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Q6P4Q7 (CNNM4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Metal transporter CNNM4
Alternative name(s):
Ancient conserved domain-containing protein 4
Cyclin-M4
Gene names
Name:CNNM4
Synonyms:ACDP4, KIAA1592
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length775 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions By similarity. May play a role in biomineralization and retinal function. Ref.4 Ref.10

Subunit structure

Interacts with COX11. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.8.

Tissue specificity

Widely expressed. Highly expressed in heart. Ref.5

Involvement in disease

Jalili syndrome (JALIS) [MIM:217080]: A syndrome characterized by the association of cone-rod dystrophy and amelogenesis imperfecta.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.10

Miscellaneous

Shares weak sequence similarity with the cyclin family, explaining its name. However, it has no cyclin-like function in vivo.

Sequence similarities

Belongs to the ACDP family.

Contains 2 CBS domains.

Contains 1 DUF21 domain.

Sequence caution

The sequence AAF86370.1 differs from that shown. Reason: Frameshift at positions 108 and 120.

The sequence AAY14963.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAB14266.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6P4Q7-1)

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: Q6P4Q7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-513: Missing.
     711-775: ITRQQYQNGL...LHKASHENAI → PQSWPCFSRP...HPHGELGREV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 775775Metal transporter CNNM4
PRO_0000295765

Regions

Topological domain1 – 178178Extracellular Potential
Transmembrane179 – 19921Helical; Potential
Topological domain200 – 24041Cytoplasmic Potential
Intramembrane241 – 26121Helical; Potential
Topological domain262 – 2643Cytoplasmic Potential
Transmembrane265 – 28521Helical; Potential
Topological domain286 – 2938Extracellular Potential
Transmembrane294 – 31623Helical; Potential
Topological domain317 – 775459Cytoplasmic Potential
Domain185 – 358174DUF21
Domain377 – 43862CBS 1
Domain445 – 51167CBS 2

Amino acid modifications

Modified residue6641Phosphoserine By similarity
Modified residue7701Phosphoserine By similarity
Glycosylation851N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 513513Missing in isoform 2.
VSP_054271
Alternative sequence711 – 77565ITRQQ…HENAI → PQSWPCFSRPGDRVCLPAPP SMNSSLPHADHSAAVPERAA GFSHGEQPSVSHRRVHHPHG ELGREV in isoform 2.
VSP_054272
Natural variant1261G → R. Ref.3
Corresponds to variant rs17855817 [ dbSNP | Ensembl ].
VAR_033365
Natural variant1341V → L in a breast cancer sample; somatic mutation. Ref.9
VAR_035946
Natural variant1961S → P in JALIS. Ref.10
VAR_058319
Natural variant2001S → Y in JALIS. Ref.10
VAR_058320
Natural variant2361R → Q in JALIS. Ref.4
VAR_058321
Natural variant3241L → P in JALIS. Ref.4 Ref.10
VAR_058322

Experimental info

Sequence conflict3021T → I in AAF86370. Ref.5

Sequences

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

Last modified March 3, 2009. Version 3.
Checksum: D159303834A9416C

FASTA77586,607
        10         20         30         40         50         60 
MAPVGGGGRP VGGPARGRLL LAAPVLLVLL WALGARGQGS PQQGTIVGMR LASCNKSCGT 

        70         80         90        100        110        120 
NPDGIIFVSE GSTVNLRLYG YSLGNISSNL ISFTEVDDAE TLHKSTSCLE LTKDLVVQQL 

       130        140        150        160        170        180 
VNVSRGNTSG VLVVLTKFLR RSESMKLYAL CTRAQPDGPW LKWTDKDSLL FMVEEPGRFL 

       190        200        210        220        230        240 
PLWLHILLIT VLLVLSGIFS GLNLGLMALD PMELRIVQNC GTEKERRYAR KIEPIRRKGN 

       250        260        270        280        290        300 
YLLCSLLLGN VLVNTSLTIL LDNLIGSGLM AVASSTIGIV IFGEILPQAL CSRHGLAVGA 

       310        320        330        340        350        360 
NTILLTKFFM LLTFPLSFPI SKLLDFFLGQ EIRTVYNREK LMEMLKVTEP YNDLVKEELN 

       370        380        390        400        410        420 
MIQGALELRT KTVEDIMTQL QDCFMIRSDA ILDFNTMSEI MESGYTRIPV FEDEQSNIVD 

       430        440        450        460        470        480 
ILYVKDLAFV DPDDCTPLKT ITRFYNHPVH FVFHDTKLDA MLEEFKKGKS HLAIVQKVNN 

       490        500        510        520        530        540 
EGEGDPFYEV LGLVTLEDVI EEIIKSEILD ESDMYTDNRS RKRVSEKNKR DFSAFKDADN 

       550        560        570        580        590        600 
ELKVKISPQL LLAAHRFLAT EVSQFSPSLI SEKILLRLLK YPDVIQELKF DEHNKYYARH 

       610        620        630        640        650        660 
YLYTRNKPAD YFILILQGKV EVEAGKENMK FETGAFSYYG TMALTSVPSD RSPAHPTPLS 

       670        680        690        700        710        720 
RSASLSYPDR TDVSTAATLA GSSNQFGSSV LGQYISDFSV RALVDLQYIK ITRQQYQNGL 

       730        740        750        760        770 
LASRMENSPQ FPIDGCTTHM ENLAEKSELP VVDETTTLLN ERNSLLHKAS HENAI 

« Hide

Isoform 2 [UniParc].

