Q6P4Q7 (CNNM4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metal transporter CNNM4

Alternative name(s):
Ancient conserved domain-containing protein 4
Cyclin-M4

Gene names

Name:	CNNM4
Synonyms:	ACDP4, KIAA1592

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	775 AA.
Sequence status	Complete.
Protein existence	Evidence 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.9 Ref.10
Subunit structure	Interacts with COX11. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.7.
Tissue specificity	Widely expressed. Highly expressed in heart. Ref.3
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.9 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.

Ontologies

Keywords
Biological process	Biomineralization Ion transport Sensory transduction Transport Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Amelogenesis imperfecta Cone-rod dystrophy Disease mutation
Domain	CBS domain Repeat Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	biomineral tissue development Inferred from electronic annotation. Source: UniProtKB-KW ion transport Inferred from electronic annotation. Source: UniProtKB-KW response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 775	775	Metal transporter CNNM4		PRO_0000295765
Regions
	Topological domain	1 – 178	178	Extracellular Potential
	Transmembrane	179 – 199	21	Helical; Potential
	Topological domain	200 – 240	41	Cytoplasmic Potential
	Intramembrane	241 – 261	21	Helical; Potential
	Topological domain	262 – 264	3	Cytoplasmic Potential
	Transmembrane	265 – 285	21	Helical; Potential
	Topological domain	286 – 293	8	Extracellular Potential
	Transmembrane	294 – 316	23	Helical; Potential
	Topological domain	317 – 775	459	Cytoplasmic Potential
	Domain	185 – 358	174	DUF21
	Domain	377 – 438	62	CBS 1
	Domain	445 – 511	67	CBS 2
Amino acid modifications
	Modified residue	770	1	Phosphoserine By similarity
	Glycosylation	85	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	126	1	G → R. Ref.2 Corresponds to variant rs17855817 [ dbSNP | Ensembl ].		VAR_033365
	Natural variant	134	1	V → L in a breast cancer sample; somatic mutation. Ref.8		VAR_035946
	Natural variant	196	1	S → P in JALIS. Ref.10		VAR_058319
	Natural variant	200	1	S → Y in JALIS. Ref.10		VAR_058320
	Natural variant	236	1	R → Q in JALIS. Ref.9		VAR_058321
	Natural variant	324	1	L → P in JALIS. Ref.9 Ref.10		VAR_058322
Experimental info
	Sequence conflict	302	1	T → I in AAF86370. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q6P4Q7 [UniParc]. Last modified March 3, 2009. Version 3. Checksum: D159303834A9416C	FASTA	775	86,607
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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. , 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].
[2]	"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], VARIANT ARG-126. Tissue: Placenta.
[3]	"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, TISSUE SPECIFICITY. Tissue: Brain.
[4]	"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.
[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 570-775. Tissue: Teratocarcinoma.
[6]	"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.
[7]	"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.
[8]	"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. , 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.
[9]	"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: VARIANTS JALIS GLN-236 AND PRO-324, FUNCTION.
[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	AC092636 Genomic DNA. Translation: AAY14963.1. Different initiation. BC063295 mRNA. Translation: AAH63295.2. AF202777 mRNA. Translation: AAF86370.1. Frameshift. AB046812 mRNA. Translation: BAB13418.1. AK022833 mRNA. Translation: BAB14266.1. Different initiation.
IPI	IPI00418426.
RefSeq	NP_064569.3. NM_020184.3.
UniGene	Hs.175043.
3D structure databases
ProteinModelPortal	Q6P4Q7.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000366275.
PTM databases
PhosphoSite	Q6P4Q7.
Polymorphism databases
DMDM	224471892.
Proteomic databases
PaxDb	Q6P4Q7.
PRIDE	Q6P4Q7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377075; ENSP00000366275; ENSG00000158158.
GeneID	26504.
KEGG	hsa:26504.
UCSC	uc002swx.3. human.
Organism-specific databases
CTD	26504.
GeneCards	GC02P097426.
H-InvDB	HIX0002279. HIX0161875.
HGNC	HGNC:105. CNNM4.
HPA	HPA017732.
MIM	217080. phenotype. 607805. gene.
neXtProt	NX_Q6P4Q7.
Orphanet	1873. Jalili syndrome.
PharmGKB	PA26671.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1253.
HOGENOM	HOG000231947.
HOVERGEN	HBG074775.
InParanoid	Q6P4Q7.
KO	K16302.
OMA	GNTSGML.
OrthoDB	EOG405S0M.
Gene expression databases
ArrayExpress	Q6P4Q7.
Bgee	Q6P4Q7.
CleanEx	HS_CNNM4.
Genevestigator	Q6P4Q7.
Family and domain databases
Gene3D	2.60.120.10. 2 hits.
InterPro	IPR000595. cNMP-bd_dom. IPR000644. Cysta_beta_synth_core. IPR002550. DUF21. IPR014710. RmlC-like_jellyroll. [Graphical view]
Pfam	PF00571. CBS. 1 hit. PF01595. DUF21. 1 hit. [Graphical view]
SMART	SM00100. cNMP. 1 hit. [Graphical view]
PROSITE	PS51371. CBS. 2 hits. PS50042. CNMP_BINDING_3. 1 hit. Uncertain. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CNNM4. human.
GenomeRNAi	26504.
NextBio	48782.
SOURCE	Search...

Entry information

Entry name

CNNM4_HUMAN

Accession

Primary (citable) accession number: Q6P4Q7
Secondary accession number(s): Q53RE5 , Q9H9G3, Q9HCI0, Q9NRN1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 24, 2007
Last sequence update:	March 3, 2009
Last modified:	May 1, 2013
This is version 79 of the entry and version 3 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.