Q9C004 (SPY4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein sprouty homolog 4
Short name=Spry-4

Gene names

Name:

SPRY4

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	299 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras. Inhibits Ras-independent, but not Ras-dependent, activation of RAF1. Ref.6
Subunit structure	Interacts with the C-terminus of TESK1. Interacts with RAF1. Ref.1 Ref.6
Subcellular location	Cytoplasm. Cell projection › ruffle membrane; Peripheral membrane protein; Cytoplasmic side Potential Ref.1.
Domain	The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Sequence similarities	Belongs to the sprouty family. Contains 1 SPR (sprouty) domain.
Sequence caution	The sequence AAK00652.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TESK1	Q15569	4	EBI-354861,EBI-354852

Alternative products

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

Isoform A (identifier: Q9C004-1)

Also known as: Sprouty-4A;

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 C (identifier: Q9C004-2)

Also known as: Sprouty-4C;

The sequence of this isoform differs from the canonical sequence as follows:
     97-106: SSVSSSSSTS → CSATCLPPAA
     107-299: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 299	299	Protein sprouty homolog 4		PRO_0000076905
Regions
	Domain	166 – 273	108	SPR
	Compositional bias	97 – 107	11	Poly-Ser
	Compositional bias	159 – 283	125	Cys-rich
Amino acid modifications
	Modified residue	125	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	97 – 106	10	SSVSSSSSTS → CSATCLPPAA in isoform C.		VSP_006219
	Alternative sequence	107 – 299	193	Missing in isoform C.		VSP_006220
Experimental info
	Sequence conflict	102	1	S → N in AAI25097. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (Sprouty-4A) [UniParc]. Last modified July 11, 2001. Version 2. Checksum: 105F6F1BE9F7B6C3	FASTA	299	32,541
	10 20 30 40 50 60 MEPPIPQSAP LTPNSVMVQP LLDSRMSHSR LQHPLTILPI DQVKTSHVEN DYIDNPSLAL 70 80 90 100 110 120 TTGPKRTRGG APELAPTPAR CDQDVTHHWI SFSGRPSSVS SSSSTSSDQR LLDHMAPPPV 130 140 150 160 170 180 ADQASPRAVR IQPKVVHCQP LDLKGPAVPP ELDKHFLLCE ACGKCKCKEC ASPRTLPSCW 190 200 210 220 230 240 VCNQECLCSA QTLVNYGTCM CLVQGIFYHC TNEDDEGSCA DHPCSCSRSN CCARWSFMGA 250 260 270 280 290 LSVVLPCLLC YLPATGCVKL AQRGYDRLRR PGCRCKHTNS VICKAASGDA KTSRPDKPF
	Isoform C (Sprouty-4C) [UniParc]. Checksum: 6158571E3477A598	FASTA	106	11,482
	10 20 30 40 50 60 MEPPIPQSAP LTPNSVMVQP LLDSRMSHSR LQHPLTILPI DQVKTSHVEN DYIDNPSLAL 70 80 90 100 TTGPKRTRGG APELAPTPAR CDQDVTHHWI SFSGRPCSAT CLPPAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1." Leeksma O.C., van Achterberg T.A.E., Tsumura Y., Toshima J., Eldering E., Kroes W.G.M., Mellink C., Spaargaren M., Mizuno K., Pannekoek H., de Vries C.J.M. Eur. J. Biochem. 269:2546-2556(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C), CHARACTERIZATION, SUBCELLULAR LOCATION, INTERACTION WITH TESK1. Tissue: Umbilical artery.
[2]	"Genomic structure and promoter characterization of the human Sprouty4 gene, a novel regulator of lung morphogenesis." Ding W., Bellusci S., Shi W., Warburton D. Am. J. Physiol. 287:L52-L59(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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] (ISOFORM A). Tissue: Brain.
[4]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM A).
[6]	"Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1." Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., Kuriyama M., Saito N., Shibuya M., Yoshimura A. Nat. Cell Biol. 5:427-432(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAF1.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF227516 mRNA. Translation: AAK00652.1. Different initiation.
AF227517 mRNA. Translation: AAK00653.1.
AY538661 Genomic DNA. Translation: AAS46253.1.
AK096464 mRNA. Translation: BAC04798.1.
AC091825 Genomic DNA. No translation available.
BC125095 mRNA. Translation: AAI25096.1.
BC125096 mRNA. Translation: AAI25097.1.

IPI

IPI00221316.
IPI00895795.

RefSeq

NP_001120968.1. NM_001127496.1.
NP_112226.2. NM_030964.3.

UniGene

Hs.323308.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BUN	X-ray	2.00	A	46-58	[»]

ProteinModelPortal

Q9C004.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9C004. 1 interaction.

MINT

MINT-6538953.

STRING

9606.ENSP00000344967.

PTM databases

PhosphoSite

Q9C004.

Polymorphism databases

DMDM

14916719.

Proteomic databases

PaxDb

Q9C004.

PRIDE

Q9C004.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344120; ENSP00000344967; ENSG00000187678.
ENST00000434127; ENSP00000399468; ENSG00000187678.

GeneID

81848.

KEGG

hsa:81848.

UCSC

uc003lml.2. human.

Organism-specific databases

CTD

81848.

GeneCards

GC05M141670.

HGNC

HGNC:15533. SPRY4.

HPA

CAB008086.

MIM

607984. gene.

neXtProt

NX_Q9C004.

PharmGKB

PA37975.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG68509.

HOGENOM

HOG000233079.

HOVERGEN

HBG003544.

InParanoid

Q9C004.

KO

K04704.

OrthoDB

EOG4THVTX.

Gene expression databases

ArrayExpress

Q9C004.

Bgee

Q9C004.

CleanEx

HS_SPRY4.

Genevestigator

Q9C004.

GermOnline

ENSG00000187678. Homo sapiens.

Family and domain databases

InterPro

IPR007875. Sprouty.
[Graphical view]

Pfam

PF05210. Sprouty. 1 hit.
[Graphical view]

PROSITE

PS51227. SPR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SPRY4. human.

EvolutionaryTrace

Q9C004.

GenomeRNAi

81848.

NextBio

72154.

SOURCE

Search...

Entry information

Entry name

SPY4_HUMAN

Accession

Primary (citable) accession number: Q9C004
Secondary accession number(s): A4FVB2 , A4FVB3, Q6QIX2, Q9C003

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2001
Last sequence update:	July 11, 2001
Last modified:	April 3, 2013
This is version 101 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.