P08582 (TRFM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Melanotransferrin

Alternative name(s):
Melanoma-associated antigen p97
CD_antigen=CD228

Gene names

Name:	MFI2
Synonyms:	MAP97

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	738 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	Involved in iron cellular uptake. Seems to be internalized and then recycled back to the cell membrane. Binds a single atom of iron per subunit. Could also bind zinc. Ref.6
Subcellular location	Isoform 1: Cell membrane; Lipid-anchor › GPI-anchor.
Tissue specificity	Found predominantly in human melanomas and in certain fetal tissues; also found in liver, epithelium, umbilical chord, placenta and sweat gland ducts.
Sequence similarities	Belongs to the transferrin family. Contains 2 transferrin-like domains.

Ontologies

Keywords
Biological process	Ion transport Iron transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal
Ligand	Iron Metal-binding Zinc
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular iron ion homeostasis Inferred from electronic annotation. Source: InterPro iron ion transport Inferred from electronic annotation. Source: InterPro
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Inferred from electronic annotation. Source: InterPro integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ferric iron binding Inferred from electronic annotation. Source: InterPro iron ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P08582-1)

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: P08582-2)

The sequence of this isoform differs from the canonical sequence as follows:
     238-302: GKTLPSWGQA...FRLLNEGQRL → ESPSRRQTWT...KRAKSRDMLG
     303-738: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Ref.4
	Chain	20 – 709	690	Melanotransferrin Potential		PRO_0000035739
	Propeptide	710 – 738	29	Removed in mature form Potential		PRO_0000035740
Regions
	Domain	23 – 357	335	Transferrin-like 1
	Domain	366 – 706	341	Transferrin-like 2
	Region	20 – 30	11	Antigenic epitope
Sites
	Metal binding	78	1	Iron 1 By similarity
	Metal binding	107	1	Iron 1 By similarity
	Metal binding	210	1	Iron 1 By similarity
	Metal binding	279	1	Iron 1 By similarity
	Metal binding	421	1	Iron 2 By similarity
	Metal binding	451	1	Iron 2 By similarity
	Metal binding	556	1	Iron 2 By similarity
	Metal binding	625	1	Iron 2 By similarity
	Binding site	132	1	Carbonate 1 By similarity
	Binding site	136	1	Carbonate 1 By similarity
	Binding site	138	1	Carbonate 1; via amide nitrogen By similarity
	Binding site	139	1	Carbonate 1; via amide nitrogen By similarity
Amino acid modifications
	Lipidation	709	1	GPI-anchor amidated cysteine Potential
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	135	1	N-linked (GlcNAc...) Potential
	Glycosylation	515	1	N-linked (GlcNAc...) Potential
	Disulfide bond	26 ↔ 63		By similarity
	Disulfide bond	36 ↔ 54		By similarity
	Disulfide bond	130 ↔ 216		By similarity
	Disulfide bond	172 ↔ 189		By similarity
	Disulfide bond	186 ↔ 199		By similarity
	Disulfide bond	257 ↔ 271		By similarity
Natural variations
