Q60598 (SRC8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Src substrate cortactin

Gene names

Name:	Cttn
Synonyms:	Ems1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	546 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Contributes to the organization of the actin cytoskeleton and cell structure. In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement By similarity. Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density By similarity. Plays a role in the regulation of cell migration. Plays a role in the invasiveness of cancer cells, and the formation of metastases. Ref.7 Ref.12
Subunit structure	Interacts with SHANK2 and SHANK3 (via its SH3 domain). Interacts with PLXDC2 and SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3 domain) with ASAP1 (via Pro-rich region). Interacts with DNM2 and FER. Forms a complex with ABL1 and MYLK By similarity. Interacts with FGD1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ABL2. Interacts with CTTNBP2NL; this interaction may target CTTN to stress fibers. Interacts with CTTNBP2; this interaction may target CTTN at the cell cortex or dendritic spines. Ref.5 Ref.6 Ref.12 Ref.13 Ref.14
Subcellular location	Cytoplasm › cytoskeleton. Cell projection › lamellipodium. Cell projection › ruffle. Cytoplasm › cell cortex. Cell projection › dendritic spine By similarity. Cell projection › dendrite By similarity. Note: Associated with membrane ruffles and lamellipodia. In the presence of CTTNBP2NL, colocalizes with stress fibers. In the presence of CTTNBP2, localizes at the cell cortex. In response to neuronal activation by glutamate, redistributes from dendritic spines to the dendritic shaft By similarity. Ref.6 Ref.12 Ref.13
Tissue specificity	Expressed in most tissues, except in B-lymphocytes or plasma cells.
Domain	The SH3 motif may mediate binding to the cytoskeleton.
Post-translational modification	Phosphorylated by FER. Phosphorylated in response to FGR activation. Phosphorylation by SRC promotes MYLK binding By similarity. Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation. Phosphorylated by PKN2 at both serine and threonine residues in a GTP-bound Rac1-dependent manner in hyaluronan-induced astrocytes and hence down-regulated CTTN ability to associate with filamentous actin. Ref.7 Ref.11
Sequence similarities	Contains 7 cortactin repeats. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Cytoskeleton
Domain	Repeat SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	cell cortex Inferred from direct assay Ref.6. Source: MGI cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell dendritic spine Inferred from electronic annotation. Source: UniProtKB-SubCell lamellipodium Inferred from direct assay Ref.6. Source: UniProtKB ruffle Inferred from direct assay PubMed 10637315Ref.6. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTR3	P61157	4	EBI-397955,EBI-351419	From a different organism.
Actr3	Q99JY9	5	EBI-397955,EBI-773994
Cfl1	P45592	2	EBI-397955,EBI-917556	From a different organism.
Dnm2	P39054	2	EBI-397955,EBI-642337
WASL	Q95107	2	EBI-397955,EBI-6162776	From a different organism.
Wasl	Q91YD9	4	EBI-397955,EBI-642417
WIPF1	O43516	3	EBI-397955,EBI-346356	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 546

