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Feline leukemia virus subgroup C receptor-related protein 2 (Calcium-chelate transporter) (CCT)

 FLVC2_HUMAN             Reviewed;         526 AA.
Q9UPI3; B7Z485; Q53ZT9; Q96JY3; Q9NX90;
13-APR-2004, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
25-OCT-2017, entry version 135.
RecName: Full=Feline leukemia virus subgroup C receptor-related protein 2;
AltName: Full=Calcium-chelate transporter;
Short=CCT;
Name=FLVCR2; Synonyms=C14orf58;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
TISSUE=Pituitary;
PubMed=14729055; DOI=10.1016/j.yexcr.2003.10.002;
Brasier G., Tikellis C., Xuereb L., Craigie J., Casley D.,
Kovacs C.S., Fudge N.J., Kalnins R., Cooper M.E., Wookey P.J.;
"Novel hexad repeats conserved in a putative transporter with
restricted expression in cell types associated with growth, calcium
exchange and homeostasis.";
Exp. Cell Res. 293:31-42(2004).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Brown J., Pirani H., Tailor C.S.;
"An aspartic acid in the presumptive extracellular loop six of
subgroup C feline leukemia virus receptor FLVCR1 is involved in virus
infection.";
Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
ALA-16.
TISSUE=Placenta, and Umbilical cord blood;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12508121; DOI=10.1038/nature01348;
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.;
"The DNA sequence and analysis of human chromosome 14.";
Nature 421:601-607(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
FUNCTION.
PubMed=20823265; DOI=10.1128/MCB.00690-10;
Duffy S.P., Shing J., Saraon P., Berger L.C., Eiden M.V., Wilde A.,
Tailor C.S.;
"The Fowler syndrome-associated protein FLVCR2 is an importer of
heme.";
Mol. Cell. Biol. 30:5318-5324(2010).
[8]
VARIANTS PVHH ARG-280; VAL-398 AND ARG-430.
PubMed=20206334; DOI=10.1016/j.ajhg.2010.02.004;
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.;
"Mutations in FLVCR2 are associated with proliferative vasculopathy
and hydranencephaly-hydrocephaly syndrome (Fowler syndrome).";
Am. J. Hum. Genet. 86:471-478(2010).
[9]
VARIANTS PVHH 110-ASN--PHE-112 DELINS ILE; VAL-326 AND VAL-398.
PubMed=20518025; DOI=10.1002/humu.21293;
Lalonde E., Albrecht S., Ha K.C., Jacob K., Bolduc N.,
Polychronakos C., Dechelotte P., Majewski J., Jabado N.;
"Unexpected allelic heterogeneity and spectrum of mutations in Fowler
syndrome revealed by next-generation exome sequencing.";
Hum. Mutat. 31:918-923(2010).
[10]
VARIANTS PVHH HIS-84; ARG-352; VAL-398; ARG-412 AND MET-430.
PubMed=20690116; DOI=10.1002/humu.21329;
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.;
"High-throughput sequencing of a 4.1 Mb linkage interval reveals
FLVCR2 deletions and mutations in lethal cerebral vasculopathy.";
Hum. Mutat. 31:1134-1141(2010).
-!- FUNCTION: Acts as an importer of heme. Also acts as a transporter
for a calcium-chelator complex, important for growth and calcium
metabolism. {ECO:0000269|PubMed:20823265}.
-!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9UPI3-1; Sequence=Displayed;
Name=2;
IsoId=Q9UPI3-2; Sequence=VSP_043048, VSP_043049;
Note=No experimental confirmation available.;
-!- 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.
-!- 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.
{ECO:0000269|PubMed:20206334, ECO:0000269|PubMed:20518025,
ECO:0000269|PubMed:20690116}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the major facilitator superfamily. Feline
leukemia virus subgroup C receptor (TC 2.A.1.28.1) family.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BAB55381.1; Type=Erroneous initiation; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AY260572; AAP86633.1; -; mRNA.
EMBL; AY260577; AAP86638.1; -; mRNA.
EMBL; AF456126; AAO15528.1; -; mRNA.
EMBL; AK000378; BAA91126.1; -; mRNA.
EMBL; AK027804; BAB55381.1; ALT_INIT; mRNA.
EMBL; AK297002; BAH12471.1; -; mRNA.
EMBL; AC007182; AAD51374.1; -; Genomic_DNA.