	Alternative sequence	238 – 302	65	GKTLP…EGQRL → ESPSRRQTWTRSEEEEGECP AHEEARRTMRSSAGQAWKWA PVHRPQDESDKGEFGKRAKS RDMLG in isoform 2.		VSP_006557
	Alternative sequence	303 – 738	436	Missing in isoform 2.		VSP_006558
	Natural variant	294	1	R → W. Corresponds to variant rs2276790 [ dbSNP | Ensembl ].		VAR_020413
	Natural variant	559	1	A → T. Corresponds to variant rs17129219 [ dbSNP | Ensembl ].		VAR_057304
Experimental info
	Sequence conflict	431	1	T → K in AAA59992. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 28, 2011. Version 2. Checksum: B0F08B708D2A0A0F	FASTA	738	80,215
	10 20 30 40 50 60 MRGPSGALWL LLALRTVLGG MEVRWCATSD PEQHKCGNMS EAFREAGIQP SLLCVRGTSA 70 80 90 100 110 120 DHCVQLIAAQ EADAITLDGG AIYEAGKEHG LKPVVGEVYD QEVGTSYYAV AVVRRSSHVT 130 140 150 160 170 180 IDTLKGVKSC HTGINRTVGW NVPVGYLVES GRLSVMGCDV LKAVSDYFGG SCVPGAGETS 190 200 210 220 230 240 YSESLCRLCR GDSSGEGVCD KSPLERYYDY SGAFRCLAEG AGDVAFVKHS TVLENTDGKT 250 260 270 280 290 300 LPSWGQALLS QDFELLCRDG SRADVTEWRQ CHLARVPAHA VVVRADTDGG LIFRLLNEGQ 310 320 330 340 350 360 RLFSHEGSSF QMFSSEAYGQ KDLLFKDSTS ELVPIATQTY EAWLGHEYLH AMKGLLCDPN 370 380 390 400 410 420 RLPPYLRWCV LSTPEIQKCG DMAVAFRRQR LKPEIQCVSA KSPQHCMERI QAEQVDAVTL 430 440 450 460 470 480 SGEDIYTAGK TYGLVPAAGE HYAPEDSSNS YYVVAVVRRD SSHAFTLDEL RGKRSCHAGF 490 500 510 520 530 540 GSPAGWDVPV GALIQRGFIR PKDCDVLTAV SEFFNASCVP VNNPKNYPSS LCALCVGDEQ 550 560 570 580 590 600 GRNKCVGNSQ ERYYGYRGAF RCLVENAGDV AFVRHTTVFD NTNGHNSEPW AAELRSEDYE 610 620 630 640 650 660 LLCPNGARAE VSQFAACNLA QIPPHAVMVR PDTNIFTVYG LLDKAQDLFG DDHNKNGFKM 670 680 690 700 710 720 FDSSNYHGQD LLFKDATVRA VPVGEKTTYR GWLGLDYVAA LEGMSSQQCS GAAAPAPGAP 730 LLPLLLPALA ARLLPPAL
	Isoform 2 [UniParc]. Checksum: 0D51C8347D9EBD8F	FASTA	302	32,723
	10 20 30 40 50 60 MRGPSGALWL LLALRTVLGG MEVRWCATSD PEQHKCGNMS EAFREAGIQP SLLCVRGTSA 70 80 90 100 110 120 DHCVQLIAAQ EADAITLDGG AIYEAGKEHG LKPVVGEVYD QEVGTSYYAV AVVRRSSHVT 130 140 150 160 170 180 IDTLKGVKSC HTGINRTVGW NVPVGYLVES GRLSVMGCDV LKAVSDYFGG SCVPGAGETS 190 200 210 220 230 240 YSESLCRLCR GDSSGEGVCD KSPLERYYDY SGAFRCLAEG AGDVAFVKHS TVLENTDESP 250 260 270 280 290 300 SRRQTWTRSE EEEGECPAHE EARRTMRSSA GQAWKWAPVH RPQDESDKGE FGKRAKSRDM LG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the human melanoma-associated antigen p97 (melanotransferrin) deduced from the mRNA sequence." Rose T.M., Plowman G.D., Teplow D.B., Dreyer W.J., Hellstroem K.E., Brown J.P. Proc. Natl. Acad. Sci. U.S.A. 83:1261-1265(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Melanoma.
[2]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [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 2). Tissue: Skin and Uterus.
[4]	"A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97." Furukawa K.S., Furukawa K., Real F.X., Old L.J., Lloyd K.O. J. Exp. Med. 169:585-590(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-30.
[5]	"Transport and expression in human melanomas of a transferrin-like glycosylphosphatidylinositol-anchored protein." Food M.R., Rothenberger S., Gabathuler R., Haidl I.D., Reid G., Jefferies W.A. J. Biol. Chem. 269:3034-3040(1994) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR.
