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Q9UPI3 (FLVC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length526 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processTransport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainRepeat
Transmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processheme transport

Inferred from direct assay Ref.7. Source: GOC

transmembrane transport

Inferred from electronic annotation. Source: InterPro

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionheme 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 526526Feline leukemia virus subgroup C receptor-related protein 2
PRO_0000084846

Regions

Transmembrane103 – 12321Helical; Potential
Transmembrane125 – 14521Helical; Potential
Transmembrane152 – 17221Helical; Potential
Transmembrane176 – 19621Helical; Potential
Transmembrane217 – 23721Helical; Potential
Transmembrane252 – 27221Helical; Potential
Transmembrane310 – 33021Helical; Potential
Transmembrane349 – 36921Helical; Potential
Transmembrane386 – 40621Helical; Potential
Transmembrane407 – 42721Helical; Potential
Transmembrane436 – 45621Helical; Potential
Transmembrane471 – 49121Helical; Potential
Repeat25 – 3061
Repeat31 – 3662
Repeat37 – 4263
Repeat43 – 4864
Repeat49 – 5465
Repeat55 – 6066; approximate
Repeat61 – 6667; approximate
Repeat67 – 7268
Region25 – 72488 X 6 AA tandem repeats of P-S-[VS]-S-[VIAG]-[HNP]
Compositional bias507 – 5115Poly-Glu

Natural variations

Alternative sequence1 – 1818MVNEG…TPVPE → MSADNSSTICVCRSVRQE in isoform 2.
VSP_043048
Alternative sequence19 – 223205Missing in isoform 2.
VSP_043049
Natural variant161V → A. Ref.3
Corresponds to variant rs2287015 [ dbSNP | Ensembl ].
VAR_018271
Natural variant841R → H in PVHH. Ref.10
VAR_064410
Natural variant110 – 1123NIF → I in PVHH.
VAR_064411
Natural variant2801P → R in PVHH. Ref.8
VAR_064043
Natural variant3261A → V in PVHH. Ref.9
VAR_064412
Natural variant3521T → R in PVHH. Ref.10
VAR_064413
Natural variant3981L → V in PVHH. Ref.8 Ref.9 Ref.10
VAR_064044
Natural variant4121G → R in PVHH. Ref.10
VAR_064414
Natural variant4301T → M in PVHH. Ref.10
VAR_064415
Natural variant4301T → R in PVHH. Ref.8
VAR_064045
Natural variant4811A → T.
Corresponds to variant rs35126362 [ dbSNP | Ensembl ].
VAR_050299

Experimental info

Sequence conflict4191L → H in BAB55381. Ref.3
Sequence conflict4391S → F in BAA91126. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: D233C07350B17870

FASTA52657,241
        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 

« Hide

Isoform 2 [UniParc].

Checksum: DC129F2BDAFF1DA3
Show »

FASTA32135,262

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS55933.1. [Q9UPI3-2]
CCDS9844.1. [Q9UPI3-1]
RefSeqNP_001182212.1. NM_001195283.1. [Q9UPI3-2]
NP_060261.2. NM_017791.2. [Q9UPI3-1]
UniGeneHs.509966.

3D structure databases

ProteinModelPortalQ9UPI3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-4724942.

Protein family/group databases

TCDB2.A.1.28.4. the major facilitator superfamily (mfs).

PTM databases

PhosphoSiteQ9UPI3.

Polymorphism databases

DMDM46396034.

Proteomic databases

MaxQBQ9UPI3.
PaxDbQ9UPI3.
PRIDEQ9UPI3.

Protocols and materials databases

DNASU55640.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000238667; ENSP00000238667; ENSG00000119686. [Q9UPI3-1]
ENST00000539311; ENSP00000443439; ENSG00000119686. [Q9UPI3-2]
GeneID55640.
KEGGhsa:55640.
UCSCuc001xrs.2. human. [Q9UPI3-1]
uc010tvd.1. human. [Q9UPI3-2]

Organism-specific databases

CTD55640.
GeneCardsGC14P076045.
H-InvDBHIX0037867.
HGNCHGNC:20105. FLVCR2.
HPAHPA037984.
MIM225790. phenotype.
610865. gene.
neXtProtNX_Q9UPI3.
Orphanet221126. Fowler syndrome.
PharmGKBPA162388720.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297699.
HOGENOMHOG000019717.
HOVERGENHBG051631.
InParanoidQ9UPI3.
KOK08220.
OMAQPHLFPV.
OrthoDBEOG7KQ21D.
PhylomeDBQ9UPI3.
TreeFamTF314292.

Gene expression databases

ArrayExpressQ9UPI3.
BgeeQ9UPI3.
CleanExHS_FLVCR2.
GenevestigatorQ9UPI3.

Family and domain databases

InterProIPR011701. MFS.
IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
[Graphical view]
PfamPF07690. MFS_1. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi55640.
NextBio60326.
PROQ9UPI3.
SOURCESearch...

Entry information

Entry nameFLVC2_HUMAN
AccessionPrimary (citable) accession number: Q9UPI3
Secondary accession number(s): B7Z485 expand/collapse secondary AC list , Q53ZT9, Q96JY3, Q9NX90
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM