Q9UPI3 (FLVC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Feline leukemia virus subgroup C receptor-related protein 2

Alternative name(s):
Calcium-chelate transporter
Short name=CCT

Gene names

Name:	FLVCR2
Synonyms:	C14orf58

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	526 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as an importer of heme. Also acts as a transporter for a calcium-chelator complex, important for growth and calcium metabolism. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in non-hematopoietic tissues, with relative abundant expression in brain, placenta, lung, liver and kidney. Also expressed in hematopoietic tissues (fetal liver, spleen, lymph node, thymus, leukocytes and bone marrow). Found in acidophil cells of the pituitary that secrete growth hormone and prolactin.
Involvement in disease	Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH) [MIM:225790]: A rare prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. Hydranencephaly is a condition where the greater portions of the cerebral hemispheres and corpus striatum are replaced by cerebrospinal fluid and glial tissue. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the major facilitator superfamily. Feline leukemia virus subgroup C receptor (TC 2.A.1.28.1) family. [View classification]
Sequence caution	The sequence BAB55381.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	transmembrane transport Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	heme binding Inferred from direct assay Ref.7. Source: UniProtKB heme transporter activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UPI3-1)

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.

Isoform 2 (identifier: Q9UPI3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MVNEGPNQEESDDTPVPE → MSADNSSTICVCRSVRQE
     19-223: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 526	526	Feline leukemia virus subgroup C receptor-related protein 2		PRO_0000084846
Regions
	Transmembrane	103 – 123	21	Helical; Potential
	Transmembrane	125 – 145	21	Helical; Potential
	Transmembrane	152 – 172	21	Helical; Potential
	Transmembrane	176 – 196	21	Helical; Potential
	Transmembrane	217 – 237	21	Helical; Potential
	Transmembrane	252 – 272	21	Helical; Potential
	Transmembrane	310 – 330	21	Helical; Potential
	Transmembrane	349 – 369	21	Helical; Potential
	Transmembrane	386 – 406	21	Helical; Potential
	Transmembrane	407 – 427	21	Helical; Potential
	Transmembrane	436 – 456	21	Helical; Potential
	Transmembrane	471 – 491	21	Helical; Potential
	Repeat	25 – 30	6	1
	Repeat	31 – 36	6	2
	Repeat	37 – 42	6	3
	Repeat	43 – 48	6	4
	Repeat	49 – 54	6	5
	Repeat	55 – 60	6	6; approximate
	Repeat	61 – 66	6	7; approximate
	Repeat	67 – 72	6	8
	Region	25 – 72	48	8 X 6 AA tandem repeats of P-S-[VS]-S-[VIAG]-[HNP]
	Compositional bias	507 – 511	5	Poly-Glu
Natural variations
	Alternative sequence	1 – 18	18	MVNEG…TPVPE → MSADNSSTICVCRSVRQE in isoform 2.		VSP_043048
	Alternative sequence	19 – 223	205	Missing in isoform 2.		VSP_043049
	Natural variant	16	1	V → A. Ref.3 Corresponds to variant rs2287015 [ dbSNP | Ensembl ].		VAR_018271
	Natural variant	84	1	R → H in PVHH. Ref.10		VAR_064410
