Reviewed, UniProtKB/Swiss-Prot Q7Z699 (SPRE1_HUMAN)

Names and origin

Protein names

Recommended name:
    Sprouty-related, EVH1 domain-containing protein 1
      Short name=Spred-1
      Short name=hSpred1

Gene names

Name:

SPRED1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase. Negatively regulates hematopoiesis of bone marrow By similarity.
Subunit structure	Interacts with Ras By similarity. Homodimer and heterodimer. Interacts with CAV1. Able to interact with SPRED2 to form heterodimers.
Subcellular location	Cell membrane › caveola; Peripheral membrane protein. Nucleus. Note= Localized in cholesterol-rich membrane raft/caveola fractions.
Tissue specificity	Weakly expressed in embryonic cell line (HEK-293).
Post-translational modification	Phosphorylated on tyrosine By similarity.
Involvement in disease	Defects in SPRED1 are the cause of neurofibromatosis type 1-like syndrome (NFLS) [MIM:611431]. Neurofibromatosis type 1 (NF1) is one of the most frequent autosomal dominant diseases. It belongs to the group of disorders known as the 'neuro-cardio-facial-cutaneous' syndromes, present with a variable degree of cognitive impairment, facial dysmorphism, congenital heart defects and skin abnormalities. NFLS is a form of these disorders with autosomal dominant trait consisting of multiple cafe-au-lait spots, axillary freckling, macrocephaly and a Noonan-like dysmorphy in some individuals.
Sequence similarities	Contains 1 KBD domain. Contains 1 SPR (sprouty) domain. Contains 1 WH1 domain.
Sequence caution	The sequence AAH18015.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Nucleus
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	inactivation of MAPK activity Inferred from sequence or structural similarity. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: InterPro regulation of signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	stem cell factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 444	444	Sprouty-related, EVH1 domain-containing protein 1		PRO_0000076907
Regions
	Domain	6 – 123	118	WH1
	Domain	233 – 285	53	KBD
	Domain	334 – 442	109	SPR
	Compositional bias	147 – 150	4	Poly-Ser
Experimental info
	Sequence conflict	6 – 7	2	AT → GL in AAP59414. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q7Z699-1 [UniParc]. Last modified January 4, 2005. Version 2. Checksum: 6FFDECCE590DB311	FASTA	444	50,477
	10 20 30 40 50 60 MSEETATSDN DNSYARVRAV VMTRDDSSGG WLPLGGSGLS SVTVFKVPHQ EENGCADFFI 70 80 90 100 110 120 RGERLRDKMV VLECMLKKDL IYNKVTPTFH HWKIDDKKFG LTFQSPADAR AFDRGIRRAI 130 140 150 160 170 180 EDISQGCPES KNEAEGADDL QANEEDSSSS LVKDHLFQQE TVVTSEPYRS SNIRPSPFED 190 200 210 220 230 240 LNARRVYMQS QANQITFGQP GLDIQSRSME YVQRQISKEC GSLKSQNRVP LKSIRHVSFQ 250 260 270 280 290 300 DEDEIVRINP RDILIRRYAD YRHPDMWKND LERDDADSSI QFSKPDSKKS DYLYSCGDET 310 320 330 340 350 360 KLSSPKDSVV FKTQPSSLKI KKSKRRKEDG ERSRCVYCQE RFNHEENVRG KCQDAPDPIK 370 380 390 400 410 420 RCIYQVSCML CAESMLYHCM SDSEGDFSDP CSCDTSDDKF CLRWLALVAL SFIVPCMCCY 430 440 VPLRMCHRCG EACGCCGGKH KAAG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Distinct requirements for the Sprouty domain for functional activity of Spred proteins." King J.A.J., Straffon A.F.L., D'Abaco G.M., Poon C.L.C., I S.T.T., Smith C.M., Buchert M., Corcoran N.M., Hall N.E., Callus B.A., Sarcevic B., Martin D., Lock P., Hovens C.M. Biochem. J. 388:445-454(2005) [PubMed: 15683364] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SPRED2. Tissue: Glioblastoma.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-268. Tissue: Brain.
[4]	"Expression and subcellular localization of Spred proteins in mouse and human tissues." Engelhardt C.M., Bundschu K., Messerschmitt M., Renne T., Walter U., Reinhard M., Schuh K. Histochem. Cell Biol. 122:527-538(2004) [PubMed: 15580519] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"The Sprouty-related protein, Spred-1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin-1." Nonami A., Taketomi T., Kimura A., Saeki K., Takaki H., Sanada T., Taniguchi K., Harada M., Kato R., Yoshimura A. Genes Cells 10:887-895(2005) [PubMed: 16115197] [Abstract] Cited for: INTERACTION WITH CAV1, SUBCELLULAR LOCATION.
[6]	"Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype." Brems H., Chmara M., Sahbatou M., Denayer E., Taniguchi K., Kato R., Somers R., Messiaen L., De Schepper S., Fryns J.-P., Cools J., Marynen P., Thomas G., Yoshimura A., Legius E. Nat. Genet. 39:1120-1126(2007) [PubMed: 17704776] [Abstract] Cited for: INVOLVEMENT IN NFLS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY299089 mRNA. Translation: AAP59414.1. AK091222 mRNA. Translation: BAC03614.1. BC018015 mRNA. Translation: AAH18015.1. Sequence problems.
RefSeq	NP_689807.1.
UniGene	Hs.525781
3D structure databases
HSSP	HSSP built from PDB template 1EGX based on UniProtKB P50552.
SMR	Q7Z699. Positions 10-126.
ModBase	Search...
PTM databases
PhosphoSite	Q7Z699.
Genome annotation databases
Ensembl	ENSG00000166068. Homo sapiens. [Contig view]
GeneID	161742.
KEGG	hsa:161742.
Organism-specific databases
HGNC	HGNC:20249. SPRED1.
MIM	609291. gene. 611431. phenotype.
Orphanet	137605. Neurofibromatosis 1-like syndrome.
PharmGKB	PA134897382.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q7Z699.
HOVERGEN	Q7Z699.
Gene expression databases
ArrayExpress	Q7Z699.
CleanEx	HS_SPRED1.
GermOnline	ENSG00000166068. Homo sapiens.
Family and domain databases
InterPro	IPR000697. EVH1. IPR011993. PH_type. IPR007875. Sprouty. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF05210. Sprouty. 1 hit. PF00568. WH1. 1 hit. [Graphical view]
PROSITE	PS51227. SPR. 1 hit. PS50229. WH1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	88102.
SOURCE	Search...

Entry information

Entry name

SPRE1_HUMAN

Accession

Primary (citable) accession number: Q7Z699
Secondary accession number(s): Q05D53, Q8N256

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	November 25, 2008
This is version 44 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)