EMBL; CH471061; EAW81235.1; -; Genomic_DNA.
EMBL; BC019087; AAH19087.1; -; mRNA.
CCDS; CCDS55933.1; -. [Q9UPI3-2]
CCDS; CCDS9844.1; -. [Q9UPI3-1]
RefSeq; NP_001182212.1; NM_001195283.1. [Q9UPI3-2]
RefSeq; NP_060261.2; NM_017791.2. [Q9UPI3-1]
UniGene; Hs.509966; -.
ProteinModelPortal; Q9UPI3; -.
BioGrid; 120777; 4.
MINT; MINT-4724942; -.
STRING; 9606.ENSP00000238667; -.
TCDB; 2.A.1.28.4; the major facilitator superfamily (mfs).
iPTMnet; Q9UPI3; -.
PhosphoSitePlus; Q9UPI3; -.
BioMuta; FLVCR2; -.
DMDM; 46396034; -.
PaxDb; Q9UPI3; -.
PeptideAtlas; Q9UPI3; -.
PRIDE; Q9UPI3; -.
DNASU; 55640; -.
Ensembl; ENST00000238667; ENSP00000238667; ENSG00000119686. [Q9UPI3-1]
Ensembl; ENST00000539311; ENSP00000443439; ENSG00000119686. [Q9UPI3-2]
GeneID; 55640; -.
KEGG; hsa:55640; -.
UCSC; uc001xrs.3; human. [Q9UPI3-1]
CTD; 55640; -.
DisGeNET; 55640; -.
EuPathDB; HostDB:ENSG00000119686.9; -.
GeneCards; FLVCR2; -.
H-InvDB; HIX0037867; -.
HGNC; HGNC:20105; FLVCR2.
HPA; HPA037984; -.
MalaCards; FLVCR2; -.
MIM; 225790; phenotype.
MIM; 610865; gene.
neXtProt; NX_Q9UPI3; -.
OpenTargets; ENSG00000119686; -.
Orphanet; 221126; Fowler syndrome.
PharmGKB; PA162388720; -.
eggNOG; KOG2563; Eukaryota.
eggNOG; ENOG410XSTK; LUCA.
GeneTree; ENSGT00530000062892; -.
HOGENOM; HOG000019717; -.
HOVERGEN; HBG051631; -.
InParanoid; Q9UPI3; -.
KO; K08220; -.
OMA; FMHFYGV; -.
OrthoDB; EOG091G0FJM; -.
PhylomeDB; Q9UPI3; -.
TreeFam; TF314292; -.
GenomeRNAi; 55640; -.
PRO; PR:Q9UPI3; -.
Proteomes; UP000005640; Chromosome 14.
Bgee; ENSG00000119686; -.
CleanEx; HS_FLVCR2; -.
ExpressionAtlas; Q9UPI3; baseline and differential.
Genevisible; Q9UPI3; HS.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0020037; F:heme binding; IDA:UniProtKB.
GO; GO:0015232; F:heme transporter activity; IDA:UniProtKB.
GO; GO:0055085; P:transmembrane transport; IEA:InterPro.
CDD; cd06174; MFS; 1.
InterPro; IPR011701; MFS.
InterPro; IPR020846; MFS_dom.
InterPro; IPR036259; MFS_trans_sf.
Pfam; PF07690; MFS_1; 1.
SUPFAM; SSF103473; SSF103473; 1.
PROSITE; PS50850; MFS; 1.
1: Evidence at protein level;
Alternative splicing; Cell membrane; Complete proteome;
Disease mutation; Membrane; Phosphoprotein; Polymorphism;
Reference proteome; Repeat; Transmembrane; Transmembrane helix;
Transport.
CHAIN 1 526 Feline leukemia virus subgroup C
receptor-related protein 2.
/FTId=PRO_0000084846.
TRANSMEM 103 123 Helical. {ECO:0000255}.
TRANSMEM 125 145 Helical. {ECO:0000255}.
TRANSMEM 152 172 Helical. {ECO:0000255}.
TRANSMEM 176 196 Helical. {ECO:0000255}.
TRANSMEM 217 237 Helical. {ECO:0000255}.
TRANSMEM 252 272 Helical. {ECO:0000255}.
TRANSMEM 310 330 Helical. {ECO:0000255}.
TRANSMEM 349 369 Helical. {ECO:0000255}.
TRANSMEM 386 406 Helical. {ECO:0000255}.
