Q16270 (IBP7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Insulin-like growth factor-binding protein 7
Short name=IBP-7
Short name=IGF-binding protein 7
Short name=IGFBP-7

Alternative name(s):
IGFBP-rP1
MAC25 protein
PGI2-stimulating factor
Prostacyclin-stimulating factor
Tumor-derived adhesion factor
Short name=TAF

Gene names

Name:	IGFBP7
Synonyms:	MAC25, PSF

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	282 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	Binds IGF-I and IGF-II with a relatively low affinity. Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion. Ref.8 Ref.10
Subunit structure	May interact with VPS24/CHMP3; the relevance of such interaction however remains unclear.
Subcellular location	Secreted.
Post-translational modification	N-glycosylated. Ref.10
Involvement in disease	Retinal arterial macroaneurysm with supravalvular pulmonic stenosis (RAMSVPS) [MIM:614224]: An autosomal recessive condition characterized by the bilateral appearance of 'beading' along the major retinal arterial trunks, with the subsequent formation of macroaneurysms. Affected individuals also have supravalvular pulmonic stenosis, often requiring surgical correction. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 IGFBP N-terminal domain. Contains 1 Kazal-like domain.
RNA editing	Edited at positions 78 and 95. Partially edited. In the brain, position 78 is edited at about 55% and position 95 at about 31%. Ref.1 Ref.12

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism RNA editing
Domain	Immunoglobulin domain Signal
Ligand	Growth factor binding
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from direct assay Ref.8. Source: UniProtKB inner ear development Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Traceable author statement Ref.10. Source: ProtInc regulation of cell growth Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular space Inferred from direct assay PubMed 20551380. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q16270-1)

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: Q16270-2)