	Natural variant	110 – 112	3	NIF → I in PVHH.		VAR_064411
	Natural variant	280	1	P → R in PVHH. Ref.8		VAR_064043
	Natural variant	326	1	A → V in PVHH. Ref.9		VAR_064412
	Natural variant	352	1	T → R in PVHH. Ref.10		VAR_064413
	Natural variant	398	1	L → V in PVHH. Ref.8 Ref.9 Ref.10		VAR_064044
	Natural variant	412	1	G → R in PVHH. Ref.10		VAR_064414
	Natural variant	430	1	T → M in PVHH. Ref.10		VAR_064415
	Natural variant	430	1	T → R in PVHH. Ref.8		VAR_064045
	Natural variant	481	1	A → T. Corresponds to variant rs35126362 [ dbSNP | Ensembl ].		VAR_050299
Experimental info
	Sequence conflict	419	1	L → H in BAB55381. Ref.3
	Sequence conflict	439	1	S → F in BAA91126. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: D233C07350B17870	FASTA	526	57,241
	10 20 30 40 50 60 MVNEGPNQEE SDDTPVPESA LQADPSVSVH PSVSVHPSVS INPSVSVHPS SSAHPSALAQ 70 80 90 100 110 120 PSGLAHPSSS GPEDLSVIKV SRRRWAVVLV FSCYSMCNSF QWIQYGSINN IFMHFYGVSA 130 140 150 160 170 180 FAIDWLSMCY MLTYIPLLLP VAWLLEKFGL RTIALTGSAL NCLGAWVKLG SLKPHLFPVT 190 200 210 220 230 240 VVGQLICSVA QVFILGMPSR IASVWFGANE VSTACSVAVF GNQLGIAIGF LVPPVLVPNI 250 260 270 280 290 300 EDRDELAYHI SIMFYIIGGV ATLLLILVII VFKEKPKYPP SRAQSLSYAL TSPDASYLGS 310 320 330 340 350 360 IARLFKNLNF VLLVITYGLN AGAFYALSTL LNRMVIWHYP GEEVNAGRIG LTIVIAGMLG 370 380 390 400 410 420 AVISGIWLDR SKTYKETTLV VYIMTLVGMV VYTFTLNLGH LWVVFITAGT MGFFMTGYLP 430 440 450 460 470 480 LGFEFAVELT YPESEGISSG LLNISAQVFG IIFTISQGQI IDNYGTKPGN IFLCVFLTLG 490 500 510 520 AALTAFIKAD LRRQKANKET LENKLQEEEE ESNTSKVPTA VSEDHL
	Isoform 2 [UniParc]. Checksum: DC129F2BDAFF1DA3	FASTA	321	35,262
	10 20 30 40 50 60 MSADNSSTIC VCRSVRQELG IAIGFLVPPV LVPNIEDRDE LAYHISIMFY IIGGVATLLL 70 80 90 100 110 120 ILVIIVFKEK PKYPPSRAQS LSYALTSPDA SYLGSIARLF KNLNFVLLVI TYGLNAGAFY 130 140 150 160 170 180 ALSTLLNRMV IWHYPGEEVN AGRIGLTIVI AGMLGAVISG IWLDRSKTYK ETTLVVYIMT 190 200 210 220 230 240 LVGMVVYTFT LNLGHLWVVF ITAGTMGFFM TGYLPLGFEF AVELTYPESE GISSGLLNIS 250 260 270 280 290 300 AQVFGIIFTI SQGQIIDNYG TKPGNIFLCV FLTLGAALTA FIKADLRRQK ANKETLENKL 310 320 QEEEEESNTS KVPTAVSEDH L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel hexad repeats conserved in a putative transporter with restricted expression in cell types associated with growth, calcium exchange and homeostasis." Brasier G., Tikellis C., Xuereb L., Craigie J., Casley D., Kovacs C.S., Fudge N.J., Kalnins R., Cooper M.E., Wookey P.J. Exp. Cell Res. 293:31-42(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Pituitary.
[2]	"An aspartic acid in the presumptive extracellular loop six of subgroup C feline leukemia virus receptor FLVCR1 is involved in virus infection." Brown J., Pirani H., Tailor C.S. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] (ISOFORMS 1 AND 2), VARIANT ALA-16. Tissue: Placenta and Umbilical cord blood.
[4]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Colon.
[7]	"The Fowler syndrome-associated protein FLVCR2 is an importer of heme." Duffy S.P., Shing J., Saraon P., Berger L.C., Eiden M.V., Wilde A., Tailor C.S. Mol. Cell. Biol. 30:5318-5324(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome)." Meyer E., Ricketts C., Morgan N.V., Morris M.R., Pasha S., Tee L.J., Rahman F., Bazin A., Bessieres B., Dechelotte P., Yacoubi M.T., Al-Adnani M., Marton T., Tannahill D., Trembath R.C., Fallet-Bianco C., Cox P., Williams D., Maher E.R. Am. J. Hum. Genet. 86:471-478(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PVHH ARG-280; VAL-398 AND ARG-430.
