P35443 (TSP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thrombospondin-4

Gene names

Name:	THBS4
Synonyms:	TSP4

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	961 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	Acts as an extracellular mitogen and stimulates early erythroid progenitors proliferation in presence of EPO. Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Can bind to fibrinogen, fibronectin, laminin and type V collagen. Ref.6
Subunit structure	Homopentamer; disulfide-linked. Interacts with PTBP3. Ref.2 Ref.6
Sequence similarities	Belongs to the thrombospondin family. Contains 4 EGF-like domains. Contains 1 laminin G-like domain. Contains 1 TSP C-terminal (TSPC) domain. Contains 8 TSP type-3 repeats.

Ontologies

Keywords
Biological process	Cell adhesion
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Growth factor Mitogen
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endothelial cell-cell adhesion Inferred from direct assay PubMed 12952849. Source: UniProtKB myoblast migration Inferred from direct assay PubMed 7519904. Source: UniProtKB negative regulation of angiogenesis Inferred from expression pattern PubMed 18802666. Source: UniProtKB positive regulation of cell division Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of endothelial cell proliferation Inferred from direct assay PubMed 12952849. Source: UniProtKB positive regulation of neutrophil chemotaxis Inferred from direct assay PubMed 16099885. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 16099885. Source: UniProtKB
Cellular_component	basement membrane Inferred from direct assay PubMed 17927980. Source: UniProtKB extracellular space Inferred from direct assay PubMed 12952849PubMed 18802666. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from direct assay PubMed 16246837Ref.2. Source: UniProtKB heparin binding Inferred from direct assay Ref.2. Source: UniProtKB integrin binding Inferred from direct assay PubMed 16099885. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 961	935	Thrombospondin-4		PRO_0000035852
Regions
	Domain	27 – 192	166	Laminin G-like
	Domain	286 – 325	40	EGF-like 1
	Domain	326 – 363	38	EGF-like 2; calcium-binding Potential
	Domain	379 – 419	41	EGF-like 3; calcium-binding Potential
	Domain	420 – 462	43	EGF-like 4
	Repeat	463 – 495	33	TSP type-3 1
	Repeat	496 – 531	36	TSP type-3 2
	Repeat	532 – 554	23	TSP type-3 3
	Repeat	555 – 590	36	TSP type-3 4
	Repeat	591 – 613	23	TSP type-3 5
	Repeat	614 – 651	38	TSP type-3 6
	Repeat	652 – 691	40	TSP type-3 7
	Repeat	692 – 727	36	TSP type-3 8
	Domain	731 – 945	215	TSP C-terminal
	Motif	562 – 564	3	Cell attachment site Potential
Amino acid modifications
	Glycosylation	612	1	N-linked (GlcNAc...) Potential
	Glycosylation	941	1	N-linked (GlcNAc...) Potential
	Disulfide bond	258		Interchain Probable
	Disulfide bond	261		Interchain Probable
	Disulfide bond	290 ↔ 301		By similarity
	Disulfide bond	295 ↔ 310		By similarity
	Disulfide bond	313 ↔ 324		By similarity
	Disulfide bond	330 ↔ 341		By similarity
	Disulfide bond	335 ↔ 350		By similarity
	Disulfide bond	353 ↔ 377		By similarity
	Disulfide bond	383 ↔ 394		By similarity
	Disulfide bond	388 ↔ 403		By similarity
	Disulfide bond	406 ↔ 418		By similarity
