Q13433 (S39A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc transporter ZIP6

Alternative name(s):
Estrogen-regulated protein LIV-1
Solute carrier family 39 member 6
Zrt- and Irt-like protein 6
Short name=ZIP-6

Gene names

Name:	SLC39A6
Synonyms:	LIV1, ZIP6

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	755 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May act as a zinc-influx transporter. Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.8.
Tissue specificity	Highly expressed in the breast, prostate, placenta, kidney, pituitary and corpus callosum. Weakly expressed in heart and intestine. Also highly expressed in cells derived from an adenocarcinoma of the cervix and lung carcinoma. Ref.8
Induction	Up-regulated by estrogen in breast cancer cells lines. Ref.7
Post-translational modification	N-glycosylated. Ref.8
Sequence similarities	Belongs to the ZIP transporter (TC 2.A.5) family. [View classification]
Sequence caution	The sequence BAG61161.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Transport Zinc transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Signal Transmembrane Transmembrane helix
Ligand	Zinc
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular zinc ion homeostasis Inferred from direct assay PubMed 15642354. Source: BHF-UCL zinc ion transmembrane import Inferred from direct assay PubMed 15642354. Source: BHF-UCL
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from direct assay PubMed 15642354. Source: BHF-UCL lamellipodium membrane Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	zinc ion transmembrane transporter activity Inferred from direct assay PubMed 15642354. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q13433-1)