TRANSMEM 407 427 Helical. {ECO:0000255}.
TRANSMEM 436 456 Helical. {ECO:0000255}.
TRANSMEM 471 491 Helical. {ECO:0000255}.
REPEAT 25 30 1.
REPEAT 31 36 2.
REPEAT 37 42 3.
REPEAT 43 48 4.
REPEAT 49 54 5.
REPEAT 55 60 6; approximate.
REPEAT 61 66 7; approximate.
REPEAT 67 72 8.
REGION 25 72 8 X 6 AA tandem repeats of P-S-[VS]-S-
[VIAG]-[HNP].
COMPBIAS 507 511 Poly-Glu.
MOD_RES 512 512 Phosphoserine.
{ECO:0000250|UniProtKB:Q9Y5Y0}.
MOD_RES 515 515 Phosphoserine.
{ECO:0000250|UniProtKB:Q91X85}.
VAR_SEQ 1 18 MVNEGPNQEESDDTPVPE -> MSADNSSTICVCRSVRQE
(in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_043048.
VAR_SEQ 19 223 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_043049.
VARIANT 16 16 V -> A (in dbSNP:rs2287015).
{ECO:0000269|PubMed:14702039}.
/FTId=VAR_018271.
VARIANT 84 84 R -> H (in PVHH).
{ECO:0000269|PubMed:20690116}.
/FTId=VAR_064410.
VARIANT 110 112 NIF -> I (in PVHH).
{ECO:0000269|PubMed:20518025}.
/FTId=VAR_064411.
VARIANT 280 280 P -> R (in PVHH; dbSNP:rs267606823).
{ECO:0000269|PubMed:20206334}.
/FTId=VAR_064043.
VARIANT 326 326 A -> V (in PVHH; dbSNP:rs267606824).
{ECO:0000269|PubMed:20518025}.
/FTId=VAR_064412.
VARIANT 352 352 T -> R (in PVHH).
{ECO:0000269|PubMed:20690116}.
/FTId=VAR_064413.
VARIANT 398 398 L -> V (in PVHH; dbSNP:rs267606822).
{ECO:0000269|PubMed:20206334,
ECO:0000269|PubMed:20518025,
ECO:0000269|PubMed:20690116}.
/FTId=VAR_064044.
VARIANT 412 412 G -> R (in PVHH).
{ECO:0000269|PubMed:20690116}.
/FTId=VAR_064414.
VARIANT 430 430 T -> M (in PVHH; dbSNP:rs267606825).
{ECO:0000269|PubMed:20690116}.
/FTId=VAR_064415.
VARIANT 430 430 T -> R (in PVHH; dbSNP:rs267606825).
{ECO:0000269|PubMed:20206334}.
/FTId=VAR_064045.
VARIANT 481 481 A -> T (in dbSNP:rs35126362).
/FTId=VAR_050299.
CONFLICT 419 419 L -> H (in Ref. 3; BAB55381).
{ECO:0000305}.
CONFLICT 439 439 S -> F (in Ref. 3; BAA91126).
{ECO:0000305}.
SEQUENCE 526 AA; 57241 MW; D233C07350B17870 CRC64;
MVNEGPNQEE SDDTPVPESA LQADPSVSVH PSVSVHPSVS INPSVSVHPS SSAHPSALAQ
PSGLAHPSSS GPEDLSVIKV SRRRWAVVLV FSCYSMCNSF QWIQYGSINN IFMHFYGVSA
FAIDWLSMCY MLTYIPLLLP VAWLLEKFGL RTIALTGSAL NCLGAWVKLG SLKPHLFPVT
VVGQLICSVA QVFILGMPSR IASVWFGANE VSTACSVAVF GNQLGIAIGF LVPPVLVPNI
EDRDELAYHI SIMFYIIGGV ATLLLILVII VFKEKPKYPP SRAQSLSYAL TSPDASYLGS
IARLFKNLNF VLLVITYGLN AGAFYALSTL LNRMVIWHYP GEEVNAGRIG LTIVIAGMLG
AVISGIWLDR SKTYKETTLV VYIMTLVGMV VYTFTLNLGH LWVVFITAGT MGFFMTGYLP
LGFEFAVELT YPESEGISSG LLNISAQVFG IIFTISQGQI IDNYGTKPGN IFLCVFLTLG
AALTAFIKAD LRRQKANKET LENKLQEEEE ESNTSKVPTA VSEDHL


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