P21246 (PTN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pleiotrophin
Short name=PTN

Alternative name(s):
Heparin-binding brain mitogen
Short name=HBBM
Heparin-binding growth factor 8
Short name=HBGF-8
Heparin-binding growth-associated molecule
Short name=HB-GAM
Heparin-binding neurite outgrowth-promoting factor 1
Short name=HBNF-1
Osteoblast-specific factor 1
Short name=OSF-1

Gene names

Name:	PTN
Synonyms:	HBNF1, NEGF1

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	168 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	Secreted growth factor that induces neurite outgrowth and which is mitogenic for fibroblasts, epithelial, and endothelial cells. Binds anaplastic lymphoma kinase (ALK) which induces MAPK pathway activation, an important step in the anti-apoptotic signaling of PTN and regulation of cell proliferation. Ref.3 Ref.17
Subunit structure	Interacts with ALK and NEK6. Ref.17 Ref.18
Subcellular location	Secreted.
Tissue specificity	Osteoblast and brain.
Induction	By heparin and retinoic acid. Ref.3 Ref.15
Post-translational modification	Phosphorylated by NEK6. Ref.18
Sequence similarities	Belongs to the pleiotrophin family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Ligand	Heparin-binding
Molecular function	Growth factor Mitogen
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bone mineralization Inferred from electronic annotation. Source: Compara learning Inferred from electronic annotation. Source: Compara nervous system development Traceable author statement Ref.2. Source: ProtInc positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell proliferation Traceable author statement Ref.2. Source: ProtInc transmembrane receptor protein tyrosine phosphatase signaling pathway Traceable author statement PubMed 10706604. Source: ProtInc
Cellular_component	endoplasmic reticulum Inferred from direct assay. Source: LIFEdb extracellular space Traceable author statement PubMed 10706604. Source: ProtInc
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW protein phosphatase inhibitor activity Traceable author statement PubMed 10706604. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Ref.13 Ref.14 Ref.15
	Chain	33 – 168	136	Pleiotrophin		PRO_0000024659
Amino acid modifications
	Disulfide bond	47 ↔ 76		Ref.16
	Disulfide bond	55 ↔ 85		Ref.16
	Disulfide bond	62 ↔ 89		Ref.16
	Disulfide bond	99 ↔ 131		Ref.16
	Disulfide bond	109 ↔ 141		Ref.16
Experimental info
	Sequence conflict	42	1	V → K AA sequence Ref.14
	Sequence conflict	47	1	C → D AA sequence Ref.14
	Sequence conflict	75	1	E → G in AAV38498. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	P21246 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 0359C08B6497B579	FASTA	168	18,942
	10 20 30 40 50 60 MQAQQYQQQR RKFAAAFLAF IFILAAVDTA EAGKKEKPEK KVKKSDCGEW QWSVCVPTSG 70 80 90 100 110 120 DCGLGTREGT RTGAECKQTM KTQRCKIPCN WKKQFGAECK YQFQAWGECD LNTALKTRTG 130 140 150 160 SLKRALHNAE CQKTVTISKP CGKLTKPKPQ AESKKKKKEG KKQEKMLD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of mouse and human cDNA clones encoding a protein expressed specifically in osteoblasts and brain tissues." Tezuka K.I., Takeshita S., Hakeda Y., Kumegawa M., Kikuno R., Hashimoto-Gotoh T. Biochem. Biophys. Res. Commun. 173:246-251(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity." Li Y.-S., Milner P.G., Chauhan A.K., Watson M.A., Hoffman R.M., Kodner C.M., Milbrandt J., Deuel T.F. Science 250:1690-1694(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins." Kretschmer P.J., Fairhurst J.L., Decker M.M., Chan C.P., Gluzman Y., Boehlen P., Kovesdi I. Growth Factors 5:99-114(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION.
[4]	"Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene." Milner P.G., Shah D., Veile R., Donis-Keller H., Kumar B.V. Biochemistry 31:12023-12028(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant." Kretschmer P.J., Fairhurst J.L., Hulmes J.D., Popjes M.L., Boehlen P., Kovesdi I. Biochem. Biophys. Res. Commun. 192:420-429(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1." Masuda H., Tsujimura A., Yoshioka M., Arai Y., Kuboki Y., Mukai T., Nakamura T., Tsuji H., Nakagawa M., Hashimoto-Gotoh T. Biochem. Biophys. Res. Commun. 238:528-533(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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]. Tissue: Brain and Cerebellum.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"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 (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[10]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	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].
[12]	"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]. Tissue: Prostate.
[13]	"Amino-terminal sequences of a novel heparin-binding protein from human, bovine, rat, and chick brain: high interspecies homology." Huber D., Gautschi-Sova P., Bohlen P. Neurochem. Res. 15:435-439(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-58. Tissue: Brain.
[14]	"A heparin-binding growth factor secreted from breast cancer cells homologous to a developmentally regulated cytokine." Wellsein A., Fang W., Khatri A., Lu Y., Swain S.S., Dickson R.B., Sasse J., Riegel A.T., Lippman M.E. J. Biol. Chem. 267:2582-2587(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-52.
[15]	"Identification of novel heparin-releasable proteins, as well as the cytokines midkine and pleiotrophin, in human postheparin plasma." Novotny W.F., Maffi T., Mehta R.L., Milner P.G. Arterioscler. Thromb. 13:1798-1805(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 33-49, INDUCTION. Tissue: Plasma.
[16]	"Comparison of the disulfide bond arrangements of human recombinant and bovine brain heparin binding neurite-promoting factors." Hulmes J.D., Seddon A.P., Decker M.M., Bohlen P. Biochem. Biophys. Res. Commun. 192:738-746(1993) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[17]	"Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin." Stoica G.E., Kuo A., Aigner A., Sunitha I., Souttou B., Malerczyk C., Caughey D.J., Wen D., Karavanov A., Riegel A.T., Wellstein A. J. Biol. Chem. 276:16772-16779(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ALK, FUNCTION.
[18]	"Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome." Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., Paes Leme A.F., Kobarg J. J. Proteome Res. 9:6298-6316(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK6, PHOSPHORYLATION BY NEK6.
+	Additional computationally mapped references.

