Q9Y5Y0 (FLVC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:	FLVCR1
Synonyms:	FLVCR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	555 AA.
Sequence status	Complete.
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	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: 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. Ref.13 Ref.14
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	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cellular iron ion homeostasis Traceable author statement. Source: Reactome embryonic digit morphogenesis Inferred from electronic annotation. Source: Compara erythrocyte differentiation Inferred from electronic annotation. Source: Compara head morphogenesis Inferred from electronic annotation. Source: Compara heme export Inferred from mutant phenotype Ref.7. Source: UniProtKB in utero embryonic development Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara multicellular organismal development Traceable author statement PubMed 10648427. Source: ProtInc regulation of organ growth Inferred from electronic annotation. Source: Compara spleen development Inferred from electronic annotation. Source: Compara transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement PubMed 10648427. Source: ProtInc
Molecular_function	heme transporter activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 555	555	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	56	1	Phosphoserine Ref.9
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.13		VAR_065158
	Natural variant	192	1	C → R in PCARP. Ref.13		VAR_065159
	Natural variant	241	1	A → T in PCARP. Ref.13		VAR_065160
	Natural variant	493	1	G → R in PCARP. Ref.14		VAR_065161
	Natural variant	544	1	T → M. Ref.4 Corresponds to variant rs3207090 [ dbSNP | Ensembl ].		VAR_050298

Sequences

	Sequence		Length	Mass (Da)
	Q9Y5Y0 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: D0EBA9886CC8E747	FASTA	555	59,863
	10 20 30 40 50 60 MARPDDEEGA AVAPGHPLAK GYLPLPRGAP VGKESVELQN GPKAGTFPVN GAPRDSLAAA 70 80 90 100 110 120 SGVLGGPQTP LAPEEETQAR LLPAGAGAET PGAESSPLPL TALSPRRFVV LLIFSLYSLV 130 140 150 160 170 180 NAFQWIQYSI ISNVFEGFYG VTLLHIDWLS MVYMLAYVPL IFPATWLLDT RGLRLTALLG 190 200 210 220 230 240 SGLNCLGAWI KCGSVQQHLF WVTMLGQCLC SVAQVFILGL PSRIASVWFG PKEVSTACAT 250 260 270 280 290 300 AVLGNQLGTA VGFLLPPVLV PNTQNDTNLL ACNISTMFYG TSAVATLLFI LTAIAFKEKP 310 320 330 340 350 360 RYPPSQAQAA LQDSPPEEYS YKKSIRNLFK NIPFVLLLIT YGIMTGAFYS VSTLLNQMIL 370 380 390 400 410 420 TYYEGEEVNA GRIGLTLVVA GMVGSILCGL WLDYTKTYKQ TTLIVYILSF IGMVIFTFTL 430 440 450 460 470 480 DLRYIIIVFV TGGVLGFFMT GYLPLGFEFA VEITYPESEG TSSGLLNASA QIFGILFTLA 490 500 510 520 530 540 QGKLTSDYGP KAGNIFLCVW MFIGIILTAL IKSDLRRHNI NIGITNVDVK AIPADSPTDQ 550 EPKTVMLSKQ SESAI

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., 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] [Europe PMC] [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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HPX.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS PCARP ASP-121; ARG-192 AND THR-241.
[14]	"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] [Europe PMC] [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.7055.
3D structure databases
ProteinModelPortal	Q9Y5Y0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000355938.
Protein family/group databases
TCDB	2.A.1.28.1. major facilitator superfamily (MFS).
PTM databases
PhosphoSite	Q9Y5Y0.
Polymorphism databases
DMDM	46396053.
Proteomic databases
PaxDb	Q9Y5Y0.
PRIDE	Q9Y5Y0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366971; ENSP00000355938; ENSG00000162769.
GeneID	28982.
KEGG	hsa:28982.
UCSC	uc001hjt.3. human.
Organism-specific databases
CTD	28982.
GeneCards	GC01P213031.
HGNC	HGNC:24682. FLVCR1.
HPA	HPA046646.
MIM	609033. phenotype. 609144. gene.
neXtProt	NX_Q9Y5Y0.
Orphanet	88628. Posterior column ataxia - retinitis pigmentosa.
PharmGKB	PA162388695.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG297699.
HOGENOM	HOG000019717.
HOVERGEN	HBG051631.
InParanoid	Q9Y5Y0.
KO	K08220.
OMA	AWIKCGS.
OrthoDB	EOG4HT8RV.
PhylomeDB	Q9Y5Y0.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
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]
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
GenomeRNAi	28982.
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

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 88 of the entry and version 1 of the sequence. [Complete history]

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.