546

Src substrate cortactin

PRO_0000072190

Regions

Repeat

80 – 116

37

Cortactin 1

Repeat

117 – 153

37

Cortactin 2

Repeat

154 – 190

37

Cortactin 3

Repeat

191 – 227

37

Cortactin 4

Repeat

228 – 264

37

Cortactin 5

Repeat

265 – 301

37

Cortactin 6

Repeat

302 – 324

23

Cortactin 7; truncated

Domain

488 – 546

59

SH3

Amino acid modifications

Modified residue

87

1

N6-acetyllysine By similarity

Modified residue

198

1

N6-acetyllysine By similarity

Modified residue

235

1

N6-acetyllysine By similarity

Modified residue

272

1

N6-acetyllysine By similarity

Modified residue

304

1

N6-acetyllysine By similarity

Modified residue

309

1

N6-acetyllysine By similarity

Modified residue

401

1

Phosphothreonine Ref.9 Ref.10

Modified residue

405

1

Phosphoserine Ref.9

Modified residue

407

1

Phosphoserine Ref.9

Modified residue

417

1

Phosphoserine By similarity

Modified residue

418

1

Phosphoserine Ref.8

Modified residue

421

1

Phosphotyrosine By similarity

Modified residue

442

1

Phosphotyrosine By similarity

Modified residue

482

1

Phosphotyrosine; by SRC Ref.11

Modified residue

485

1

Phosphotyrosine; by SRC Ref.11

Experimental info

Sequence conflict

9

1

A → R AA sequence Ref.2

Sequence conflict

298

1

S → P in AAA19689. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

546

Helix Strand Turn

Details...

Beta strand

493 – 495

3

Beta strand

514 – 519

6

Beta strand

522 – 530

9

Beta strand

533 – 538

6

Helix

539 – 541

3

Beta strand

542 – 544

3

Sequences

	Sequence		Length	Mass (Da)
	Q60598 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 8F5CA026ACCD6D4F	FASTA	546	61,250
	10 20 30 40 50 60 MWKASAGHAV SITQDDGGAD DWETDPDFVN DVSEKEQRWG AKTVQGSGHQ EHINIHKLRE 70 80 90 100 110 120 NVFQEHQTLK EKELETGPKA SHGYGGKFGV EQDRMDRSAV GHEYQSKLSK HCSQVDSVRG 130 140 150 160 170 180 FGGKFGVQMD RVDQSAVGFE YQGKTEKHAS QKDYSSGFGG KYGVQADRVD KSAVGFDYQG 190 200 210 220 230 240 KTEKHESQKD YSKGFGGKYG IDKDKVDKSA VGFEYQGKTE KHESQKDYVK GFGGKFGVQT 250 260 270 280 290 300 DRQDKCALGW DHQEKLQLHE SQKDYKTGFG GKFGVQSERQ DSSAVGFDYK ERLAKHESQQ 310 320 330 340 350 360 DYAKGFGGKY GVQKDRMDKN ASTFEEVVQV PSAYQKTVPI EAVTSKTSNI RANFENLAKE 370 380 390 400 410 420 REQEDRRKAE AERAQRMAKE RQEQEEARRK LEEQARAKKQ TPPASPSPQP IEDRPPSSPI 430 440 450 460 470 480 YEDAAPFKAE PSYRGSEPEP EYSIEAAGIP EAGSQQGLTY TSEPVYETTE APGHYQAEDD 490 500 510 520 530 540 TYDGYESDLG ITAIALYDYQ AAGDDEISFD PDDIITNIEM IDDGWWRGVC KGRYGLFPAN YVELRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The protein tyrosine kinase substrate cortactin is differentially expressed in murine B lymphoid tumors." Miglarese M.R., Mannion-Henderson J., Wu H., Parsons J.T., Bender T.P. Oncogene 9:1989-1997(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Murine cortactin is phosphorylated in response to fibroblast growth factor-1 on tyrosine residues late in the G1 phase of the BALB/c 3T3 cell cycle." Zhan X., Hu X., Hampton B., Burgess W.H., Friesel R., Maciag T. J. Biol. Chem. 268:24427-24431(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 125-138; 273-289 AND 534-543.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Amnion and Heart.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling." Cavallaro U., Niedermeyer J., Fuxa M., Christofori G. Nat. Cell Biol. 3:650-657(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; SHC1; FGFR4 AND GAP43.
[6]	"Fgd1, the Cdc42 GEF responsible for faciogenital dysplasia, directly interacts with cortactin and mAbp1 to modulate cell shape." Hou P., Estrada L., Kinley A.W., Parsons J.T., Vojtek A.B., Gorski J.L. Hum. Mol. Genet. 12:1981-1993(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH FGD1.
[7]	"Hyaluronan-CD44 interaction stimulates Rac1 signaling and PKN gamma kinase activation leading to cytoskeleton function and cell migration in astrocytes." Bourguignon L.Y., Gilad E., Peyrollier K., Brightman A., Swanson R.A. J. Neurochem. 101:1002-1017(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIN BUNDLE FORMATION, PHOSPHORYLATION.
[8]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, MASS SPECTROMETRY. Tissue: Brain cortex.
[9]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401; SER-405 AND SER-407, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-401, MASS SPECTROMETRY. Tissue: Melanoma.
[11]	"Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin." Mukherjee M., Chow S.Y., Yusoff P., Seetharaman J., Ng C., Sinniah S., Koh X.W., Asgar N.F., Li D., Yim D., Jackson R.A., Yew J., Qian J., Iyu A., Lim Y.P., Zhou X., Sze S.K., Guy G.R., Sivaraman J. EMBO J. 31:1308-1319(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-482 AND TYR-485.
[12]	"Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance." Chen Y.K., Hsueh Y.P. J. Neurosci. 32:1043-1055(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CTTNBP2, SUBCELLULAR LOCATION.
[13]	"CTTNBP2, but not CTTNBP2NL, regulates dendritic spinogenesis and synaptic distribution of the striatin-PP2A complex." Chen Y.K., Chen C.Y., Hu H.T., Hsueh Y.P. Mol. Biol. Cell 23:4383-4392(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CTTNBP2NL, SUBCELLULAR LOCATION.
[14]	"Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin-Arg-lysozyme complex." Liu W., MacGrath S.M., Koleske A.J., Boggon T.J. Acta Crystallogr. F 68:154-158(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 487-546 IN COMPLEX WITH ABL2, INTERACTION WITH ABL2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U03184 mRNA. Translation: AAA19689.1.
AK146856 mRNA. Translation: BAE27485.1.
AK148010 mRNA. Translation: BAE28287.1.
AK168699 mRNA. Translation: BAE40543.1.
CH466531 Genomic DNA. Translation: EDL18251.1.