Web resources

Wikipedia

Pleiotrophin entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	D90226 mRNA. Translation: BAA14261.1. X52946 mRNA. Translation: CAA37121.1. M57399 mRNA. Translation: AAA35961.1. S50409 , S50405, S50408, S50394 Genomic DNA. Translation: AAB24425.1. S60110 , S59641, S60111, S60736 Genomic DNA. Translation: AAB26456.1. AB004306 Genomic DNA. Translation: BAA22944.1. AK290488 mRNA. Translation: BAF83177.1. AK313424 mRNA. Translation: BAG36216.1. CR450338 mRNA. Translation: CAG29334.1. BT019692 mRNA. Translation: AAV38498.1. CH236950 Genomic DNA. Translation: EAL24052.1. CH471070 Genomic DNA. Translation: EAW83869.1. BC005916 mRNA. Translation: AAH05916.1.
IPI	IPI00412264.
PIR	C37780. JN0474.
RefSeq	NP_002816.1. NM_002825.5.
UniGene	Hs.371249.
3D structure databases
ProteinModelPortal	P21246.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-5953N.
IntAct	P21246. 83 interactions.
MINT	MINT-1374580.
STRING	9606.ENSP00000341170.
PTM databases
PhosphoSite	P21246.
Polymorphism databases
DMDM	131553.
Proteomic databases
PaxDb	P21246.
PRIDE	P21246.
Protocols and materials databases
DNASU	5764.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000348225; ENSP00000341170; ENSG00000105894.
GeneID	5764.
KEGG	hsa:5764.
UCSC	uc003vtq.2. human.
Organism-specific databases
CTD	5764.
GeneCards	GC07M136912.
HGNC	HGNC:9630. PTN.
HPA	CAB017685.
MIM	162095. gene.
neXtProt	NX_P21246.
PharmGKB	PA33974.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39583.
HOGENOM	HOG000231473.
HOVERGEN	HBG008317.
InParanoid	P21246.
KO	K16642.
OMA	QQRRMFT.
OrthoDB	EOG4CRM1M.
PhylomeDB	P21246.
Enzyme and pathway databases
Pathway_Interaction_DB	syndecan_3_pathway. Syndecan-3-mediated signaling events.
Gene expression databases
ArrayExpress	P21246.
Bgee	P21246.
CleanEx	HS_PTN.
Genevestigator	P21246.
GermOnline	ENSG00000105894. Homo sapiens.
Family and domain databases
Gene3D	2.20.60.10. 1 hit. 2.30.90.10. 1 hit.
InterPro	IPR000762. Midkine_heparin-bd_GF. IPR020090. PTN/MK_heparin-bd_GF_C_dom. IPR020091. PTN/MK_heparin-bd_GF_diS. IPR020089. PTN/MK_heparin-bd_GF_N_dom. IPR020092. PTN_MK_heparin-bd_GF_CS. [Graphical view]
PANTHER	PTHR13850. PTHR13850. 1 hit.
Pfam	PF01091. PTN_MK_C. 1 hit. PF05196. PTN_MK_N. 1 hit. [Graphical view]
PRINTS	PR00269. PTNMIDKINE.
ProDom	PD005592. PTN_MK_hepar_bd. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00193. PTN. 1 hit. [Graphical view]
SUPFAM	SSF57288. PTN_MK_hepar_bd. 2 hits.
PROSITE	PS00619. PTN_MK_1. 1 hit. PS00620. PTN_MK_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PTN. human.
GenomeRNAi	5764.
NextBio	22426.
PMAP-CutDB	P21246.
SOURCE	Search...

Entry information

Entry name

PTN_HUMAN

Accession

Primary (citable) accession number: P21246
Secondary accession number(s): Q5U0B0, Q6ICQ5, Q9UCC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 130 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.