P46109 (CRKL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Crk-like protein

Gene names

Name:

CRKL

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

General annotation (Comments)

Function	May mediate the transduction of intracellular signals.
Subunit structure	Interacts with INPP5D/SHIP1. Interacts with DOCK2 and EPOR. Interacts with phosphorylated CBLB and IRS4. Ref.6 Ref.7 Ref.8 Ref.9
Sequence similarities	Belongs to the CRK family. Contains 1 SH2 domain. Contains 2 SH3 domains.

Ontologies

Keywords
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	JNK cascade Traceable author statement. Source: ProtInc Ras protein signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	SH3/SH2 adaptor activity Traceable author statement. Source: ProtInc protein tyrosine kinase activity Traceable author statement. Source: ProtInc signal transducer activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Kidins220	Q9EQG6	2	EBI-910,EBI-976654	From a different organism.
MAP4K1	Q92918	5	EBI-910,EBI-881

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 303

303

Crk-like protein

PRO_0000079347

Regions

Domain

14 – 102

89

SH2

Domain

123 – 183

61

SH3 1

Domain

235 – 296

62

SH3 2

Amino acid modifications

Modified residue

107

1

Phosphoserine By similarity

Modified residue

127

1

Phosphotyrosine Ref.13

Modified residue

132

1

Phosphotyrosine Ref.11 Ref.12

Modified residue

198

1

Phosphotyrosine Ref.11

Modified residue

207

1

Phosphotyrosine Ref.10 Ref.12

Modified residue

251

1

Phosphotyrosine Ref.10 Ref.12

Secondary structure

1

.

.

.

.

.

.

.

.

.

303

Helix Strand Turn

Details...

Beta strand

240 – 242

3

Beta strand

271 – 276

6

Beta strand

285 – 287

3

Helix

288 – 290

3

Beta strand

291 – 293

3

Sequences

	Sequence		Length	Mass (Da)
	P46109 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 294CF1EE2CD44B81	FASTA	303	33,777
	10 20 30 40 50 60 MSSARFDSSD RSAWYMGPVS RQEAQTRLQG QRHGMFLVRD SSTCPGDYVL SVSENSRVSH 70 80 90 100 110 120 YIINSLPNRR FKIGDQEFDH LPALLEFYKI HYLDTTTLIE PAPRYPSPPM GSVSAPNLPT 130 140 150 160 170 180 AEDNLEYVRT LYDFPGNDAE DLPFKKGEIL VIIEKPEEQW WSARNKDGRV GMIPVPYVEK 190 200 210 220 230 240 LVRSSPHGKH GNRNSNSYGI PEPAHAYAQP QTTTPLPAVS GSPGAAITPL PSTQNGPVFA 250 260 270 280 290 300 KAIQKRVPCA YDKTALALEV GDIVKVTRMN INGQWEGEVN GRKGLFPFTH VKIFDPQNPD ENE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and chromosomal localization of CRKL, a human crk-like gene." ten Hoeve J., Morris C., Heisterkamp N., Groffen J. Oncogene 8:2469-2474(1993) [PubMed: 8361759] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction." Koval A.P., Karas M., Zick Y., LeRoith D. J. Biol. Chem. 273:14780-14787(1998) [PubMed: 9614078] [Abstract] Cited for: INTERACTION WITH IRS4.
[7]	"Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation." Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C. Oncogene 18:1147-1156(1999) [PubMed: 10022120] [Abstract] Cited for: INTERACTION WITH CBLB.
[8]	"DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines." Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S. Blood 100:3968-3974(2002) [PubMed: 12393632] [Abstract] Cited for: INTERACTION WITH DOCK2.
[9]	"CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling." Arai A., Kanda E., Nosaka Y., Miyasaka N., Miura O. J. Biol. Chem. 276:33282-33290(2001) [PubMed: 11443118] [Abstract] Cited for: INTERACTION WITH EPOR.
[10]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207 AND TYR-251, MASS SPECTROMETRY.
[11]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-132 AND TYR-198, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-132; TYR-207 AND TYR-251, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-127, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Solution structures of the SH3 domain of human CRK-like protein." RIKEN structural genomics initiative (RSGI) Submitted (DEC-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 220-303.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X59656 mRNA. Translation: CAA42199.1.
CR456423 mRNA. Translation: CAG30309.1.
AK292909 mRNA. Translation: BAF85598.1.
CH471176 Genomic DNA. Translation: EAX02932.1.
CH471176 Genomic DNA. Translation: EAX02933.1.
CH471176 Genomic DNA. Translation: EAX02934.1.
BC043500 mRNA. Translation: AAH43500.1.

IPI

IPI00004839.

PIR

S41754.

RefSeq

NP_005198.1. NM_005207.3.

UniGene

Hs.5613.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BZX	X-ray	2.80	A	237-303	[»]
2BZY	X-ray	2.50	A/B	237-303	[»]
2DBK	NMR	-	A	229-303	[»]
2EO3	NMR	-	A	1-104	[»]

ProteinModelPortal

P46109.

SMR

P46109. Positions 3-180, 229-303.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29165N.

IntAct

P46109. 26 interactions.

MINT

MINT-137265.

STRING

P46109.

PTM databases

PhosphoSite

P46109.

Polymorphism databases

DMDM

1169094.

2D gel databases

OGP

P46109.

Proteomic databases

PeptideAtlas

P46109.

PRIDE

P46109.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000354336; ENSP00000346300; ENSG00000099942.
ENST00000411769; ENSP00000396646; ENSG00000099942.

GeneID

1399.

KEGG

hsa:1399.

UCSC

uc002ztf.1. human.

Organism-specific databases

CTD

1399.

GeneCards

GC22P021272.

H-InvDB

HIX0203154.

HGNC

HGNC:2363. CRKL.

HPA

HPA001100.

MIM

602007. gene.

neXtProt

NX_P46109.

PharmGKB

PA26881.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG07522.

GeneTree

ENSGT00390000001475.

HOGENOM

HBG314739.

HOVERGEN

HBG105616.

InParanoid

P46109.

OMA

QNRLQGQ.

OrthoDB

EOG4NS3C3.

PhylomeDB

P46109.

Enzyme and pathway databases

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
epopathway. EPO signaling pathway.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
tcrjnkpathway. JNK signaling in the CD4+ TCR pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrapathway. PDGFR-alpha signaling pathway.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P46109.

Bgee

P46109.

CleanEx

HS_CRKL.

Genevestigator

P46109.

GermOnline

ENSG00000099942. Homo sapiens.

Family and domain databases

InterPro

IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

KO

K04438.

Pfam

PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.

SMART

SM00252. SH2. 1 hit.
SM00326. SH3. 2 hits.
[Graphical view]

SUPFAM

SSF50044. SH3. 2 hits.

PROSITE

PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

5727.

SOURCE

Search...

Entry information

Entry name

CRKL_HUMAN

Accession

Primary (citable) accession number: P46109
Secondary accession number(s): A8KA44, D3DX35

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 118 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.