[6]	"A novel iron uptake mechanism mediated by GPI-anchored human p97." Kennard M.L., Richardson D.R., Gabathuler R., Ponka P., Jefferies W.A. EMBO J. 14:4178-4186(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Human melanotransferrin (p97) has only one functional iron-binding site." Baker E.N., Baker H.M., Smith C.A., Stebbins M.R., Kahn M., Hellstroem K.E., Hellstroem I. FEBS Lett. 298:215-218(1992) [PubMed] [Europe PMC] [Abstract] Cited for: IRON-BINDING.
[8]	"A molecular model for the tumour-associated antigen, p97, suggests a Zn-binding function." Garrat R.C., Jhoti H. FEBS Lett. 305:55-61(1992) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M12154 mRNA. Translation: AAA59992.1. AC068302 Genomic DNA. No translation available. BC001875 mRNA. Translation: AAH01875.1. BC002623 mRNA. Translation: AAH02623.1. BC007550 mRNA. Translation: AAH07550.1. BC071910 mRNA. Translation: AAH71910.1.
IPI	IPI00029275. IPI00218301.
PIR	TFHUM. A23814.
RefSeq	NP_005920.2. NM_005929.5. NP_201573.1. NM_033316.3.
UniGene	Hs.184727.
3D structure databases
ProteinModelPortal	P08582.
SMR	P08582. Positions 23-710.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-5000908.
STRING	9606.ENSP00000296350.
Protein family/group databases
MEROPS	S60.973.
PTM databases
PhosphoSite	P08582.
Polymorphism databases
DMDM	136204.
Proteomic databases
PaxDb	P08582.
PRIDE	P08582.
Protocols and materials databases
DNASU	4241.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296350; ENSP00000296350; ENSG00000163975. ENST00000296351; ENSP00000296351; ENSG00000163975.
GeneID	4241.
KEGG	hsa:4241.
UCSC	uc003fxk.4. human.
Organism-specific databases
CTD	4241.
GeneCards	GC03M196715.
H-InvDB	HIX0031062.
HGNC	HGNC:7037. MFI2.
HPA	HPA004880.
MIM	155750. gene.
neXtProt	NX_P08582.
PharmGKB	PA30774.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG87503.
HOGENOM	HOG000043759.
HOVERGEN	HBG000055.
InParanoid	P08582.
KO	K06569.
OMA	DGGLIFR.
OrthoDB	EOG4G4GPZ.
PhylomeDB	P08582.
Gene expression databases
ArrayExpress	P08582.
Bgee	P08582.
CleanEx	HS_MFI2.
Genevestigator	P08582.
GermOnline	ENSG00000163975. Homo sapiens.
Family and domain databases
InterPro	IPR016357. Transferrin. IPR001156. Transferrin_fam. IPR018195. Transferrin_Fe_BS. [Graphical view]
PANTHER	PTHR11485. PTHR11485. 1 hit.
Pfam	PF00405. Transferrin. 2 hits. [Graphical view]
PIRSF	PIRSF002549. Transferrin. 1 hit.
PRINTS	PR00422. TRANSFERRIN.
SMART	SM00094. TR_FER. 2 hits. [Graphical view]
PROSITE	PS00205. TRANSFERRIN_LIKE_1. 2 hits. PS00206. TRANSFERRIN_LIKE_2. 2 hits. PS00207. TRANSFERRIN_LIKE_3. 2 hits. PS51408. TRANSFERRIN_LIKE_4. 2 hits. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4241.
NextBio	16723.
SOURCE	Search...

Entry information

Entry name

TRFM_HUMAN

Accession

Primary (citable) accession number: P08582
Secondary accession number(s): Q9BQE2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	June 28, 2011
Last modified:	May 1, 2013
This is version 137 of the entry and version 2 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.