	Disulfide bond	424 ↔ 438		By similarity
	Disulfide bond	432 ↔ 448		By similarity
	Disulfide bond	450 ↔ 461		By similarity
	Disulfide bond	477 ↔ 482		By similarity
	Disulfide bond	487 ↔ 507		By similarity
	Disulfide bond	523 ↔ 543		By similarity
	Disulfide bond	546 ↔ 566		By similarity
	Disulfide bond	582 ↔ 602		By similarity
	Disulfide bond	605 ↔ 625		By similarity
	Disulfide bond	643 ↔ 663		By similarity
	Disulfide bond	683 ↔ 703		By similarity
	Disulfide bond	719 ↔ 940		By similarity
Natural variations
	Natural variant	55	1	L → Q. Ref.4 Corresponds to variant rs17881847 [ dbSNP | Ensembl ].		VAR_019951
	Natural variant	387	1	A → P. Ref.3 Ref.4 Corresponds to variant rs1866389 [ dbSNP | Ensembl ].		VAR_019952
	Natural variant	420	1	A → V. Ref.1 Ref.2 Ref.4 Corresponds to variant rs17882372 [ dbSNP | Ensembl ].		VAR_019953
	Natural variant	646	1	V → I. Ref.4 Corresponds to variant rs2229396 [ dbSNP | Ensembl ].		VAR_019954
	Natural variant	737	1	V → I. Corresponds to variant rs2229398 [ dbSNP | Ensembl ].		VAR_052659
Experimental info
	Sequence conflict	96	1	N → S no nucleotide entry Ref.1
	Sequence conflict	96	1	N → S Ref.2
	Sequence conflict	276	1	P → A no nucleotide entry Ref.1
	Sequence conflict	276	1	P → A in CAA79635. Ref.2
	Sequence conflict	737	1	V → G no nucleotide entry Ref.1
	Sequence conflict	737	1	V → G in CAA79635. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P35443 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: 18F867AA5FFDA54B	FASTA	961	105,869
	10 20 30 40 50 60 MLAPRGAAVL LLHLVLQRWL AAGAQATPQV FDLLPSSSQR LNPGALLPVL TDPALNDLYV 70 80 90 100 110 120 ISTFKLQTKS SATIFGLYSS TDNSKYFEFT VMGRLNKAIL RYLKNDGKVH LVVFNNLQLA 130 140 150 160 170 180 DGRRHRILLR LSNLQRGAGS LELYLDCIQV DSVHNLPRAF AGPSQKPETI ELRTFQRKPQ 190 200 210 220 230 240 DFLEELKLVV RGSLFQVASL QDCFLQQSEP LAATGTGDFN RQFLGQMTQL NQLLGEVKDL 250 260 270 280 290 300 LRQQVKETSF LRNTIAECQA CGPLKFQSPT PSTVVPPAPP APPTRPPRRC DSNPCFRGVQ 310 320 330 340 350 360 CTDSRDGFQC GPCPEGYTGN GITCIDVDEC KYHPCYPGVH CINLSPGFRC DACPVGFTGP 370 380 390 400 410 420 MVQGVGISFA KSNKQVCTDI DECRNGACVP NSICVNTLGS YRCGPCKPGY TGDQIRGCKA 430 440 450 460 470 480 ERNCRNPELN PCSVNAQCIE ERQGDVTCVC GVGWAGDGYI CGKDVDIDSY PDEELPCSAR 490 500 510 520 530 540 NCKKDNCKYV PNSGQEDADR DGIGDACDED ADGDGILNEQ DNCVLIHNVD QRNSDKDIFG 550 560 570 580 590 600 DACDNCLSVL NNDQKDTDGD GRGDACDDDM DGDGIKNILD NCPKFPNRDQ RDKDGDGVGD 610 620 630 640 650 660 ACDSCPDVSN PNQSDVDNDL VGDSCDTNQD SDGDGHQDST DNCPTVINSA QLDTDKDGIG 670 680 690 700 710 720 DECDDDDDND GIPDLVPPGP DNCRLVPNPA QEDSNSDGVG DICESDFDQD QVIDRIDVCP 730 740 750 760 770 780 ENAEVTLTDF RAYQTVVLDP EGDAQIDPNW VVLNQGMEIV QTMNSDPGLA VGYTAFNGVD 790 800 810 820 830 840 FEGTFHVNTQ TDDDYAGFIF GYQDSSSFYV VMWKQTEQTY WQATPFRAVA EPGIQLKAVK 850 860 870 880 890 900 SKTGPGEHLR NSLWHTGDTS DQVRLLWKDS RNVGWKDKVS YRWFLQHRPQ VGYIRVRFYE 910 920 930 940 950 960 GSELVADSGV TIDTTMRGGR LGVFCFSQEN IIWSNLKYRC NDTIPEDFQE FQTQNFDRFD N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The evolution of the thrombospondin gene family." Lawler J., Duquette M., Urry L., McHenry K., Smith T.F. J. Mol. Evol. 36:509-516(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-420. Tissue: Heart.
