TreeFamiTF314292.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiView protein in InterPro
IPR011701. MFS.
IPR020846. MFS_dom.
PfamiView protein in Pfam
PF07690. MFS_1. 1 hit.
SUPFAMiSSF103473. SSF103473. 1 hit.
PROSITEiView protein in PROSITE
PS50850. MFS. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y5Y0-1) [UniParc]FASTAAdd to basket
Also known as: FLVC1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN
60 70 80 90 100
GAPRDSLAAA SGVLGGPQTP LAPEEETQAR LLPAGAGAET PGAESSPLPL
110 120 130 140 150
TALSPRRFVV LLIFSLYSLV NAFQWIQYSI ISNVFEGFYG VTLLHIDWLS
160 170 180 190 200
MVYMLAYVPL IFPATWLLDT RGLRLTALLG SGLNCLGAWI KCGSVQQHLF
210 220 230 240 250
WVTMLGQCLC SVAQVFILGL PSRIASVWFG PKEVSTACAT AVLGNQLGTA
260 270 280 290 300
VGFLLPPVLV PNTQNDTNLL ACNISTMFYG TSAVATLLFI LTAIAFKEKP
310 320 330 340 350
RYPPSQAQAA LQDSPPEEYS YKKSIRNLFK NIPFVLLLIT YGIMTGAFYS
360 370 380 390 400
VSTLLNQMIL TYYEGEEVNA GRIGLTLVVA GMVGSILCGL WLDYTKTYKQ
410 420 430 440 450
TTLIVYILSF IGMVIFTFTL DLRYIIIVFV TGGVLGFFMT GYLPLGFEFA
460 470 480 490 500
VEITYPESEG TSSGLLNASA QIFGILFTLA QGKLTSDYGP KAGNIFLCVW
510 520 530 540 550
MFIGIILTAL IKSDLRRHNI NIGITNVDVK AIPADSPTDQ EPKTVMLSKQ

SESAI
Length:555
Mass (Da):59,863
Last modified:November 1, 1999 - v1
Checksum:iD0EBA9886CC8E747
GO
Isoform 2 (identifier: Q9Y5Y0-2) [UniParc]FASTAAdd to basket
Also known as: FLVC1b, mitochondrial

The sequence of this isoform differs from the canonical sequence as follows:
     1-276: Missing.

Note: Has a probable mitochondrial transit peptide at positions 1-38.
Show »
Length:279
Mass (Da):30,744
Checksum:iFA59C9CBEE5CE3CA
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05029752A → P1 PublicationCorresponds to variant dbSNP:rs11120047Ensembl.1
Natural variantiVAR_065158121N → D in PCARP. 1 PublicationCorresponds to variant dbSNP:rs267606820Ensembl.1
Natural variantiVAR_065159192C → R in PCARP; also found in a patient with sensory neuropathy and pain insensitivity. 2 PublicationsCorresponds to variant dbSNP:rs267606821Ensembl.1
Natural variantiVAR_077884221P → S Probable disease-associated mutation found in a patient with sensory neuropathy and pain insensitivity. 1 Publication1
Natural variantiVAR_065160241A → T in PCARP. 1 PublicationCorresponds to variant dbSNP:rs267606819Ensembl.1
Natural variantiVAR_065161493G → R in PCARP. 1 Publication1
Natural variantiVAR_050298544T → M1 PublicationCorresponds to variant dbSNP:rs3207090Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0478661 – 276Missing in isoform 2. 2 PublicationsAdd BLAST276

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF118637 mRNA. Translation: AAD45243.1.
AK001419 mRNA. Translation: BAA91679.1.
DQ496107 Genomic DNA. Translation: ABF47096.1.
CH471100 Genomic DNA. Translation: EAW93374.1.
BC048312 mRNA. Translation: AAH48312.1.
CCDSiCCDS1510.1. [Q9Y5Y0-1]
RefSeqiNP_054772.1. NM_014053.3. [Q9Y5Y0-1]
UniGeneiHs.7055.

Genome annotation databases

EnsembliENST00000366971; ENSP00000355938; ENSG00000162769. [Q9Y5Y0-1]
GeneIDi28982.
KEGGihsa:28982.
UCSCiuc001hjt.3. human. [Q9Y5Y0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF118637 mRNA. Translation: AAD45243.1.
AK001419 mRNA. Translation: BAA91679.1.
DQ496107 Genomic DNA. Translation: ABF47096.1.
CH471100 Genomic DNA. Translation: EAW93374.1.
BC048312 mRNA. Translation: AAH48312.1.
CCDSiCCDS1510.1. [Q9Y5Y0-1]
RefSeqiNP_054772.1. NM_014053.3. [Q9Y5Y0-1]
UniGeneiHs.7055.

3D structure databases

ProteinModelPortaliQ9Y5Y0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118803. 19 interactors.
IntActiQ9Y5Y0. 2 interactors.
STRINGi9606.ENSP00000355938.

Protein family/group databases

TCDBi2.A.1.28.1. the major facilitator superfamily (mfs).

PTM databases

iPTMnetiQ9Y5Y0.
PhosphoSitePlusiQ9Y5Y0.

Polymorphism and mutation databases

BioMutaiFLVCR1.
DMDMi46396053.

Proteomic databases

EPDiQ9Y5Y0.
PaxDbiQ9Y5Y0.
PeptideAtlasiQ9Y5Y0.
PRIDEiQ9Y5Y0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366971; ENSP00000355938; ENSG00000162769. [Q9Y5Y0-1]
GeneIDi28982.
KEGGihsa:28982.
UCSCiuc001hjt.3. human. [Q9Y5Y0-1]

Organism-specific databases

CTDi28982.
DisGeNETi28982.
GeneCardsiFLVCR1.
HGNCiHGNC:24682. FLVCR1.
HPAiHPA046646.
MalaCardsiFLVCR1.
MIMi609033. phenotype.
609144. gene.
neXtProtiNX_Q9Y5Y0.
OpenTargetsiENSG00000162769.
Orphaneti88628. Posterior column ataxia - retinitis pigmentosa.
PharmGKBiPA162388695.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2563. Eukaryota.
ENOG410XSTK. LUCA.
GeneTreeiENSGT00530000062892.
HOGENOMiHOG000019717.
HOVERGENiHBG051631.
InParanoidiQ9Y5Y0.
KOiK08220.
OMAiVIAFKEK.
OrthoDBiEOG090B06SF.
PhylomeDBiQ9Y5Y0.
TreeFamiTF314292.

Enzyme and pathway databases

ReactomeiR-HSA-917937. Iron uptake and transport.

Miscellaneous databases

ChiTaRSiFLVCR1. human.
GeneWikiiFLVCR1.
GenomeRNAii28982.
PROiQ9Y5Y0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162769.
CleanExiHS_FLVCR1.
ExpressionAtlasiQ9Y5Y0. baseline and differential.
GenevisibleiQ9Y5Y0. HS.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiView protein in InterPro
IPR011701. MFS.
IPR020846. MFS_dom.
PfamiView protein in Pfam
PF07690. MFS_1. 1 hit.
SUPFAMiSSF103473. SSF103473. 1 hit.
PROSITEiView protein in PROSITE
PS50850. MFS. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFLVC1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5Y0
Secondary accession number(s): Q1HE16, Q86XY9, Q9NVR9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: November 1, 1999
Last modified: February 15, 2017
This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.