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: Q13433-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-275: Missing.
     707-708: PE → SF
     709-755: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 28	28	Ref.6
	Chain	29 – 755	727	Zinc transporter ZIP6		PRO_0000041650
Regions
	Topological domain	29 – 325	297	Extracellular Potential
	Transmembrane	326 – 346	21	Helical; Name=1; Potential
	Topological domain	347 – 355	9	Cytoplasmic Potential
	Transmembrane	356 – 376	21	Helical; Name=2; Potential
	Topological domain	377 – 423	47	Extracellular Potential
	Transmembrane	424 – 444	21	Helical; Name=3; Potential
	Topological domain	445 – 657	213	Cytoplasmic Potential
	Transmembrane	658 – 678	21	Helical; Name=4; Potential
	Topological domain	679 – 686	8	Extracellular Potential
	Transmembrane	687 – 707	21	Helical; Name=5; Potential
	Topological domain	708 – 724	17	Cytoplasmic Potential
	Transmembrane	725 – 745	21	Helical; Name=6; Potential
	Topological domain	746 – 755	10	Extracellular Potential
	Coiled coil	464 – 480	17	Potential
	Compositional bias	91 – 134	44	His-rich
	Compositional bias	376 – 391	16	His-rich
	Compositional bias	448 – 453	6	Poly-Lys
	Compositional bias	513 – 516	4	Poly-Glu
	Compositional bias	541 – 578	38	His-rich
Amino acid modifications
	Glycosylation	67	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	68	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	241	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	266	1	N-linked (GlcNAc...) Potential
	Glycosylation	283	1	N-linked (GlcNAc...) Potential
	Glycosylation	684	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 275	275	Missing in isoform 2.		VSP_014309
	Alternative sequence	707 – 708	2	PE → SF in isoform 2.		VSP_014310
	Alternative sequence	709 – 755	47	Missing in isoform 2.		VSP_014311
	Natural variant	119	1	E → D. Ref.1 Ref.2 Ref.4 Corresponds to variant rs1789528 [ dbSNP | Ensembl ].		VAR_059964
Experimental info
	Sequence conflict	127 – 132	6	Missing in AAA96258. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 23, 2010. Version 3. Checksum: 8BC1D02CA116DD25	FASTA	755	85,047
	10 20 30 40 50 60 MARKLSVILI LTFALSVTNP LHELKAAAFP QTTEKISPNW ESGINVDLAI STRQYHLQQL 70 80 90 100 110 120 FYRYGENNSL SVEGFRKLLQ NIGIDKIKRI HIHHDHDHHS DHEHHSDHER HSDHEHHSEH 130 140 150 160 170 180 EHHSDHDHHS HHNHAASGKN KRKALCPDHD SDSSGKDPRN SQGKGAHRPE HASGRRNVKD 190 200 210 220 230 240 SVSASEVTST VYNTVSEGTH FLETIETPRP GKLFPKDVSS STPPSVTSKS RVSRLAGRKT 250 260 270 280 290 300 NESVSEPRKG FMYSRNTNEN PQECFNASKL LTSHGMGIQV PLNATEFNYL CPAIINQIDA 310 320 330 340 350 360 RSCLIHTSEK KAEIPPKTYS LQIAWVGGFI AISIISFLSL LGVILVPLMN RVFFKFLLSF 370 380 390 400 410 420 LVALAVGTLS GDAFLHLLPH SHASHHHSHS HEEPAMEMKR GPLFSHLSSQ NIEESAYFDS 430 440 450 460 470 480 TWKGLTALGG LYFMFLVEHV LTLIKQFKDK KKKNQKKPEN DDDVEIKKQL SKYESQLSTN 490 500 510 520 530 540 EEKVDTDDRT EGYLRADSQE PSHFDSQQPA VLEEEEVMIA HAHPQEVYNE YVPRGCKNKC 550 560 570 580 590 600 HSHFHDTLGQ SDDLIHHHHD YHHILHHHHH QNHHPHSHSQ RYSREELKDA GVATLAWMVI 610 620 630 640 650 660 MGDGLHNFSD GLAIGAAFTE GLSSGLSTSV AVFCHELPHE LGDFAVLLKA GMTVKQAVLY 670 680 690 700 710 720 NALSAMLAYL GMATGIFIGH YAENVSMWIF ALTAGLFMYV ALVDMVPEML HNDASDHGCS 730 740 750 RWGYFFLQNA GMLLGFGIML LISIFEHKIV FRINF
	Isoform 2 [UniParc]. Checksum: 72B8B90BD0A1867B	FASTA	433	48,605
	10 20 30 40 50 60 MGIQVPLNAT EFNYLCPAII NQIDARSCLI HTSEKKAEIP PKTYSLQIAW VGGFIAISII 70 80 90 100 110 120 SFLSLLGVIL VPLMNRVFFK FLLSFLVALA VGTLSGDAFL HLLPHSHASH HHSHSHEEPA 130 140 150 160 170 180 MEMKRGPLFS HLSSQNIEES AYFDSTWKGL TALGGLYFMF LVEHVLTLIK QFKDKKKKNQ 190 200 210 220 230 240 KKPENDDDVE IKKQLSKYES QLSTNEEKVD TDDRTEGYLR ADSQEPSHFD SQQPAVLEEE 250 260 270 280 290 300 EVMIAHAHPQ EVYNEYVPRG CKNKCHSHFH DTLGQSDDLI HHHHDYHHIL HHHHHQNHHP 310 320 330 340 350 360 HSHSQRYSRE ELKDAGVATL AWMVIMGDGL HNFSDGLAIG AAFTEGLSSG LSTSVAVFCH 370 380 390 400 410 420 ELPHELGDFA VLLKAGMTVK QAVLYNALSA MLAYLGMATG IFIGHYAENV SMWIFALTAG 430 LFMYVALVDM VSF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Green C., Morgan H.E. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-119.
[2]	"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] (ISOFORM 1), VARIANT ASP-119. Tissue: Teratocarcinoma and Trachea.
[3]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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], VARIANT ASP-119.
[5]	"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 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 382-755 (ISOFORM 1). Tissue: Eye and Lymph.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 29-43.
[7]	"Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line." Manning D.L., Daly R.J., Lord P.G., Kelly K.F., Green C.D. Mol. Cell. Endocrinol. 59:205-212(1988) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[8]	"Structure-function analysis of LIV-1, the breast cancer-associated protein that belongs to a new subfamily of zinc transporters." Taylor K.M., Morgan H.E., Johnson A., Hadley L.J., Nicholson R.I. Biochem. J. 375:51-59(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-67; ASN-68 AND ASN-241, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	U41060 mRNA. Translation: AAA96258.2. AK299102 mRNA. Translation: BAG61161.1. Different initiation. AK304079 mRNA. Translation: BAG64986.1. AC091060 Genomic DNA. No translation available. CH471088 Genomic DNA. Translation: EAX01372.1. BC008317 mRNA. Translation: AAH08317.2. BC039498 mRNA. Translation: AAH39498.1.
IPI	IPI00298702. IPI00607564.
PIR	G02273.
RefSeq	NP_001092876.1. NM_001099406.1. NP_036451.3. NM_012319.3.
UniGene	Hs.79136.
3D structure databases
ProteinModelPortal	Q13433.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000269187.
PTM databases
PhosphoSite	Q13433.
Polymorphism databases
DMDM	292495066.
Proteomic databases
PaxDb	Q13433.
PRIDE	Q13433.
Protocols and materials databases
DNASU	25800.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000269187; ENSP00000269187; ENSG00000141424. ENST00000440549; ENSP00000401139; ENSG00000141424. ENST00000590986; ENSP00000465915; ENSG00000141424.
GeneID	25800.
KEGG	hsa:25800.
UCSC	uc002kzj.2. human. uc010dmy.3. human.
Organism-specific databases
CTD	25800.
GeneCards	GC18M033688.
HGNC	HGNC:18607. SLC39A6.
HPA	HPA042377.
MIM	608731. gene.
neXtProt	NX_Q13433.
PharmGKB	PA134905551.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0428.
HOGENOM	HOG000013093.
HOVERGEN	HBG055748.
InParanoid	Q13433.
KO	K14712.
OMA	FNYLCPA.
OrthoDB	EOG4WDDBC.
PhylomeDB	Q13433.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
Bgee	Q13433.
CleanEx	HS_SLC39A6.
Genevestigator	Q13433.
GermOnline	ENSG00000141424. Homo sapiens.
Family and domain databases
InterPro	IPR003689. ZIP. [Graphical view]
Pfam	PF02535. Zip. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC39A6. human.
GenomeRNAi	25800.
NextBio	46997.
SOURCE	Search...

Entry information

Entry name

S39A6_HUMAN

Accession

Primary (citable) accession number: Q13433
Secondary accession number(s): B4DR49 , B4E224, Q8IXR3, Q96HP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	March 23, 2010
Last modified:	May 29, 2013
This is version 102 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.