The sequence of this isoform differs from the canonical sequence as follows:
     278-282: EGAEL → TQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Ref.8 Ref.9 Ref.10
	Chain	27 – 282	256	Insulin-like growth factor-binding protein 7		PRO_0000014392
Regions
	Domain	28 – 106	79	IGFBP N-terminal
	Domain	105 – 158	54	Kazal-like
	Domain	160 – 264	105	Ig-like C2-type
Amino acid modifications
	Glycosylation	171	1	N-linked (GlcNAc...) Probable
	Disulfide bond	181 ↔ 248		By similarity
Natural variations
	Alternative sequence	278 – 282	5	EGAEL → TQ in isoform 2.		VSP_045297
	Natural variant	11	1	L → F. Ref.1 Ref.4 Corresponds to variant rs11573021 [ dbSNP | Ensembl ].		VAR_018959
	Natural variant	78	1	R → G in RNA edited version.		VAR_063638
	Natural variant	95	1	K → R in RNA edited version.		VAR_063639
Experimental info
	Sequence conflict	4	1	P → A in AAA16187. Ref.1
	Sequence conflict	13	1	A → P in AAA16187. Ref.1
	Sequence conflict	69	1	E → G in BAH14453. Ref.5
	Sequence conflict	273 – 282	10	PVKKGEGAEL → ASEKR in AAA16187. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 75F96EBC3B444D37	FASTA	282	29,130
	10 20 30 40 50 60 MERPSLRALL LGAAGLLLLL LPLSSSSSSD TCGPCEPASC PPLPPLGCLL GETRDACGCC 70 80 90 100 110 120 PMCARGEGEP CGGGGAGRGY CAPGMECVKS RKRRKGKAGA AAGGPGVSGV CVCKSRYPVC 130 140 150 160 170 180 GSDGTTYPSG CQLRAASQRA ESRGEKAITQ VSKGTCEQGP SIVTPPKDIW NVTGAQVYLS 190 200 210 220 230 240 CEVIGIPTPV LIWNKVKRGH YGVQRTELLP GDRDNLAIQT RGGPEKHEVT GWVLVSPLSK 250 260 270 280 EDAGEYECHA SNSQGQASAS AKITVVDALH EIPVKKGEGA EL
	Isoform 2 [UniParc]. Checksum: 3281F44D371F721E	FASTA	279	28,860
	10 20 30 40 50 60 MERPSLRALL LGAAGLLLLL LPLSSSSSSD TCGPCEPASC PPLPPLGCLL GETRDACGCC 70 80 90 100 110 120 PMCARGEGEP CGGGGAGRGY CAPGMECVKS RKRRKGKAGA AAGGPGVSGV CVCKSRYPVC 130 140 150 160 170 180 GSDGTTYPSG CQLRAASQRA ESRGEKAITQ VSKGTCEQGP SIVTPPKDIW NVTGAQVYLS 190 200 210 220 230 240 CEVIGIPTPV LIWNKVKRGH YGVQRTELLP GDRDNLAIQT RGGPEKHEVT GWVLVSPLSK 250 260 270 EDAGEYECHA SNSQGQASAS AKITVVDALH EIPVKKGTQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of genes differentially expressed in meningiomas." Murphy M., Pykett M.J., Harnish P., Zang K.D., George D.L. Cell Growth Differ. 4:715-722(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PHE-11, RNA EDITING OF POSITION 95. Tissue: Leptomeninges.
[2]	"Purification and molecular cloning of prostacyclin-stimulating factor from serum-free conditioned medium of human diploid fibroblast cells." Yamauchi T., Umeda F., Masakado M., Isaji M., Mizushima S., Nawata H. Biochem. J. 303:591-598(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-11.
[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] (ISOFORM 2). Tissue: Thalamus and Trachea.
[6]	"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].
[7]	"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: Testis and Uterus.
[8]	"Cell adhesion activity of a 30-kDa major secreted protein from human bladder carcinoma cells." Akaogi K., Okabe Y., Funahashi K., Yoshitake Y., Nishikawa K., Yasumitsu H., Umeda M., Miyazaki K. Biochem. Biophys. Res. Commun. 198:1046-1053(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-46, FUNCTION. Tissue: Urinary bladder carcinoma.
[9]	"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 27-41.
[10]	"Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II." Oh Y., Nagalla S.R., Yamanaka Y., Kim H.-S., Wilson E., Rosenfeld R.G. J. Biol. Chem. 271:30322-30325(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-36, FUNCTION, GLYCOSYLATION.
[11]	"Interaction of IGF-binding protein-related protein 1 with a novel protein, neuroendocrine differentiation factor, results in neuroendocrine differentiation of prostate cancer cells." Wilson E.M., Oh Y., Hwa V., Rosenfeld R.G. J. Clin. Endocrinol. Metab. 86:4504-4511(2001) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INTERACTION WITH CHMP3.
[12]	"Screening of human SNP database identifies recoding sites of A-to-I RNA editing." Gommans W.M., Tatalias N.E., Sie C.P., Dupuis D., Vendetti N., Smith L., Kaushal R., Maas S. RNA 14:2074-2085(2008) [PubMed] [Europe PMC] [Abstract] Cited for: RNA EDITING OF POSITIONS 78 AND 95.
[13]	"Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms." Abu-Safieh L., Abboud E.B., Alkuraya H., Shamseldin H., Al-Enzi S., Al-Abdi L., Hashem M., Colak D., Jarallah A., Ahmad H., Bobis S., Nemer G., Bitar F., Alkuraya F.S. Am. J. Hum. Genet. 89:313-319(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN RAMSVPS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	L19182 mRNA. Translation: AAA16187.1. S75725 mRNA. Translation: AAB32370.1. AY518539 Genomic DNA. Translation: AAR89912.1. BT006654 mRNA. Translation: AAP35300.1. AK303915 mRNA. Translation: BAG64844.1. AK316082 mRNA. Translation: BAH14453.1. AC069307 Genomic DNA. No translation available. AC111197 Genomic DNA. No translation available. BC017201 mRNA. Translation: AAH17201.1. BC066339 mRNA. Translation: AAH66339.1.
IPI	IPI00016915.
PIR	I52825. PC2030. S50031.
RefSeq	NP_001240764.1. NM_001253835.1. NP_001544.1. NM_001553.2.
UniGene	Hs.479808. Hs.691061.
3D structure databases
ProteinModelPortal	Q16270.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16270. 8 interactions.
MINT	MINT-7006618.
STRING	9606.ENSP00000295666.
Protein family/group databases
MEROPS	I43.001.
PTM databases
PhosphoSite	Q16270.
Polymorphism databases
DMDM	23396609.
Proteomic databases
PaxDb	Q16270.
PeptideAtlas	Q16270.
PRIDE	Q16270.
Protocols and materials databases
DNASU	3490.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000295666; ENSP00000295666; ENSG00000163453. ENST00000537922; ENSP00000444146; ENSG00000163453.
GeneID	3490.
KEGG	hsa:3490.
UCSC	uc003hcn.3. human. uc011cag.2. human.
Organism-specific databases
CTD	3490.
GeneCards	GC04M057897.
HGNC	HGNC:5476. IGFBP7.
HPA	CAB020668. HPA002196.
MIM	602867. gene. 614224. phenotype.
neXtProt	NX_Q16270.
Orphanet	284247. Familial retinal arterial macroaneurysm.
PharmGKB	PA29709.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40288.
HOGENOM	HOG000261684.
HOVERGEN	HBG031621.
InParanoid	Q16270.
OMA	HCAPGME.
OrthoDB	EOG44TP8X.
PhylomeDB	Q16270.
Gene expression databases
ArrayExpress	Q16270.
Bgee	Q16270.
CleanEx	HS_IGFBP7.
Genevestigator	Q16270.
GermOnline	ENSG00000163453. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR013098. Ig_I-set. IPR003599. Ig_sub. IPR000867. IGFBP-like. IPR011390. IGFBP_rP_mac25. IPR002350. Kazal_dom. [Graphical view]
PANTHER	PTHR14186. PTHR14186. 1 hit.
Pfam	PF07679. I-set. 1 hit. PF00219. IGFBP. 1 hit. PF07648. Kazal_2. 1 hit. [Graphical view]
PIRSF	PIRSF018239. IGFBP_rP_mac25. 1 hit.
SMART	SM00121. IB. 1 hit. SM00409. IG. 1 hit. SM00280. KAZAL. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 1 hit. PS51323. IGFBP_N_2. 1 hit. PS51465. KAZAL_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	IGFBP7. human.
DrugBank	DB00047. Insulin Glargine recombinant. DB00046. Insulin Lyspro recombinant. DB00030. Insulin recombinant. DB00071. Insulin, porcine.
GenomeRNAi	3490.
NextBio	13726.
SOURCE	Search...

Entry information

Entry name

IBP7_HUMAN

Accession

Primary (citable) accession number: Q16270
Secondary accession number(s): B4E1N2 , B7Z9W7, Q07822, Q53YE6, Q9UCA8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 127 of the entry and version 1 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.