IPI

IPI00118143.

PIR

I48899.

RefSeq

NP_031829.2. NM_007803.5.

UniGene

Mm.205601.
Mm.490123.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F9X	model	-	A	1-546	[»]
3ULR	X-ray	1.65	B	487-546	[»]

ProteinModelPortal

Q60598.

SMR

Q60598. Positions 487-546.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31562N.

IntAct

Q60598. 23 interactions.

MINT

MINT-100616.

PTM databases

PhosphoSite

Q60598.

Proteomic databases

PaxDb

Q60598.

PRIDE

Q60598.

Protocols and materials databases

DNASU

13043.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000103079; ENSMUSP00000099368; ENSMUSG00000031078.

GeneID

13043.

KEGG

mmu:13043.

UCSC

uc009kqh.2. mouse.

Organism-specific databases

CTD

2017.

MGI

MGI:99695. Cttn.

Phylogenomic databases

eggNOG

NOG123488.

GeneTree

ENSGT00530000062953.

HOGENOM

HOG000006523.

HOVERGEN

HBG005994.

InParanoid

Q3UGC2.

KO

K06106.

OMA

SQQDYSK.

OrthoDB

EOG4RNB86.

Gene expression databases

ArrayExpress

Q60598.

Bgee

Q60598.

CleanEx

MM_CTTN.

Genevestigator

Q60598.

GermOnline

ENSMUSG00000031078. Mus musculus.

Family and domain databases

InterPro

IPR015503. Cortactin.
IPR003134. Hs1_Cortactin.
IPR000108. p67phox.
IPR001452. SH3_domain.
[Graphical view]

PANTHER

PTHR10829:SF4. PTHR10829:SF4. 1 hit.

Pfam

PF02218. HS1_rep. 7 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

SMART

SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.

PROSITE

PS51090. CORTACTIN. 7 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

282940.

SOURCE

Search...

Entry information

Entry name

SRC8_MOUSE

Accession

Primary (citable) accession number: Q60598
Secondary accession number(s): Q3UGC2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program