Checksum: 8AB7D712AD2BCC84
Show »

FASTA26329,485

References

« Hide 'large scale' references
[1]"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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 570-775 (ISOFORM 1).
Tissue: Cerebellum and Teratocarcinoma.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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), VARIANT ARG-126.
Tissue: Placenta.
[4]"Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta."
Polok B., Escher P., Ambresin A., Chouery E., Bolay S., Meunier I., Nan F., Hamel C., Munier F.L., Thilo B., Megarbane A., Schorderet D.F.
Am. J. Hum. Genet. 84:259-265(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-467, VARIANTS JALIS GLN-236 AND PRO-324, FUNCTION.
[5]"Molecular cloning and characterization of a novel gene family of four ancient conserved domain proteins (ACDP)."
Wang C.-Y., Shi J.-D., Yang P., Kumar P.G., Li Q.-Z., Run Q.-G., Su Y.-C., Scott H.S., Kao K.-J., She J.-X.
Gene 306:37-44(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 49-775 (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[6]"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.
DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-775 (ISOFORM 1).
[7]"Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis."
Guo D., Ling J., Wang M.-H., She J.-X., Gu J., Wang C.-Y.
Mol. Pain 1:15-15(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COX11.
[8]"Membrane topology and intracellular processing of Cyclin M2 (CNNM2)."
de Baaij J.H., Stuiver M., Meij I.C., Lainez S., Kopplin K., Venselaar H., Mueller D., Bindels R.J., Hoenderop J.G.
J. Biol. Chem. 287:13644-13655(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY.
[9]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-134.
[10]"Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta."
Parry D.A., Mighell A.J., El-Sayed W., Shore R.C., Jalili I.K., Dollfus H., Bloch-Zupan A., Carlos R., Carr I.M., Downey L.M., Blain K.M., Mansfield D.C., Shahrabi M., Heidari M., Aref P., Abbasi M., Michaelides M., Moore A.T., Kirkham J., Inglehearn C.F.
Am. J. Hum. Genet. 84:266-273(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS JALIS PRO-196; TYR-200 AND PRO-324, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK022833 mRNA. Translation: BAB14266.1. Different initiation.
AK293915 mRNA. Translation: BAH11626.1.
AC092636 Genomic DNA. Translation: AAY14963.1. Different initiation.
BC063295 mRNA. Translation: AAH63295.2.
FJ619522 Genomic DNA. Translation: ACV32670.1.
FJ619523 Genomic DNA. Translation: ACV32671.1.
FJ619524 Genomic DNA. Translation: ACV32672.1.
AF202777 mRNA. Translation: AAF86370.1. Frameshift.
AB046812 mRNA. Translation: BAB13418.1.
CCDSCCDS2024.2.
RefSeqNP_064569.3. NM_020184.3. [Q6P4Q7-1]
UniGeneHs.175043.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4IY3X-ray3.60A/B/C/D359-511[»]
ProteinModelPortalQ6P4Q7.
SMRQ6P4Q7. Positions 360-508.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117711. 3 interactions.
STRING9606.ENSP00000366275.

Protein family/group databases

TCDB9.A.40.3.4. the hlyc/corc (hcc) family.

PTM databases

PhosphoSiteQ6P4Q7.

Polymorphism databases

DMDM224471892.

Proteomic databases

MaxQBQ6P4Q7.
PaxDbQ6P4Q7.
PRIDEQ6P4Q7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377075; ENSP00000366275; ENSG00000158158.
ENST00000540067; ENSP00000444806; ENSG00000158158.
GeneID26504.
KEGGhsa:26504.
UCSCuc002swx.3. human. [Q6P4Q7-1]

Organism-specific databases

CTD26504.
GeneCardsGC02P097426.
H-InvDBHIX0002279.
HIX0161875.
HGNCHGNC:105. CNNM4.
HPAHPA017732.
MIM217080. phenotype.
607805. gene.
neXtProtNX_Q6P4Q7.
Orphanet1873. Jalili syndrome.
PharmGKBPA26671.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1253.
HOGENOMHOG000231947.
HOVERGENHBG074775.
InParanoidQ6P4Q7.
KOK16302.
OMARREILIP.
OrthoDBEOG72ZCD7.
PhylomeDBQ6P4Q7.
TreeFamTF101012.

Gene expression databases

ArrayExpressQ6P4Q7.
BgeeQ6P4Q7.
CleanExHS_CNNM4.
GenevestigatorQ6P4Q7.

Family and domain databases

Gene3D2.60.120.10. 2 hits.
InterProIPR000644. CBS_dom.
IPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR002550. DUF21.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamPF00571. CBS. 1 hit.
PF01595. DUF21. 1 hit.
[Graphical view]
SMARTSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 2 hits.
PROSITEPS51371. CBS. 2 hits.
PS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCNNM4. human.
GenomeRNAi26504.
NextBio35478818.
PROQ6P4Q7.
SOURCESearch...

Entry information

Entry nameCNNM4_HUMAN
AccessionPrimary (citable) accession number: Q6P4Q7
Secondary accession number(s): B7Z1U0 expand/collapse secondary AC list , C7SQM3, C7SQM4, C7SQM5, Q53RE5, Q9H9G3, Q9HCI0, Q9NRN1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: March 3, 2009
Last modified: July 9, 2014
This is version 91 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 2

Human chromosome 2: entries, gene names and cross-references to MIM