[9]	"Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing." Lalonde E., Albrecht S., Ha K.C., Jacob K., Bolduc N., Polychronakos C., Dechelotte P., Majewski J., Jabado N. Hum. Mutat. 31:918-923(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PVHH 110-ASN--PHE-112 DELINS ILE; VAL-326 AND VAL-398.
[10]	"High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy." Thomas S., Encha-Razavi F., Devisme L., Etchevers H., Bessieres-Grattagliano B., Goudefroye G., Elkhartoufi N., Pateau E., Ichkou A., Bonniere M., Marcorelle P., Parent P., Manouvrier S., Holder M., Laquerriere A., Loeuillet L., Roume J., Martinovic J. , Mougou-Zerelli S., Gonzales M., Meyer V., Wessner M., Feysot C.B., Nitschke P., Leticee N., Munnich A., Lyonnet S., Wookey P., Gyapay G., Foliguet B., Vekemans M., Attie-Bitach T. Hum. Mutat. 31:1134-1141(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PVHH HIS-84; ARG-352; VAL-398; ARG-412 AND MET-430.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY260572 mRNA. Translation: AAP86633.1. AY260577 mRNA. Translation: AAP86638.1. AF456126 mRNA. Translation: AAO15528.1. AK000378 mRNA. Translation: BAA91126.1. AK027804 mRNA. Translation: BAB55381.1. Different initiation. AK297002 mRNA. Translation: BAH12471.1. AC007182 Genomic DNA. Translation: AAD51374.1. CH471061 Genomic DNA. Translation: EAW81235.1. BC019087 mRNA. Translation: AAH19087.1.
IPI	IPI00100520. IPI00976985.
RefSeq	NP_001182212.1. NM_001195283.1. NP_060261.2. NM_017791.2.
UniGene	Hs.509966. Hs.615289.
3D structure databases
ProteinModelPortal	Q9UPI3.
SMR	Q9UPI3. Positions 110-138.
ModBase	Search...
PTM databases
PhosphoSite	Q9UPI3.
Polymorphism databases
DMDM	46396034.
Proteomic databases
PaxDb	Q9UPI3.
PRIDE	Q9UPI3.
Protocols and materials databases
DNASU	55640.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000238667; ENSP00000238667; ENSG00000119686. ENST00000539311; ENSP00000443439; ENSG00000119686.
GeneID	55640.
KEGG	hsa:55640.
UCSC	uc001xrs.2. human.
Organism-specific databases
CTD	55640.
GeneCards	GC14P076045.
H-InvDB	HIX0037867.
HGNC	HGNC:20105. FLVCR2.
HPA	HPA037984.
MIM	225790. phenotype. 610865. gene.
neXtProt	NX_Q9UPI3.
Orphanet	221126. Fowler syndrome.
PharmGKB	PA162388720.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG297699.
HOGENOM	HOG000019717.
HOVERGEN	HBG051631.
InParanoid	Q9UPI3.
KO	K08220.
OMA	INNIFMH.
OrthoDB	EOG4BRWKN.
PhylomeDB	Q9UPI3.
Gene expression databases
ArrayExpress	Q9UPI3.
Bgee	Q9UPI3.
CleanEx	HS_FLVCR2.
Genevestigator	Q9UPI3.
GermOnline	ENSG00000119686. 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	55640.
NextBio	60326.
SOURCE	Search...

Entry information

Entry name

FLVC2_HUMAN

Accession

Primary (citable) accession number: Q9UPI3
Secondary accession number(s): B7Z485 , Q53ZT9, Q96JY3, Q9NX90

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 100 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.