[2]	"Characterization of human thrombospondin-4." Lawler J., McHenry K., Duquette M., Derick L. J. Biol. Chem. 270:2809-2814(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-420, SUBUNIT.
[3]	"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], VARIANT PRO-387. Tissue: Synovium.
[4]	SeattleSNPs variation discovery resource Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-55; PRO-387; VAL-420 AND ILE-646.
[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]. Tissue: PNS.
[6]	"Regulator of differentiation 1 (ROD1) binds to the amphipathic C-terminal peptide of thrombospondin-4 and is involved in its mitogenic activity." Sadvakassova G., Dobocan M.C., Difalco M.R., Congote L.F. J. Cell. Physiol. 220:672-679(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, INTERACTION WITH PTBP3.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z19585 mRNA. Translation: CAA79635.1. AK313587 mRNA. Translation: BAG36356.1. AY566253 Genomic DNA. Translation: AAS66982.1. BC050456 mRNA. Translation: AAH50456.1.
IPI	IPI00328550.
PIR	TSHUP4. A55710.
RefSeq	NP_003239.2. NM_003248.4.
UniGene	Hs.211426.
3D structure databases
ProteinModelPortal	P35443.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35443. 1 interaction.
STRING	9606.ENSP00000339730.
PTM databases
PhosphoSite	P35443.
Polymorphism databases
DMDM	55977790.
Proteomic databases
PaxDb	P35443.
PeptideAtlas	P35443.
PRIDE	P35443.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000350881; ENSP00000339730; ENSG00000113296.
GeneID	7060.
KEGG	hsa:7060.
UCSC	uc021yaw.1. human.
Organism-specific databases
CTD	7060.
GeneCards	GC05P079287.
HGNC	HGNC:11788. THBS4.
HPA	CAB004597.
MIM	600715. gene.
neXtProt	NX_P35443.
PharmGKB	PA36500.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG12793.
HOGENOM	HOG000007542.
HOVERGEN	HBG000636.
InParanoid	P35443.
KO	K04659.
OMA	DSNPCFR.
OrthoDB	EOG4X0MRM.
PhylomeDB	P35443.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P35443.
Bgee	P35443.
CleanEx	HS_THBS4.
Genevestigator	P35443.
GermOnline	ENSG00000113296. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.200. 1 hit.
InterPro	IPR008985. ConA-like_lec_gl_sf. IPR013320. ConA-like_subgrp. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR018097. EGF_Ca-bd_CS. IPR001791. Laminin_G. IPR024665. Thbs/COMP_coiled-coil. IPR003367. Thrombospondin_3-like_rpt. IPR017897. Thrombospondin_3_rpt. IPR008859. Thrombospondin_C. [Graphical view]
Pfam	PF11598. COMP. 1 hit. PF07645. EGF_CA. 2 hits. PF02412. TSP_3. 6 hits. PF05735. TSP_C. 1 hit. [Graphical view]
SMART	SM00181. EGF. 2 hits. SM00179. EGF_CA. 2 hits. SM00210. TSPN. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 2 hits.
PROSITE	PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 4 hits. PS01187. EGF_CA. 2 hits. PS50025. LAM_G_DOMAIN. False negative. PS51234. TSP3. 8 hits. PS51236. TSP_CTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7060.
NextBio	27609.
SOURCE	Search...

Entry information

Entry name

TSP4_HUMAN

Accession

Primary (citable) accession number: P35443
Secondary accession number(s): B2R909, Q86TG2

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	November 23, 2004
Last modified:	May 1, 2013
This is version 135 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.